Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy.

PubMed

Booth, Clair A; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W; Randall, Andrew D; Brown, Jonathan T

2016-01-13

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. Copyright © 2016 Booth, Witton et al.

Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB.

PubMed

Polito, Vinicia A; Li, Hongmei; Martini-Stoica, Heidi; Wang, Baiping; Yang, Li; Xu, Yin; Swartzlander, Daniel B; Palmieri, Michela; di Ronza, Alberto; Lee, Virginia M-Y; Sardiello, Marco; Ballabio, Andrea; Zheng, Hui

2014-09-01

Accumulating evidence implicates impairment of the autophagy-lysosome pathway in Alzheimer's disease (AD). Recently discovered, transcription factor EB (TFEB) is a molecule shown to play central roles in cellular degradative processes. Here we investigate the role of TFEB in AD mouse models. In this study, we demonstrate that TFEB effectively reduces neurofibrillary tangle pathology and rescues behavioral and synaptic deficits and neurodegeneration in the rTg4510 mouse model of tauopathy with no detectable adverse effects when expressed in wild-type mice. TFEB specifically targets hyperphosphorylated and misfolded Tau species present in both soluble and aggregated fractions while leaving normal Tau intact. We provide in vitro evidence that this effect requires lysosomal activity and we identify phosphatase and tensin homolog (PTEN) as a direct target of TFEB that is required for TFEB-dependent aberrant Tau clearance. The specificity and efficacy of TFEB in mediating the clearance of toxic Tau species makes it an attractive therapeutic target for treating diseases of tauopathy including AD. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Hsp90 activator Aha1 drives production of pathological tau aggregates

PubMed Central

Shelton, Lindsey B.; Baker, Jeremy D.; Zheng, Dali; Sullivan, Leia E.; Solanki, Parth K.; Webster, Jack M.; Sun, Zheying; Sabbagh, Jonathan J.; Nordhues, Bryce A.; Koren, John; Ghosh, Suman; Blagg, Brian S. J.; Dickey, Chad A.

2017-01-01

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. PMID:28827321

Metabolic changes over the course of aging in a mouse model of tau deposition

PubMed Central

Joly-Amado, Aurélie; Serraneau, Karisa S.; Brownlow, Milene; Marín de Evsikova, Caralina; Speakman, John R.; Gordon, Marcia N.; Morgan, Dave

2016-01-01

Weight loss and food intake disturbances that often precede cognitive decline and diagnosis have been extensively reported in Alzheimer’s disease patients. Previously, we observed that transgenic mice overexpressing tau seemed to eat more food, yet weigh less than non-transgenic littermates. Thus the present longitudinal study measured the time course of changes in metabolic state over the lifespan of the tau depositing Tg4510 mouse model of tau deposition. Although body weight was comparable to non-transgenic littermates at 2 months of age, Tg4510 mice weighed less at older ages. This was accompanied by the accumulation of tau pathology and by dramatically increased activity in all phases of the 24-hour cycle. Resting metabolic rate was also increased at 7 months of age. At 12 months near the end of the Tg4510 lifespan, there was a wasting phase, with a considerable decrease of resting metabolic rate, although hyperactivity was maintained. These diverse changes in metabolism in a mouse model of tau deposition are discussed in the context of known changes in energy metabolism in Alzheimer’s disease. PMID:27318134

RANK/RANKL/OPG Signalization Implication in Periodontitis: New Evidence from a RANK Transgenic Mouse Model

PubMed Central

Sojod, Bouchra; Chateau, Danielle; Mueller, Christopher G.; Babajko, Sylvie; Berdal, Ariane; Lézot, Frédéric; Castaneda, Beatriz

2017-01-01

Periodontitis is based on a complex inflammatory over-response combined with possible genetic predisposition factors. The RANKL/RANK/OPG signaling pathway is implicated in bone resorption through its key function in osteoclast differentiation and activation, as well as in the inflammatory response. This central element of osteo-immunology has been suggested to be perturbed in several diseases, including periodontitis, as it is a predisposing factor for this disease. The aim of the present study was to validate this hypothesis using a transgenic mouse line, which over-expresses RANK (RTg) and develops a periodontitis-like phenotype at 5 months of age. RTg mice exhibited severe alveolar bone loss, an increased number of TRAP positive cells, and disorganization of periodontal ligaments. This phenotype was more pronounced in females. We also observed dental root resorption lacunas. Hyperplasia of the gingival epithelium, including Malassez epithelial rests, was visible as early as 25 days, preceding any other symptoms. These results demonstrate that perturbations of the RANKL/RANK/OPG system constitute a core element of periodontitis, and more globally, osteo-immune diseases. PMID:28596739

In Vivo Imaging of Tau Pathology Using Magnetic Resonance Imaging Textural Analysis

PubMed Central

Colgan, Niall; Ganeshan, Balaji; Harrison, Ian F.; Ismail, Ozama; Holmes, Holly E.; Wells, Jack A.; Powell, Nick M.; O'Callaghan, James M.; O'Neill, Michael J.; Murray, Tracey K.; Ahmed, Zeshan; Collins, Emily C.; Johnson, Ross A.; Groves, Ashley; Lythgoe, Mark F.

2017-01-01

Background: Non-invasive characterization of the pathological features of Alzheimer's disease (AD) could enhance patient management and the development of therapeutic strategies. Magnetic resonance imaging texture analysis (MRTA) has been used previously to extract texture descriptors from structural clinical scans in AD to determine cerebral tissue heterogeneity. In this study, we examined the potential of MRTA to specifically identify tau pathology in an AD mouse model and compared the MRTA metrics to histological measures of tau burden. Methods: MRTA was applied to T2 weighted high-resolution MR images of nine 8.5-month-old rTg4510 tau pathology (TG) mice and 16 litter matched wild-type (WT) mice. MRTA comprised of the filtration-histogram technique, where the filtration step extracted and enhanced features of different sizes (fine, medium, and coarse texture scales), followed by quantification of texture using histogram analysis (mean gray level intensity, mean intensity, entropy, uniformity, skewness, standard-deviation, and kurtosis). MRTA was applied to manually segmented regions of interest (ROI) drawn within the cortex, hippocampus, and thalamus regions and the level of tau burden was assessed in equivalent regions using histology. Results: Texture parameters were markedly different between WT and TG in the cortex (E, p < 0.01, K, p < 0.01), the hippocampus (K, p < 0.05) and in the thalamus (K, p < 0.01). In addition, we observed significant correlations between histological measurements of tau burden and kurtosis in the cortex, hippocampus and thalamus. Conclusions: MRTA successfully differentiated WT and TG in brain regions with varying degrees of tau pathology (cortex, hippocampus, and thalamus) based on T2 weighted MR images. Furthermore, the kurtosis measurement correlated with histological measures of tau burden. This initial study indicates that MRTA may have a role in the early diagnosis of AD and the assessment of tau pathology using routinely acquired structural MR images. PMID:29163005

Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

PubMed

Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

2017-03-07

Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons

PubMed Central

Ali, Yousuf O.; Bradley, Gillian; Lu, Hui-Chen

2017-01-01

Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons. PMID:28266613

47 CFR 32.4510 - Capital stock.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Capital stock. 32.4510 Section 32.4510 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.4510 Capital stock. (a...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Identification of Aircraft and Related Products § 45.10 Marking. No person may mark a...

Computer predictions of ground storage effects on performance of Galileo and ISPM generators

NASA Technical Reports Server (NTRS)

Chmielewski, A.

1983-01-01

Radioisotope Thermoelectric Generators (RTG) that will supply electrical power to the Galileo and International Solar Polar Mission (ISPM) spacecraft are exposed to several degradation mechanisms during the prolonged ground storage before launch. To assess the effect of storage on the RTG flight performance, a computer code has been developed which simulates all known degradation mechanisms that occur in an RTG during storage and flight. The modeling of these mechanisms and their impact on the RTG performance are discussed.

10 CFR 4.510 - Self-evaluation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Self-evaluation. 4.510 Section 4.510 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission § 4.510 Self-evaluation. (a) The...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

Temperature-time distribution and thermal stresses on the RTG fins and shell during water cooling

NASA Technical Reports Server (NTRS)

Turner, R. H.

1983-01-01

Radioisotope thermoelectric generator (RTG) packages designed for space missions generally do not require active cooling. However, the heat they generate cannot remain inside of the launch vehicle bay and requires active removal. Therefore, before the Shuttle bay door is closed, the RTG coolant tubes attached to the heat rejection fins must be filled with water, which will circulate and remove most of the heat from the cargo bay. There is concern that charging a system at initial temperature around 200 C with water at 24 C can cause unacceptable thermal stresses in the RTG shell and fins. A computer model is developed to estimate the transient temperature distribution resulting from such charging. The thermal stresses resulting from the temperature gradients do not exceed the elastic deformation limit for the material. Since the simplified mathematical model for thermal stresses tends to overestimate stresses, it is concluded that the RTG can be cooled by introducing water at 24 C to the initially hot fin coolant tubes while the RTG is in the Shuttle cargo bay.

10 CFR 4.510 - Self-evaluation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Self-evaluation. 4.510 Section 4.510 Energy NUCLEAR... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission § 4.510 Self-evaluation. (a) The... agency shall provide an opportunity to interested persons, including disabled persons or organizations...

10 CFR 4.510 - Self-evaluation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Self-evaluation. 4.510 Section 4.510 Energy NUCLEAR... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission § 4.510 Self-evaluation. (a) The... representing handicapped persons, to participate in the self-evaluation process by submitting comments (both...

Characteristics and Impact Factors of Renal Threshold for Glucose Excretion in Patients with Type 2 Diabetes Mellitus.

PubMed

Yue, Xiao Dan; Wang, Jing Yu; Zhang, Xin Rong; Yang, Ju Hong; Shan, Chun Yan; Zheng, Miao Yan; Ren, Hui Zhu; Zhang, Yi; Yang, Shao Hua; Guo, Zhen Hong; Chang, Bai; Chang, Bao Cheng

2017-04-01

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RT(G)) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RT(G) and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RT(G) was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RT(G) were investigated. The risk factors for high RT(G) were analyzed using non-conditional logistic regression analysis. Our results found that RT(G) of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RT(G). Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RT(G) (P < 0.05). Further stratified analysis revealed that RT(G) in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RT(G) is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors. © 2017 The Korean Academy of Medical Sciences.

Comparative studies of saxitoxin (STX) -induced cytotoxicity in Neuro-2a and RTG-2 cell lines: An explanation with respect to changes in ROS.

PubMed

Zhou, Zhongyuan; Tang, Xuexi; Chen, Hongmei; Wang, You

2018-02-01

Saxitoxin (STX), a paralytic shellfish toxin (PST) produced from toxic bloom-forming dinoflagellates, was selected to comparatively investigate the induction of cytotoxicity and apoptosis and a possible mechanism based on changes in the antioxidant defence system of two cellular strains: the mouse neuroblastoma cell line Neuro-2a and the rainbow trout fish cell line RTG-2. Increasing concentrations of STX (0-256 nM) presented little cytotoxic or apoptotic effects on the two cell lines. Measurements of cellular viability, lethal ratio and LDH leakage showed slight changes in Neuro-2a and RTG-2 cells (p > 0.05), and similar results were observed for cellular morphology and apoptotic rates. The contents of the main reactive oxygen species (ROS) components, superoxide anion (O 2 - ) and hydrogen peroxide (H 2 O 2 ), were markedly increased in Neuro-2a cell with STX exposure at middle (15 nM) and high (150 nM) concentrations (p < 0.05), and the simultaneous increase of the ratio of reduced/oxidized glutathione (GSH/GSSG) (p < 0.05) inferred the occurrence of oxidative stress. However, little difference was observed in all treated groups of RTG-2 cells. The activities of three antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR), were significantly enhanced in Neuro-2a cells in the middle and high concentration groups (p < 0.05), while glutathione peroxidase (GPX) obviously decreased (p < 0.05) in all treated groups. Little change was found in RTG-2 cells with the same exposures. These results provided evidence that STX exposure altered the redox status of Neuro-2a cells and resulted in oxidative stress, but the same exposure exerted little effect on RTG-2 cells. Therefore, Neuro-2a cells are more sensitive than reproductive cells to STX exposure, and the antioxidant systems appears to be partly responsible for this differentiation response. Copyright © 2017 Elsevier Ltd. All rights reserved.

47 CFR 32.4510 - Capital stock.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Capital stock. 32.4510 Section 32.4510 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS...) This account shall include the par value, stated amount, or in the case of no-par stock, the amount...

47 CFR 32.4510 - Capital stock.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Capital stock. 32.4510 Section 32.4510 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS...) This account shall include the par value, stated amount, or in the case of no-par stock, the amount...

47 CFR 32.4510 - Capital stock.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Capital stock. 32.4510 Section 32.4510 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS...) This account shall include the par value, stated amount, or in the case of no-par stock, the amount...

47 CFR 32.4510 - Capital stock.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Capital stock. 32.4510 Section 32.4510 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS...) This account shall include the par value, stated amount, or in the case of no-par stock, the amount...

28 CFR 45.10 - Procedures to promote compliance with crime victims' rights obligations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 18 U.S.C. 3771. Employee of the Department of Justice means an attorney, investigator, law... crime victims' rights obligations. 45.10 Section 45.10 Judicial Administration DEPARTMENT OF JUSTICE... implements the provisions of the Justice for All Act that relate to protection of the rights of crime victims...

43 CFR 45.10 - Who may represent a party, and what requirements apply to a representative?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Who may represent a party, and what requirements apply to a representative? 45.10 Section 45.10 Public Lands: Interior Office of the Secretary of the Interior CONDITIONS AND PRESCRIPTIONS IN FERC HYDROPOWER LICENSES Hearing Process Representatives...

RTG Safety Tests

NASA Technical Reports Server (NTRS)

1989-01-01

The primary objective of STS-34 was to launch Galileo on its trip to Jupiter. The Galileo spacecraft contains two Radioisotope Thermoelectric Generators (RTG), which contains plutonium. This videotape shows and the accompanying material explains the tests that the RTG containment vessel has been subjected to, and the results of the tests. The videotape shows the trajectory of the Galileo spacecraft, a cutaway view of an RTG, the Plutonium-238 fuel capsule, and seven of the tests on the RTG.

Feasibility investigation of the Accelerated Skill Acquisition Program (ASAP): insights into reach-to-grasp coordination of individuals with postacute stroke.

PubMed

Tretriluxana, Jarugool; Runnarong, Nuttakarn; Tretriluxana, Suradej; Prayoonwiwat, Naraporn; Vachalathiti, Roongtiwa; Winstein, Carolee

2013-01-01

Skill acquisition, capacity building, and motivational enhancements are the basis of the Accelerated Skill Acquisition Program (ASAP) and form the foundation for effective incorporation of the paretic upper extremity into life activities. This is the first phase I trial to deliver ASAP during the postacute interval in mildly to moderately impaired stroke survivors and to include an assessment of paretic reach-to-grasp (RTG) coordination using RTG task and cross-correlation analyses. Two baseline and posttreatment evaluations consisted of RTG actions, the Wolf Motor Function Test (WMFT), and the Stroke Impact Scale (SIS). An individualized arm therapy program using ASAP principles was administered for a total of 30 hours, 2 hours per day, for 2 to 4 days per week over 5 weeks. Dependent measures were kinematics of RTG actions, RTG coordination, total time score of WMFT, and stroke recovery score of SIS. All participants tolerated ASAP well, and none reported any adverse effects during or after the protocol. When the 2 baseline evaluations were compared, there were no changes in any RTG kinematics or RTG coordination. In contrast, after 30 hours of ASAP, total movement time and deceleration time of RTG actions markedly decreased, maximum reach (transport) velocity strikingly increased, and time of maximum aperture was accomplished later. Additionally, the maximal RTG correlation coefficient increased with a shorter associated time lag. A similar pattern was observed for the clinical outcome measures of WMFT and SIS. The findings demonstrate the feasibility of using an ASAP protocol for patients 1 to 3 months post stroke. Under ASAP, WMFT tasks and RTG actions were performed faster with higher peak transport velocity and a more coordinated RTG pattern. The next step is to determine whether the immediate gains in the skilled RTG actions persist 6 months alter.

Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

PubMed

Brownlow, Milene L; Benner, Leif; D'Agostino, Dominic; Gordon, Marcia N; Morgan, Dave

2013-01-01

Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

TAGS 85/2N RTG Power for Viking Lander Capsule

DOE R&D Accomplishments Database

1969-08-01

Results of studies performed by Isotopes, Inc., Nuclear Systems Division, to optimize and baseline a TAGS 85/2N RTG for the Viking Lander Capsule prime electrical power source are presented. These studies generally encompassed identifying the Viking RTG mission profile and design requirements, and establishing a baseline RTG design consistent with these requirements.

Status of modular RTG technology

NASA Astrophysics Data System (ADS)

Hartman, Robert F.

Radioisotope thermoelectric generators (RTGs) have been employed safely and reliably since 1961 to provide spacecraft electrical power for various NASA and Department of Defense missions. Historically, RTG development, fabrication and qualification have been performed under the sponsorship of the Department of Energy's Office of Special Nuclear Projects and its predecessor groups. RTG technology improvement programs have been conducted over the years by the DOE to improve RTG efficiency and operating performance. The modular RTG design concept resulted from such a program and is currently being developed by the General Electric Company for the DOE.

Divergent branches of mitochondrial signaling regulate specific genes and the viability of specialized cell types of differentiated yeast colonies.

PubMed

Podholová, Kristýna; Plocek, Vítězslav; Rešetárová, Stanislava; Kučerová, Helena; Hlaváček, Otakar; Váchová, Libuše; Palková, Zdena

2016-03-29

Mitochondrial retrograde signaling mediates communication from altered mitochondria to the nucleus and is involved in many normal and pathophysiological changes, including cell metabolic reprogramming linked to cancer development and progression in mammals. The major mitochondrial retrograde pathway described in yeast includes three activators, Rtg1p, Rtg2p and Rtg3p, and repressors, Mks1p and Bmh1p/Bmh2p. Using differentiated yeast colonies, we show that Mks1p-Rtg pathway regulation is complex and includes three branches that divergently regulate the properties and fate of three specifically localized cell subpopulations via signals from differently altered mitochondria. The newly identified RTG pathway-regulated genes ATO1/ATO2 are expressed in colonial upper (U) cells, the cells with active TORC1 that metabolically resemble tumor cells, while CIT2 is a typical target induced in one subpopulation of starving lower (L) cells. The viability of the second L cell subpopulation is strictly dependent on RTG signaling. Additional co-activators of Rtg1p-Rtg3p specific to particular gene targets of each branch are required to regulate cell differentiation.

12 CFR 614.4510 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Requirements; State Agricultural Loan Mediation Programs; Right of First Refusal § 614.4510 General. Direct... for maintaining control, for the proper analysis of such data, and prompt action as needed; (ii... objectives, financing programs, organizational structure, and operating methods, and appropriate analysis of...

Simulating the Gradually Deteriorating Performance of an RTG

NASA Technical Reports Server (NTRS)

Wood, Eric G.; Ewell, Richard C.; Patel, Jagdish; Hanks, David R.; Lozano, Juan A.; Snyder, G. Jeffrey; Noon, Larry

2008-01-01

Degra (now in version 3) is a computer program that simulates the performance of a radioisotope thermoelectric generator (RTG) over its lifetime. Degra is provided with a graphical user interface that is used to edit input parameters that describe the initial state of the RTG and the time-varying loads and environment to which it will be exposed. Performance is computed by modeling the flows of heat from the radioactive source and through the thermocouples, also allowing for losses, to determine the temperature drop across the thermocouples. This temperature drop is used to determine the open-circuit voltage, electrical resistance, and thermal conductance of the thermocouples. Output power can then be computed by relating the open-circuit voltage and the electrical resistance of the thermocouples to a specified time-varying load voltage. Degra accounts for the gradual deterioration of performance attributable primarily to decay of the radioactive source and secondarily to gradual deterioration of the thermoelectric material. To provide guidance to an RTG designer, given a minimum of input, Degra computes the dimensions, masses, and thermal conductances of important internal structures as well as the overall external dimensions and total mass.

Munitions Detection Using Unmanned Underwater Vehicles Equipped with Advanced Sensors

DTIC Science & Technology

2012-06-29

buried target. The RTG is a small passive magnetic sensor using fluxgate magnetometers measuring 3- orthogonal magnetic-field vector components at 3...surveys. Figure 6 shows the RTG magnetic sensor in both an open (showing the fluxgate magnetometers ) and enclosed state (mode for integration onto...7.6 Real-time Tracking Gradiometer (RTG) System The RTG is a small passive magnetic sensor using fluxgate magnetometers measuring 3- orthogonal

Computational modeling of Radioisotope Thermoelectric Generators (RTG) for interplanetary and deep space travel

NASA Astrophysics Data System (ADS)

Nejat, Cyrus; Nejat, Narsis; Nejat, Najmeh

2014-06-01

This research project is part of Narsis Nejat Master of Science thesis project that it is done at Shiraz University. The goals of this research are to make a computer model to evaluate the thermal power, electrical power, amount of emitted/absorbed dose, and amount of emitted/absorbed dose rate for static Radioisotope Thermoelectric Generators (RTG)s that is include a comprehensive study of the types of RTG systems and in particular RTG’s fuel resulting from both natural and artificial isotopes, calculation of the permissible dose radioisotope selected from the above, and conceptual design modeling and comparison between several NASA made RTGs with the project computer model pointing out the strong and weakness points for using this model in nuclear industries for simulation. The heat is being converted to electricity by two major methods in RTGs: static conversion and dynamic conversion. The model that is created for this project is for RTGs that heat is being converted to electricity statically. The model approximates good results as being compared with SNAP-3, SNAP-19, MHW, and GPHS RTGs in terms of electrical power, efficiency, specific power, and types of the mission and amount of fuel mass that is required to accomplish the mission.

A Survey of Current Russion RTG Capabilities

NASA Technical Reports Server (NTRS)

Chmielewski, A.; Borshchevsky, A.; Lange, R.; Cook, B.

1994-01-01

Supplying radioisotope thermoelectric generators (RTG) to American space missions became very complex. The process is marred by many obstacles: high cost, lack of new developments, difficult launch approval and NEPA compliance. At the same time there are many ambitious space missions for which an RTG would indisputably be the lightest, smallest and most robust power source. An American delegation investigated status of RTG production in Russia to decide if our product line could be supplemented by the Russian designs.

Detection of fibrin generation alterations in dogs with haemangiosarcoma using resonance thrombography.

PubMed

Mischke, R; Wohlsein, P; Schoon, H-A

2005-01-01

The objective of the study was to examine the alterations of fibrin generation in dogs with haemangiosarcoma using resonance thrombography. The second objective was to evaluate the sensitivity of this method for the detection of hypofibrinogenaemia and/or increased fibrin(ogen) degradation product (FDP) concentration. Resonance thrombogram (RTG) measurements with two different instruments were performed in 30 unselected dogs with haemangiosarcoma, 14 of which had decreased fibrinogen and 28 of which had an increased FDP concentration (p<0.0001). The RTG-reaction time was less sensitive than the fibrin formation time (RTG-f) and fibrin amplitude (RTG-F). The RTG-f and RTG-F indicated reliably a decrease in fibrinogen concentration (sensitivity: 0.93). The sensitivity of detection of increased FDP levels was considerably higher than that of thrombin time. However, false-negative results were found even at FDP concentrations > or =120 mg/l, especially in cases with high fibrinogen level. Both machines showed similar sensitivity. The results of this study indicate that canine haemangiosarcoma is frequently associated with severe alterations of fibrin generation due to low fibrinogen and high FDP levels leading to distinct RTG abnormalities. The global test RTG reacts sensitively to a decreased fibrinogen level whereas its accuracy to detect FDP concentrations occurring under pathophysiological conditions is limited. A significant alteration of fibrin generation induced by FDPs may not occur until the serum FDP concentration exceeds 60 mg/l.

Test and evaluation of the Navy half-watt RTG. [Radioisotope Thermoelectric Generator

NASA Technical Reports Server (NTRS)

Rosell, F. E., Jr.; Lane, S. D.; Eggers, P. E.; Gawthrop, W. E.; Rouklove, P. G.; Truscello, V. C.

1976-01-01

The radioisotope thermoelectric generator (RTG) considered is to provide a continuous minimum power output of 0.5 watt at 6.0 to 8.5 volts for a minimum period of 15 years. The mechanical-electrical evaluation phase discussed involved the conduction of shock and vibration tests. The thermochemical-physical evaluation phase consisted of an analysis of the materials and the development of a thermal model. The thermoelectric evaluation phase included the accelerated testing of the thermoelectric modules.

Virological and immunological responses to raltegravir and dolutegravir in the gut-associated lymphoid tissue of HIV-infected men and women.

PubMed

Weber, Michael D; Andrews, Elizabeth; Prince, Heather A; Sykes, Craig; Rosen, Elias P; Bay, Camden; Shaheen, Nicholas J; Madanick, Ryan D; Dellon, Evan S; De Paris, Kristina; Nelson, Julie Ae; Gay, Cynthia L; Kashuba, Angela Dm

2018-05-01

Raltegravir (RTG) and dolutegravir (DTG) have different pharmacokinetic patterns in the gastrointestinal tract. To determine if this results in pharmacodynamic differences, we compared HIV RNA, HIV DNA, and immunological markers in gut-associated lymphoid tissue (GALT) of HIV-infected participants receiving RTG or DTG with tenofovir+emtricitabine (TDF/FTC). GALT specimens from the terminal ileum, splenic flexure, and rectum were obtained by colonoscopy at a single time point in 20 adults treated with RTG (n=10) or DTG (n=10) with HIV RNA <50 copies/mL. Flow cytometry, drug concentrations, and HIV RNA and DNA were analyzed in tissue. CD4/8 + T cells were tested for γδ TCR, and markers of T cell activation and exhaustion. Data are reported as median (Q1,Q3). 15 men and 5 women were enrolled. There was no difference in time since HIV diagnosis for those on RTG [9.5 (4-22) yr] and DTG [17 (1-24) yr] (p = 0.6), although time on RTG [5.4 (2.3-6.7) yr] was greater than DTG [1.0 (0.1-1.5) yr] (P < 0.001). Concentrations of RTG and DTG in rectal tissue (RT) were similar to previous reports: median tissue:plasma ratio was 11.25 for RTG and 0.44 for DTG. RNA:DNA ratios were [1.14 (0.18-5.10)] for the RTG group and [0.90 (0.30-18.87)] for the DTG group (p = 0.95). No differences (p ≥ 0.1) between CD4 + and CD8 + T cell markers were found. RTG produced higher tissue exposures than DTG, but no significant differences in GALT HIV RNA, DNA, or most immunologic markers were observed.

The long-term performance degradation of a radioisotope thermoelectric generator using silicon germanium

NASA Technical Reports Server (NTRS)

Stapfer, G.; Truscello, V. C.

1976-01-01

The successful utilization of a radioisotope thermoelectric generator (RTG) as the power source for spaceflight missions requires that the performance of such an RTG be predictable throughout the mission. Several mechanisms occur within the generator which tend to degrade the performance as a function of operating time. The impact which these mechanisms have on the available output power of an RTG depends primarily on such factors as time, temperature and self-limiting effects. The relative magnitudes, rates and temperature dependency of these various degradation mechanisms have been investigated separately by coupon experiments as well as 4-couple and 18-couple module experiments. This paper discusses the different individual mechanisms and summarizes their combined influence on the performance of an RTG. Also presented as part of the RTG long-term performance characteristics is the sensitivity of the available RTG output power to variations of the individual degradation mechanisms thus identifying the areas of greatest concern for a successful long-term mission.

Lack of effect of ezogabine/retigabine on the pharmacokinetics of digoxin in healthy individuals: results from a drug–drug interaction study

PubMed Central

Tompson, Debra J; Crean, Christopher S; Buraglio, Mauro; Arumugham, Thangam

2014-01-01

Introduction The potential for ezogabine/retigabine (EZG/RTG) and its N-acetyl metabolite (NAMR) to inhibit the transporter protein P-glycoprotein-(P-gp)-mediated digoxin transport was tested in vitro. EZG/RTG did not inhibit P-gp. However, NAMR inhibited P-gp in a concentration-dependent manner. Based on these in vitro results, NAMR had the potential to inhibit P-gp at therapeutic doses of EZG/RTG (600–1,200 mg/day). As digoxin has a narrow therapeutic index, inhibition of digoxin clearance may have an impact on its safety. Methods An open-label, single-center, two session, fixed-sequence study was conducted to assess the effect of co-administration of therapeutic doses of EZG/RTG on digoxin pharmacokinetics in healthy adults. In session 1, subjects received a single dose of digoxin 0.25 mg. In session 2, EZG/RTG was up-titrated over 6 weeks. Digoxin 0.25 mg was co-administered at EZG/RTG steady-state doses of 600, 900, and, based on tolerability, 1,050/1,200 mg/day. Blood samples were collected over 144 hours for determination of digoxin, EZG/RTG, and NAMR concentrations. Urine samples were collected over 48 hours for determination of digoxin concentrations. Results Of 30 subjects enrolled, 29 were included in the pharmacokinetic analysis. Compared with digoxin alone, co-administration with EZG/RTG led to small increases in the digoxin plasma area under the concentration–time curve (AUC)0–120 at doses of 600, 900, and 1,050/1,200 mg (geometric mean ratio 1.08, 90% confidence interval [CI] 1.01–1.15; 1.18, 90% CI 1.10–1.27; 1.13, 90% CI 1.05–1.21, respectively). Safety was consistent with previous repeat-dose studies of EZG/RTG in healthy subjects. Conclusion Co-administration of EZG/RTG across the therapeutic range resulted in small, non-dose-dependent and non-clinically relevant increases in digoxin systemic exposure, suggesting that digoxin dose adjustment is not necessary. PMID:25342921

Induction of antiviral genes, Mx and vig-1, by dsRNA and Chum salmon reovirus in rainbow trout monocyte/macrophage and fibroblast cell lines.

PubMed

DeWitte-Orr, Stephanie J; Leong, Jo-Ann C; Bols, Niels C

2007-09-01

The expression of potential antiviral genes, Mx1, Mx2, Mx3 and vig-1, was studied in two rainbow trout cell lines: monocyte/macrophage RTS11 and fibroblast-like RTG-2. Transcripts were monitored by RT-PCR; Mx protein by Western blotting. In unstimulated cultures Mx1 and vig-1 transcripts were seen occasionally in RTS11 but rarely in RTG-2. A low level of Mx protein was seen in unstimulated RTS11 but not in RTG-2. In both cell lines, Mx and vig-1 transcripts were induced by a dsRNA, poly inosinic: poly cytidylic acid (poly IC), and by Chum salmon reovirus (CSV). Medium conditioned by cells previously exposed to poly IC or CSV and assumed to contain interferon (IFN) induced the antiviral genes in RTS11. However, RTG-2 responded only to medium conditioned by RTG-2 exposed previously to CSV. In both cell lines, poly IC and CSV induced Mx transcripts in the presence of cycloheximide, suggesting a direct induction mechanism, independent of IFN, was also possible. For CSV, ribavirin blocked induction in RTS11 but not in RTG-2, suggesting viral RNA synthesis was required for induction only in RTS11. In both RTS11 and RTG-2 cultures, Mx protein showed enhanced accumulation by 24h after exposure to poly IC and CSV, but subsequently Mx protein levels declined back to control levels in RTS11 but not in RTG-2. These results suggest that Mx can be regulated differently in macrophages and fibroblasts.

Quaternized Q-PEIPAAm-Based Antimicrobial Reverse Thermal Gel: A Potential for Surgical Incision Drapes.

PubMed

Bortot, Maria; Laughter, Melissa Ronni; Stein, Madia; Rocker, Adam; Patel, Vikas; Park, Daewon

2018-05-16

A quaternized reverse thermal gel (RTG) aimed at replacing current surgical incision drapes (SIDs) was designed and characterized. The antimicrobial efficacy of the quaternized RTG was analyzed using both in vitro and in vivo models and was compared to standard SIDs. Polymer characterization was completed using both nuclear magnetic resonance ( 1 H NMR) and lower critical solution temperature (LCST) analysis. Biocompatibility was assessed using a standard cell viability assay. The in vitro antimicrobial efficacy of the polymer was analyzed against four common bacteria species using a time-kill test. The in vivo antimicrobial efficacy of the polymer and standard SIDs were compared using a murine model aimed at mimicking surgical conditions. NMR confirmed the polymer structure and presence of quaternized groups and alkyl chains. The polymer displayed a LCST of 34 °C and a rapid rate of gelation, allowing stable gel formation when applied to skin. Once quaternized, the polymer displayed an increase in kill-rate of bacteria compared to unquaternized polymer. In experiments aimed at mimicking surgical conditions, the quaternized polymer showed statistically comparable bacteria-killing capacity to the standard SID and even surpassed the SID for killing capacity at various time points. A novel approach to replacing current SIDs was developed using an antimicrobial polymer system with RTG properties. The RTG properties of this polymer maintain a liquid state at low temperatures and a gel upon heating, allowing this polymer to form a tight coating when applied to skin. Furthermore, this polymer achieved excellent antimicrobial properties in both in vitro and in vivo models. With further optimization, this polymer system has the potential to replace and streamline presurgical patient preparations through its easy application and beneficial antimicrobial properties.

Ketogenic Diet Improves Motor Performance but Not Cognition in Two Mouse Models of Alzheimer’s Pathology

PubMed Central

Brownlow, Milene L.; Benner, Leif; D’Agostino, Dominic; Gordon, Marcia N.; Morgan, Dave

2013-01-01

Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer’s disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition. PMID:24069439

A novel design for a dose finding, safety, and drug interaction study of an antiepileptic drug (retigabine) in early clinical development.

PubMed

Sachdeo, Rajesh; Partiot, Arnaud; Biton, Victor; Rosenfeld, William E; Nohria, Virinder; Tompson, Debra; DeRossett, Sarah; Porter, Roger J

2014-06-01

To obtain information on the acceptable doses of the antiepileptic drug (AED) retigabine (RTG), the maximum tolerated dose (MTD), drug interactions, safety and tolerability, and preliminary evidence of efficacy when administered as adjunctive therapy and as monotherapy. Study 202 was an open-label, add-on study in patients with partial or generalized epilepsy treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), or topiramate (TPM) as monotherapy. Following baseline assessments, patients entered a dose titration phase of 28 – 56 days. The initial daily RTG dose was 100 or 200 mg (2 or 3 × daily). The RTG dose was increased every 1 - 2 weeks by 50 - 200 mg to a maximum of 1,600 mg/day. Once the RTG MTD had been attained, patients entered a 14-day maintenance period. Following this, the patient's background AED dose could be reduced, with the possibility of achieving RTG monotherapy. The final dosing regimen attained was maintained for an additional 14 days. Patients who completed study 202 could choose to continue treatment with RTG (with or without other AEDs) in study 208, the long-term extension of study 202. Safety assessments included adverse event (AE) monitoring, clinical laboratory evaluations, electrocardiograms, and physical and neurologic examinations. Patients' seizure diaries to assess the frequency and type of seizures, the percentage change in seizure rate, and the responder rate (>= 50% reduction in seizure rate from baseline) were evaluated. 60 patients (mean age 37.2, range 16 - 64 years) were enrolled in study 202, and 47 (78%) continued treatment with RTG in the extension study (208). In study 202, the most commonly reported AEs were: dizziness (53%), asthenia (42%), somnolence (33%), nausea (27%), speech disorder (27%), and tremor (27%). In the extension study, AEs were similar and included dizziness, somnolence, diplopia, feeling "drunk", confusion, fatigue, and dysarthria. The median percent reductions in 28-day seizure rate, relative to baseline in Studies 202 and 208, were ~ 20% and 47%, respectively. RTG did not alter the pharmacokinetics of the four monotherapy AEDs investigated. CBZ and PHT increased RTG clearance by 27% and 36%, respectively, whereas TPM and VPA had no effect on RTG clearance. Studies 202 and 208 provided critical information on RTG safety and tolerability, and reductions in seizure rates towards the design and conduct of subsequent pivotal clinical trials. Likewise, information regarding the appropriate dosage of RTG with VPA, CBZ, PHT, or TPM was obtained, which permitted the subsequent pivotal trials to be performed appropriately. *Currently at Shire Pharmaceuticals, Behavioral Health Business Unit, Wayne, PA, USA **Currently at University of Pennsylvania, Department of Neurology, Philadelphia, PA, USA.

Anti-melanogenic effects of resveratryl triglycolate, a novel hybrid compound derived by esterification of resveratrol with glycolic acid.

PubMed

Park, Soojin; Seok, Jin Kyung; Kwak, Jun Yup; Choi, Yun-Hyeok; Hong, Seong Su; Suh, Hwa-Jin; Park, Woncheol; Boo, Yong Chool

2016-07-01

Resveratrol is known to inhibit cellular melanin synthesis by multiple mechanisms. Glycolic acid (GA) is used in skin care products for its excellent skin penetration. The purpose of this study was to examine the anti-melanogenic effects of resveratryl triglycolate (RTG), a novel hybrid compound of resveratrol and GA, in comparison with resveratrol, GA, resveratryl triacetate (RTA) and arbutin. Resveratrol, RTG, and RTA inhibited the catalytic activity human tyrosinase (TYR) more potently than arbutin or GA did. Their cytotoxic and anti-melanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEMs). The cytotoxicity of RTG was similar to that of resveratrol and RTA. RTG at 3-10 μM decreased melanin levels and cellular TYR activities in α-melanocyte-stimulating hormone-stimulated B16/F10 cells, and L-tyrosine-stimulated HEMs. RTG also suppressed mRNA and protein expression of TYR, tyrosinase-related protein 1, L-3,4-dihydroxyphenylalanine chrome tautomerase, and microphthalmia-associated transcription factor (MITF) in HEMs stimulated with L-tyrosine. This study suggests that, like resveratrol and RTA, RTG can attenuate cellular melanin synthesis effectively through the suppression of MITF-dependent expression of melanogenic enzymes and the inhibition of catalytic activity of TYR enzyme. RTG therefore has potential for use as a cosmeceutical ingredient for skin whitening.

Design and spacecraft-integration of RTGs for solar probe

NASA Technical Reports Server (NTRS)

Schock, A.; Noravian, H.; Or, T.; Sankarankandath, V.

1990-01-01

The design, analysis, and spacecraft integration of radioisotope thermoelectric generators (RTG) to power the Solar Probe under study at NASA JPL is described. The mission of the Solar Probe is to explore the solar corona by performing in situ measurements at up to four solar radii to the sun. Design constraints for the RTG are discussed. The chief challenge in the design and system integration of the Solar Probe's RTG is a heat rejection problem. Two RTG orientations, horizontal and oblique, are analyzed for effectiveness and results are summarized in chart form. A number of cooling strategies are also investigated, including heat-pipe and reflector-cooled options. A methodology and general computer code are presented for analyzing the performance of arbitrarily obstructed RTGs with both axial and circumferential temperature, voltage, and current variation. This methodology is applied to the specific example of the Solar Probe RTG obstructed by a semicylindrical reflector of 15-inch radius.

Final safety analysis report for the Galileo Mission: Volume 2: Book 1, Accident model document

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The Accident Model Document (AMD) is the second volume of the three volume Final Safety Analysis Report (FSAR) for the Galileo outer planetary space science mission. This mission employs Radioisotope Thermoelectric Generators (RTGs) as the prime electrical power sources for the spacecraft. Galileo will be launched into Earth orbit using the Space Shuttle and will use the Inertial Upper Stage (IUS) booster to place the spacecraft into an Earth escape trajectory. The RTG's employ silicon-germanium thermoelectric couples to produce electricity from the heat energy that results from the decay of the radioisotope fuel, Plutonium-238, used in the RTG heat source.more » The heat source configuration used in the RTG's is termed General Purpose Heat Source (GPHS), and the RTG's are designated GPHS-RTGs. The use of radioactive material in these missions necessitates evaluations of the radiological risks that may be encountered by launch complex personnel as well as by the Earth's general population resulting from postulated malfunctions or failures occurring in the mission operations. The FSAR presents the results of a rigorous safety assessment, including substantial analyses and testing, of the launch and deployment of the RTGs for the Galileo mission. This AMD is a summary of the potential accident and failure sequences which might result in fuel release, the analysis and testing methods employed, and the predicted source terms. Each source term consists of a quantity of fuel released, the location of release and the physical characteristics of the fuel released. Each source term has an associated probability of occurrence. 27 figs., 11 tabs.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrell, P.C.

This SARP describes the RTG Transportation System Package, a Type B(U) packaging system that is used to transport an RTG or similar payload. The payload, which is included in this SARP, is a generic, enveloping payload that specifically encompasses the General Purpose Heat Source (GPHS) RTG payload. The package consists of two independent containment systems mounted on a shock isolation transport skid and transported within an exclusive-use trailer.

Developing the next Generation of Education Researchers: UCLA's Experience with the Spencer Foundation Research Training Grant

ERIC Educational Resources Information Center

Dorr, Aimee; Arms, Emily; Hall, Valerie

2008-01-01

Background/Context: In the early 1990s, the Spencer Foundation instituted an Institutional Research Training Grant (RTG) program to improve the preparation of the next generation of education researchers. UCLA received an RTG in the first round of competition. Purpose/Objective/Research Question/Focus of Study: UCLA's Spencer RTG program sought to…

Cassini RTG acceptance test results and RTG performance on Galileo and Ulysses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelly, C.E.; Klee, P.M.

Flight acceptance testing has been completed for the RTGs to be used on the Cassini spacecraft which is scheduled for an October 6, 1997 launch to Saturn. The acceptance test program includes vibration tests, magnetic field measurements, mass properties (weight and c.g.) and thermal vacuum test. This paper presents the thermal vacuum test results. Three RTGs are to be used, F-2, F-6, and F-7. F-5 is the backup RTG, as it was for the Galileo and Ulysses missions launched in 1989 and 1990, respectively. RTG performance measured during the thermal vacuum tests carried out at the Mound Laboratory facility metmore » all specification requirements. Beginning of mission (BOM) and end of mission (EOM) power predictions have been made based on these tests results. BOM power is predicted to be 888 watts compared to the minimum requirement of 826 watts. Degradation models predict the EOM power after 16 years is to be 640 watts compared to a minimum requirement of 596 watts. Results of small scale module tests are also shown. The modules contain couples from the qualification and flight production runs. The tests have exceeded 28,000 hours (3.2 years) and are continuing to provide increased confidence in the predicted long term performance of the Cassini RTGs. All test results indicate that the power requirements of the Cassini spacecraft will be met. BOM and EOM power margins of over 5% are predicted. Power output from telemetry for the two Galileo RTGs are shown from the 1989 launch to the recent Jupiter encounter. Comparisons of predicted, measured and required performance are shown. Telemetry data are also shown for the RTG on the Ulysses spacecraft which completed its planned mission in 1995 and is now in the extended mission.« less

Cassini RTG acceptance test results and RTG performance on Galileo and Ulysses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelly, C.E.; Klee, P.M.

Flight acceptance testing has been completed for the RTGs to be used on the Cassini spacecraft which is scheduled for an October 6, 1997 launch to Saturn. The acceptance test program includes vibration tests, magnetic field measurements, properties (weight and c.g.) and thermal vacuum test. This paper presents The thermal vacuum test results. Three RTGs are to be used, F-2, F-6, and F-7. F-5 is tile back-up RTG, as it was for the Galileo and Ulysses missions launched in 1989 and 1990, respectively. RTG performance measured during the thermal vacuum tests carried out at die Mound Laboratory facility met allmore » specification requirements. Beginning of mission (BOM) and end of mission (EOM) power predictions have been made based on than tests results. BOM power is predicted to be 888 watts compared to the minimum requirement of 826 watts. Degradation models predict the EOM power after 16 years is to be 640 watts compared to a minimum requirement of 596 watts. Results of small scale module tests are also showing. The modules contain couples from the qualification and flight production runs. The tests have exceeded 28,000 hours (3.2 years) and are continuing to provide increased confidence in the predicted long term performance of the Cassini RTGs. All test results indicate that the power requirements of the Cassini spacecraft will be met. BOM and EOM power margins of over five percent are predicted. Power output from telemetry for the two Galileo RTGs are shown from the 1989 launch to the recent Jupiter encounter. Comparisons of predicted, measured and required performance are shown. Telemetry data are also shown for the RTG on the Ulysses spacecraft which completed its planned mission in 1995 and is now in the extended mission.« less

Cassini RTG Acceptance Test Results and RTG Performance on Galileo and Ulysses

DOE R&D Accomplishments Database

Kelly, C. E.; Klee, P. M.

1997-06-01

Flight acceptance testing has been completed for the RTGs to be used on the Cassini spacecraft which is scheduled for an October 6, 1997 launch to Saturn. The acceptance test program includes vibration tests, magnetic field measurements, properties (weight and c.g.) and thermal vacuum test. This paper presents The thermal vacuum test results. Three RTGs are to be used, F 2, F 6, and F 7. F 5 is tile back up RTG, as it was for the Galileo and Ulysses missions launched in 1989 and 1990, respectively. RTG performance measured during the thermal vacuum tests carried out at die Mound Laboratory facility met all specification requirements. Beginning of mission (BOM) and end of mission (EOM) power predictions have been made based on than tests results. BOM power is predicted to be 888 watts compared to the minimum requirement of 826 watts. Degradation models predict the EOM power after 16 years is to be 640 watts compared to a minimum requirement of 596 watts. Results of small scale module tests are also showing. The modules contain couples from the qualification and flight production runs. The tests have exceeded 28,000 hours (3.2 years) and are continuing to provide increased confidence in the predicted long term performance of the Cassini RTGs. All test results indicate that the power requirements of the Cassini spacecraft will be met. BOM and EOM power margins of over five percent are predicted. Power output from telemetry for the two Galileo RTGs are shown from the 1989 launch to the recent Jupiter encounter. Comparisons of predicted, measured and required performance are shown. Telemetry data are also shown for the RTG on the Ulysses spacecraft which completed its planned mission in 1995 and is now in the extended mission.

Adverse Heart-Lung Interactions in Ventilator-induced Lung Injury.

PubMed

Katira, Bhushan H; Giesinger, Regan E; Engelberts, Doreen; Zabini, Diana; Kornecki, Alik; Otulakowski, Gail; Yoshida, Takeshi; Kuebler, Wolfgang M; McNamara, Patrick J; Connelly, Kim A; Kavanagh, Brian P

2017-12-01

In the original 1974 in vivo study of ventilator-induced lung injury, Webb and Tierney reported that high Vt with zero positive end-expiratory pressure caused overwhelming lung injury, subsequently shown by others to be due to lung shear stress. To reproduce the lung injury and edema examined in the Webb and Tierney study and to investigate the underlying mechanism thereof. Sprague-Dawley rats weighing approximately 400 g received mechanical ventilation for 60 minutes according to the protocol of Webb and Tierney (airway pressures of 14/0, 30/0, 45/10, 45/0 cm H 2 O). Additional series of experiments (20 min in duration to ensure all animals survived) were studied to assess permeability (n = 4 per group), echocardiography (n = 4 per group), and right and left ventricular pressure (n = 5 and n = 4 per group, respectively). The original Webb and Tierney results were replicated in terms of lung/body weight ratio (45/0 > 45/10 ≈ 30/0 ≈ 14/0; P < 0.05) and histology. In 45/0, pulmonary edema was overt and rapid, with survival less than 30 minutes. In 45/0 (but not 45/10), there was an increase in microvascular permeability, cyclical abolition of preload, and progressive dilation of the right ventricle. Although left ventricular end-diastolic pressure decreased in 45/10, it increased in 45/0. In a classic model of ventilator-induced lung injury, high peak pressure (and zero positive end-expiratory pressure) causes respiratory swings (obliteration during inspiration) in right ventricular filling and pulmonary perfusion, ultimately resulting in right ventricular failure and dilation. Pulmonary edema was due to increased permeability, which was augmented by a modest (approximately 40%) increase in hydrostatic pressure. The lung injury and acute cor pulmonale is likely due to pulmonary microvascular injury, the mechanism of which is uncertain, but which may be due to cyclic interruption and exaggeration of pulmonary blood flow.

Improved techniques for predicting spacecraft power

NASA Technical Reports Server (NTRS)

Chmielewski, A. B.

1987-01-01

Radioisotope Thermoelectric Generators (RTGs) are going to supply power for the NASA Galileo and Ulysses spacecraft now scheduled to be launched in 1989 and 1990. The duration of the Galileo mission is expected to be over 8 years. This brings the total RTG lifetime to 13 years. In 13 years, the RTG power drops more than 20 percent leaving a very small power margin over what is consumed by the spacecraft. Thus it is very important to accurately predict the RTG performance and be able to assess the magnitude of errors involved. The paper lists all the error sources involved in the RTG power predictions and describes a statistical method for calculating the tolerance.

Hunting Sea Mines with UUV-Based Magnetic and Electro-Optic Sensors

DTIC Science & Technology

2010-06-01

assembly of four 3-axis fluxgate magnetometers and (c) magnetometer package for underwater deployment in flooded body section. data are automatically...features the Real-time Tracking Gradiometer (RTG), which is a multi-channel tensor gradiometer using conventional fluxgate technology. Also in this...integrated together into a Bluefin12 AUV [5]. A. RTG Sensor Technology The RTG is a multi-channel tensor gradiometer using conventional fluxgate

Development of a New Generation of High-Temperature Thermoelectric Unicouples for Space Applications

NASA Technical Reports Server (NTRS)

Caillat, Thierry; Gogna, P.; Sakamoto, J.; Jewell, A.; Cheng, J.; Blair, R.; Fleurial, J. -P.; Ewell, R.

2006-01-01

RTG's have enabled surface and deep space missions since 1961: a) 26 flight missions without any RTG failures; and b) Mission durations in excess of 25 years. Future NASA missions require RTG s with high specific power and high efficiency, while retaining long life (> 14 years) and high reliability, (i.e. 6-8 W/kg, 10-15% efficiency). JPL in partnership with NASA-GRC, NASA-MSFC, DOE, Universities and Industry is developing advanced thermoelectric materials and converters to meet future NASA needs.

Real-Time-Simulation of IEEE-5-Bus Network on OPAL-RT-OP4510 Simulator

NASA Astrophysics Data System (ADS)

Atul Bhandakkar, Anjali; Mathew, Lini, Dr.

2018-03-01

The Real-Time Simulator tools have high computing technologies, improved performance. They are widely used for design and improvement of electrical systems. The advancement of the software tools like MATLAB/SIMULINK with its Real-Time Workshop (RTW) and Real-Time Windows Target (RTWT), real-time simulators are used extensively in many engineering fields, such as industry, education, and research institutions. OPAL-RT-OP4510 is a Real-Time Simulator which is used in both industry and academia. In this paper, the real-time simulation of IEEE-5-Bus network is carried out by means of OPAL-RT-OP4510 with CRO and other hardware. The performance of the network is observed with the introduction of fault at various locations. The waveforms of voltage, current, active and reactive power are observed in the MATLAB simulation environment and on the CRO. Also, Load Flow Analysis (LFA) of IEEE-5-Bus network is computed using MATLAB/Simulink power-gui load flow tool.

Nucleotide Sequence of the blaRTG-2 (CARB-5) Gene and Phylogeny of a New Group of Carbenicillinases

PubMed Central

Choury, Daniele; Szajnert, Marie-France; Joly-Guillou, Marie-Laure; Azibi, Kemal; Delpech, Marc; Paul, Gérard

2000-01-01

We determined the nucleotide sequence of the bla gene for the Acinetobacter calcoaceticus β-lactamase previously described as CARB-5. Alignment of the deduced amino acid sequence with those of known β-lactamases revealed that CARB-5 possesses an RTG triad in box VII, as described for the Proteus mirabilis GN79 enzyme, instead of the RSG consensus characteristic of the other carbenicillinases. Phylogenetic studies showed that these RTG enzymes constitute a new, separate group, possibly ancestors of the carbenicillinase family. PMID:10722515

NCEP SST Analysis

Science.gov Websites

Branches Global Climate & Weather Modeling Mesoscale Modeling Marine Modeling and Analysis Contact EMC , state and local government Web resources and services. Real-time, global, sea surface temperature (RTG_SST_HR) analysis For a regional map, click the desired area in the global SST analysis and anomaly maps

A power conditioning system for radioisotope thermoelectric generator energy sources

NASA Technical Reports Server (NTRS)

Gillis, J. A., Jr.

1974-01-01

The use of radioisotope thermoelectric generators (RTG) as the primary source of energy in unmanned spacecraft is discussed. RTG output control, power conditioning system requirements, the electrical design, and circuit performance are also discussed.

Specification for strontium-90 500-watt(e) radioisotopic thermoelectric generator

NASA Astrophysics Data System (ADS)

Hammel, T.; Himes, J.; Lieberman, A.; McGrew, J. W.; Owings, D.; Schumann, F.

1983-04-01

A conceptual design for a demonstration 500-watt(e) radioisotopic thermoelectric generator (RTG) was created. The design effort was divided into two tasks, viz., create a design specification for a capsule strenth member that utilizes a standard Strontium 90 fluoride filled WESF inner liner, and create a conceptual design for a 500-watt(e) RTG. The strength member specification was designed to survive an external pressure of 24,500 psi and meet the requirements of special form radioisotope heat sources. Therefore the capsule is if desired, licensed for domestic and international transport. The design for the RTG features a radioisotopic heat source, an array of nine capsules in a tungsten biological shield, four current technology series connected thermoelectric conversion modules, low conductivity thermal insulation, and a passive finned housing radiator for waste heat dissipation. The preliminary RTG specification formulated previous to contract award was met or exceeded.

Dopaminergic Modulation of Cortical Plasticity in Alzheimer's Disease Patients

PubMed Central

Koch, Giacomo; Di Lorenzo, Francesco; Bonnì, Sonia; Giacobbe, Viola; Bozzali, Marco; Caltagirone, Carlo; Martorana, Alessandro

2014-01-01

In animal models of Alzheimer's disease (AD), mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) are impaired. In AD patients, LTP-like cortical plasticity is abolished, whereas LTD seems to be preserved. Dopaminergic transmission has been hypothesized as a new player in ruling mechanisms of cortical plasticity in AD. We aimed at investigating whether administration of the dopamine agonist rotigotine (RTG) could modulate cortical plasticity in AD patients, as measured by theta burst stimulation (TBS) protocols of repetitive transcranial stimulation applied over the primary motor cortex. Thirty mild AD patients were tested in three different groups before and after 4 weeks of treatment with RTG, rivastigmine (RVT), or placebo (PLC). Each patient was evaluated for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS protocols. Short-latency afferent inhibition (SAI) protocol was performed to indirectly assess central cholinergic activity. A group of age-matched healthy controls was recruited for baseline comparisons. Results showed that at baseline, AD patients were characterized by impaired LTP-like cortical plasticity, as assessed by iTBS. These reduced levels of LTP-like cortical plasticity were increased and normalized after RTG administration. No effect was induced by RVT or PLC on LTP. LTD-like cortical plasticity was not modulated in any condition. Cholinergic activity was increased by both RTG and RVT. Our findings reveal that dopamine agonists may restore the altered mechanisms of LTP-like cortical plasticity in AD patients, thus providing novel implications for therapies based on dopaminergic stimulation. PMID:24859851

GPHS-RTG's in support of the Cassini mission

NASA Astrophysics Data System (ADS)

1993-10-01

The following tasks were reported: Spacecraft integration and liaison; engineering support; safety; qualified unicouple fabrication; ETG fabrication/assembly/test; ground support equipment; RTG shipping and launch support; designs/reviews/mission applications; and project management/quality assurance/contract changes.

Requirements and Designs for Mars Rover RTGs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schock, Alfred; Shirbacheh, M; Sankarankandath, V

The current-generation RTGs (both GPHS and MOD) are designed for operation in a vacuum environment. The multifoil thermal insulation used in those RTGs only functions well in a good vacuum. Current RTGs are designed to operate with an inert cover gas before launch, and to be vented to space vacuum after launch. Both RTGs are sealed with a large number of metallic C-rings. Those seals are adequate for retaining the inert-gas overpressure during short-term launch operations, but would not be adequate to prevent intrusion of the Martian atmospheric gases during long-term operations there. Therefore, for the Mars Rover application, thosemore » RTGs just be modified to prevent the buildup of significant pressures of Mars atmosphere or of helium (from alpha decay of the fuel). In addition, a Mars Rover RTG needs to withstand a long-term dynamic environment that is much more severe than that seen by an RTG on an orbiting spacecraft or on a stationary planetary lander. This paper describes a typical Rover mission, its requirements, the environment it imposes on the RTG, and a design approach for making the RTG operable in such an environment. Specific RTG designs for various thermoelectric element alternatives are presented.; Reference CID #9268 and CID #9276.« less

Detecting tau in serum of transgenic animal models after tau immunotherapy treatment.

PubMed

d'Abramo, Cristina; Acker, Christopher M; Schachter, Joel B; Terracina, Giuseppe; Wang, Xiaohai; Forest, Stefanie K; Davies, Peter

2016-01-01

In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely. Copyright © 2016 Elsevier Inc. All rights reserved.

Validation Database Based Thermal Analysis of an Advanced RPS Concept

NASA Technical Reports Server (NTRS)

Balint, Tibor S.; Emis, Nickolas D.

2006-01-01

Advanced RPS concepts can be conceived, designed and assessed using high-end computational analysis tools. These predictions may provide an initial insight into the potential performance of these models, but verification and validation are necessary and required steps to gain confidence in the numerical analysis results. This paper discusses the findings from a numerical validation exercise for a small advanced RPS concept, based on a thermal analysis methodology developed at JPL and on a validation database obtained from experiments performed at Oregon State University. Both the numerical and experimental configurations utilized a single GPHS module enabled design, resembling a Mod-RTG concept. The analysis focused on operating and environmental conditions during the storage phase only. This validation exercise helped to refine key thermal analysis and modeling parameters, such as heat transfer coefficients, and conductivity and radiation heat transfer values. Improved understanding of the Mod-RTG concept through validation of the thermal model allows for future improvements to this power system concept.

Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

PubMed

Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

2016-01-01

The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

Underwater magnetic gradiometer for magnetic anomaly detection, localization, and tracking

NASA Astrophysics Data System (ADS)

Kumar, S.; Sulzberger, G.; Bono, J.; Skvoretz, D.; Allen, G. I.; Clem, T. R.; Ebbert, M.; Bennett, S. L.; Ostrom, R. K.; Tzouris, A.

2007-04-01

GE Security and the Naval Surface Warfare Center, Panama City (NSWC-PC) have collaborated to develop a magnetic gradiometer, called the Real-time Tracking Gradiometer or RTG that is mounted inside an unmanned underwater vehicle (UUV). The RTG is part of a buried mine hunting platform being developed by the United States Navy. The RTG has been successfully used to make test runs on mine-like targets buried off the coast of Florida. We will present a general description of the system and latest results describing system performance. This system can be also potentially used for other applications including those in the area of Homeland Security.

Influence of society for academic emergency medicine grant mechanisms on postaward academic productivity.

PubMed

Safdar, Basmah; Paradise, Summer A; McMillian, Melissa; Holmes, James F

2015-02-01

The Society for Academic Emergency Medicine (SAEM) provides research training grants, but the future productivity of award recipients and nonrecipients is unclear. The study objective was to assess the association of the two SAEM research training mechanisms with scholarly productivity and rates of subsequent funding between nonrecipients and recipients. A secondary goal was to evaluate the productivity metrics for fellows trained at the Institutional Research Training Grant (IRTG) programs. The authors surveyed all 2002 through 2011 Research Training Grant (RTG; n = 64) and Institutional Research Training Grant (IRTG; n = 38) applicants. RTG outcomes were federal funding as a principal investigator (PI) or co-PI using National Institutes of Health RePORTER and scholarly productivity using PubMed. IRTG outcomes were SAEM-approved research fellowships and National Heart, Lung and Blood Institute K12 training awards. Sites applying for or receiving the IRTG multiple times were only counted once. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Over 10 years, nine of 64 (14%) RTG and 10 of 38 (26%) IRTG applications were funded (two sites received multiple awards). Federal funding was obtained by seven of nine (78%) RTG recipients and 22 of 55 (40%) RTG nonrecipients (RR = 1.94, 95% CI = 1.21 to 3.13). All nine (100%, 95% CI = 72% to 100%) of RTG recipients had at least one manuscript, compared to 48 of the 55 (87%, 95% CI = 76% to 95%) nonrecipients. All nine (100%, 95% CI = 72% to 100%) RTG recipients remained in academics versus 44 of 55 (80%, 95% CI = 67% to 90%) nonrecipients. For the IRTG, four of seven awardees (57%, 95% CI = 18% to 90%) versus 0 of the 16 (0%, 95% CI = 0 to 17%) nonrecipients received National Heart, Lung and Blood Institute K12 awards (RR = 19.1, 95% CI = 1.16 to 314.0). Additionally, five of seven (71%, 95% CI = 29% to 96%) institutions became SAEM-approved fellowships compared to one of 16 (6%, 95% CI = 0 to 30%) nonrecipients (RR = 11.4, 95% CI = 1.61 to 80.7). SAEM RTG recipients were more likely to obtain federal funding postaward than nonrecipients. IRTG recipients were more likely to develop successful research training programs than nonrecipients. © 2015 by the Society for Academic Emergency Medicine.

[Cultivation of a permanent fish cell line in serum-free media special experiences with a cytotoxicity test for waste water samples

PubMed

Kohlpoth, Martin; Rusche, Brigitte

1997-01-01

The use of fetal calf serum (FCS) as standard medium additive for the cell cultivation must be regarded critically from the point of view of animal welfare as well as for scientific reasons and makes it necessary to look for alternatives. In the last years an in vitro cytotoxicity assay for the testing of industrial waste waters with the permanent fish cell line RTG-2 was established and pre-validated as an alternative to the fish test with the golden orfe. The application of FCS is also a special problem with regard to the testing of waste waters in a cytotoxicity test so that FCS-alternatives were tested. The RTG-2 cells were successfully adapted to the two solvents Basal Medium Supplement (BMS) and Ultroser-G (U-G) that are used to replace serum. The characterisation of these adapted cell lines showed no significant differences in growth rate, adhesion rate, viability and sensitivity to chemicals in comparison to the original RTG-2 cells. On the determination of the cytotoxicity of industrial waste waters the RTG-2 cells adapted to the BMS medium indicated a clearly higher toxicity of the waste water samples than the original RTG-2 cells. This result confirms the thesis that serum components react with waste water elements and thus change the bio-availability of toxic compounds.

Sfp1 and Rtg3 reciprocally modulate carbon source‐conditional stress adaptation in the pathogenic yeast Candida albicans

PubMed Central

Kastora, Stavroula L.; Herrero‐de‐Dios, Carmen; Avelar, Gabriela M.; Munro, Carol A.

2017-01-01

Summary The pathogenicity of the clinically important yeast, Candida albicans, is dependent on robust responses to host‐imposed stresses. These stress responses have generally been dissected in vitro at 30°C on artificial growth media that do not mimic host niches. Yet host inputs, such as changes in carbon source or temperature, are known to affect C. albicans stress adaptation. Therefore, we performed screens to identify novel regulators that promote stress resistance during growth on a physiologically relevant carboxylic acid and at elevated temperatures. These screens revealed that, under these ‘non‐standard’ growth conditions, numerous uncharacterised regulators are required for stress resistance in addition to the classical Hog1, Cap1 and Cta4 stress pathways. In particular, two transcription factors (Sfp1 and Rtg3) promote stress resistance in a reciprocal, carbon source‐conditional manner. SFP1 is induced in stressed glucose‐grown cells, whereas RTG3 is upregulated in stressed lactate‐grown cells. Rtg3 and Sfp1 regulate the expression of key stress genes such as CTA4, CAP1 and HOG1 in a carbon source‐dependent manner. These mechanisms underlie the stress sensitivity of C. albicans sfp1 cells during growth on glucose, and rtg3 cells on lactate. The data suggest that C. albicans exploits environmentally contingent regulatory mechanisms to retain stress resistance during host colonisation. PMID:28574606

Cost Comparison in 2015 Dollars for Radioisotope Power Systems -- Cassini and Mars Science Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werner, James Elmer; Johnson, Stephen Guy; Dwight, Carla Chelan

Radioisotope power systems (RPSs) have enabled missions requiring reliable, long-lasting power in remote, harsh environments such as space since the early 1960s. Costs for RPSs are high, but are often misrepresented due to the complexity of space missions and inconsistent charging practices among the many and changing participant organizations over the years. This paper examines historical documentation associated with two past successful flight missions, each with a different RPS design, to provide a realistic cost basis for RPS production and deployment. The missions and their respective RPSs are Cassini, launched in 1997, that uses the general purpose heat source (GPHS)more » radioisotope thermoelectric generator (RTG), and Mars Science Laboratory (MSL), launched in 2011, that uses the multi-mission RTG (MMRTG). Actual costs in their respective years are discussed for each of the two RTG designs and the missions they enabled, and then present day values to 2015 are computed to compare the costs. Costs for this analysis were categorized into two areas: development of the specific RTG technology, and production and deployment of an RTG. This latter category includes material costs for the flight components (including Pu-238 and fine weave pierced fabric (FWPF)); manufacturing of flight components; assembly, testing, and transport of the flight RTG(s); ground operations involving the RTG(s) through launch; nuclear safety analyses for the launch and for the facilities housing the RTG(s) during all phases of ground operations; DOE’s support for NEPA analyses; and radiological contingency planning. This analysis results in a fairly similar 2015 normalized cost for the production and deployment of an RTG—approximately $118M for the GPHS-RTG and $109M for the MMRTG. In addition to these two successful flight missions, the costs for development of the MMRTG are included to serve as a future reference. Note that development costs included herein for the MMRTG do not include costs from NASA staff or facilities for their development efforts—they only include the amounts costed by DOE and DOE contractors. The 2015 value for MMRTG development is $83M. Both of the RPS types analyzed herein use the general purpose heat source (GPHS) module as the “heart of the RPS.” The estimates presented herein do not include development costs for the GPHS. These estimates also do not include the RPS infrastructure cost to maintain the facilities, equipment, and personnel necessary to enable the production of RPSs, except to the extent that the infrastructure is utilized during the production campaigns to provide RPSs for missions. It was not until after the Cassini mission that an RPS infrastructure funding structure was defined and funded separately from mission-specific elements. The information presented herein could allow for more accurate budget planning estimates for space missions being considered over the next decade and beyond.« less

Modular Radioisotope Thermoelectric Generator (RTG) Program. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-12-31

Section 2.0 of this report summarizes the MOD-RTG reference flight design, and Section 3.0 discusses the Ground Demonstration System design. Multicouple technology development is discussed in Section 4.0, and Section 5.0 lists all published technical papers prepared during the course of the contract.

RTG Waste Heat System for the Cassini Propulsion Module

NASA Technical Reports Server (NTRS)

Mireles, V.; Stultz, J.

1994-01-01

This paper describes the thermal design for the propulsion module subsystem (PMS), and presents the results from the radioisotope thermoelectric generator (RTG) waste heat thermal test, and it summarizes the adjustment techniques and their relative effectiveness; it also shows the resulting predicted PMS flight temperatures relative to the requirements.

The program at JPL to investigate the nuclear interaction of RTG's with scientific instruments on deep space probes

NASA Technical Reports Server (NTRS)

Truscello, V.

1972-01-01

A major concern in the integration of a radioisotope thermoelectric generator (RTG) with a spacecraft designed to explore the outer planets is the effect of the emitted radiation on the normal operation of scientific instruments. The necessary techniques and tools developed to allow accurate calculation of the neutron and gamma spectrum emanating from the RTG. The specific sources of radiation were identified and quantified. Monte Carlo techniques are then employed to perform the nuclear transport calculations. The results of these studies are presented. An extensive experimental program was initiated to measure the response of a number of scientific components to the nuclear radiation.

Thermal vacuum life test facility for radioisotope thermoelectric generators

NASA Astrophysics Data System (ADS)

Deaton, R. L.; Goebel, C. J.; Amos, W. R.

In the late 1970's, the Department of Energy (DOE) assigned Monsanto Research Corporation, Mound Facility, now operated by EG and G Mound Applied Technologies, the responsibility for assembling and testing General Purpose Heat Source (GPHS) radioisotope thermoelectric generators (RTGs). Assembled and tested were five RTGs, which included four flight units and one non-flight qualification unit. Figure 1 shows the RTG, which was designed by General Electric AstroSpace Division (GE/ASD) to produce 285 W of electrical power. A detailed description of the processes for RTG assembly and testing is presented by Amos and Goebel (1989). The RTG performance data are described by Bennett, et al., (1986). The flight units will provide electrical power for the National Aeronautics and Space Administration's (NASA) Galileo mission to Jupiter (two RTGs) and the joint NASA/European Space Agency (ESA) Ulysses mission to study the polar regions of the sun (one RTG). The remaining flight unit will serve as the spare for both missions, and a non-flight qualification unit was assembled and tested to ensure that performance criteria were adequately met.

Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity

USGS Publications Warehouse

Park, J.-W.; Moon, C.H.; Harmache, A.; Wargo, A.R.; Purcell, M.K.; Bremont, M.; Kurath, G.

2011-01-01

Previously, we demonstrated that a representative M genogroup type strain of infectious haematopoietic necrosis virus (IHNV) from rainbow trout grows well in rainbow trout-derived RTG-2 cells, but a U genogroup type strain from sockeye salmon has restricted growth, associated with reduced genome replication and mRNA transcription. Here, we analysed further the mechanisms for this growth restriction of U-type IHNV in RTG-2 cells, using strategies that assessed differences in viral genes, host immune regulation and phosphorylation. To determine whether the viral glycoprotein (G) or non-virion (NV) protein was responsible for the growth restriction, four recombinant IHNV viruses were generated in which the G gene of an infectious IHNV clone was replaced by the G gene of U- or M-type IHNV and the NV gene was replaced by NV of U- or M-type IHNV. There was no significant difference in the growth of these recombinants in RTG-2 cells, indicating that G and NV proteins are not major factors responsible for the differential growth of the U- and M-type strains. Poly I:C pretreatment of RTG-2 cells suppressed the growth of both U- and M-type IHNV, although the M virus continued to replicate at a reduced level. Both viruses induced type 1 interferon (IFN1) and the IFN1 stimulated gene Mx1, but the expression levels in M-infected cells were significantly higher than in U-infected cells and an inhibitor of the IFN1-inducible protein kinase PKR, 2-aminopurine (2-AP), did not affect the growth of U- or M-type IHNV in RTG-2 cells. These data did not indicate a role for the IFN1 system in the restricted growth of U-type IHNV in RTG-2 cells. Prediction of kinase-specific phosphorylation sites in the viral phosphoprotein (P) using the NetPhosK program revealed differences between U- and M-type P genes at five phosphorylation sites. Pretreatment of RTG-2 cells with a PKC inhibitor or a p38MAPK inhibitor did not affect the growth of the U- and M-type viruses. However, 100 μm of the casein kinase II (CKII) inhibitor, 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB), reduced the titre of the U type 8.3-fold at 24 h post-infection. In contrast, 100 μm of the CKII inhibitor reduced the titre of the M type only 1.3-fold at 48 h post-infection. Our data suggest that the different growth of U- and M-type IHNV in RTG-2 cells may be linked to a differential requirement for cellular protein kinases such as CKII for their growth.

KSC-10941f07

NASA Image and Video Library

1997-05-27

Jet Propulsion Laboratory (JPL) technicians finish mounting a thermal model of a radioisotope thermoelectric generator (RTG) on the installation cart which will be used to install the RTG in the Cassini spacecraft at Level 14 of Space Launch Complex 40, Cape Canaveral Air Station. The technicians use the thermal model to practice installation procedures. The three actual RTGs which will provide electrical power to Cassini on its 6.7-mile trip to the Saturnian system, and during its four-year mission at Saturn, are being tested and monitored in the Radioisotope Thermoelectric Generator Storage Building in KSC's Industrial Area. The RTGs use heat from the natural decay of plutonium to generate electric power. RTGs enable spacecraft to operate far from the Sun where solar power systems are not feasible. The RTGs on Cassini are of the same design as those flying on the already deployed Galileo and Ulysses spacecraft. The Cassini mission is targeted for an October 6 launch aboard a Titan IVB/Centaur expendable launch vehicle. Cassini is built and managed for NASA by JPL

Applicability of STEM-RTG and High-Power SRG Power Systems to the Discovery and Scout Mission Capabilities Expansion (DSMCE) Study of ASRG-Based Missions

NASA Technical Reports Server (NTRS)

Colozza, Anthony J.; Cataldo, Robert L.

2015-01-01

This study looks at the applicability of utilizing the Segmented Thermoelectric Modular Radioisotope Thermoelectric Generator (STEM-RTG) or a high-power radioisotope generator to replace the Advanced Stirling Radioisotope Generator (ASRG), which had been identified as the baseline power system for a number of planetary exploration mission studies. Nine different Discovery-Class missions were examined to determine the applicability of either the STEM-RTG or the high-power SRG power systems in replacing the ASRG. The nine missions covered exploration across the solar system and included orbiting spacecraft, landers and rovers. Based on the evaluation a ranking of the applicability of each alternate power system to the proposed missions was made.

SNAP 19 Viking Program. Bimonthly technical progress report, October 1979-November 1979

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1979-12-01

Monitoring and evaluation of Viking 1 Lander power system data continued. The RTG series power range as measured at the PCDA was 65 to 68 watts at fin root temperatures between 280/sup 0/F and 310/sup 0/F. The Mars landed performance history of Viking 1 include both the minimum and maximum data for each of the SOL days. Monitoring and evaluation of Viking 2 Lander power system data continued. The RTG series power range as measured at the PCDA was 71 to 72 watts at fin root temperatures between 230/sup 0/F and 260/sup 0/F. The Mars landed performance history of Vikingmore » 2 include both the minimum and maximum data for each of the SOL days. The performance of both power systems continues to be very satisfactory. Power system performance data for Pioneer 10 and Pioneer 11 spacecraft were monitored through the reporting period. The estimated RTG system net power was 116 watts for Pioneer 10 and 118 watts for Pioneer Saturn. The September 1 encounter with Saturn appears to have had no deleterious effect on the RTG's of the spacecraft power system. The telemetry signals from both spacecrafts remain satisfactory.« less

Termination of aquired and natural immunological tolerance with specific complexes

PubMed Central

1975-01-01

It was possible to terminate the induced unresponsive state to bovine serum albumin (BSA) and the natural unresponsive state to autologous thyroglobulin in rabbits (RTg) by immunization with complexes composed of heterologous cross-reacting antibody and the tolerated antigens. The unresponsive state was terminated in rabbits made unresponsive by neonatal injections of BSA and then 3 mo later injected with complexes composed of BSA and guinea pig antihuman serum albumin. This termination was manifested by the presence of anti-BSA plaque-forming cells. Similarly, the natural unresponsive state was terminated in adult rabbits injected with complexes between RTg and guinea pig antibovine thyroglobulin (BTg) in that thyroid lesions and circulating anti-RTg were produced. The results can be best explained by the presence of unresponsive T cells and competent B cells, where the guinea pig gamma globulin (antibody) activates T cells specific for the guinea pig gamma globulin portion of the complexes and thus permits stimulation of B cells competent to the exposed determinants of the tolerated (BSA or RTg) portion of the complexes. The detailed mechanism for the activation of B cells in tolerant animals is discussed. PMID:1095680

GPHS RTGs in Support of the Cassini RTG Program. Final Technical Report, January 11, 1991 - April 30, 1998

DOE R&D Accomplishments Database

1998-08-01

As noted in the historical summary, this program encountered a number of changes in direction, schedule, and scope over the period 11 January 1991 to 31 December 1998. The report provides a comprehensive summary of all the varied aspects of the program over its seven and a quarter years, and highlights those aspects that provide information beneficial to future radioisotope programs. In addition to summarizing the scope of the Cassini GPHS RTG Program provided as background, the introduction includes a discussion of the scope of the final report and offers reference sources for information on those topics not covered. Much of the design heritage of the GPHS RTG comes from the Multi Hundred Watt (MHW) RTGs used on the Lincoln Experimental Satellites (LES) 8/9 and Voyager spacecraft. The design utilized for the Cassini program was developed, in large part, under the GPHS RTG program which produced the Galileo and Ulysses RTGs. Reports from those programs included detailed documentation of the design, development, and testing of converter components and full converters that were identical to, or similar to, components used in the Cassini program.

So What's an RTG and Are They Safe?

NASA Technical Reports Server (NTRS)

Barret, Chris; Hughes, R. W. (Technical Monitor)

2001-01-01

When one considers space missions to the outer edges of our solar system and far beyond, our sun cannot be relied on to produce the required spacecraft (s/c) power. Solar energy diminishes as the square of the distance from the Sun. At Mars it is only 43% of that at earth. At Jupiter, it falls off to only 3.6% of Earth's. By the time we get out to Pluto, solar energy is only .066% what it is on Earth. Beyond the orbit of Mars, it is not practical to depend on solar power for a s/c. However, the farther out we go the more power we need to heat the s/c and to transmit data back to Earth over the long distances. On Earth, knowledge is power. In the outer solar system, power is knowledge. Solar arrays only operate at 19% efficiency, are very vulnerable to damage from radiation and temperature extremes, and cannot be used for even nearby missions that operate in extended darkness, or under the surface of a planet or moon. Twenty-six U.S. space missions, from the Transit to Cassini, have used radioisotope power systems and heater units to take s/c to the far reaches of our solar system and have demonstrated an outstanding record of safety and reliability. Radioisotope thermoelectric generators (RTG's) have proven to be safe, reliable, maintenance-free, and capable of providing both thermal and electrical power for decades under the harsh environments of deep space. RTG's have no problem operating in the high radiation belts of space, the extreme temperatures, or the severe dust storms of Mars, and they have proven to be the most reliable power source ever flown on U.S. s/c. For example, the two Pioneer s/c operated for more than two decades and the Voyager s/c may last for 40 years. RTG's are not nuclear reactors, they serve only as power generators and are not involved in the propulsion of the s/c. They operate on the principle of thermoelectric generation that converts heat directly into electricity, they have no moving parts, are extremely reliable, and have met or exceeded all safety and performance expectations. Federal laws and regulations require analysis and evaluation of the safety risks and any potential environmental impacts. Extensive safety testing of RTG's and RTG components has been performed by the U.S. Department of Energy (DOE) to demonstrate the ability to survive accidents related to Space Shuttle launches and assure that the systems would be safe under all accident conditions, including accidents at or near the launch pad or during orbital reentry. Many design improvements have been made over the four decades that RTG's have been flown on space missions. This paper outlines the operation and safety standards of RTG's and the advanced developments expected to be used on future deep space missions such as the Europa Orbiter, Pluto/Kuiper Express, Solar Probe, Europa Lander, and Titan Explorer missions.

Reach-to-grasp movement as a minimization process.

PubMed

Yang, Fang; Feldman, Anatol G

2010-02-01

It is known that hand transport and grasping are functionally different but spatially coordinated components of reach-to-grasp (RTG) movements. As an extension of this notion, we suggested that body segments involved in RTG movements are controlled as a coherent ensemble by a global minimization process associated with the necessity for the hand to reach the motor goal. Different RTG components emerge following this process without pre-programming. Specifically, the minimization process may result from the tendency of neuromuscular elements to diminish the spatial gap between the actual arm-hand configuration and its virtual (referent) configuration specified by the brain. The referent configuration is specified depending on the object shape, localization, and orientation. Since the minimization process is gradual, it can be interrupted and resumed following mechanical perturbations, at any phase during RTG movements, including hand closure. To test this prediction of the minimization hypothesis, we asked subjects to reach and grasp a cube placed within the reach of the arm. Vision was prevented during movement until the hand returned to its initial position. As predicted, by arresting wrist motion at different points of hand transport in randomly selected trials, it was possible to halt changes in hand aperture at any phase, not only during hand opening but also during hand closure. Aperture changes resumed soon after the wrist was released. Another test of the minimization hypothesis was made in RTG movements to an object placed beyond the reach of the arm. It has previously been shown (Rossi et al. in J Physiol 538:659-671, 2002) that in such movements, the trunk motion begins to contribute to hand transport only after a critical phase when the shifts in the referent arm configuration have finished (at about the time when hand velocity is maximal). The minimization rule suggests that when the virtual contribution of the arm to hand transport is completed, guidance of hand aperture switches from the arm to the trunk control system. As a consequence, hand aperture changes can be halted by trunk arrests but only if they are prolonged beyond a critical phase. As predicted, hand transport and hand aperture in RTG movements beyond the reach of the arm were halted by trunk arrests only if they were prolonged beyond the time of peak hand velocity. Hand motion and aperture changes resumed only when the trunk was released. While supporting the minimization hypothesis, our findings imply that not only spatial but also temporal characteristics of each component, including the shortest, hand closure component of RTG movements, are controlled in a flexible, task-specific way.

An evaluation of some special techniques for nuclear waste disposal in space

NASA Technical Reports Server (NTRS)

Mackay, J. S.

1973-01-01

A preliminary examination is reported of several special ways for space disposal of nuclear waste material which utilize the radioactive heat in the waste to assist in the propulsion for deep space trajectories. These include use of the wastes in a thermoelectric generator (RTG) which operates an electric propulsion device and a radioisotope - thermal thruster which uses hydrogen or ammonia as the propellant. These propulsive devices are compared to the space tug and the space tug/solar electric propulsion combination for disposal of waste on a solar system escape trajectory. Such comparisons indicate that the waste-RTG approach has considerable potential provided the combined specific mass of the waste container - RTG system does not exceed approximately 150 kg/kw sub e. Several exploratory numerical calculations have been made for high earth orbit and Earth escape destinations.

Underwater (UW) Unexploded Ordnance (UXO) Multi-Sensor Data Base (MSDB) Collection

DTIC Science & Technology

2009-07-01

11 FIGURE 6 RTG SENSOR. FOUR SENSOR TRIADS ARE SHOWN, EACH WITH A 3-AXIS FLUXGATE MAGNETOMETER ...used by RTG to measure the gradients. Each triad includes a 3-axis fluxgate magnetometer and a set of feedback coils. The outputs of three triad...each with a 3-axis fluxgate magnetometer (internal, not clearly visible) and a set of 3 feedback coils. The upper triad 3-axis magnetometer

Summary of miscellaneous hazard environments for hypothetical Space Shuttle and Titan IV launch abort accidents

NASA Technical Reports Server (NTRS)

Eck, M.; Mukunda, M.

1989-01-01

The various analyses described here were aimed at obtaining a more comprehensive understanding and definition of the environments in the vicinity of the Radioisotope Thermal Generator (RTG) during certain Space Transportation System (STS) and Titan IV launch abort accidents. Addressed here are a number of issues covering explosion environments and General Purpose Heat Source Radioisotope Thermoelectric Generator (GPHS-RTG) responses to those environments.

Buried Object Classification using a Sediment Volume Imaging SAS and Electromagnetic Gradiometer

DTIC Science & Technology

2006-09-01

field data with simulated RTG data using AST’s in-house magnetic modeling tool EMAGINE . Given a set of input dipole moments, or pa- rameters to...approximate a moment by assuming the object is a prolate ellipsoid shell, EMAGINE uses Green’s func- tion formulations to generate three-component

A Simple Technique for Creating Regional Composites of Sea Surface Temperature from MODIS for Use in Operational Mesoscale NWP

NASA Technical Reports Server (NTRS)

Knievel, Jason C.; Rife, Daran L.; Grim, Joseph A.; Hahmann, Andrea N.; Hacker, Joshua P.; Ge, Ming; Fisher, Henry H.

2010-01-01

This paper describes a simple technique for creating regional, high-resolution, daytime and nighttime composites of sea surface temperature (SST) for use in operational numerical weather prediction (NWP). The composites are based on observations from NASA s Moderate Resolution Imaging Spectroradiometer (MODIS) aboard Aqua and Terra. The data used typically are available nearly in real time, are applicable anywhere on the globe, and are capable of roughly representing the diurnal cycle in SST. The composites resolution is much higher than that of many other standard SST products used for operational NWP, including the low- and high-resolution Real-Time Global (RTG) analyses. The difference in resolution is key because several studies have shown that highly resolved SSTs are important for driving the air sea interactions that shape patterns of static stability, vertical and horizontal wind shear, and divergence in the planetary boundary layer. The MODIS-based composites are compared to in situ observations from buoys and other platforms operated by the National Data Buoy Center (NDBC) off the coasts of New England, the mid-Atlantic, and Florida. Mean differences, mean absolute differences, and root-mean-square differences between the composites and the NDBC observations are all within tenths of a degree of those calculated between RTG analyses and the NDBC observations. This is true whether or not one accounts for the mean offset between the skin temperatures of the MODIS dataset and the bulk temperatures of the NDBC observations and RTG analyses. Near the coast, the MODIS-based composites tend to agree more with NDBC observations than do the RTG analyses. The opposite is true away from the coast. All of these differences in point-wise comparisons among the SST datasets are small compared to the 61.08C accuracy of the NDBC SST sensors. Because skin-temperature variations from land to water so strongly affect the development and life cycle of the sea breeze, this phenomenon was chosen for demonstrating the use of the MODIS-based composite in an NWP model. A simulated sea breeze in the vicinity of New York City and Long Island shows a small, net, but far from universal improvement when MODIS-based composites are used in place of RTG analyses. The timing of the sea breeze s arrival is more accurate at some stations, and the near-surface temperature, wind, and humidity within the breeze are more realistic.

The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine.

PubMed

Syeda, Ruhma; Santos, Jose S; Montal, Mauricio

2016-02-05

KCNQ (voltage-gated K(+) channel family 7 (Kv7)) channels control cellular excitability and underlie the K(+) current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K(+) current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Design of multihundredwatt DIPS for robotic space missions

NASA Technical Reports Server (NTRS)

Bents, D. J.; Geng, S. M.; Schreiber, J. G.; Withrow, C. A.; Schmitz, P. C.; Mccomas, Thomas J.

1991-01-01

Design of a dynamic isotope power system (DIPS) general purpose heat source (GPHS) and small free piston Stirling engine (FPSE) is being pursued as a potential lower cost alternative to radioisotope thermoelectric generators (RTG's). The design is targeted at the power needs of future unmanned deep space and planetary surface exploration missions ranging from scientific probes to SEI precursor missions. These are multihundredwatt missions. The incentive for any dynamic system is that it can save fuel which reduces cost and radiological hazard. However, unlike a conventional DIPS based on turbomachinery converions, the small Stirling DIPS can be advantageously scaled to multihundred watt unit size while preserving size and weight competitiveness with RTG's. Stirling conversion extends the range where dynamic systems are competitive to hundreds of watts (a power range not previously considered for dynamic systems). The challenge of course is to demonstrate reliability similar to RTG experience. Since the competative potential of FPSE as an isotope converter was first identified, work has focused on the feasibility of directly integrating GPHS with the Stirling heater head. Extensive thermal modeling of various radiatively coupled heat source/heater head geometries were performed using data furnished by the developers of FPSE and GPHS. The analysis indicates that, for the 1050 K heater head configurations considered, GPHS fuel clad temperatures remain within safe operating limits under all conditions including shutdown of one engine. Based on these results, preliminary characterizations of multihundred watt units were established.

The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine*

PubMed Central

Syeda, Ruhma; Santos, Jose S.; Montal, Mauricio

2016-01-01

KCNQ (voltage-gated K+ channel family 7 (Kv7)) channels control cellular excitability and underlie the K+ current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K+ current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. PMID:26627826

SCO-1, a Novel Plasmid-Mediated Class A β-Lactamase with Carbenicillinase Characteristics from Escherichia coli▿

PubMed Central

Papagiannitsis, C. C.; Loli, A.; Tzouvelekis, L. S.; Tzelepi, E.; Arlet, G.; Miriagou, V.

2007-01-01

A novel class A β-lactamase (SCO-1) encoded by an 80-kb self-transferable plasmid from Escherichia coli is described. The interaction of SCO-1 with β-lactams was similar to that of the CARB-type enzymes. Also, SCO-1 exhibited a 51% amino acid sequence identity with the RTG subgroup of chromosomal carbenicillinases (RTG-1, CARB-5, and CARB-8). PMID:17353248

Adavanced RTG and thermoelectric materials study

NASA Technical Reports Server (NTRS)

Eggers, P. E.

1971-01-01

A comprehensive, generalized two-dimensional RTG analysis computer program was developed. This program is capable of analyzing any specified RTG design under a wide range of transient as well as steady-state operating conditions. The feasibility of a new concept for the design of segmented (or single-phase) thermoelectric couples was demonstrated. A SiGe-PbTe segmented couple involving pressure contacted junctions at the intermediate- and hot-junction temperatures was successfully encapsulated in a hermetically sealed bellows enclosure. This bellows-encapsulated couple was operated between a hot- and cold-junction temperature of 1200 K and 450 K, respectively, with a measured energy conversion efficiency of 7.6 + or - .5 per cent. An experimental study of selected sublimation barrier schemes revealed that a significant reduction in the sublimation rate of p-type PbTe could be achieved by using multiple layers of SiO2 fibers. A comparison of the barrier effectiveness is given for three different barrier designs.

The CRAF/Cassini power subsystem - Preliminary design update

NASA Technical Reports Server (NTRS)

Atkins, Kenneth L.; Brisendine, Philip; Clark, Karla; Klein, John; Smith, Richard

1991-01-01

A chronology is provided of the rationale leading from the early Mariner spacecraft to the CRAF/Cassini Mariner Mark II power subsystem architecture. The display pathway began with a hybrid including a solar photovoltaic array, a radioisotope thermoelectric generator (RTG), and a battery supplying a power profile with a peak loading of about 300 W. The initial concept was to distribute power through a new solid-state, programmable switch controlled by an embedded microprocessor. As the overall mission, science, and project design matured, the power requirements increased. The design evolved from the hybrid to two RTG plus batteries to meet peak loadings of near 500 W in 1989. Later that year, circumstances led to abandonment of the distributed computer concept and a return to centralized control. Finally, as power requirements continued to grow, a third RTG was added to the design and the battery removed, with the return to the discharge-controller for transients during fault recovery procedures.

Visual imaging control systems of the Mariner to Jupiter and Saturn spacecraft

NASA Technical Reports Server (NTRS)

Larks, L.

1979-01-01

Design and fabrication of optical systems for the Mariner Jupiter Saturn (Voyager) mission is described. Because of the long distances of these planets from the sun, the spacecraft was designed without solar panels with the electricity generated on-board by radio-isotope thermal generators (RTG). The presence of RTG's and Jupiter radiation environment required that the optical systems be fabricated out of radiation stabilized materials. A narrow angle and a wide angle camera are located on the spacecraft scan platform, with the narrow angle lens a modification of the Mariner 10 lens. The optical system is described, noting that the lens was modified by moving the aperture correctors forward and placing a spider mounted secondary mirror in the original back surface of the second aperture corrector. The wide angle lens was made out of cerium doped, radiation stabilized optical glass with greatest blue transmittance, which would be resistant to RTG and Jupiter radiation.

Apollo 12 Mission image - Alan Bean unloads ALSEP RTG fuel element

NASA Image and Video Library

1969-11-19

AS12-46-6790 (19 Nov. 1969) --- Astronaut Alan L. Bean, lunar module pilot, is photographed at quadrant II of the Lunar Module (LM) during the first Apollo 12 extravehicular activity (EVA) on the moon. This picture was taken by astronaut Charles Conrad Jr., commander. Here, Bean is using a fuel transfer tool to remove the fuel element from the fuel cask mounted on the LM's descent stage. The fuel element was then placed in the Radioisotope Thermoelectric Generator (RTG), the power source for the Apollo Lunar Surface Experiments Package (ALSEP) which was deployed on the moon by the two astronauts. The RTG is next to Bean's right leg. While astronauts Conrad and Bean descended in the LM "Intrepid" to explore the Ocean of Storms region of the moon, astronaut Richard F. Gordon Jr., command module pilot, remained with the Command and Service Modules (CSM) "Yankee Clipper" in lunar orbit.

Milliwatt Generator Project

NASA Astrophysics Data System (ADS)

Latimer, T. W.; Rinehart, G. H.

1992-05-01

This report covers progress on the Milliwatt Generator Project from April 1986 through March 1988. Activities included fuel processing and characterization, production of heat sources, fabrication of pressure-burst test units, compatibility studies, impact testing, and examination of surveillance units. The major task of the Los Alamos Milliwatt Generator Project is to fabricate MC2893A heat sources (4.0 W) for MC2730A radioisotope thermoelectric generators (RTG's) and MC3599 heat sources (4.5 W) for MC3500 RTG's. The MWG Project interfaces with the following contractors: Sandia National Laboratories, Albuquerque (designer); E.I. du Pont de Nemours and Co. (Inc.), Savannah River Plant (fuel); Monsanto Research Corporation, Mound Facility (metal hardware); and General Electric Company, Neutron Devices Department (RTG's). In addition to MWG fabrication activities, Los Alamos is involved in (1) fabrication of pressure-burst test units, (2) compatibility testing and evaluation, (3) examination of surveillance units, and (4) impact testing and subsequent examination of compatibility and surveillance units.

On thermal stress failure of the SNAP-19A RTG heat shield

NASA Technical Reports Server (NTRS)

Pitts, W. C.; Anderson, L. A.

1974-01-01

Results of a study on thermal stress problems in an amorphous graphite heat shield that is part of the launch-abort protect system for the SNAP-19A radio-isotope thermoelectric generators (RTG) that will be used on the Viking Mars Lander are presended. The first result is from a thermal stress analysis of a full-scale RTG heat source that failed to survive a suborbital entry flight test, possibly due to thermal stress failure. It was calculated that the maximum stress in the heat shield was only 50 percent of the ultimate strength of the material. To provide information on the stress failure criterion used for this calculation, some heat shield specimens were fractured under abort entry conditions in a plasma arc facility. It was found that in regions free of stress concentrations the POCO graphite heat shield material did fracture when the local stress reached the ultimate uniaxial stress of the material.

Stratified Shear Flows In Pipe Geometries

NASA Astrophysics Data System (ADS)

Harabin, George; Camassa, Roberto; McLaughlin, Richard; UNC Joint Fluids Lab Team Team

2015-11-01

Exact and series solutions to the full Navier-Stokes equations coupled to the advection diffusion equation are investigated in tilted three-dimensional pipe geometries. Analytic techniques for studying the three-dimensional problem provide a means for tackling interesting questions such as the optimal domain for mass transport, and provide new avenues for experimental investigation of diffusion driven flows. Both static and time dependent solutions will be discussed. NSF RTG DMS-0943851, NSF RTG ARC-1025523, NSF DMS-1009750.

Long term behavior of silicon germanium thermoelectric generators

NASA Technical Reports Server (NTRS)

Shields, V.

1981-01-01

Results of tests of the long term performance of SiGe radioisotope thermoelectric generators (RTG) are presented. Three modules were monitored for 17,000-32,300 hr at hot junction temperatures of 1,085, 1,055, and 1,000 C; coating the unicouples with a 12,000 A thick layer of Si3N4 protected the modules from Si sublimation. Output degraded less than 0.3-0.4%/1,000 hr over the testing period. Life tests on a multihundredwatt (MHW) SiGe generator with 312 couples at a hot shoe temperature of 1,040 C dealt with power of 150 W at 30 V, with 0.5%/1,000 hr performance degradation. Si deposition on the insulation was found to enhance electrical conductance until a saturation point was reached. Disassembly of a test module after 16,750 hr revealed a Mo build-up, SiN4 coating deterioration, and Ti diffustion from the hot shoe to cooler regions of the junction. The presence of an Al2O3 insulator was recognized as preventing coating loss. Performance records from the Voyager and Les-8 satellites' RTG's are compared and show similar, 0.25%/1,000 hr degradation rates; RTG storage is judged to be feasible and the tests lead to projections of a 600,000 hr lifetime for a SiGe RTG.

Radioisotope Thermoelectric Generators Emplaced in the Deep Ocean, Recover or Dispose in Situ

DTIC Science & Technology

1986-03-01

00 0 M! Technical Report 1106 Cll ) March 1986 Radioisotope Thermoelectric 00 Generators Emplaced in the Deep Ocean Recover or Dispose In Situ? 00...PROGRAM ELEMENT NO PROJECT NO8 TASK NO WORK UN IT NO NAV’COMPT 141 N� A8 WR00026 I I TITLE i,cmvd. Secunty CIaxssIoe,o’,) Radioisotope Thermoelectric ...disposal alternatives. . RTG DESCRIPTIONS Each RTG consists of a strontium-90 titanate heat source, thermoelectric generator, thermal insulation

Explicit Pore Pressure Material Model in Carbon-Cloth Phenolic

NASA Technical Reports Server (NTRS)

Gutierrez-Lemini, Danton; Ehle, Curt

2003-01-01

An explicit material model that uses predicted pressure in the pores of a carbon-cloth phenolic (CCP) composite has been developed. This model is intended to be used within a finite-element model to predict phenomena specific to CCP components of solid-fuel-rocket nozzles subjected to high operating temperatures and to mechanical stresses that can be great enough to cause structural failures. Phenomena that can be predicted with the help of this model include failures of specimens in restrained-thermal-growth (RTG) tests, pocketing erosion, and ply lifting

Small Stirling dynamic isotope power system for robotic space missions

NASA Technical Reports Server (NTRS)

Bents, D. J.

1992-01-01

The design of a multihundred-watt Dynamic Isotope Power System (DIPS), based on the U.S. Department of Energy (DOE) General Purpose Heat Source (GPHS) and small (multihundred-watt) free-piston Stirling engine (FPSE), is being pursued as a potential lower cost alternative to radioisotope thermoelectric generators (RTG's). The design is targeted at the power needs of future unmanned deep space and planetary surface exploration missions ranging from scientific probes to Space Exploration Initiative precursor missions. Power level for these missions is less than a kilowatt. The incentive for any dynamic system is that it can save fuel and reduce costs and radiological hazard. Unlike DIPS based on turbomachinery conversion (e.g. Brayton), this small Stirling DIPS can be advantageously scaled to multihundred-watt unit size while preserving size and mass competitiveness with RTG's. Stirling conversion extends the competitive range for dynamic systems down to a few hundred watts--a power level not previously considered for dynamic systems. The challenge for Stirling conversion will be to demonstrate reliability and life similar to RTG experience. Since the competitive potential of FPSE as an isotope converter was first identified, work has focused on feasibility of directly integrating GPHS with the Stirling heater head. Thermal modeling of various radiatively coupled heat source/heater head geometries has been performed using data furnished by the developers of FPSE and GPHS. The analysis indicates that, for the 1050 K heater head configurations considered, GPHS fuel clad temperatures remain within acceptable operating limits. Based on these results, preliminary characterizations of multihundred-watt units have been established.

47 CFR 32.4520 - Additional paid-in capital.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.4520... includable in Account 4510, Capital Stock, unless such difference results in a debit balance for that class...

Design of small Stirling dynamic isotope power system for robotic space missions

NASA Technical Reports Server (NTRS)

Bents, D. J.; Schreiber, J. G.; Withrow, C. A.; Mckissock, B. I.; Schmitz, P. C.

1992-01-01

Design of a multihundred-watt Dynamic Isotope Power System (DIPS) based on the U.S. Department of Energy (DOE) General Purpose Heat Source (GPHS) and small (multihundred-watt) free-piston Stirling engine (FPSE) technology is being pursued as a potential lower cost alternative to radioisotope thermoelectric generators (RTG's). The design is targeted at the power needs of future unmanned deep space and planetary surface exploration missions ranging from scientific probes to Space Exploration Initiative precursor missions. Power level for these missions is less than a kilowatt. Unlike previous DIPS designs which were based on turbomachinery conversion (e.g. Brayton), this small Stirling DIPS can be advantageously scaled down to multihundred-watt unit size while preserving size and mass competitiveness with RTG's. Preliminary characterization of units in the output power ranges 200-600 We indicate that on an electrical watt basis the GPHS/small Stirling DIPS will be roughly equivalent to an advanced RTG in size and mass but require less than a third of the isotope inventory.

SNAP 19 Viking Program. Bimonthly technical progress report, April-May 1980

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-01-01

Monitoring and evaluation of Viking Lander 1 power system data continued. The RTG series power range as measured at the PCDA was 65 to 67 watts at finroot temperatures between 280/sup 0/F and 310/sup 0/F. The Mars Lander performance history of Viking 1 include both the minimum and maximum data for each of the SOL days. Final available power system data for Viking Lander 2 are shown. Typical SOL day cycles for mission day 1193 are presented. The RTG series power ranged from 69 to 70 watts at finroot temperatures between 270/sup 0/F and 300/sup 0/F. The Mars Lander performancemore » history for Viking 2 is shown. Power system performance data for Pioneer 10 and Pioneer Saturn (initially designated Pioneer 11) were monitored through the reporting period. After adjusting for the telemetry characteristics, the estimated RTG system net power was 114 watts for both Pioneer 10 and Pioneer Saturn.« less

Retrograde Signaling as a Mechanism of Yeast Adaptation to Unfavorable Factors.

PubMed

Trendeleva, T A; Zvyagilskaya, R A

2018-02-01

Mitochondria perform many essential functions in eukaryotic cells. Being the main producers of ATP and the site of many catabolic and anabolic reactions, they participate in intracellular signaling, proliferation, aging, and formation of reactive oxygen species. Mitochondrial dysfunction is the cause of many diseases and even cell death. The functioning of mitochondria in vivo is impossible without interaction with other cellular compartments. Mitochondrial retrograde signaling is a signaling pathway connecting mitochondria and the nucleus. The major signal transducers in the yeast retrograde response are Rtg1p, Rtg2p, and Rtg3p proteins, as well as four additional negative regulatory factors - Mks1p, Lst8p, and two 14-3-3 proteins (Bmh1/2p). In this review, we analyze current information on the retrograde signaling in yeast that is regarded as a stress or homeostatic response mechanism to changes in various metabolic and biosynthetic activities that occur upon mitochondrial dysfunction. We also discuss relations between retrograde signaling and other signaling pathways in the cell.

Apollo 12 Mission image - Modular Equipment Stowage Assemble (MESA) and the Fuel Cask on the Lunar Module (LM)

NASA Image and Video Library

1969-11-19

AS12-48-7034 (19 Nov. 1969) --- A close-up view of a portion of quadrant II of the descent stage of the Apollo 12 Lunar Module (LM), photographed during the Apollo 12 extravehicular activity (EVA). At lower left is the LM's Y footpad. The empty Radioisotope Thermoelectric Generator (RTG) fuel cask is at upper right. The fuel capsule has already been removed and placed in the RTG. The RTG furnishes power for the Apollo Lunar Surface Experiments Package (ALSEP) which the Apollo 12 astronauts deployed on the moon. The LM's descent engine skirt is in the center background. The rod-like object protruding out from under the footpad is a lunar surface sensing probe. Astronaut Richard F. Gordon Jr., command module pilot, remained with the Command and Service Modules (CSM) in lunar orbit while astronauts Charles Conrad Jr., commander; and Alan L. Bean, lunar module pilot, descended in the LM to explore the moon.

RTG performance on Galileo and Ulysses and Cassini test results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelly, C. Edward; Klee, Paul M.

Power output from telemetry for the two Galileo RTGs are shown from the 1989 launch to the recent Jupiter encounter. Comparisons of predicted, measured and required performance are shown. Similar comparisons are made for the RTG on the Ulysses spacecraft which completed its planned mission in 1995. Also presented are test results from small scale thermoelectric modules and full scale converters performed for the Cassini program. The Cassini mission to Saturn is scheduled for an October 1997 launch. Small scale module test results on thermoelectric couples from the qualification and flight production runs are shown. These tests have exceeded 19,000more » hours are continuing to provide increased confidence in the predicted long term performance of the Cassini RTGs. Test results are presented for full scale units both ETGs (E-6, E-7) and RTGs (F-2, F-5) along with mission power predictions. F-5, fueled in 1985, served as a spare for the Galileo and Ulysses missions and plays the same role in the Cassini program. It has successfully completed all acceptance testing. The ten years storage between thermal vacuum tests is the longest ever experienced by an RTG. The data from this test are unique in providing the effects of long term low temperature storage on power output. All ETG and RTG test results to date indicate that the power requirements of the Cassini spacecraft will be met. BOM and EOM power margins of at least five percent are predicted.« less

Effects of structured testing versus routine testing of blood glucose in diabetes self-management: A randomized controlled trial.

PubMed

Nishimura, Akiko; Harashima, Shin-Ichi; Fujita, Yoshihito; Tanaka, Daisuke; Wang, Yu; Liu, Yanyan; Inagaki, Nobuya

2017-01-01

To compare the effects of structured and routine testing regimens used in self-monitoring of blood glucose (SMBG) on glycemic control and diabetes self-management in insulin-naïve type 2 diabetes patients. Sixty-two outpatients with insulin-naïve type 2 diabetes were randomly allocated into two less-frequent SMBG usage groups: a structured testing group (STG) and a routine testing group (RTG). Subjects in STG measured 7-points on SMBG for 3 consecutive days once every two months without daily testing; subjects in RTG measured SMBG 3 times each week before breakfast on Monday and Friday and before dinner on Wednesday. The primary endpoint was HbA1c reduction. The secondary endpoints were change in body weight, blood pressure, treatment change, and self-management performance change. HbA1c levels were significantly decreased by 0.32% (3.50mmol/mol) in STG, partly because physicians changed medications more actively. In contrast, body weight and systolic/diastolic blood pressure were significantly reduced by 0.94kg and 6.8/4.7mmHg, respectively, in RTG, possibly related to the increased diet and exercise score in RTG. Structured testing without daily testing is beneficial for glycemic control; routine testing 3 times a week is more helpful for daily self-management. In low SMBG frequency usage, these two regimens can be utilized according to individual diabetic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

RTG resource book for western states and provinces: Final proceedings

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The Western Interstate Energy Board held a workshop and liaison activities among western states, provinces, and utilities on the formation of Regional Transmission Groups (RTGs). Purpose of the activities was to examine the policy implications for western states and provinces in the formation of RTGs in the West, the implications for western ratepayers and utilities of the RTG formation and potential impacts of RTGs on the western electricity system. The workshop contributed to fulfilling the transmission access and competition objectives of Title VII of the Energy Policy Act of 1992.

RTG performance on Galileo and Ulysses and Cassini test results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelly, C.E.; Klee, P.M.

Power output from telemetry for the two Galileo RTGs are shown from the 1989 launch to the recent Jupiter encounter. Comparisons of predicted, measured and required performance are shown. Similar comparisons are made for the RTG on the Ulysses spacecraft which completed its planned mission in 1995. Also presented are test results from small scale thermoelectric modules and full scale converters performed for the Cassini program. The Cassini mission to Saturn is scheduled for an October 1997 launch. Small scale module test results on thermoelectric couples from the qualification and flight production runs are shown. These tests have exceeded 19,000more » hours are continuing to provide increased confidence in the predicted long term performance of the Cassini RTGs. Test results are presented for full scale units both ETGs (E-6, E-7) and RTGs (F-2, F-5) along with mission power predictions. F-5, fueled in 1985, served as a spare for the Galileo and Ulysses missions and plays the same role in the Cassini program. It has successfully completed all acceptance testing. The ten years storage between thermal vacuum tests is the longest ever experienced by an RTG. The data from this test are unique in providing the effects of long term low temperature storage on power output. All ETG and RTG test results to date indicate that the power requirements of the Cassini spacecraft will be met. BOM and EOM power margins of at least five percent are predicted. {copyright} {ital 1997 American Institute of Physics.}« less

Sustainable land management practices as providers of several ecosystem services under rainfed Mediterranean agroecosystems

NASA Astrophysics Data System (ADS)

Almagro, María; de Vente, Joris; Boix-Fayós, Carolina; García-Franco, Noelia; Melgares de Aguilar, Javier; González, David; Solé-Benet, Albert; Martínez-Mena, María

2015-04-01

Little is known about the multiple impacts of sustainable land management practices on soil and water conservation, carbon sequestration, mitigation of global warming, and crop yield productivity in semiarid Mediterranean agroecosystems. We hypothesized that a shift from intensive tillage to more conservative tillage management practices (reduced tillage optionally combined with green manure) leads to an improvement in soil structure and quality and will reduce soil erosion and enhance carbon sequestration in semiarid Mediterranean rainfed agroecosystems. To test the hypothesis, we assessed the effects of different tillage treatments (conventional (CT), reduced (RT), reduced tillage combined with green manure (RTG), and no tillage (NT)) on soil structure and soil water content, runoff and erosion control, soil CO2 emissions, crop yield and carbon sequestration in two semiarid agroecosystems with organic rainfed almond in the Murcia Region southeast Spain). It was found that reduction and suppression of tillage under almonds led to an increase in soil water content in both agroecosystems. Crop yields ranged from 775 to 1766 kg ha-1 between tillage 18 treatments, but we did not find a clear relation between soil water content and crop yield. RT and RTG treatments showed lower soil erosion rates and higher crop yields of almonds than under CT treatment. Overall, higher soil organic carbon contents and aggregate stability were observed under RTG treatment than under RT or CT treatment. It is concluded that conversion from CT to RTG is suitable to increase carbon inputs without enhancing soil CO2 emissions in semiarid Mediterranean agroecosystems.

Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.

PubMed

Biton, Victor; Gil-Nagel, Antonio; Brodie, Martin J; Derossett, Sarah E; Nohria, Virinder

2013-11-01

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG. Copyright © 2013 Elsevier B.V. All rights reserved.

GPHS-RTGs in support of the Cassini RTG Program

NASA Astrophysics Data System (ADS)

1995-04-01

The technical progress achieved during the period 26 Sep. 1994 - 2 Apr. 1995 on Contract DE-AC03-91SF-18852 Radioisotope Thermoelectric Generators and Ancillary Activities is described herein. Monthly technical activity for the period 27 Feb. - 2 Apr. 1995 is included in this progress report. The report addresses tasks, including: spacecraft integration and liaison; engineering support; safety; qualified unicouple production; ETG fabrication, assembly, and test; ground support equipment; RTG shipping and launch support; designs, reviews, and mission applications; project management, quality assurance, reliability, contract changes, CAGO acquisition (operating funds), and CAGO maintenance and repair; and CAGO acquisition (capital funds).

41 CFR 109-45.1002 - Agency responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... organizations are responsible for establishing a program for the recovery of precious metals. ... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS UTILIZATION AND DISPOSAL 45-SALE, ABANDONMENT, OR DESTRUCTION OF PERSONAL PROPERTY 45.10-Recovery of Precious Metals § 109-45...

41 CFR 109-45.1002 - Agency responsibilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... organizations are responsible for establishing a program for the recovery of precious metals. ... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS UTILIZATION AND DISPOSAL 45-SALE, ABANDONMENT, OR DESTRUCTION OF PERSONAL PROPERTY 45.10-Recovery of Precious Metals § 109-45...

76 FR 58490 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

..., October 04, 2011. Docket Numbers: ER11-4186-001. Applicants: Wolverine Power Supply Cooperative, Inc., Midwest Independent Transmission System Operator, Inc. Description: Wolverine Power Supply Cooperative..., October 04, 2011. Docket Numbers: ER11-4510-000. Applicants: Pacific Power (Previously Pacificorp, PA...

Preliminary assessment of rover power systems for the Mars Rover Sample Return Mission

NASA Technical Reports Server (NTRS)

Bents, D. J.

1989-01-01

Four isotope power system concepts were presented and compared on a common basis for application to on-board electrical prime power for an autonomous planetary rover vehicle. A representative design point corresponding to the Mars Rover Sample Return (MRSR) preliminary mission requirements (500 W) was selected for comparison purposes. All systems concepts utilize the General Purpose Heat Source (GPHS) isotope heat source developed by DOE. Two of the concepts employ thermoelectric (TE) conversion: one using the GPHS Radioisotope Thermoelectric Generator (RTG) used as a reference case, the other using an advanced RTG with improved thermoelectric materials. The other two concepts employed are dynamic isotope power systems (DIPS): one using a closed Brayton cycle (CBC) turboalternator, and the other using a free piston Stirling cycle engine/linear alternator (FPSE) with integrated heat source/heater head. Near-term technology levels have been assumed for concept characterization using component technology figure-of-merit values taken from the published literature. For example, the CBC characterization draws from the historical test database accumulated from space Brayton cycle subsystems and components from the NASA B engine through the mini-Brayton rotating unit. TE system performance is estimated from Voyager/multihundred Watt (MHW)-RTG flight experience through Mod-RTG performance estimates considering recent advances in TE materials under the DOD/DOE/NASA SP-100 and NASA Committee on Scientific and Technological Information programs. The Stirling DIPS system is characterized from scaled-down Space Power Demonstrator Engine (SPDE) data using the GPHS directly incorporated into the heater head. The characterization/comparison results presented here differ from previous comparison of isotope power (made for LEO applications) because of the elevated background temperature on the Martian surface compared to LEO, and the higher sensitivity of dynamic systems to elevated s

In vitro cellular responses in the RTG-2 cell line to complex mixtures of dioxins and dioxin-like PCDDs, PCDFs and PCBs.

PubMed

Babín, María del Mar; Sanz, Paloma; Concejero, Miguel Angel; Martínez, María Angeles; Tarazona, José Vicente

2010-08-01

High-resolution gas chromatography/mass spectrometry (HRGC/MS) is the standard method for analysing dioxin, furan and polybrominated retardants in hazardous waste. Determination of dioxin-like compounds using in vitro bioassays such as ethoxyresorufin-O-deethylase (EROD) is an important tool to evaluate their Ah receptor-mediated toxic effects, because it detects all arylhydrocarbon receptor ligands in a variety of sample matrices. In the present work, we compared RTG-2 cell line EROD bioassay with HRGC/MS for assessing waste samples (liquid and solid) contaminated with polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls (dioxin-like PCBs) and other xenobiotics. For liquid samples, HRGC/MS-toxic equivalent (HRGC/MS-TEQ) values ranged from 273.26 to 5.84 ng TEQ l(-1) and correlated well (correlation coefficient 0.99) with values obtained by EROD-TEQ, which ranged from 128 to 2.5 ng TEQ l(-1). For solid samples, HRGC/MS-TEQ values ranged from 3.44 to 0.49 ng TEQ g(-1) and correlated less well than liquid samples (correlation coefficient 0.64) with values obtained by EROD-TEQ ranging from 2.27 to 0.93 ng TEQ g(-1). The overestimation of RTG-2 EROD-TEQ (1.2 +/- 0.92 of values established by HRGC/MS) and the absence of false-negative results may limit analytical costs by eliminating the need for follow-up GC/MS analysis on the negative samples. We suggest that RTG-2 EROD bioassay is an inexpensive means for preliminary dioxin and furan positive screenings of waste samples. (c) 2010 John Wiley & Sons, Ltd.

Impact of High Resolution SST Data on Regional Weather Forecasts

NASA Technical Reports Server (NTRS)

Jedlovec, Gary J.; Case, Jonathon; LaFontaine, Frank; Vazquez, Jorge; Mattocks, Craig

2010-01-01

Past studies have shown that the use of coarse resolution SST products such as from the real-time global (RTG) SST analysis[1] or other coarse resolution once-a-day products do not properly portray the diurnal variability of fluxes of heat and moisture from the ocean that drive the formation of low level clouds and precipitation over the ocean. For example, the use of high resolution MODIS SST composite [2] to initialize the Advanced Research Weather Research and Forecast (WRF) (ARW) [3] has been shown to improve the prediction of sensible weather parameters in coastal regions [4][5}. In an extend study, [6] compared the MODIS SST composite product to the RTG SST analysis and evaluated forecast differences for a 6 month period from March through August 2007 over the Florida coastal regions. In a comparison to buoy data, they found that that the MODIS SST composites reduced the bias and standard deviation over that of the RTG data. These improvements led to significant changes in the initial and forecasted heat fluxes and the resulting surface temperature fields, wind patterns, and cloud distributions. They also showed that the MODIS composite SST product, produced for the Terra and Aqua satellite overpass times, captured a component of the diurnal cycle in SSTs not represented in the RTG or other one-a-day SST analyses. Failure to properly incorporate these effects in the WRF initialization cycle led to temperature biases in the resulting short term forecasts. The forecast impact was limited in some situations however, due to composite product inaccuracies brought about by data latency during periods of long-term cloud cover. This paper focuses on the forecast impact of an enhanced MODIS/AMSR-E composite SST product designed to reduce inaccuracies due data latency in the MODIS only composite product.

An approach to design a 90Sr radioisotope thermoelectric generator using analytical and Monte Carlo methods with ANSYS, COMSOL, and MCNP.

PubMed

Khajepour, Abolhasan; Rahmani, Faezeh

2017-01-01

In this study, a 90 Sr radioisotope thermoelectric generator (RTG) with power of milliWatt was designed to operate in the determined temperature (300-312K). For this purpose, the combination of analytical and Monte Carlo methods with ANSYS and COMSOL software as well as the MCNP code was used. This designed RTG contains 90 Sr as a radioisotope heat source (RHS) and 127 coupled thermoelectric modules (TEMs) based on bismuth telluride. Kapton (2.45mm in thickness) and Cryotherm sheets (0.78mm in thickness) were selected as the thermal insulators of the RHS, as well as a stainless steel container was used as a generator chamber. The initial design of the RHS geometry was performed according to the amount of radioactive material (strontium titanate) as well as the heat transfer calculations and mechanical strength considerations. According to the Monte Carlo simulation performed by the MCNP code, approximately 0.35 kCi of 90 Sr is sufficient to generate heat power in the RHS. To determine the optimal design of the RTG, the distribution of temperature as well as the dissipated heat and input power to the module were calculated in different parts of the generator using the ANSYS software. Output voltage according to temperature distribution on TEM was calculated using COMSOL. Optimization of the dimension of the RHS and heat insulator was performed to adapt the average temperature of the hot plate of TEM to the determined hot temperature value. This designed RTG generates 8mW in power with an efficiency of 1%. This proposed approach of combination method can be used for the precise design of various types of RTGs. Copyright © 2016 Elsevier Ltd. All rights reserved.

GPS Software Packages Deliver Positioning Solutions

NASA Technical Reports Server (NTRS)

2010-01-01

"To determine a spacecraft s position, the Jet Propulsion Laboratory (JPL) developed an innovative software program called the GPS (global positioning system)-Inferred Positioning System and Orbit Analysis Simulation Software, abbreviated as GIPSY-OASIS, and also developed Real-Time GIPSY (RTG) for certain time-critical applications. First featured in Spinoff 1999, JPL has released hundreds of licenses for GIPSY and RTG, including to Longmont, Colorado-based DigitalGlobe. Using the technology, DigitalGlobe produces satellite imagery with highly precise latitude and longitude coordinates and then supplies it for uses within defense and intelligence, civil agencies, mapping and analysis, environmental monitoring, oil and gas exploration, infrastructure management, Internet portals, and navigation technology."

Technology-based design and scaling for RTGs for space exploration in the 100 W range

NASA Astrophysics Data System (ADS)

Summerer, Leopold; Pierre Roux, Jean; Pustovalov, Alexey; Gusev, Viacheslav; Rybkin, Nikolai

2011-04-01

This paper presents the results of a study on design considerations for a 100 W radioisotope thermo-electric generator (RTG). Special emphasis has been put on designing a modular, multi-purpose system with high overall TRL levels and making full use of the extensive Russian heritage in the design of radioisotope power systems. The modular approach allowed insight into the scaling of such RTGs covering the electric power range from 50 to 200 W e (EoL). The retained concept is based on a modular thermal block structure, a radiative inner-RTG heat transfer and using a two-stage thermo-electric conversion system.

SNAP 19 Pioneer F and G. Final Report

DOE R&D Accomplishments Database

1973-06-01

The generator developed for the Pioneer mission evolved from the SNAP 19 RTG`s launched aboard the NIMBUS III spacecraft. In order to satisfy the power requirements and environment of earth escape trajectory, significant modifications were made to the thermoelectric converter, heat source, and structural configuration. Specifically, a TAGS 2N thermoelectric couple was designed to provide higher efficiency and improved long term power performance, and the electrical circuitry was modified to yield very low magnetic field from current flow in the RTG. A new heat source was employed to satisfy operational requirements and its integration with the generator required alteration to the method of providing support to the fuel capsule.

Centaur in-tank explosion flow fields within STS and Titan 4 payload spaces

NASA Technical Reports Server (NTRS)

Eck, M.; Mukunda, M.

1988-01-01

Explosions are examined which result from the mixing of liquid hydrogen and liquid oxygen (LH2-LO2) such that the reactants are confined by the missile (CBM) body. Explosion which were confined by the ground surface (CBGS) were also studied, with results reported elsewhere. Initial attempts to predict the reported PYRO experimental results were unsuccessful. A new reaction energy addition hypothesis was then developed and tested. The results obtained provide reasonable agreement with the experiments both in the near and far field. Calculations were performed to predict the environment which would occur at the Galileo Radioisotope Thermoelectric Generator (RTG) location given a Centaur G' upper stage and an STS launch vehicle. It was concluded that the principle threat to the RTG in this environment would be the impact of a slug of LH2. No analyses were conducted to assess the response of the Galileo RTG to such an environment. It was shown that the flow field resulting from the failure of the Centaur G' tankage was benign. It was concluded that while the cryogen particle velocity was very high, the flow field density was extremely low. As a result, the dynamic pressure was a trivial eight psia.

Impact of Lake Okeechobee Sea Surface Temperatures on Numerical Predictions of Summertime Convective Systems over South Florida

NASA Technical Reports Server (NTRS)

Case, Jonathan L.; Splitt, Michael E.; Fuell, Kevin K.; Santos, Pablo; Lazarus, Steven M.; Jedlovec, Gary J.

2009-01-01

The NASA Short-term Prediction Research and Transition (SPoRT) Center, the Florida Institute of Technology, and the NOAA/NWS Weather Forecast Office at Miami, FL (MFL) are collaborating on a project to investigate the impact of using high-resolution, 2-km Moderate Resolution Imaging Spectroradiometer (MODIS) sea surface temperature (SST) composites within the Weather Research and Forecasting (WRF) prediction system. The NWS MFL is currently running WRF in real-time to support daily forecast operations, using the National Centers for Environmental Prediction Nonhydrostatic Mesoscale Model dynamical core within the NWS Science and Training Resource Center's Environmental Modeling System (EMS) software. Twenty-seven hour forecasts are run daily initialized at 0300, 0900, 1500, and 2100 UTC on a domain with 4-km grid spacing covering the southern half of Florida and adjacent waters of the Gulf of Mexico and Atlantic Ocean. The SSTs are initialized with the NCEP Real-Time Global (RTG) analyses at 1/12deg resolution. The project objective is to determine whether more accurate specification of the lower-boundary forcing over water using the MODIS SST composites within the 4-km WRF runs will result in improved sea fluxes and hence, more accurate e\\olutiono f coastal mesoscale circulations and the associated sensible weather elements. SPoRT conducted parallel WRF EMS runs from February to August 2007 identical to the operational runs at NWS MFL except for the use of MODIS SST composites in place of the RTG product as the initial and boundary conditions over water. During the course of this evaluation, an intriguing case was examined from 6 May 2007, in which lake breezes and convection around Lake Okeechobee evolved quite differently when using the high-resolution SPoRT MODIS SST composites versus the lower-resolution RTG SSTs. This paper will analyze the differences in the 6 May simulations, as well as examine other cases from the summer 2007 in which the WRF-simulated Lake Okeechobee breezes evolved differently due to the SST initialization. The effects on wind fields and precipitation systems will be emphasized, including validation against surface mesonet observations and Stage IV precipitation grids.

76 FR 2721 - Affirmative Decisions on Petitions for Modification Granted in Whole or in Part

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

...-2010-004-C FR Notice: 75 FR 12796 March 17, 2010). Petitioner: Jim Walter Resources, Inc., P.O. Box 133... W. Silvey, Certifying Officer. [FR Doc. 2011-686 Filed 1-13-11; 8:45 am] BILLING CODE 4510-43-P ...

77 FR 48550 - Investigations Regarding Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

...). 81840 Sykes Enterprise Langhorne, PA 08/01/12 07/31/12 (Workers). 81841 Heidtman Steel Baltimore, MD 08..., PA 08/03/12 08/02/12 (Company). [FR Doc. 2012-19915 Filed 8-13-12; 8:45 am] BILLING CODE 4510-FN-P ...

Pump for delivering heated fluids

NASA Technical Reports Server (NTRS)

Sabelman, E. E. (Inventor)

1973-01-01

A thermomechanical pump particularly suited for use in pumping a warming fluid obtained from an RTG (Radioisotope Thermal Generator) through science and flight instrumentation aboard operative spacecraft is described. The invention is characterized by a pair of operatively related cylinders, each including a reciprocating piston head dividing the cylinder into a pressure chamber confining therein a vaporizable fluid, and a pumping chamber for propelling the warming fluid, and a fluid delivery circuit for alternately delivering the warming fluid from the RTG through the pressure chamber of one cylinder to the pumping chamber of the other cylinder, whereby the vaporizable fluid within the pair of pressure chambers alternately is vaporized and condensed for driving the associated pistons in pumping and intake strokes.

KSC-2013-4510

NASA Image and Video Library

2013-12-20

MORRO BAY, Calif. – An Erickson Sky Crane helicopter returns the SpaceX Dragon test article to Morro Bay, Cailf., following a test to evaluate the spacecraft's parachute deployment system. The test was part of a milestone under its Commercial Crew Integrated Capability agreement with NASA's Commercial Crew Program. Photo credit: NASA/Kim Shiflett

41 CFR 109-45.1003 - Recovery of silver from precious metals bearing materials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Recovery of silver from... Federal Property Management Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS UTILIZATION AND DISPOSAL 45-SALE, ABANDONMENT, OR DESTRUCTION OF PERSONAL PROPERTY 45.10-Recovery...

41 CFR 109-45.1003 - Recovery of silver from precious metals bearing materials.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Recovery of silver from... Federal Property Management Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS UTILIZATION AND DISPOSAL 45-SALE, ABANDONMENT, OR DESTRUCTION OF PERSONAL PROPERTY 45.10-Recovery...

78 FR 780 - Investigations Regarding Certifications of Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

... McCann's--a Division of Los Angeles, CA........ 11/29/12 11/28/12 Manitowoc Foodservice (Company). 82191... (Workers)... Sea Tac, WA 11/30/12 11/28/12 [FR Doc. 2012-31663 Filed 1-3-13; 8:45 am] BILLING CODE 4510-FN...

77 FR 23291 - Investigations Regarding Certifications of Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

.... Credentialing Administration (Company). [FR Doc. 2012-9247 Filed 4-17-12; 8:45 am] BILLING CODE 4510-FN-P ... DEPARTMENT OF LABOR Employment and Training Administration Investigations Regarding Certifications... Assistance, Employment and Training Administration, has instituted investigations pursuant to Section 221 (a...

Literature Reference for Shiga and Shiga-like Toxin (Journal of Clinical Microbiology. 2007. 45(10): 3377–3380)

EPA Pesticide Factsheets

This procedure describes a rapid optical immunoassay for the detection of Stx-1 and Stx-2 using a commercially available kit for presumptive analysis of aerosol, solid, particulate, liquid and water samples contaminated with Shiga and Shiga-like toxin.

40 CFR 63.4510 - What notifications must I submit?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Hazardous Air Pollutants for Surface Coating of Plastic Parts and Products Notifications... with this subpart for any or all of your plastic parts coating operations, then you must include a... subpart in regard to those plastic parts coating operations. If you are complying with another NESHAP that...

Preliminary assessment of rover power systems for the Mars Rover Sample Return Mission

NASA Technical Reports Server (NTRS)

Bents, David J.

1989-01-01

Four isotope power system concepts were presented and compared on a common basis for application to on-board electrical prime power for an autonomous planetary rover vehicle. A representative design point corresponding to the Mars Rover Sample Return (MRSR) preliminary mission requirements (500 W) was selected for comparison purposes. All systems concepts utilize the General Purpose Heat Source (GPHS) isotope heat source developed by DOE. Two of the concepts employ thermoelectric (TE) conversion: one using the GPHS Radioisotope Thermoelectric Generator (RTG) used as a reference case, the other using an advanced RTG with improved thermoelectric materials. The other two concepts employed are dynamic isotope power systems (DIPS): one using a closed Brayton cycle (CBC) turboalternator, and the other using a free piston Stirling cycle engine/linear alternator (FPSE) with integrated heat source/heater head. Near term technology levels have been assumed for concept characterization using component technology figure-of-merit values taken from the published literature. For example, the CBC characterization draws from the historical test database accumulated from space Brayton cycle subsystems and components from the NASA B engine through the mini-Brayton rotating unit. TE system performance is estimated from Voyager/multihundred Watt (MHW)-RTG flight experience through Mod-RTG performance estimates considering recent advances in TE materials under the DOD/DOE/NASA SP-100 and NASA Committee on Scientific and Technological Information programs. The Stirling DIPS system is characterized from scaled-down Space Power Demonstrator Engine (SPDE) data using the GPHS directly incorporated into the heater head. The characterization/comparison results presented here differ from previous comparison of isotope power (made for Low Earth Orbit (LEO) applications) because of the elevated background temperature on the Martian surface compared to LEO, and the higher sensitivity of dynamic systems to elevated sink temperature. The mass advantage of dynamic systems is significantly reduced for this application due to Mars' elevated background temperature.

Bone Density, Balance and Quality of Life of Postmenopausal Women Taking Alendronate Participating in Different Physical Activity Programs

PubMed Central

Borba-Pinheiro, Cláudio Joaquim; de Alencar Carvalho, Mauro César Gurgel; da Silva, Nádia Souza Lima; Drigo, Alexandre Janotta; Bezerra, Jani Cléria Pereira; Dantas, Estélio Henrique Martin

2010-01-01

Background: The objective of this study was to determine the effects of different physical activity (PA) programs on bone density, balance and quality of Life of postmenopausaL women taking concomitant aLendronate. A quasi-experimental study was conducted with 35 volunteers divided into four groups: practitioners of resistance training (RTG, n = 9, 49.8±4.2 years), judo (JUG, n= 11, 52.2 ±5.3 years), water aerobics (WAG, n = 8, 57.1 ±7.4 years) and the control group (CG, n = 7, 53.8±4.4 years). Methods: The following assessment tools were used: bone mineral density (BMD) measured by dual X-ray absorptiometry of the spine and proximal femur, the ‘Osteoporosis Assessment Questionnaire’ (OPAQ) and the ‘Static Balance Test with Visual Control’. The physical activities were planned for 12 months in cycles with different intensities. A two-way analysis of variance (ANOVA) was used for analysis between groups, and a Scheffe post-hoc test was used for multiple comparisons. Results: The multiple comparisons results showed that the RTG and JUG groups were significantly more efficient in the variables studied, including: Lumbar BMD (Δ% = 6.8%, p = 0.001), balance (Δ% = 21.4%, p = 0.01), OPAQ (Δ% = 9.1%, p = 0.005) and Lumbar BMD (Δ% = 6.4%, p = 0.003), balance (Δ% = U%, p = 0.02) and OPAQ (Δ% = 16.8%, p =0.000) compared with the CG. Furthermore, the RTG (Δ% = 4.8%, p =0.02) was significantly better than the WAG for the neck of femur BMD, and the JUG (Δ% = 16.8, p = 0.0003) also demonstrated superiority to the WAG in the OPAQ. Conclusions: The physical activities studied appear to improve BMD, balance and quality of Life of postmenopausaL women taking a bisphosphonate. In this small sample, the RTG and the JUG groups were superior to the other groups. PMID:22870446

Differential growth of U and M type infectious haematopoietic necrosis virus in a rainbow trout–derived cell line, RTG-2

USGS Publications Warehouse

Kurath, Gael; Purcell, Maureen K.; Wargo, Andrew; Park, Jeong Woo; Moon, Chang Hoon

2010-01-01

Infectious haematopoietic necrosis virus (IHNV) is one of the most important viral pathogens of salmonids. In rainbow trout, IHNV isolates in the M genogroup are highly pathogenic, while U genogroup isolates are significantly less pathogenic. We show here that, at a multiplicity of infection (MOI) of 1, a representative U type strain yielded 42-fold less infectious virus than an M type strain in the rainbow trout–derived RTG-2 cell line at 24 h post-infection (p.i.). However, at an MOI of 10, there was only fivefold difference in the yield of infectious virus between the U and M strains. Quantification of extracellular viral genomic RNA suggested that the number of virus particles released from cells infected with the U strain at a MOI of 1 was 47-fold lower than from M-infected cells, but U and M virions were equally infectious by particle to infectivity ratios. At an MOI of 1, U strain intracellular viral genome accumulation and transcription were 37- and 12-fold lower, respectively, than those of the M strain at 24 h p.i. Viral nucleocapsid (N) protein accumulation in U strain infections was fivefold lower than in M strain infections. These results suggest that the block in U type strain growth in RTG-2 cells was because of the effects of reduced genome replication and transcription. The reduced growth of the U strain does not seem to be caused by defective genes, because the U and M strains grew equally well in the permissive epithelioma papulosum cyprini cell line at an MOI of 1. This suggests that host-specific factors in RTG-2 cells control the growth of the IHNV U and M strains differently, leading to growth restriction of the U type virus during the RNA synthesis step.

Radiation Measurements in Cruise and on Mars by the MSL Radiation Assessment Detector

NASA Astrophysics Data System (ADS)

Zeitlin, C. J.; Hassler, D.; Wimmer-Schweingruber, R. F.; Appel, J. K.; Boehm, E.; Boettcher, S.; Brinza, D.; Burmeister, S.; Cucinotta, F.; Ehresmann, B.; Guo, J.; Kohler, J.; Lohf, H.; Martin, C.; Posner, A.; Rafkin, S. C.; Reitz, G.; Team, M.

2013-12-01

The Radiation Assessment Detector (RAD) is one of ten science instruments on the Curiosity rover. The RAD team's science objectives include the measurement of radiation dose (a purely physical quantity) and dose equivalent (a derived quantity that can be related to cancer risk) on the surface of Mars. In addition, RAD acquired data for most of the cruise to Mars, from Dec. 2011 through July 2012, providing a measurement of the radiation environment under conditions similar to those expected on a human trip to Mars or other deep space destinations. The dose and dose equivalent measurements made during cruise have been published, but are presented in more detail here. Rates measured in cruise are compared to similar measurements made during Curiosity's first 269 sols on the surface of Mars. In the simplest picture, one expects rates to be a factor of two lower on the surface of a large airless body compared to free space, owing to the two-pi shielding geometry. The situation on Mars is complicated by the non-negligible shielding effects of the atmosphere, particularly in Gale Crater where diurnal variations in atmospheric column depth are significant. The diurnal variations - caused by the well-known thermal tides on Mars - result in reduced shielding of the surface in the afternoon as compared to the night and early morning hours. A major challenge in analyzing the surface data is the treatment of the background radiation dose coming from Curiosity's Radioisotope Thermoelectric Generator (RTG). Prior to launch, RAD acquired data in the full cruise configuration so that this background could be measured with only sea-level cosmic ray muons present - that is, almost all of what was measured was due to the RTG. Those effects could therefore be subtracted from the cruise measurements in a straightforward way. However, the situation on the surface is somewhat different than in cruise, in that the mass that was present above RAD - and caused scattering of particles into the detector - is no longer there. The RTG-induced dose rate in the surface configuration must therefore be less than it was in the cruise configuration, but there is no way to get a direct measurement of the background. Quantifying the change in RTG background is difficult but essential, as the subtraction affects every aspect of the dosimetry. Two approaches have been developed and yield roughly similar results. The differences allow us to estimate the uncertainties arising from the RTG subtraction, and propagate those into the dosimetry results.

KSC-97PC1069

NASA Image and Video Library

1997-07-18

Jet Propulsion Laboratory (JPL) workers David Rice, at left, and Johnny Melendez rotate a radioisotope thermoelectric generator (RTG) to the horizontal position on a lift fixture in the Payload Hazardous Servicing Facility. The RTG is one of three generators which will provide electrical power for the Cassini spacecraft mission to the Saturnian system. The RTGs will be installed on the powered-up spacecraft for mechanical and electrical verification testing. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate far from the Sun where solar power systems are not feasible. The Cassini mission is scheduled for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle. Cassini is built and managed for NASA by JPL

KSC-97PC1088

NASA Image and Video Library

1997-07-18

This radioisotope thermoelectric generator (RTG), at center, is ready for electrical verification testing now that it has been installed on the Cassini spacecraft in the Payload Hazardous Servicing Facility. A handling fixture, at far left, remains attached. This is the third and final RTG to be installed on Cassini for the prelaunch tests. The RTGs will provide electrical power to Cassini on its 6.7-year trip to the Saturnian system and during its four-year mission at Saturn. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate at great distances from the Sun where solar power systems are not feasible. The Cassini mission is targeted for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle

Magnetic gradiometer for underwater detection applications

NASA Astrophysics Data System (ADS)

Kumar, S.; Skvoretz, D. C.; Moeller, C. R.; Ebbert, M. J.; Perry, A. R.; Ostrom, R. K.; Tzouris, A.; Bennett, S. L.; Czipott, P. V.; Sulzberger, G.; Allen, G. I.; Bono, J.; Clem, T. R.

2006-05-01

We have designed and constructed a magnetic gradiometer for underwater mine detection, location and tracking. The United States Naval Surface Warfare Center (NSWC PC) in Panama City, FL has conducted sea tests of the system using an unmanned underwater vehicle (UUV). The Real-Time Tracking Gradiometer (RTG) measures the magnetic field gradients caused by the presence of a mine in the Earth's magnetic field. These magnetic gradients can then be used to detect and locate a target with the UUV in motion. Such a platform can also be used for other applications, including the detection and tracking of vessels and divers for homeland (e.g., port) security and the detection of underwater pipelines. Data acquired by the RTG in sea tests is presented in this paper.

77 FR 66658 - Self-Regulatory Organizations; NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-06

... Account Information), and adopting the Rule 4510A Series (Books and Records Requirements). The series includes Rule 4511A (General Requirement), which incorporates FINRA Rule 4511; Rule 4512A (Customer Account Information), which incorporates FINRA Rule 4512; Rule 4513A (Records of Written Customer Complaints), which...

40 CFR 63.4510 - What notifications must I submit?

Code of Federal Regulations, 2013 CFR

2013-07-01

... not need to submit copies of any test reports. (i) Mass fraction of organic HAP for one coating, for one thinner and/or other additive, and for one cleaning material. (ii) Mass fraction of coating solids... required. (iv) The amount of waste materials and the mass of organic HAP contained in the waste materials...

40 CFR 63.4510 - What notifications must I submit?

Code of Federal Regulations, 2011 CFR

2011-07-01

... not need to submit copies of any test reports. (i) Mass fraction of organic HAP for one coating, for one thinner and/or other additive, and for one cleaning material. (ii) Mass fraction of coating solids... required. (iv) The amount of waste materials and the mass of organic HAP contained in the waste materials...

40 CFR 63.4510 - What notifications must I submit?

Code of Federal Regulations, 2012 CFR

2012-07-01

... not need to submit copies of any test reports. (i) Mass fraction of organic HAP for one coating, for one thinner and/or other additive, and for one cleaning material. (ii) Mass fraction of coating solids... required. (iv) The amount of waste materials and the mass of organic HAP contained in the waste materials...

40 CFR 63.4510 - What notifications must I submit?

Code of Federal Regulations, 2014 CFR

2014-07-01

... not need to submit copies of any test reports. (i) Mass fraction of organic HAP for one coating, for one thinner and/or other additive, and for one cleaning material. (ii) Mass fraction of coating solids... required. (iv) The amount of waste materials and the mass of organic HAP contained in the waste materials...

41 CFR 109-45.1002-3 - Precious metals recovery program monitor.

Code of Federal Regulations, 2010 CFR

2010-07-01

... program monitor. 109-45.1002-3 Section 109-45.1002-3 Public Contracts and Property Management Federal... UTILIZATION AND DISPOSAL 45-SALE, ABANDONMENT, OR DESTRUCTION OF PERSONAL PROPERTY 45.10-Recovery of Precious Metals § 109-45.1002-3 Precious metals recovery program monitor. The DPMO shall be the precious metals...

CTEF 2.0 - Assessment and Improvement of Command Team Effectiveness: Verification of Model and Instrument (CTEF 2.0 - Diagnostic et Amelioration de l’Efficacite d’un Team de Commandement: Verification du Modele et de l’Instrument)

DTIC Science & Technology

2010-09-01

what level of detail is needed to build their teams, and they can add more detailed items from the model in order to tap deeper in the performance of...of a project on ‘Command Team Effectiveness’ by Task Group 127 for the RTO Human Factors and Medicine Panel (RTG HFM-127). Published...vérification du modèle et de l’instrument) This Technical Report documents the findings of a project on ‘Command Team Effectiveness’ by Task Group

RTGs on Transit

NASA Astrophysics Data System (ADS)

Dassoulas, John; McNutt, Ralph L.

2007-01-01

Transit, the US Navy's Navigation Satellite System was conceived at the Applied Physics Laboratory in 1957 by observing the Doppler shift while tracking Sputnik I. As spacecraft development proceeded there was concern about the ability of batteries to maintain the hermetic seal over a 5-year operational life requirement; therefore, alternate energy sources were investigated. The radioisotope thermoelectric generator (RTG) concept was pursued and resulted in the launch of SNAP 3s, providing partial power on both Transit 4A and 4B. SNAP 9s provided full power on three Transit 5BNs. All launches occurred in the early 1960s. When the U.S. conducted the high altitude nuclear test from Johnson Island, several spacecraft were lost due to artificial enhancement of charged particles in the Earth's magnetosphere resulting in rapid degradation of solar cell power production. This led to the decision to have both an RTG and Solar cell/battery design for Transit power systems; hence, a new RTG design, with a separable heat source and radiative coupling to the thermoelectric elements, was flown on TRIAD. This pioneering effort provided the impetus for future RTGs on interplanetary spacecraft. This paper describes the origin and purpose of the Transit program and provides details on the five satellites in that program that were powered by the first American RTGs used in space. The rationale and some of the challenges inherent in that use are also described.

Environmental analysis of the logistics of agricultural products from roof top greenhouses in Mediterranean urban areas.

PubMed

Sanyé-Mengual, Esther; Cerón-Palma, Ileana; Oliver-Solà, Jordi; Montero, Juan Ignacio; Rieradevall, Joan

2013-01-15

As urban populations increase so does the amount of food transported to cities worldwide, and innovative agro-urban systems are being developed to integrate agricultural production into buildings; for example, by using roof top greenhouses (RTGs). This paper aims to quantify and compare, through a life cycle assessment, the environmental impact of the current linear supply system with a RTG system by using a case study for the production of tomatoes. The main results indicate that a change from the current linear system to the RTG system could result in a reduction, per kilogram of tomatoes (the functional unit), in the range of 44.4-75.5% for the different impact categories analysed, and savings of up to 73.5% in energy requirements. These savings are associated with re-utilisation of packaging systems (55.4-85.2%), minimisation of transport requirements (7.6-15.6%) and reduction of the loss of product during transportation and retail stages (7.3-37%). The RTG may become a strategic factor in the design of low-carbon cities in Mediterranean areas. Short-term implementation in the city of Barcelona could result in savings of 66.1 tonnes of CO₂ eq. ha(-1) when considering the global warming potential, and of 71.03 t ha(-1) when considering that the transformation from woodland to agricultural land is avoided. Copyright © 2012 Society of Chemical Industry.

Contact | Office of Cancer Genomics

Cancer.gov

For more information about the Office of Cancer Genomics, please contact: Office of Cancer Genomics National Cancer Institute 31 Center Drive, 10A07 Bethesda, Maryland 20892-2580 Phone: (240) 781-3280 Fax: (240) 541-4510 Email: ocg@mail.nih.gov *Please note that this site will not function properly in Internet Explorer unless you completely turn off the Compatibility View*

77 FR 4510 - Air Quality Implementation Plans; Kentucky; Attainment Plan for the Kentucky Portion of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-30

... and population based apportionment of the area and nonroad sectors to support the mobile source... and nitrogen oxides (NO X ) for the mobile source contribution to ambient PM 2.5 levels for the.... Attainment Date B. Insignificance Determination for the Mobile Source Contribution to PM 2.5 and NO X...

17 CFR 45.10 - Reporting to a single swap data repository.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the swap data repository to which the first report of required swap creation data is made pursuant to... designated contract market that reports required swap creation data as required by § 45.3 shall report all... of the swap data repository to which required swap creation data is reported by the swap execution...

17 CFR 45.10 - Reporting to a single swap data repository.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., which shall be the swap data repository to which the first report of required swap creation data is made... designated contract market that reports required swap creation data as required by § 45.3 shall report all... of the swap data repository to which required swap creation data is reported by the swap execution...

17 CFR 45.10 - Reporting to a single swap data repository.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the swap data repository to which the first report of required swap creation data is made pursuant to... designated contract market that reports required swap creation data as required by § 45.3 shall report all... of the swap data repository to which required swap creation data is reported by the swap execution...

77 FR 1955 - Request for Certification of Compliance-Rural Industrialization Loan and Grant Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-12

... Product/Purpose: The loan, guarantee, or grant application is to finance building construction and to... Dakota. The NAICS industry code for this enterprise is: 311611 (beef produced in slaughtering plants..., Assistant Secretary for Employment and Training. [FR Doc. 2012-448 Filed 1-11-12; 8:45 am] BILLING CODE 4510...

Radioisotopic Thermoelectric Generator (RTG) Surveillance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mulford, Roberta Nancy

2016-09-29

This lecture discusses stockpile stewardship efforts and the role surveillance plays in the process. Performance of the RTGs is described, and the question of the absence of anticipated He is addressed.

Astronaut John Young stands at ALSEP deployment site during first EVA

NASA Technical Reports Server (NTRS)

1972-01-01

Astronaut John W. Young, commander of the Apollo 16 lunar landing mission, stands at the Apollo Lunar Surface Experiments Package (ALSEP) deployment site during the first Apollo 16 extravehicular activity (EVA-1) at the Descartes landing site. The components of the ALSEP are in the background. The lunar surface drill is just behind and to the right of Young. The drill's rack and bore stems are to the left. The three sensor Lunar Surface Magnetometer is beyond the rack. The dark object in the right background is the Radioisotope Thermoelectric Generator (RTG). Between the RTG and the drill is the Heat Flow Experiment. A part of the Central Station is at the right center edge of the picture. This photograph was taken by Astronaut Charles M. Duke Jr., lunar module pilot.

Regulatory regions in the promoters of the Saccharomyces cerevisiae PYC1 and PYC2 genes encoding isoenzymes of pyruvate carboxylase.

PubMed

Menéndez, J; Gancedo, C

1998-07-15

We have identified regions in the promoters of the PYC1 and PYC2 genes from Saccharomyces cerevisiae involved in their regulation in different culture conditions. In the case of PYC1, a UAS in the region between -330/-297 and three repressing sequences with the common central core CCGCC at positions -457, -432 and -399 were identified. Specific binding of nuclear proteins to the -330/-214 DNA fragment was abolished in rtg mutants suggesting a role for the RTG genes in the control of PYC1 expression. In the case of the PYC2 promoter, elimination of a fragment from -417 to -291 brings about a two-fold decrease in the expression in repressed conditions and a similar increase in derepression.

Stirling Radioisotope Power System as an Alternative for NASAs Deep Space Missions

NASA Astrophysics Data System (ADS)

Shaltens, R. K.; Mason, L. S.; Schreiber, J. G.

2001-01-01

The NASA Glenn Research Center (GRC) and the Department of Energy (DOE) are developing a free-piston Stirling convertor for a Stirling Radioisotope Power System (SRPS) to provide on-board electric power for future NASA deep space missions. The SRPS currently being developed provides about 100 watts and reduces the amount of radioisotope fuel by a factor of four over conventional Radioisotope Thermoelectric Generators (RTG). The present SRPS design has a specific power of approximately 4 W/kg which is comparable to an RTG. GRC estimates for advanced versions of the SRPS with improved heat source integration, lightweight Stirling convertors, composite radiators, and chip-packaged controllers improves the specific mass to about 8 W/kg. Additional information is contained in the original extended abstract.

Cassini's RTGs undergo mechanical and electrical verification tests in the PHSF

NASA Technical Reports Server (NTRS)

1997-01-01

This radioisotope thermoelectric generator (RTG), at center, is ready for electrical verification testing now that it has been installed on the Cassini spacecraft in the Payload Hazardous Servicing Facility. A handling fixture, at far left, remains attached. This is the third and final RTG to be installed on Cassini for the prelaunch tests. The RTGs will provide electrical power to Cassini on its 6.7-year trip to the Saturnian system and during its four-year mission at Saturn. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate at great distances from the Sun where solar power systems are not feasible. The Cassini mission is targeted for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle.

Lunar Surface Stirling Power Systems Using Am-241

NASA Technical Reports Server (NTRS)

Schmitz, Paul C.; Penswick, L. Barry; Shaltens, Richard K.

2009-01-01

For many years NASA has used the decay of Pu-238 (in the form of the General Purpose Heat Source (GPHS)) as a heat source for Radioisotope Thermoelectric Generators (RTG), which have provided electrical power for many NASA missions. While RTG's have an impressive reliability record for the missions in which they have been used, their relatively low thermal to electric conversion efficiency (-5% efficiency) and the scarcity of Plutoinium-238 (Pu-238) has led NASA to consider other power conversion technologies. NASA is considering returning both robotic and human missions to the lunar surface and, because of the long lunar nights (14 earth days) isotope power systems are an attractive candidate to generate electrical power. NASA is currently developing the Advanced Stirling Radioisotope Generator (ASRG) as a candidate higher efficiency power system that produces greater than 160 watts with 2 GPHS modules at the beginning of life (BOL) (-30% efficiency). The ASRG uses the same Pu-238 GPHS modules, which are used in RTG, but by coupling them to a Stirling convertor provides a 4-fold reduction in the number of GPHS modules. This study considers the use of Americium 241 (Am-241) as a substitute for the Pu-238 in Stirling convertor based Radioisotope Power Systems (RPS) for power levels from 1 O's of watts to 5 kWe. The Am-241 is used as a replacement for the Pu-238 in GPHS modules. Depending on power level, different Stirling heat input and removal systems are modeled. It was found that substituting Am-241 GPHS modules into the ASRG reduces power output by about 1/5 while maintaining approximately the same system mass. In order to obtain the nominal 160 watts electrical output of the Pu-238 ASRG requires 10 Am-241 GPHS modules. Higher power systems require changing from conductive coupling heat input and removal from the Stirling convertor to either pumped loops or heat pipes. Liquid metal pumped loops are considered as the primary heat transportation on the hot end and water pumped loop/heat pipe radiator is considered for the heat rejection side for power levels above 1 kWe.

41 CFR 109-45.1004 - Recovery and use of precious metals through the DOD Precious Metals Recovery Program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... precious metals through the DOD Precious Metals Recovery Program. 109-45.1004 Section 109-45.1004 Public... PERSONAL PROPERTY 45.10-Recovery of Precious Metals § 109-45.1004 Recovery and use of precious metals through the DOD Precious Metals Recovery Program. DOE operates its own precious metals pool and therefore...

41 CFR 109-45.1004 - Recovery and use of precious metals through the DOD Precious Metals Recovery Program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... precious metals through the DOD Precious Metals Recovery Program. 109-45.1004 Section 109-45.1004 Public... PERSONAL PROPERTY 45.10-Recovery of Precious Metals § 109-45.1004 Recovery and use of precious metals through the DOD Precious Metals Recovery Program. DOE operates its own precious metals pool and therefore...

Credit BG. Northwest facade of Building 4504 (Deluge Water Booster ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit BG. Northwest facade of Building 4504 (Deluge Water Booster Station) is in view at left, with 500,000 gallon water tank (Building 4503) at right. Fenced electrical substation in view between the above structures is Building 4510. Building 4505 is in background - Edwards Air Force Base, North Base, Deluge Water Booster Station, Northeast of A Street, Boron, Kern County, CA

Orbital Transfer Vehicle Oxygen Turbopump Technology. Final Report, Volume 1. Design, Fabrication, and Hydrostatic Bearing Testing

DTIC Science & Technology

1990-12-01

Temperature Distance Sensors -. ...................... 188 Start Transient 4.5-7 Distance Sensor Signal as a Function of Speed...189 4.5-8 Distance Sensor Signal as a Function of Speed ......................................... 190 4.5-9 Cryogenic Operation of...Distance Sensors at 72,000 RPM ........................ 192 Steady State 4.5-10 Cryogenic Operation of Distance Sensor Through Start

75 FR 17428 - Accreditation and Approval of Intertek USA, Inc., as a Commercial Gauger and Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

...) 344-1060. The inquiry may also be sent to [email protected] . Please reference the Web site listed... Pennsylvania Avenue, NW., Suite 1500N, Washington, DC 20229, 202-344- 1060. Dated: March 26, 2010. Ira S. Reese, Executive Director, Laboratories and Scientific Services. [FR Doc. 2010-7686 Filed 4-5-10; 8:45 am] BILLING...

Modeling of 1.5 μm range gated imaging for small surface vessel identification

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Steinvall, Ove; Elmquist, Magnus; Karlsson, Kjell

2010-10-01

Within the framework of the NATO group (NATO SET-132/RTG-72) on imaging ladars, a test was performed to collect simultaneous multi-mode LADAR signatures of maritime objects entering and leaving San Diego Harbor. Beside ladars, passive sensors were also employed during the test which occurred during April 2009 from Point Loma and the harbor in San Diego. This paper will report on 1.5 μm gated imaging on a number of small civilian surface vessels with the aim to present human perception experimental results and comparisons with sensor performance models developed by US Army RDECOM CERDEC NVESD. We use controlled human perception tests to measure target identification performance and compare the experimental results with model predictions.

KSC-97PC1091

NASA Image and Video Library

1997-07-19

Lockheed Martin Missile and Space Co. employees Joe Collingwood, at right, and Ken Dickinson retract pins in the storage base to release a radioisotope thermoelectric generator (RTG) in preparation for hoisting operations. This RTG and two others will be installed on the Cassini spacecraft for mechanical and electrical verification testing in the Payload Hazardous Servicing Facility. The RTGs will provide electrical power to Cassini on its 6.7-year trip to the Saturnian system and during its four-year mission at Saturn. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate at great distances from the Sun where solar power systems are not feasible. The Cassini mission is targeted for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle. Cassini is built and managed by NASA’s Jet Propulsion Laboratory

KSC-97PC1093

NASA Image and Video Library

1997-07-19

Supported on a lift fixture, this radioisotope thermoelectric generator (RTG), at center, is hoisted from its storage base using the airlock crane in the Payload Hazardous Servicing Facility (PHSF). Jet Propulsion Laboratory (JPL) workers are preparing to install the RTG onto the Cassini spacecraft, in background at left, for mechanical and electrical verification testing. The three RTGs on Cassini will provide electrical power to the spacecraft on its 6.7-year trip to the Saturnian system and during its four-year mission at Saturn. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate at great distances from the Sun where solar power systems are not feasible. The Cassini mission is targeted for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle. Cassini is built and managed by JPL

Astronaut John Young stands at ALSEP deployment site during first EVA

NASA Image and Video Library

1972-04-21

AS16-114-18388 (21 April 1972) --- Astronaut John W. Young, commander of the Apollo 16 lunar landing mission, stands at the Apollo Lunar Surface Experiments Package (ALSEP) deployment site during the first Apollo 16 extravehicular activity (EVA) at the Descartes landing site. The components of the ALSEP are in the background. The lunar surface drill is just behind and to the right of astronaut Young. The drill's rack and bore stems are to the left. The three-sensor Lunar Surface Magnetometer is beyond the rack. The dark object in the right background is the Radioisotope Thermoelectric Generator (RTG). Between the RTG and the drill is the Heat Flow Experiment. A part of the Central Station is at the right center edge of the picture. This photograph was taken by astronaut Charles M. Duke Jr., lunar module pilot.

Mitochondrial Energy and Redox Signaling in Plants

PubMed Central

Schwarzländer, Markus

2013-01-01

Abstract Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. Antioxid. Redox Signal. 18, 2122–2144. PMID:23234467

Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

PubMed

Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

2016-09-01

Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and rats, and corneal-kindled mice. This study highlights the challenge of predicting clinical adverse effects with preclinical models. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

DEVELOPMENT OF AN ENVIRONMENTAL ESTROGEN SCREEN USING TRANSIENTLY TRANSFECTED RAINBOW TROUT CELL LINES

EPA Science Inventory

Rainbow troutp hepatoma (RTH-149) and gonad cells (RTG-2) were used to develop a screening protocol for estrogen disrupting chemicals. Transfection of an estrogen-responsive luciferase reporter plasmid into...

Cassini's RTGs undergo mechanical and electrical verification tests in the PHSF

NASA Technical Reports Server (NTRS)

1997-01-01

Lockheed Martin Missile and Space Co. employees Joe Collingwood, at right, and Ken Dickinson retract pins in the storage base to release a radioisotope thermoelectric generator (RTG) in preparation for hoisting operations. This RTG and two others will be installed on the Cassini spacecraft for mechanical and electrical verification testing in the Payload Hazardous Servicing Facility. The RTGs will provide electrical power to Cassini on its 6.7-year trip to the Saturnian system and during its four-year mission at Saturn. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate at great distances from the Sun where solar power systems are not feasible. The Cassini mission is targeted for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle. Cassini is built and managed by NASA's Jet Propulsion Laboratory.

Development and Use of the Galileo and Ulysses Power Sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, Gary L; Hemler, Richard J; Schock, Alfred

Paper presented at the 45th Congress of the International Astronautical Federation, October 1994. The Galileo mission to Jupiter and the Ulysses mission to explore the polar regions of the Sun required a new power source: the general-purpose heat source radioisotope thermoelectric generator (GPHS-RTG), the most powerful RTG yet flow. Four flight-qualified GPHS-RTGs were fabricated with one that is being used on Ulysses, two that are being used on Galileo and one that was a common spare (and is now available for the Cassini mission to Saturn). In addition, and Engineering Unit and a Qualification Unit were fabricated to qualify themore » design for space through rigorous ground tests. This paper summarizes the ground testing and performance predictions showing that the GPHS-RTGs have met and will continue to meet or exceed the performance requirements of the ongoing Galileo and Ulysses missions. There are two copies in the file.« less

KSC-97pc1065

NASA Image and Video Library

1997-07-18

Jet Propulsion Laboratory (JPL) workers prepare the installation cart (atop the platform) for removal of a radioisotope thermoelectric generator (RTG) from the adjacent Cassini spacecraft. This is the second of three RTGs being removed from Cassini after undergoing mechanical and electrical verification tests in the Payload Hazardous Servicing Facility. The third RTG to be removed is in background at left. The three RTGs will then be temporarily stored before being re-installed for flight. The RTGs will provide electrical power to Cassini on its 6.7-year trip to the Saturnian system and during its four-year mission at Saturn. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate far from the Sun where solar power systems are not feasible. The Cassini mission is scheduled for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle. Cassini is built and managed for NASA by JPL

Thermoelectric Outer Planets Spacecraft (TOPS)

NASA Technical Reports Server (NTRS)

1973-01-01

The research and advanced development work is reported on a ballistic-mode, outer planet spacecraft using radioisotope thermoelectric generator (RTG) power. The Thermoelectric Outer Planet Spacecraft (TOPS) project was established to provide the advanced systems technology that would allow the realistic estimates of performance, cost, reliability, and scheduling that are required for an actual flight mission. A system design of the complete RTG-powered outer planet spacecraft was made; major technical innovations of certain hardware elements were designed, developed, and tested; and reliability and quality assurance concepts were developed for long-life requirements. At the conclusion of its active phase, the TOPS Project reached its principal objectives: a development and experience base was established for project definition, and for estimating cost, performance, and reliability; an understanding of system and subsystem capabilities for successful outer planets missions was achieved. The system design answered long-life requirements with massive redundancy, controlled by on-board analysis of spacecraft performance data.

A Multi-Season Study of the Effects of MODIS Sea-Surface Temperatures on Operational WRF Forecasts at NWS Miami, FL

NASA Technical Reports Server (NTRS)

Case, Jonathan L.; Santos, Pablo; Lazarus, Steven M.; Splitt, Michael E.; Haines, Stephanie L.; Dembek, Scott R.; Lapenta, William M.

2008-01-01

Studies at the Short-term Prediction Research and Transition (SPORT) Center have suggested that the use of Moderate Resolution Imaging Spectroradiometer (MODIS) sea-surface temperature (SST) composites in regional weather forecast models can have a significant positive impact on short-term numerical weather prediction in coastal regions. Recent work by LaCasse et al (2007, Monthly Weather Review) highlights lower atmospheric differences in regional numerical simulations over the Florida offshore waters using 2-km SST composites derived from the MODIS instrument aboard the polar-orbiting Aqua and Terra Earth Observing System satellites. To help quantify the value of this impact on NWS Weather Forecast Offices (WFOs), the SPORT Center and the NWS WFO at Miami, FL (MIA) are collaborating on a project to investigate the impact of using the high-resolution MODIS SST fields within the Weather Research and Forecasting (WRF) prediction system. The project's goal is to determine whether more accurate specification of the lower-boundary forcing within WRF will result in improved land/sea fluxes and hence, more accurate evolution of coastal mesoscale circulations and the associated sensible weather elements. The NWS MIA is currently running WRF in real-time to support daily forecast operations, using the National Centers for Environmental Prediction Nonhydrostatic Mesoscale Model dynamical core within the NWS Science and Training Resource Center's Environmental Modeling System (EMS) software. Twenty-seven hour forecasts are run dally initialized at 0300, 0900, 1500, and 2100 UTC on a domain with 4-km grid spacing covering the southern half of Florida and adjacent waters of the Gulf of Mexico and Atlantic Ocean. Each model run is initialized using the Local Analysis and Prediction System (LAPS) analyses available in AWIPS. The SSTs are initialized with the NCEP Real-Time Global (RTG) analyses at 1/12deg resolution (approx.9 km); however, the RTG product does not exhibit fine-scale details consistent with its grid resolution. SPORT is conducting parallel WRF EMS runs identical to the operational runs at NWS MIA except for the use of MODIS SST composites in place of the RTG product as the initial and boundary conditions over water, The MODIS SST composites for initializing the SPORT WRF runs are generated on a 2-km grid four times daily at 0400, 0700, 1600, and 1900 UTC, based on the times of the overhead passes of the Aqua and Terra satellites. The incorporation of the MODIS SST data into the SPORT WRF runs is staggered such that SSTs are updated with a new composite every six hours in each of the WRF runs. From mid-February to July 2007, over 500 parallel WRF simulations have been collected for analysis and verification. This paper will present verification results comparing the NWS MIA operational WRF runs to the SPORT experimental runs, and highlight any substantial differences noted in the predicted mesoscale phenomena for specific cases.

RTG-History, the Curiosity, Voyager, and New Horizons

Science.gov Websites

solar system for many years. Prior to New Horizons, the Apollo missions to the Moon, the Viking missions Report, January 11, 1991--April 30, 1998, DOE Technical Report Download Adobe PDF Reader , August 1998

Gravitational Lens: Deep Space Probe Design

DTIC Science & Technology

2012-03-01

Lieutenant, USAF Approved: Timothy Lawrence, Col, USAF (Chairman) Date Carl Hartsfield, Lt Col, USAF (Member) Date Marc G. Millis (Member) Date Abstract A...23 RTG Radioisotope Thermoelectric Generators . . . . . . . . . . . . . . . . . 26 EOL End of Life...26 ASRG Advanced Stirling Radioisotope Generator . . . . . . . . . . . . . . . . 26 GPHS

The significance of sweep in Appalachian hardwood sawlogs

Treesearch

Thomas W., Jr. Church

1973-01-01

Sweep is one of the major stem-form defects in hardwood sawtimber. Some sweep is removed during bucking. But we found sweep of 2 inches or more on 17 percent of the 4,510 logs measured at Appalachian sawmills. Volume deductions for sweep scaled at least 10 percent in 1 of every 7 sample logs and at least 15 percent in 1 of every 9 sample logs. Reduction in the severity...

Nuclear energy technology

NASA Technical Reports Server (NTRS)

Buden, David

1992-01-01

An overview of space nuclear energy technologies is presented. The development and characteristics of radioisotope thermoelectric generators (RTG's) and space nuclear power reactors are discussed. In addition, the policy and issues related to public safety and the use of nuclear power sources in space are addressed.

Technical, analytical and computer support

NASA Technical Reports Server (NTRS)

1972-01-01

The development of a rigorous mathematical model for the design and performance analysis of cylindrical silicon-germanium thermoelectric generators is reported that consists of two parts, a steady-state (static) and a transient (dynamic) part. The material study task involves the definition and implementation of a material study that aims to experimentally characterize the long term behavior of the thermoelectric properties of silicon-germanium alloys as a function of temperature. Analytical and experimental efforts are aimed at the determination of the sublimation characteristics of silicon germanium alloys and the study of sublimation effects on RTG performance. Studies are also performed on a variety of specific topics on thermoelectric energy conversion.

The Effects of Atropine Sulfate on Aviator Performance

DTIC Science & Technology

1989-09-01

Bozzetti, L. P. (1976). Simulated flying performance after marihuana intoxication. Aviation, Space, and Environmental Medicine , 47(2), 124-128. 14. Taylor... Medicine , 46(3), 304-308. 8. Asknes, E. G. (1954). Effects of small doses of alcohol upon performance in a Link trainer. Journal of Aviation Medicine ...assessed by two Link trainer tasks using experienced pilots. Aerospace Medicine , 45(10), 1180-1189. 10. Henry, P. H., Flueck, J. A., Sanford, J. F

Thermal Energy Conversion Branch

NASA Technical Reports Server (NTRS)

Bielozer, Matthew C.; Schreiber, Jeffrey, G.; Wilson, Scott D.

2004-01-01

The Thermal Energy Conversion Branch (5490) leads the way in designing, conducting, and implementing research for the newest thermal systems used in space applications at the NASA Glenn Research Center. Specifically some of the most advanced technologies developed in this branch can be broken down into four main areas: Dynamic Power Systems, Primary Solar Concentrators, Secondary Solar Concentrators, and Thermal Management. Work was performed in the Dynamic Power Systems area, specifically the Stirling Engine subdivision. Today, the main focus of the 5490 branch is free-piston Stirling cycle converters, Brayton cycle nuclear reactors, and heat rejection systems for long duration mission spacecraft. All space exploring devices need electricity to operate. In most space applications, heat energy from radioisotopes is converted to electrical power. The Radioisotope Thermoelectric Generator (RTG) already supplies electricity for missions such as the Cassini Spacecraft. The focus of today's Stirling research at GRC is aimed at creating an engine that can replace the RTG. The primary appeal of the Stirling engine is its high system efficiency. Because it is so efficient, the Stirling engine will significantly reduce the plutonium fuel mission requirements compared to the RTG. Stirling is also being considered for missions such as the lunar/Mars bases and rovers. This project has focused largely on Stirling Engines of all types, particularly the fluidyne liquid piston engine. The fluidyne was developed by Colin D. West. This engine uses the same concepts found in any type of Stirling engine, with the exception of missing mechanical components. All the working components are fluid. One goal was to develop and demonstrate a working Stirling Fluidyne Engine at the 2nd Annual International Energy Conversion Engineering Conference in Providence, Rhode Island.

In vitro screening of organotin compounds and sediment extracts for cytotoxicity to fish cells.

PubMed

Giltrap, Michelle; Macken, Ailbhe; McHugh, Brendan; McGovern, Evin; Foley, Barry; Davoren, Maria

2011-01-01

The present study reports an in vitro screening method for contaminants in sediment samples utilizing an RTG-2 cell line. This technique integrates cytotoxicity testing with analytical chemistry with the aim of achieving a toxicity evaluation of the sediment sample. The toxic effect of individual organotin (OT) compounds and their presence in the sediment sample is the focus of the present study; however, other contaminants are also discussed. The following OT compounds: tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenyltin (DPT), and a sediment solvent extract are exposed to the RTG-2 fish cell line. Both the alamar blue (AB) and neutral red (NR) assays are used to assess cytotoxicity after 24-h and 96-h exposure. Methodology for preparation of a sediment solvent extract suitable for biological testing and analytical determination is also described. With the RTG-2 cells, the AB and NR assays had comparable sensitivity for each individual OT compound exposure after 24 h, with TPT being the most toxic compound tested. The individual OT compound concentrations required to induce a 50% toxic effect on the cells (369 ng ml⁻¹ TBT, 1,905 ng ml⁻¹ DBT) did not equate to the concentrations of these contaminants present in the sediment extract that induced a 50% effect on the cells (294 ng ml⁻¹ TBT, 109 ng ml⁻¹ DBT). The solvent extract therefore exhibited a greater toxicity, and this suggests that the toxic effects observed were not due to OT compounds alone. The presence of other contaminants in the solvent extract is confirmed with chemical analysis, warranting further toxicity testing of contaminant mixtures and exposure to the cell line to further elucidate a complete toxicity evaluation. © 2010 SETAC.

Transcriptional regulation of respiration in yeast metabolizing differently repressive carbon substrates.

PubMed

Fendt, Sarah-Maria; Sauer, Uwe

2010-02-18

Depending on the carbon source, Saccharomyces cerevisiae displays various degrees of respiration. These range from complete respiration as in the case of ethanol, to almost complete fermentation, and thus very low degrees of respiration on glucose. While many key regulators are known for these extreme cases, we focus here on regulators that are relevant at intermediate levels of respiration. We address this question by linking the functional degree of respiration to transcriptional regulation via enzyme abundances. Specifically, we investigated aerobic batch cultures with the differently repressive carbon sources glucose, mannose, galactose and pyruvate. Based on 13C flux analysis, we found that the respiratory contribution to cellular energy production was largely absent on glucose and mannose, intermediate on galactose and highest on pyruvate. In vivo abundances of 40 respiratory enzymes were quantified by GFP-fusions under each condition. During growth on the partly and fully respired substrates galactose and pyruvate, several TCA cycle and respiratory chain enzymes were significantly up-regulated. From these enzyme levels and the known regulatory network structure, we determined the probability for a given transcription factor to cause the coordinated expression changes. The most probable transcription factors to regulate the different degrees of respiration were Gcr1p, Cat8p, the Rtg-proteins and the Hap-complex. For the latter three ones we confirmed their importance for respiration by quantifying the degree of respiration and biomass yields in the corresponding deletion strains. Cat8p is required for wild-type like respiration, independent of its known activation of gluconeogenic genes. The Rtg-proteins and the Hap-complex are essential for wild-type like respiration under partially respiratory conditions. Under fully respiratory conditions, the Hap-complex, but not the Rtg-proteins are essential for respiration.

Shuttle data book: SRM fragment velocity model. Presented to the SRB Fragment Model Review Panel

NASA Technical Reports Server (NTRS)

1989-01-01

This study was undertaken to determine the velocity of fragments generated by the range safety destruction (RSD) or random failure of a Space Transportation System (STS) Solid Rocket Motor (SRM). The specific requirement was to provide a fragment model for use in those Galileo and Ulysses RTG safety analyses concerned with possible fragment impact on the spacecraft radioisotope thermoelectric generators (RTGS). Good agreement was obtained between predictions and observations for fragment velocity, velocity distributions, azimuths, and rotation rates. Based on this agreement with the entire data base, the model was used to predict the probable fragment environments which would occur in the event of an STS-SRM RSD or randon failure at 10, 74, 84 and 110 seconds. The results of these predictions are the basis of the fragment environments presented in the Shuttle Data Book (NSTS-08116). The information presented here is in viewgraph form.

Final safety analysis report for the Galileo Mission: Volume 2: Summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The General Purpose Heat Source Radioisotope Thermoelectric Generator (GPHS-RTG) will be used as the prime source of electric power for the spacecraft on the Galileo mission. The use of radioactive material in these missions necessitates evaluations of the radiological risks that may be encountered by launch complex personnel and by the Earth's general population resulting from postulated malfunctions or failures occurring in the mission operations. The purpose of the Final Safety Analysis Report (FSAR) is to present the analyses and results of the latest evaluation of the nuclear safety potential of the GPHS-RTG as employed in the Galileo mission. Thismore » evaluation is an extension of earlier work that addressed the planned 1986 launch using the Space Shuttle Vehicle with the Centaur as the upper stage. This extended evaluation represents the launch by the Space Shuttle/IUS vehicle. The IUS stage has been selected as the vehicle to be used to boost the Galileo spacecraft into the Earth escape trajectory after the parking orbit is attained.« less

Integration of the real-time tracking gradiometer (RTG) aboard the autonomous underwater vehicle (AUV) Morpheus

NASA Astrophysics Data System (ADS)

Allen, George I.; Matthews, Robert; Wynn, Michael

2001-10-01

In keeping with the Navy's policy to remove humans from harms way, the Autonomous Underwater Vehicle (AUV) is replacing human divers for many missions. The Advanced Marine Systems Lab at Florida Atlantic University (FAU) has developed a small, magnetically friendly, modular plastic AUV called Morpheus designed for coastal applications and especially suited for very shallow water (VSW) mine reconnaissance. Currently employed sensor technologies on AUVs have certain deficiencies and limitations when used across the wide gamut of naval targets and environments, and a strong requirement exists for a sensor or sensors to fill these niches. The Real-time Tracking Gradiometer (RTG) selected for this integration is truly such a niche sensor because its capabilities are not degraded by media interfaces or environmental conditions. It is an experimental prototype fluxgate magnetometer array developed by Quantum Magnetics for the Coastal Systems Station (CSS) and was designed to be man portable and self contained. While limited by physics in detection range, it is capable of detecting ferrous targets under the worst environmental conditions, even when the target is buried. While not having the range of sonar, the RTG does not respond to the false alarms that are indicated by sonar, and since it is capable of also providing range and bearing information, it provides an invaluable niche filling classification tool. The placing of any magnetic sensing system on a conventional AUV is a non-trivial problem. The standard AUV is designed around materials and components that were selected to maximize performance without regard to the magnetic properties of the materials used in its fabrication. To minimize the degradation of sensor performance caused by the platform, several steps must be taken. These include; the substitution of nonferrous components for ferrous, maximizing the separation between the sensor and magnetic field sources, minimizing current loops and using auxiliary current and field sensors capable of generating noise canceling signals. To maximize utility, the magnetic sensor systems should also provide range, bearing and magnetic target strength. While all data and results contained in this paper have been obtained with land-based testing, they are easily adapted to the underwater environment of the AUV. The RTG was recently attached to the Morpheus, and data collected with the unmodified Morpheus powered and undergoing simulated sea motion table. These tests indicate that integration, while not trivial, is indeed feasible, and work is continuing toward mounting the sensor internal to the AUV and implementing the required noise mitigation solutions.

The Effects of Atropine Sulfate on Aviator Performance

DTIC Science & Technology

1985-03-01

and Environmental Medicine , !_6(3), 30*4-308. 8. Asknes, 3. 0. (195*4). Effects of small doses of alcohol upon performance in a Link trainer. Journal...of Aviation Medicine , 25, 680-688. 9.- Henry, P. H., Davis, To Q., Engelken, 3. J.p Triebvasserg Jo H., &Lancaster, M. C. (1974). Alcohol-induced...performance decrements assessed by two Link trainer tasks using experienced pilots. Aerospace Medicine , *45(10), 1180-1189. 10. Henry, P. H., Flueok, J. A

P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway.

PubMed

Hunsberger, Holly C; Rudy, Carolyn C; Batten, Seth R; Gerhardt, Greg A; Reed, Miranda N

2015-01-01

Individuals at risk of developing Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability. A growing body of evidence suggests that perturbations in the glutamatergic tripartite synapse may underlie this hyperexcitability. Here, we used a tau mouse model of AD (rTg(TauP301L)4510) to examine the effects of tau pathology on hippocampal glutamate regulation. We found a 40% increase in hippocampal vesicular glutamate transporter, which packages glutamate into vesicles, and has previously been shown to influence glutamate release, and a 40% decrease in hippocampal glutamate transporter 1, the major glutamate transporter responsible for removing glutamate from the extracellular space. To determine whether these alterations affected glutamate regulation in vivo, we measured tonic glutamate levels, potassium-evoked glutamate release, and glutamate uptake/clearance in the dentate gyrus, cornu ammonis 3(CA3), and cornu ammonis 1(CA1) regions of the hippocampus. P301L tau expression resulted in a 4- and 7-fold increase in potassium-evoked glutamate release in the dentate gyrus and CA3, respectively, and significantly decreased glutamate clearance in all three regions. Both release and clearance correlated with memory performance in the hippocampal-dependent Barnes maze task. Alterations in mice expressing P301L were observed at a time when tau pathology was subtle and before readily detectable neuron loss. These data suggest novel mechanisms by which tau may mediate hyperexcitability. Pre-synaptic vesicular glutamate transporters (vGLUTs) package glutamate into vesicles before exocytosis into the synaptic cleft. Once in the extracellular space, glutamate acts on glutamate receptors. Glutamate is removed from the extracellular space by excitatory amino acid transporters, including GLT-1, predominantly localized to glia. P301L tau expression increases vGLUT expression and glutamate release, while also decreasing GLT-1 expression and glutamate clearance. © 2014 International Society for Neurochemistry.

Design and verification of a simple 3D dynamic model of speed skating which mimics observed forces and motions.

PubMed

van der Kruk, E; Veeger, H E J; van der Helm, F C T; Schwab, A L

2017-11-07

Advice about the optimal coordination pattern for an individual speed skater, could be addressed by simulation and optimization of a biomechanical speed skating model. But before getting to this optimization approach one needs a model that can reasonably match observed behaviour. Therefore, the objective of this study is to present a verified three dimensional inverse skater model with minimal complexity, which models the speed skating motion on the straights. The model simulates the upper body transverse translation of the skater together with the forces exerted by the skates on the ice. The input of the model is the changing distance between the upper body and the skate, referred to as the leg extension (Euclidean distance in 3D space). Verification shows that the model mimics the observed forces and motions well. The model is most accurate for the position and velocity estimation (respectively 1.2% and 2.9% maximum residuals) and least accurate for the force estimations (underestimation of 4.5-10%). The model can be used to further investigate variables in the skating motion. For this, the input of the model, the leg extension, can be optimized to obtain a maximal forward velocity of the upper body. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Results of an Internet-Based Dual-Frequency Global Differential GPS System

NASA Technical Reports Server (NTRS)

Muellerschoen, R.; Bertiger, W.; Lough, M.

2000-01-01

Observables from a global network of 18 GPS receivers are returned in real-time to JPL over the open Internet. 30 - 40 cm RSS global GPS orbits and precise dual-frequency GPS clocks are computed in real-time with JPL's Real Time Gipsy (RTG) software.

The Spencer Research Training Grant at the Penn Graduate School of Education: Implementation and Effects

ERIC Educational Resources Information Center

Kecskemethy, Thomas A.

2008-01-01

Background/Context: The Research Training Grant (RTG) program at the University of Pennsylvania's Graduate School of Education aimed to create strong research training experiences for predissertation fellows through generous financial aid, mentored research apprenticeships, and cocurricular experiences. Collectively these offerings sought to…

Materials property definition and generation for carbon-carbon and carbon phenolic materials

NASA Technical Reports Server (NTRS)

Canfield, A. R.; Mathis, J. R.; Starrett, H. S.; Koenig, J. R.

1987-01-01

A data base program to generate statistically significant material-property data for carbon-carbon and carbon phenolic materials to be used in designs of Space Shuttle is described. The program, which will provide data necessary for thermal and stress modeling of Shuttle nozzle and exit cone structures, includes evaluation of tension, compression, shear strength, shear modulus, thermal expansion, thermal conductivity, permeability, and emittance for both materials; the testing of carbon phenolic materials also includes CTE, off-gassing, pyrolysis, and RTG. Materials to be tested will be excised from Space Shuttle inlet, throat, and exit cone billets and modified involute carbon-carbon exit cones; coprocessed blocks, panels, and cylinders will also be tested.

Short Wavelength Electrostatic Waves in the Earth’s Magnetosheath.

DTIC Science & Technology

1982-07-01

to an antenna effect. Emissions likely to be ion-acoustic mode waves have been found up- stream of the bow shock ( foreshock ) in the solar wind...particles apparently reflected at the bow shock and associated with ion- acoustic mode waves in the Earth’s foreshock are also observed [Eastman et al...Res., 86, A 4493-4510, 1981. Eastman, T.E., 1.R. Anderson, L.A. Frank, and G.K. Parks, Upstream particles observed in the Earth’s foreshock region

SNAP 19 Viking Program. Bimonthly technical progress report, February 1980-March 1980

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-01-01

Viking 1 Lander power system data has not been available during this reporting period, but summary reports indicate no anomalies in performance. Monitoring and evaluation of Viking 2 Lander power system data continued. Temperature data were similar to those 23 months ago, but combined RTG output power was down by 7 watts from the 75 watts recorded in February of 1978. On February 7, 1980, during a scheduled relay transmission the Lander 2 battery voltage dropped below 26.5 volts. With the orbiter attitude control gas supply nearly depleted and the space network stations required for Voyager encounter with Saturn latermore » this year, the final relay from Viking Lander 2 had been scheduled to take place on April 11. The attempt was made but no data were received. Power system performance data for Pioneer 10 and Pioneer Saturn (initially designated Pioneer 11) were monitored. The estimated RTG system net power was 115 watts for both, Pioneer 10 and Pioneer Saturn. The telemetry signal quality from Pioneer Saturn remains excellent. Pioneer 10, for the first time, shows a loss of signal strength.« less

Rewiring AMPK and mitochondrial retrograde signaling for metabolic control of aging and histone acetylation in respiratory-defective cells.

PubMed

Friis, R Magnus N; Glaves, John Paul; Huan, Tao; Li, Liang; Sykes, Brian D; Schultz, Michael C

2014-04-24

Abnormal respiratory metabolism plays a role in numerous human disorders. We find that regulation of overall histone acetylation is perturbed in respiratory-incompetent (ρ(0)) yeast. Because histone acetylation is highly sensitive to acetyl-coenzyme A (acetyl-CoA) availability, we sought interventions that suppress this ρ(0) phenotype through reprogramming metabolism. Nutritional intervention studies led to the discovery that genetic coactivation of the mitochondrion-to-nucleus retrograde (RTG) response and the AMPK (Snf1) pathway prevents abnormal histone deacetylation in ρ(0) cells. Metabolic profiling of signaling mutants uncovered links between chromatin-dependent phenotypes of ρ(0) cells and metabolism of ATP, acetyl-CoA, glutathione, branched-chain amino acids, and the storage carbohydrate trehalose. Importantly, RTG/AMPK activation reprograms energy metabolism to increase the supply of acetyl-CoA to lysine acetyltransferases and extend the chronological lifespan of ρ(0) cells. Our results strengthen the framework for rational design of nutrient supplementation schemes and drug-discovery initiatives aimed at mimicking the therapeutic benefits of dietary interventions. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Space nuclear safety from a user's viewpoint

NASA Technical Reports Server (NTRS)

Campbell, R. W.

1985-01-01

The National Aeronautics and Space Administration (NASA) launched the Jet Propulsion Laboratory's (JPL) two Voyager spacecraft to Jupiter in 1977, each using three radioisotope thermoelectric generators (RTGs) supplied by the Department of Energy (DOE) for onboard electric power. In 1986 NASA will launch JPL's Galileo spacecraft to Jupiter equipped with two DOE supplied RTGs of an improved design. NASA and JPL are also responsible for obtaining a single RTG of this type from DOE and supplying it to the European Space Agency as part of its participation in the International Solar Polar Mission. As a result of these missions, JPL has been deeply involved in space nuclear safety as a user. This paper will give a brief review of the user contributions by JPL - and NASA in general - to the nuclear safety processes and relate them to the overall nuclear safety program necessary for the launch of an RTG. The two major safety areas requiring user support are the ground operations involving RTGs at the launch site and the failure modes and probabilities associated with launch accidents.

Temporal Expression Profiling Identifies Pathways Mediating Effect of Causal Variant on Phenotype

PubMed Central

Gupta, Saumya; Radhakrishnan, Aparna; Raharja-Liu, Pandu; Lin, Gen; Steinmetz, Lars M.; Gagneur, Julien; Sinha, Himanshu

2015-01-01

Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants’ effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage of analyzing allele-specific transcriptional dynamics of mediating genes. Applications in higher eukaryotes can be valuable for inferring causal molecular pathways underlying complex dynamic processes, such as development, physiology and disease progression. PMID:26039065

The Use of 2 Conditioning Programs and the Fitness Characteristics of Police Academy Cadets.

PubMed

Cocke, Charles; Dawes, Jay; Orr, Robin Marc

2016-11-01

 Police academy training must physically prepare cadets for the rigors of their occupational tasks to prevent injury and allow them to adequately perform their duties.  To compare the effects of 2 physical training programs on multiple fitness measures in police cadets.  Cohort study.  Police training academy.  We collected data from 70 male (age = 27.4 ± 5.9 years, body weight = 85.4 ± 11.8 kg) and 20 female (age = 30.5 ± 5.8 years, body weight = 62.8 ± 11.0 kg) police cadets and analyzed data from 61 male cadets (age = 27.5 ± 5.5 years, body weight = 87.7 ± 13.2 kg).  Participants completed one of two 6-month training programs. The randomized training group (RTG; n = 50), comprising 4 separate and sequential groups (n = 13, n = 11, n = 13, n = 13), completed a randomized training program that incorporated various strength and endurance exercises chosen on the day of training. The periodized group (PG; n = 11) completed a periodized training program that alternated specific phases of training.  Anthropometric fitness measures were body weight, fat mass, and lean body mass. Muscular and metabolic fitness measures were 1-repetition maximum bench press, push-up and sit-up repetitions performed in 1 minute, vertical jump, 300-m sprint, and 2.4-km run.  The RTG demonstrated improvements in all outcome measures between pretraining and posttraining; however, the improvements varied among the 4 individual RTGs. Conversely, the PG displayed improvements in only 3 outcome measures (push-ups, sit-ups, and 300-m sprint) but approached the level of significance set for this study (P < .01) in body weight, fat mass, and 1-repetition maximum bench press.  Regardless of format, physical training programs can improve the fitness of tactical athletes. In general, physical fitness measures appeared to improve more in the RTG than in the PG. However, this observation varied among groups, and injury rates were not compared.

New Horizons Launch Contingency Effort

NASA Astrophysics Data System (ADS)

Chang, Yale; Lear, Matthew H.; McGrath, Brian E.; Heyler, Gene A.; Takashima, Naruhisa; Owings, W. Donald

2007-01-01

On 19 January 2006 at 2:00 PM EST, the NASA New Horizons spacecraft (SC) was launched from the Cape Canaveral Air Force Station (CCAFS), FL, onboard an Atlas V 551/Centaur/STAR™ 48B launch vehicle (LV) on a mission to explore the Pluto Charon planetary system and possibly other Kuiper Belt Objects. It carried a single Radioisotope Thermoelectric Generator (RTG). As part of the joint NASA/US Department of Energy (DOE) safety effort, contingency plans were prepared to address the unlikely events of launch accidents leading to a near-pad impact, a suborbital reentry, an orbital reentry, or a heliocentric orbit. As the implementing organization. The Johns Hopkins University Applied Physics Laboratory (JHU/APL) had expanded roles in the New Horizons launch contingency effort over those for the Cassini mission and Mars Exploration Rovers missions. The expanded tasks included participation in the Radiological Control Center (RADCC) at the Kennedy Space Center (KSC), preparation of contingency plans, coordination of space tracking assets, improved aerodynamics characterization of the RTG's 18 General Purpose Heat Source (GPHS) modules, and development of spacecraft and RTG reentry breakup analysis tools. Other JHU/APL tasks were prediction of the Earth impact footprints (ElFs) for the GPHS modules released during the atmospheric reentry (for purposes of notification and recovery), prediction of the time of SC reentry from a potential orbital decay, pre-launch dissemination of ballistic coefficients of various possible reentry configurations, and launch support of an Emergency Operations Center (EOC) on the JHU/APL campus. For the New Horizons launch, JHU/APL personnel at the RADCC and at the EOC were ready to implement any real-time launch contingency activities. A successful New Horizons launch and interplanetary injection precluded any further contingency actions. The New Horizons launch contingency was an interagency effort by several organizations. This paper describes JHU/APL's roles and responsibilities in the launch contingency effort, and the specific tasks to fulfill those responsibilities. The overall effort contributed to mission safety and demonstrated successful cooperation between several agencies.

Lethal and sublethal effects of marine sediment extracts on fish cells and chromosomes

NASA Astrophysics Data System (ADS)

Landolt, Marsha L.; Kocan, Richard M.

1984-03-01

The cost of conducting conventional chronic bioassays with every potentially toxic compound found in marine ecosystems is prohibitive; therefore short-term toxicity tests which can be used for rapid screening were developed. The tests employ cultured fish cells to measure lethal, sublethal or genotoxic effects of pure compounds and complex mixtures. The sensitivity of these tests has been proven under laboratory conditions; the following study used two of these tests, the anaphase aberration test and a cytotoxicity assay, under field conditions. Sediment was collected from 97 stations within Puget Sound, Washington. Serial washings of the sediment in methanol and dichloromethane yielded an organic extract which was dried, dissolved in DMSO and incubated as a series of dilutions with rainbow trout gonad (RTG-2) cells. The toxic effects of the extract were measured by examining the rate of cell proliferation and the percentage of damaged anaphase figures. Anaphase figures were considered to be abnormal if they exhibited non-disjunctions, chromosome fragments, or chromosome bridges. A second cell line (bluegill fry, BF-2) was also tested for cell proliferation and was included because, unlike the RTG-2 cell line, it contains little or no mixed function oxygenase activity. Of 97 stations tested, 35 showed no genotoxic activity, 42 showed high genotoxic activity (P≤.01) and the remainder were intermediate. Among the toxic sites were several deep water stations adjacent to municipal sewage outfalls and four urban waterways contaminated by industrial and municipal effluents. Extracts from areas that showed genotoxic effects also inhibited cell proliferation and were cytotoxic to RTG-2 cells. Few effects were noted in the MFO deficient BF-2 cells. Short term in vitro tests provide aquatic toxicologists with a versatile and cost effective tool for screening complex environments. Through these tests one can identify compounds or geographic regions that exhibit high cytotoxic or genotoxic potential.

Impact of MODIS High-Resolution Sea-Surface Temperatures on WRF Forecasts at NWS Miami, FL

NASA Technical Reports Server (NTRS)

Case, Jonathan L.; LaCasse, Katherine M.; Dembek, Scott R.; Santos, Pablo; Lapenta, William M.

2007-01-01

Over the past few years,studies at the Short-term Prediction Research and Transition (SPoRT) Center have suggested that the use of Moderate Resolution Imaging Spectroradiometer (MODIS) composite sea-surface temperature (SST) products in regional weather forecast models can have a significant positive impact on short-term numerical weather prediction in coastal regions. The recent paper by LaCasse et al. (2007, Monthly Weather Review) highlights lower atmospheric differences in regional numerical simulations over the Florida offshore waters using 2-km SST composites derived from the MODIS instrument aboard the polar-orbiting Aqua and Terra Earth Observing System satellites. To help quantify the value of this impact on NWS Weather Forecast Offices (WFOs), the SPoRT Center and the NWS WFO at Miami, FL (MIA) are collaborating on a project to investigate the impact of using the high-resolution MODIS SST fields within the Weather Research and Forecasting (WRF) prediction system. The scientific hypothesis being tested is: More accurate specification of the lower-boundary forcing within WRF will result in improved land/sea fluxes and hence, more accurate evolution of coastal mesoscale circulations and the associated sensible weather elements. The NWS MIA is currently running the WRF system in real-time to support daily forecast operations, using the National Centers for Environmental Prediction Nonhydrostatic Mesoscale Model dynamical core within the NWS Science and Training Resource Center's Environmental Modeling System (EMS) software; The EMS is a standalone modeling system capable of downloading the necessary daily datasets, and initializing, running and displaying WRF forecasts in the NWS Advanced Weather Interactive Processing System (AWIPS) with little intervention required by forecasters. Twenty-seven hour forecasts are run daily with start times of 0300,0900, 1500, and 2100 UTC on a domain with 4-km grid spacing covering the southern half of Florida and the far western portions of the Bahamas, the Florida Keys, the Straights of Florida, and adjacent waters of the Gulf of Mexico and Atlantic Ocean. Each model run is initialized using the Local Analysis and Prediction System (LAPS) analyses available in AWIPS, invoking the diabatic. "hot-start" capability. In this WRF model "hot-start", the LAPS-analyzed cloud and precipitation features are converted into model microphysics fields with enhanced vertical velocity profiles, effectively reducing the model spin-up time required to predict precipitation systems. The SSTs are initialized with the NCEP Real-Time Global (RTG) analyses at l/12 degree resolution (approx. 9 km); however, the RTG product does not exhibit fine-scale details consistent with its grid resolution. SPoRT is conducting parallel WRF EMS runs identical to the operational runs at NWS MIA in every respect except for the use of MODIS SST composites in place of the RTG product as the initial and boundary conditions over water. The MODIS SST composites for initializing the SPoRT WRF runs are generated on a 2-km grid four times daily at 0400, 0700, 1600, and 1900 UTC, based on the times of the overhead passes of the Aqua and Terra satellites. The incorporation of the MODIS SST composites into the SPoRTWRF runs is staggered such that the 0400UTC composite initializes the 0900 UTC WRF, the 0700 UTC composite initializes the 1500 UTC WRF, the 1600 UTC composite initializes the 2100 UTC WRF, and the 1900 UTC composite initializes the 0300 UTC WRF. A comparison of the SPoRT and Miami forecasts is underway in 2007, and includes quantitative verification of near-surface temperature, dewpoint, and wind forecasts at surface observation locations. In addition, particular days of interest are being analyzed to determine the impact of the MODIS SST data on the development and evolution of predicted sea/land-breeze circulations, clouds, and precipitation. This paper will present verification results comparing the NWS MIA forecasts the SPoRT experimental WRF forecasts, and highlight any substantial differences noted in the predicted mesoscale phenomena.

Riverine ecosystem services and the thermoelectric sector: strategic issues facing the Northeastern United States

NASA Astrophysics Data System (ADS)

Miara, A.; Vorosmarty, C. J.; Stewart, R.; Wollheim, W. M.; Rosenzweig, B.

2013-12-01

Major strategic issues facing the global thermoelectric sector include environmental regulation, climate change and increasing electricity demand. We have addressed such issues by modeling thermoelectric generation in the Northeastern United States that is reliant on cooling under five sensitivity tests to evaluate losses/gains in power production, thermal pollution and suitable aquatic habitat, comparing the contemporary baseline (2000-2010) with potential future states. Integral to the analysis, we developed a methodology to quantify river water availability for cooling, which we define as an ecosystem service. Projected climate conditions reduce river water available for efficient power plant operations and the river's capacity to absorb waste heat, causing a loss of regional thermoelectric generation (RTG) (2.5%) in some summers that, compared to the contemporary baseline, is equal to the summertime electricity consumption of 1.3 million Northeastern US homes. Vulnerabilities to warm temperatures and thermal pollution can be alleviated through the use of more efficient natural gas (NG) power plants that have a reduced reliance on cooling water. Conversion of once-through (OT) to cooling tower (CT) systems and the Clean Water Act (CWA) temperature limit regulation, both of which reduce efficiencies at the single plant level, show potential to yield beneficial increases in RTG. This is achieved by obviating the need for large volumes of river water, thereby reducing plant-to-plant interferences through lowering the impact of upstream thermal pollution and preserving a minimum standard of cooling water. The results and methodology framework presented here, which can be extrapolated to other regional assessments with contrasting climates and thermoelectric profiles, can identify opportunities and support decision-making to achieve more efficient energy systems and riverine ecosystem protection.

Riverine ecosystem services and the thermoelectric sector: strategic issues facing the Northeastern United States

NASA Astrophysics Data System (ADS)

Miara, Ariel; Vörösmarty, Charles J.; Stewart, Robert J.; Wollheim, Wilfred M.; Rosenzweig, Bernice

2013-06-01

Major strategic issues facing the global thermoelectric sector include environmental regulation, climate change and increasing electricity demand. We have addressed such issues by modeling thermoelectric generation in the Northeastern United States that is reliant on cooling under five sensitivity tests to evaluate losses/gains in power production, thermal pollution and suitable aquatic habitat, comparing the contemporary baseline (2000-2010) with potential future states. Integral to the analysis, we developed a methodology to quantify river water availability for cooling, which we define as an ecosystem service. Projected climate conditions reduce river water available for efficient power plant operations and the river’s capacity to absorb waste heat, causing a loss of regional thermoelectric generation (RTG) (2.5%) in some summers that, compared to the contemporary baseline, is equal to the summertime electricity consumption of 1.3 million Northeastern US homes. Vulnerabilities to warm temperatures and thermal pollution can be alleviated through the use of more efficient natural gas (NG) power plants that have a reduced reliance on cooling water. Conversion of once-through (OT) to cooling tower (CT) systems and the Clean Water Act (CWA) temperature limit regulation, both of which reduce efficiencies at the single plant level, show potential to yield beneficial increases in RTG. This is achieved by obviating the need for large volumes of river water, thereby reducing plant-to-plant interferences through lowering the impact of upstream thermal pollution and preserving a minimum standard of cooling water. The results and methodology framework presented here, which can be extrapolated to other regional assessments with contrasting climates and thermoelectric profiles, can identify opportunities and support decision-making to achieve more efficient energy systems and riverine ecosystem protection.

Toward a Vibrant Research Community in Education: Investing in Early-Career Scholars

ERIC Educational Resources Information Center

Young, Lauren Jones

2008-01-01

Background/Context: In 1994, the Spencer Foundation embarked on an ambitious experimental initiative to support the preparation of education researchers. Over the 13-year span of the Research Training Grant (RTG) program, the foundation made multiyear awards to more than a dozen leading institutions in the United States and South Africa. This…

Exploring the Investment: Four Universities' Experiences with the Spencer Foundation's Research Training Grant Program--A Retrospective

ERIC Educational Resources Information Center

Neumann, Anna; Pallas, Aaron; Peterson, Penelope

2008-01-01

Background: This article serves as a conclusion to a TCR special issue devoted to understanding the impact of the Spencer Foundation's Research Training Grant (RTG) initiative. We examine four case reports prepared by scholars at the University of Wisconsin-Madison, the University of Pennsylvania, the University of California at Los Angeles…

Applied Computational Electromagnetics Society Journal, Volume 7, Number 2, Winter 1992,

DTIC Science & Technology

1992-01-01

Rensselaer Polytechnic Institute University of Utah Las Cruces. NM USA -’roy. NY USA ,. Salt Lake City. UT T SA J.R. James A. Konrad D.V. Land RMCS Cranfleld...and found a strong correspondence between the two. Figures la -b show the equation and solution residuals as functions of iteration for small...I I I I I I I I I 4510 Is 31 25 16 35 .0 45 12 Figure la : Normalized solution and equation residuals as functions of iteration for a small sphere

[Uncommon foreign body in a nose].

PubMed

Alagić-Smailbegović, Jasminka; Hadzić, Edina; Sutalo, Kamenko; Resić, Mudzahid

2007-01-01

Foreign body in the nose most frequently occurs in childhood. It could be of various origin, pieces of toys, paper and uncommon metal body. Consequences include one- sided nasal breathing problem, nasal secretion and in some cases pain and secretion become purulent. The aim of this paper is to present uncommon foreign body in the nose. RTG diagnosis and extraction are the methods of choice.

Development of a Multi-bus, Multi-source Reconfigurable Stirling Radioisotope Power System Test Bed

NASA Technical Reports Server (NTRS)

Coleman, Anthony S.

2004-01-01

The National Aeronautics and Space Administration (NASA) has typically used Radioisotope Thermoelectric Generators (RTG) as their source of electric power for deep space missions. A more efficient and potentially more cost effective alternative to the RTG, the high efficiency 110 watt Stirling Radioisotope Generator 110 (SRG110) is being developed by the Department of Energy (DOE), Lockheed Martin (LM), Stirling Technology Company (STC) and NASA Glenn Research Center (GRC). The SRG110 consists of two Stirling convertors (Stirling Engine and Linear Alternator) in a dual-opposed configuration, and two General Purpose Heat Source (GPHS) modules. Although Stirling convertors have been successfully operated as a power source for the utility grid and as a stand-alone portable generator, demonstration of the technology required to interconnect two Stirling convertors for a spacecraft power system has not been attempted. NASA GRC is developing a Power System Test Bed (PSTB) to evaluate the performance of a Stirling convertor in an integrated electrical power system application. This paper will describe the status of the PSTB and on-going activities pertaining to the PSTB in the NASA Thermal-Energy Conversion Branch of the Power and On-Board Propulsion Technology Division.

Precision Penning Trap Mass Spectrometry of S, Kr and Xe

NASA Astrophysics Data System (ADS)

Redshaw, Matthew

2005-04-01

Using a phase coherent technique to measure the cyclotron frequency of single ions in a Penning trap [1], we have performed mass measurements on ^32S and the two most abundant krypton and xenon isotopes ^84Kr, ^86Kr, ^ 129Xe and ^132Xe, to relative precisions of 0.1 ppb. This is a factor of ˜10-100 improvement in precision over current values [2]. [1] M.P. Bradley, J.V. Porto, S. Rainville, J.K. Thompson, and D.E. Pritchard, PRL 83, 4510 (1999). [2] G. Audi, A.H. Wapstra, and C. Thibault, Nucl Phys A729, 337 (2003).

Dynamic Air Traffic Control Simulation of Profile Descent and High-Speed Approach Fuel Conservation Procedures.

DTIC Science & Technology

1980-05-01

FL240 and above 271 Aircraft Cruising FL230 and below 59 All Aircraft 330 D-7 Fuel (Average Pounds per Aircraft) Aircraft Cruising FL240 and above 3,467...15000 5440 5230 5020 4810 4640 4480 4320 4170 4030 3900 3770 -15 10000 5590 5420 5220 5000 4820 4660 4510 4360 4220 4090 3990 5000 5780 5600 5400...XAS 267 262 257 252 247 242 237 232 226 221 215 __ ,000 LBS/HR 22000 21200 20400 19600 18800 18000 17300 16600 15900 15200 145C0 IAS 264 260 255 250 245

Vibration Testing of the Pluto/New Horizons Radioisotope Thermoelectric Generator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charles D. Griffin

The Radioisotopic Thermal Generator (RTG) for the Pluto/New Horizons spacecraft was subjected to a flight dynamic acceptance test to demonstrate that it would perform successfully following launch. Seven RTGs of this type had been assembled and tested at Mound, Ohio from 1984 to 1997. This paper chronicles major events in establishing a new vibration test laboratory at the Idaho National Laboratory and the nineteen days of dynamic testing.

Modular Isotopic Thermoelectric Generator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schock, Alfred

1981-01-01

Advanced RTG concepts utilizing improved thermoelectric materials and converter concepts are under study at Fairchild for DOE. The design described here is based on DOE's newly developed radioisotope heat source, and on an improved silicon-germanium material and multicouple converter module under development at Syncal. Fairchild's assignment was to combine the above into an attractive power system for use in space, and to assess the specific power and other attributes of that design.

Development of advanced thermoelectric materials

NASA Technical Reports Server (NTRS)

1984-01-01

The development of an advanced thermoelectric material for radioisotope thermoelectric generator (RTG) applications is reported. A number of materials were explored. The bulk of the effort, however, was devoted to improving silicon germanium alloys by the addition of gallium phosphide, the synthesis and evaluation of lanthanum chrome sulfide and the formulation of various mixtures of lanthanum sulfide and chrome sulfide. It is found that each of these materials exhibits promise as a thermoelectric material.

GPHS-RTGs in support of the Cassini Mission

NASA Astrophysics Data System (ADS)

1994-10-01

The progress on the radioisotope generators and ancillary activities is described. This report is organized by program task as follows: spacecraft integration and liaison; engineering support; safety; qualified unicouple fabrication; ETG fabrication, assembly, and test; ground support equipment; RTG shipping and launch support; design, reviews, and mission applications; project management, quality assurance and reliability, contract changes, non-capital CAGO acquisition, and CAGO maintenance; contractor acquired government owned property (CAGO) acquisition.

GPHS-RTGs in support of the Cassini mission

NASA Astrophysics Data System (ADS)

1992-04-01

The technical progress achieved during the period 30 Mar. - 27 Sep. 1992 is described. Topics covered include: spacecraft integration and liaison; engineering support; safety; qualified unicouple production, ETG fabrication, assembly, and test; ground support equipment; radioisotope thermoelectric generators (RTG) shipping and launch support; designs, reviews, and mission applications; project management, quality assurance, reliability, contract changes, non-capital contractor acquired government owned (CAGO) acquisitions, and CAGO maintenance; and CAGO acquisitions.

Induction of EROD and BFCOD activities in tissues of barbel (Barbus callensis) from a water reservoir in Algeria.

PubMed

Habila, Safia; Leghouchi, Essaid; Valdehita, Ana; Bermejo-Nogales, Azucena; Khelili, Smail; Navas, José M

2017-08-01

EROD and BFCOD activities were measured in liver and gills of barbel (Barbus callensis, a native North African species) captured at Beni Haroun lake, the most important water reservoir in Algeria. This lake receives wastewater from different origins. Thus, we assessed the level of pollution through the induction of detoxification activities in tissues of barbel, evaluating simultaneously the suitability of this species to be used as a sentinel. Fish were collected between March 2015 and January 2016 at three locations taking into account the pollution sources and accessibility. In liver, EROD and BFCOD showed the highest induction in October specially in the location of the dam that received pollutants. In gills, only EROD, but not BFCOD, activity was detected. Maximal EROD induction was noted in samples from January. Fish cell lines (RTG-2 and PLHC-1) were exposed to sediments extracts collected at Beni Haroun lake and enzyme activities (EROD and BFCOD, respectively) were measured. Sediment extracts did not induce BFCOD activity. The EROD induction observed in RTG-2 cells was in line with the results observed in fish tissues. Our results suggest that the lake is at risk from pollution and that Barbus callensis is a good sentinel species. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone structure regeneration after low induction magnetic field treatment in teeth chosen for extraction.

PubMed

Opalko, K; Dojs, A

2006-01-01

The aim of the work was to use and to evaluate the usefulness of the slow variable magnetic fields to aid the treatment of the teeth chosen for extraction. The marginal paradontium of periapical bone of teeth was in a state of extensive destruction. The teeth were chosen for extraction. 13 patients were chosen. 10 of them had with endo-perio changes and 3 suffered from full tooth luxation and had the teeth replanted. Those people were to have an extraction procedure or were declared as impossible to treat in other dental offices. Patients underwent non-aggressive skaling, endodontic treatment and were exposed to slow variable magnetic fields generated by Viofor JPS, accordingly to methods and parameters suggested by Department of Propaedeutics in Dentistry of Pomeranian Medical University in Szczecin. The process of healing of changes was evaluated radiologically. RTG done after 2 weeks and after 2 months were evaluated in respect of bone regeneration. They show the bone structure concentration. A RTG evaluation after half a year, two and three years show a preservation of the bone structure concentration. The use of slow variable magnetic fields contributed to bone structure regeneration and to preserve teeth with recorded endo-perio syndrome. Endodontic treatment of replanted teeth, aided with magnetostimulation has stopped the osteolisis process.

Logistical concepts associated with international shipments using the USA/9904/B(U)F RTG Transportation System (RTGTS)

NASA Astrophysics Data System (ADS)

Barklay, Chadwick D.; Miller, Roger G.; Pugh, Barry K.; Howell, Edwin I.

1997-01-01

Over the last 30 years, radioisotopes have provided heat from which electrical power is generated. For space missions, the isotope of choice has generally been 238PuO2, its long half-life making it ideal for supplying power to remote satellites and spacecraft like the Voyager, Pioneer, and Viking missions, as well as the recently launched Galileo and Ulysses missions, and the presently planned Cassini mission. Electric power for future space missions will be provided by either radioisotopic thermoelectric generators (RTG), radioisotope thermophotovoltaic systems (RTPV), alkali metal thermal to electrical conversion (AMTEC) systems, radioisotope Stirling systems, or a combination of these. The type of electrical power system has yet to be specified for the ``Pluto Express'' mission. However, the current plan does incorporate the use of Russian launch platforms for the spacecraft. The implied tasks associated with this plan require obtaining international certification for the transport of the radioisotopic power system, and resolving any logistical issues associated with the actual shipment of the selected radioisotopic power system. This paper presents a conceptual summary of the logistical considerations associated with shipping the selected radioisotopic power system using the USA/9904/B(U)F-85, Radioisotope Thermoelectric Generator Transportation System (RTGTS).

Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.

PubMed

Murrough, James W; Wade, Elizabeth; Sayed, Sehrish; Ahle, Gabriella; Kiraly, Drew D; Welch, Alison; Collins, Katherine A; Soleimani, Laili; Iosifescu, Dan V; Charney, Dennis S

2017-08-15

At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t 19 =5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t 19 =4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. Open-label, proof-of-concept design. Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaplan, D. L.; Bhalerao, V. B.; Van Kerkwijk, M. H.

Most millisecond pulsars with low-mass companions are in systems with either helium-core white dwarfs or non-degenerate (''black widow'' or ''redback'') stars. A candidate counterpart to PSR J1816+4510 was identified by Kaplan et al. whose properties were suggestive of both types of companions although identical to neither. We have assembled optical spectroscopy of the candidate companion and confirm that it is part of the binary system with a radial velocity amplitude of 343 {+-} 7 km s{sup -1}, implying a high pulsar mass, M{sub psr}sin {sup 3} i = 1.84 {+-} 0.11 M{sub Sun }, and a companion mass M{sub c}more » sin {sup 3} i = 0.193 {+-} 0.012 M{sub Sun }, where i is the inclination of the orbit. The companion appears similar to proto-white dwarfs/sdB stars, with a gravity log{sub 10}(g) = 4.9 {+-} 0.3, and effective temperature 16, 000 {+-} 500 K. The strongest lines in the spectrum are from hydrogen, but numerous lines from helium, calcium, silicon, and magnesium are present as well, with implied abundances of roughly 10 times solar (relative to hydrogen). As such, while from the spectrum the companion to PSR J1816+4510 is superficially most similar to a low-mass white dwarf, it has much lower gravity, is substantially larger, and shows substantial metals. Furthermore, it is able to produce ionized gas eclipses, which had previously been seen only for low-mass, non-degenerate companions in redback or black widow systems. We discuss the companion in relation to other sources, but find that we understand neither its nature nor its origins. Thus, the system is interesting for understanding unusual stellar products of binary evolution, as well as, independent of its nature, for determining neutron-star masses.« less

Radioisotope thermal photovoltaic application of the GaSb solar cell

NASA Technical Reports Server (NTRS)

Morgan, M. D.; Horne, W. E.; Day, A. C.

1991-01-01

An examination of a RTVP (radioisotopic thermophotovoltaic) conceptual design has shown a high potential for power densities well above those achievable with radioisotopic thermoelectric generator (RTG) systems. An efficiency of 14.4 percent and system specific power of 9.25 watts/kg were predicted for a system with sixteen GPHS (general purpose heat source) sources operating at 1100 C. The models also showed a 500 watt system power by the strontium-90 isotope at 1200 C at an efficiency of 17.0 percent and a system specific power of 11.8 watts/kg. The key to this level of performance is a high-quality photovoltaic cell with narrow bandgap and a reflective rear contact. Recent work at Boeing on GaSb cells and transparent back GaAs cells indicate that such a cell is well within reach.

Finding mouse models of human lymphomas and leukemia's using the Jackson laboratory mouse tumor biology database.

PubMed

Begley, Dale A; Sundberg, John P; Krupke, Debra M; Neuhauser, Steven B; Bult, Carol J; Eppig, Janan T; Morse, Herbert C; Ward, Jerrold M

2015-12-01

Many mouse models have been created to study hematopoietic cancer types. There are over thirty hematopoietic tumor types and subtypes, both human and mouse, with various origins, characteristics and clinical prognoses. Determining the specific type of hematopoietic lesion produced in a mouse model and identifying mouse models that correspond to the human subtypes of these lesions has been a continuing challenge for the scientific community. The Mouse Tumor Biology Database (MTB; http://tumor.informatics.jax.org) is designed to facilitate use of mouse models of human cancer by providing detailed histopathologic and molecular information on lymphoma subtypes, including expertly annotated, on line, whole slide scans, and providing a repository for storing information on and querying these data for specific lymphoma models. Copyright © 2015 Elsevier Inc. All rights reserved.

Mouse models rarely mimic the transcriptome of human neurodegenerative diseases: A systematic bioinformatics-based critique of preclinical models.

PubMed

Burns, Terry C; Li, Matthew D; Mehta, Swapnil; Awad, Ahmed J; Morgan, Alexander A

2015-07-15

Translational research for neurodegenerative disease depends intimately upon animal models. Unfortunately, promising therapies developed using mouse models mostly fail in clinical trials, highlighting uncertainty about how well mouse models mimic human neurodegenerative disease at the molecular level. We compared the transcriptional signature of neurodegeneration in mouse models of Alzheimer׳s disease (AD), Parkinson׳s disease (PD), Huntington׳s disease (HD) and amyotrophic lateral sclerosis (ALS) to human disease. In contrast to aging, which demonstrated a conserved transcriptome between humans and mice, only 3 of 19 animal models showed significant enrichment for gene sets comprising the most dysregulated up- and down-regulated human genes. Spearman׳s correlation analysis revealed even healthy human aging to be more closely related to human neurodegeneration than any mouse model of AD, PD, ALS or HD. Remarkably, mouse models frequently upregulated stress response genes that were consistently downregulated in human diseases. Among potential alternate models of neurodegeneration, mouse prion disease outperformed all other disease-specific models. Even among the best available animal models, conserved differences between mouse and human transcriptomes were found across multiple animal model versus human disease comparisons, surprisingly, even including aging. Relative to mouse models, mouse disease signatures demonstrated consistent trends toward preserved mitochondrial function protein catabolism, DNA repair responses, and chromatin maintenance. These findings suggest a more complex and multifactorial pathophysiology in human neurodegeneration than is captured through standard animal models, and suggest that even among conserved physiological processes such as aging, mice are less prone to exhibit neurodegeneration-like changes. This work may help explain the poor track record of mouse-based translational therapies for neurodegeneration and provides a path forward to critically evaluate and improve animal models of human disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Ecotoxicological evaluation of the additive butylated hydroxyanisole using a battery with six model systems and eighteen endpoints.

PubMed

Jos, Angeles; Repetto, Guillermo; Ríos, Juan Carlos; del Peso, Ana; Salguero, Manuel; Hazen, María José; Molero, María Luisa; Fernández-Freire, Paloma; Pérez-Martín, Jose Manuel; Labrador, Verónica; Cameán, Ana

2005-01-26

The occurrence and fate of additives in the aquatic environment is an emerging issue in environmental chemistry. This paper describes the ecotoxicological effects of the commonly used additive butylated hydroxyanisole (BHA) using a test battery, comprising of several different organisms and in vitro test systems, representing a proportion of the different trophic levels. The most sensitive system to BHA was the inhibition of bioluminescence in Vibrio fischeri bacteria, which resulted in an acute low observed adverse effect concentration (LOAEC) of 0.28 microM. The next most sensitive system was the immobilization of the cladoceran Daphnia magna followed by: the inhibition of the growth of the unicellular alga Chlorella vulgaris; the endpoints evaluated in Vero (mammalian) cells (total protein content, LDH activity, neutral red uptake and MTT metabolization), mitotic index and root growth inhibition in the terrestrial plant Allium cepa, and finally, the endpoints used on the RTG-2 salmonid fish cell line (neutral red uptake, total protein content, MTS metabolization, lactate dehydrogenase leakage and activity, and glucose-6-phosphate dehydrogenase activity). Morphological alterations in RTG-2 cells were also assessed and these included loss of cells, induction of cellular pleomorphism, hydropic degeneration and induction of apoptosis at high concentrations. The results from this study also indicated that micronuclei were not induced in A.cepa exposed to BHA. The differences in sensitivity for the diverse systems that were used (EC50 ranged from 1.2 to >500 microM) suggest the importance for a test battery approach in the evaluation of the ecological consequences of chemicals. According to the results, the levels of BHA reported in industrial wastewater would elicit adverse effects in the environment. This, coupled with its potential to bioaccumulate, makes BHA a pollutant of concern not only for acute exposures, but also for the long-term.

Precision Penning Trap Mass Spectrometry of ^32S, ^84,86Kr and ^129,132Xe

NASA Astrophysics Data System (ADS)

Redshaw, Matthew

2005-05-01

Using a phase coherent technique to measure the cyclotron frequency of single ions in a Penning trap [1], we have performed mass measurements on ^32S and the two most abundant krypton and xenon isotopes ^84Kr, ^86Kr, ^ 129Xe and ^132Xe, to relative precisions of 0.1 ppb. This is a factor of ˜10-100 improvement in precision over current values [2]. [1] M.P. Bradley, J.V. Porto, S. Rainville, J.K. Thompson, and D.E. Pritchard, PRL 83, 4510 (1999). [2] G. Audi, A.H. Wapstra, and C. Thibault, Nucl Phys A729, 337 (2003).

Knee arthrodesis with the Wichita fusion nail.

PubMed

Domingo, L J; Caballero, M J; Cuenca, J; Herrera, A; Sola, A; Herrero, L

2004-02-01

We reviewed 32 patients who all had knee arthrodesis performed after failed knee replacement. The minimum clinical follow-up was 1 year. The arthrodesis was performed by means of the Wichita fusion nail in 11, by external fixation in 15 cases, by plating in three and by intramedullary nailing in three. The mean patient age was 68.6 years. When the Wichita nail was used, fusion was achieved in ten out of 11 cases after a mean period of 4.5 (3-7) months. Of the remaining 21 patients, fusion was only achieved in 11 cases after a mean period of 6.5 (4.5-10) months.

The Role of AhR in Breast Cancer Development

DTIC Science & Technology

2004-07-01

The renilla luciferase vectorphRL-TK (0.05 rtg) was co-transfected with firefly luciferase reporter constructs (0.1 ptg pGudLuc, 0.5-1.0 [tg wildtype...Glo Luciferase system (Promega, Madison, WI ) which allowed sequential reading of the firefly and renilla signals. Cells were lysed according to the...Madison, WI ). The renilla signal was read after quenching the firefly output, thus allowing normalization between sample wells. The normalized firefly

NEPP Update of Independent Single Event Upset Field Programmable Gate Array Testing

NASA Technical Reports Server (NTRS)

Berg, Melanie; Label, Kenneth; Campola, Michael; Pellish, Jonathan

2017-01-01

This presentation provides a NASA Electronic Parts and Packaging (NEPP) Program update of independent Single Event Upset (SEU) Field Programmable Gate Array (FPGA) testing including FPGA test guidelines, Microsemi RTG4 heavy-ion results, Xilinx Kintex-UltraScale heavy-ion results, Xilinx UltraScale+ single event effect (SEE) test plans, development of a new methodology for characterizing SEU system response, and NEPP involvement with FPGA security and trust.

Front End Analysis of Soldier Individual Power Systems

DTIC Science & Technology

1993-05-01

in the state-of-the-art MOD-GPHS-RTG, but with the fuel being polonium 210 , with a half life of 13.1.4 days, in the form of a gadolinium polonide (GdPo...allies, and industry to evaluate state-of-the-art technologies and integrate them into a system with synergistic improvement in combat effectiveness . The...Schemes ................................................... 79 Front End Analysis of Soldier Individual Power S LIST OF FIGURES I Effect of Mission

GPHS-RTGs in support of the Cassini mission

NASA Astrophysics Data System (ADS)

1994-04-01

This report is organized by the program task structure as follows: (1) spacecraft integration and liaison; (2) engineering support; (3) safety; (4) qualified unicouple fabrication; (5) ETG fabrication, assembly, and test; (6) ground support equipment (GSE); (7) RTG shipping and launch support; (8) designs, reviews, and mission applications; (9) project management, quality assurance and reliability, contract changes, noncapital contractor acquired government owned property (CAGO) acquisition, and CAGO maintenance; and (10) CAGO acquisition.

System parameters for erythropoiesis control model: Comparison of normal values in human and mouse model

NASA Technical Reports Server (NTRS)

1979-01-01

The computer model for erythropoietic control was adapted to the mouse system by altering system parameters originally given for the human to those which more realistically represent the mouse. Parameter values were obtained from a variety of literature sources. Using the mouse model, the mouse was studied as a potential experimental model for spaceflight. Simulation studies of dehydration and hypoxia were performed. A comparison of system parameters for the mouse and human models is presented. Aside from the obvious differences expected in fluid volumes, blood flows and metabolic rates, larger differences were observed in the following: erythrocyte life span, erythropoietin half-life, and normal arterial pO2.

Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

PubMed

Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

2015-02-01

During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

PubMed

Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

2017-11-01

Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Radioisotopic energy conversion system (RECS): A new radioisotopic power cell, based on nuclear, atomic, and radiation transport principles

NASA Astrophysics Data System (ADS)

Steinfelds, Eric Victor

The topic of this thesis is the development of the Radioisotope Energy Conversion System (RECS) in a project which is utilizing analytical computational assisted design and some experimental Research in the investigation of fluorescers and effective transducers with the appropriate energy range choice for the conversion of energy. It is desirable to increase the efficiency in electrical power from the raw kinetic power available from the radioactive material within radioisotope power generators. A major step in this direction is the development and use of Radioisotope Energy Conversion Systems to supplement and ideally replace Radioactive Thermal Generators (RTG). It is possible to achieve electrical conversion efficiencies exceeding 25% for RECS power devices compared to only 9 percent efficiency for RTG's. The theoretical basis with existent materials for the potential achievability of efficiencies above 25% is documented within this thesis. The fundamental RECS consists of a radioisotope radiative source (C1), a mediating fluorescent gas (C2) which readily absorbs energy from the beta particles (or alpha's) and subsequently emits blue or UV photons, photovoltaic cells (C3) to convert the blue and UV photons into electrical energy [2], and electrical circuitry (C4). Solid State inspired component (C3), due to its theoretical (and attainable) high efficiency, is a large step ahead of the RTG design concept. The radioisotope flux source produces the beta(-) particles or alpha particles. Geometrically, presently, we prefer to have the ambient fluorescent gas surround the radioisotope flux source. Our fluorescer shall be a gas such as Krypton. Our specifically wide band-gap photovoltaic cells shall have gap energies which are slightly less than that of UV photons produced by the fluorescing gas. Diamond and Aluminum Nitride sample materials are good potential choices for photovoltaic cells, as is explained here in. Out of the material examples discussed, the highest electric power to mass ratio is found to be readily attainable with strontium-90 as the radiative source. Krypton-85 is indisputably the most efficient in RECS devices. In the conclusion in chapter VI, suggestions are given on acceptable ways of containing krypton-85 and providing sufficient shielding on deep space probes destined to use krypton-85 powered 'batteries'.

Definition phase study of the grand tour missions

NASA Technical Reports Server (NTRS)

Simpson, J. A.; Meyer, P.

1972-01-01

The research to define an energetic particle experiment for the OPTGT-MJS missions is reported. The studies reported include: (1) the use of silicon dectectors for low energy, low flux level measurements in the presence of RTG radiation and trapped electrons, (2) high energy proton damage of lithium-drifted and surface barrier silicon detectors, (3) the gas Cerenkov counter, (4) systems for detection of trapped high-energy protons in the presence of trapped electrons, and (5) reliability and redundancy.

Characterization of Pu-238 Heat Source Granule Containment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson, Paul Dean II; Sanchez, Joey Leo; Wall, Angelique Dinorah

The Milliwatt Radioisotopic Themoelectric Generator (RTG) provides power for permissive-action links. Essentially these are nuclear batteries that convert thermal energy to electrical energy using a doped silicon-germanium thermopile. The thermal energy is provided by a heat source made of 238Pu, in the form of 238PuO 2 granules. The granules are contained by 3 layers of encapsulation. A thin T-111 liner surrounds the 238PuO 2 granules and protects the second layer (strength member) from exposure to the fuel granules. An outer layer of Hastalloy-C protects the T-111 from oxygen embrittlement. The T-111 strength member is considered the critical component in thismore » 238PuO 2 containment system. Any compromise in the strength member seen during destructive testing required by the RTG surveillance program is characterized. The T-111 strength member is characterized through Scanning Electron Microscopy (SEM), and Metallography. SEM is used in the Secondary Electron mode to reveal possible grain boundary deformation and/or cracking in the region of the strength member weld. Deformation and cracking uncovered by SEM are further characterized by Metallography. Metallography sections are mounted and polished, observed using optical microscopy, then documented in the form of microphotographs. SEM mat further be used to examine polished Metallography mounts to characterize elements using the SEM mode of Energy Dispersive X-ray spectroscopy (EDS).« less

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease.

PubMed

Sato, Hiromasa; Yamamoto, Toshiyuki; Sato, Masako; Furusawa, Yoshihiko; Murata, Miho

2018-01-01

The causes of "delayed-on" and "no-on" phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. A 69-year-old man with PD presented with "delayed-on" and "no-on" phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an "off" state. Videofluoroscopic examination of swallowing in an "off" state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of "delayed-on" and "no-on" phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of "no-on" phenomena decreased. In PD patients, the "no-on" phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

Step length after discrete perturbation predicts accidental falls and fall-related injury in elderly people with a range of peripheral neuropathy.

PubMed

Allet, Lara; Kim, Hogene; Ashton-Miller, James; De Mott, Trina; Richardson, James K

2014-01-01

Distal symmetric polyneuropathy increases fall risk due to inability to cope with perturbations. We aimed to 1) identify the frontal plane lower limb sensorimotor functions which are necessary for robustness to a discrete, underfoot perturbation during gait; and 2) determine whether changes in the post-perturbed step parameters could distinguish between fallers and non fallers. Forty-two subjects (16 healthy old and 26 with diabetic PN) participated. Frontal plane lower limb sensorimotor functions were determined using established laboratory-based techniques. The subjects' most extreme alterations in step width or step length in response to a perturbation were measured. In addition, falls and fall-related injuries were prospectively recorded. Ankle proprioceptive threshold (APrT; p=.025) and hip abduction rate of torque generation (RTG; p=.041) independently predicted extreme step length after medial perturbation, with precise APrT and greater hip RTG allowing maintenance of step length. Injured subjects demonstrated greater extreme step length changes after medial perturbation than non-injured subjects (percent change = 18.5 ± 9.2 vs. 11.3 ± 4.57; p = .01). The ability to rapidly generate frontal plane hip strength and/or precisely perceive motion at the ankle is needed to maintain a normal step length after perturbation, a parameter which distinguishes between subjects sustaining a fall-related injury and those who did not. © 2014.

Comparative Cytotoxicity Study of Silver Nanoparticles (AgNPs) in a Variety of Rainbow Trout Cell Lines (RTL-W1, RTH-149, RTG-2) and Primary Hepatocytes

PubMed Central

Connolly, Mona; Fernandez-Cruz, Maria-Luisa; Quesada-Garcia, Alba; Alte, Luis; Segner, Helmut; Navas, Jose M.

2015-01-01

Among all classes of nanomaterials, silver nanoparticles (AgNPs) have potentially an important ecotoxicological impact, especially in freshwater environments. Fish are particularly susceptible to the toxic effects of silver ions and, with knowledge gaps regarding the contribution of dissolution and unique particle effects to AgNP toxicity, they represent a group of vulnerable organisms. Using cell lines (RTL-W1, RTH-149, RTG-2) and primary hepatocytes of rainbow trout (Oncorhynchus mykiss) as in vitro test systems, we assessed the cytotoxicity of the representative AgNP, NM-300K, and AgNO3 as an Ag+ ion source. Lack of AgNP interference with the cytotoxicity assays (AlamarBlue, CFDA-AM, NRU assay) and their simultaneous application point to the compatibility and usefulness of such a battery of assays. The RTH-149 and RTL-W1 liver cell lines exhibited similar sensitivity as primary hepatocytes towards AgNP toxicity. Leibovitz’s L-15 culture medium composition (high amino acid content) had an important influence on the behaviour and toxicity of AgNPs towards the RTL-W1 cell line. The obtained results demonstrate that, with careful consideration, such an in vitro approach can provide valuable toxicological data to be used in an integrated testing strategy for NM-300K risk assessment. PMID:26006119

Fish cell lines as a tool for the ecotoxicity assessment and ranking of engineered nanomaterials.

PubMed

Bermejo-Nogales, A; Fernández-Cruz, M L; Navas, J M

2017-11-01

Risk assessment of engineered nanomaterials (ENMs) is being hindered by the sheer production volume of these materials. In this regard, the grouping and ranking of ENMs appears as a promising strategy. Here we sought to evaluate the usefulness of in vitro systems based on fish cell lines for ranking a set of ENMs on the basis of their cytotoxicity. We used the topminnow (Poeciliopsis lucida) liver cell line (PLHC-1) and the rainbow trout (Oncorhynchus mykiss) fibroblast-like gonadal cell line (RTG-2). ENMs were obtained from the EU Joint Research Centre repository. The size frequency distribution of ENM suspensions in cell culture media was characterized. Cytotoxicity was evaluated after 24 h of exposure. PLHC-1 cells exhibited higher sensitivity to the ENMs than RTG-2 cells. ZnO-NM was found to exert toxicity mainly by altering lysosome function and metabolic activity, while multi-walled carbon nanotubes (MWCNTs) caused plasma membrane disruption at high concentrations. The hazard ranking for toxicity (ZnO-NM > MWCNT ≥ CeO 2 -NM = SiO 2 -NM) was inversely related to the ranking in size detected in culture medium. Our findings reveal the suitability of fish cell lines for establishing hazard rankings of ENMs in the framework of integrated approaches to testing and assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

Step length after discrete perturbation predicts accidental falls and fall-related injury in elderly people with a range of peripheral neuropathy

PubMed Central

Allet, L; Kim, H; Ashton-Miller, JA; De Mott, T; Richardson, JK

2013-01-01

Aims Distal symmetric polyneuropathy increases fall risk due to inability to cope with perturbations. We aimed to 1) identify the frontal plane lower limb sensorimotor functions which are necessary for robustness to a discrete, underfoot perturbation during gait; and 2) determine whether changes in the post-perturbed step parameters could distinguish between fallers and non fallers. Methods Forty-two subjects (16 healthy old and 26 with diabetic PN) participated. Frontal plane lower limb sensorimotor functions were determined using established laboratory-based techniques. The subjects' most extreme alterations in step width or step length in response to a perturbation were measured. In addition, falls and fall-related injuries were prospectively recorded. Results Ankle proprioceptive threshold (APrT; p=.025) and hip abduction rate of torque generation (RTG; p=.041) independently predicted extreme step length after medial perturbation, with precise APrT and greater hip RTG allowing maintenance of step length. Fallers demonstrated greater extreme step length changes after medial perturbation than non fallers (percent change = 16.41±8.42 vs 11.0±4.95; p=.06) Conclusions The ability to rapidly generate frontal plane hip strength and/or precisely perceive motion at the ankle is needed to maintain a normal step length after perturbation, a parameter, which distinguishes between fallers and non fallers. PMID:24183899

Drug discovery in prostate cancer mouse models.

PubMed

Valkenburg, Kenneth C; Pienta, Kenneth J

2015-01-01

The mouse is an important, though imperfect, organism with which to model human disease and to discover and test novel drugs in a preclinical setting. Many experimental strategies have been used to discover new biological and molecular targets in the mouse, with the hopes of translating these discoveries into novel drugs to treat prostate cancer in humans. Modeling prostate cancer in the mouse, however, has been challenging, and often drugs that work in mice have failed in human trials. The authors discuss the similarities and differences between mice and men; the types of mouse models that exist to model prostate cancer; practical questions one must ask when using a mouse as a model; and potential reasons that drugs do not often translate to humans. They also discuss the current value in using mouse models for drug discovery to treat prostate cancer and what needs are still unmet in field. With proper planning and following practical guidelines by the researcher, the mouse is a powerful experimental tool. The field lacks genetically engineered metastatic models, and xenograft models do not allow for the study of the immune system during the metastatic process. There remain several important limitations to discovering and testing novel drugs in mice for eventual human use, but these can often be overcome. Overall, mouse modeling is an essential part of prostate cancer research and drug discovery. Emerging technologies and better and ever-increasing forms of communication are moving the field in a hopeful direction.

Orthology for comparative genomics in the mouse genome database.

PubMed

Dolan, Mary E; Baldarelli, Richard M; Bello, Susan M; Ni, Li; McAndrews, Monica S; Bult, Carol J; Kadin, James A; Richardson, Joel E; Ringwald, Martin; Eppig, Janan T; Blake, Judith A

2015-08-01

The mouse genome database (MGD) is the model organism database component of the mouse genome informatics system at The Jackson Laboratory. MGD is the international data resource for the laboratory mouse and facilitates the use of mice in the study of human health and disease. Since its beginnings, MGD has included comparative genomics data with a particular focus on human-mouse orthology, an essential component of the use of mouse as a model organism. Over the past 25 years, novel algorithms and addition of orthologs from other model organisms have enriched comparative genomics in MGD data, extending the use of orthology data to support the laboratory mouse as a model of human biology. Here, we describe current comparative data in MGD and review the history and refinement of orthology representation in this resource.

Genetically Engineered Mouse Models for Studying Inflammatory Bowel Disease

PubMed Central

Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko

2015-01-01

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. PMID:26387641

Assessment of the disinfection capacity and eco-toxicological impact of atmospheric cold plasma for treatment of food industry effluents.

PubMed

Patange, Apurva; Boehm, Daniela; Giltrap, Michelle; Lu, Peng; Cullen, P J; Bourke, Paula

2018-08-01

Generation of wastewater is one of the main environmental sustainability issues across food sector industries. The constituents of food process effluents are often complex and require high energy and processing for regulatory compliance. Wastewater streams are the subject of microbiological and chemical criteria, and can have a significant eco-toxicological impact on the aquatic life. Thus, innovative treatment approaches are required to mitigate environmental impact in an energy efficient manner. Here, dielectric barrier discharge atmospheric cold plasma (ACP) was evaluated for control of key microbial indicators encountered in food industry effluent. This study also investigated the eco-toxicological impact of cold plasma treatment of the effluents using a range of aquatic bioassays. Continuous ACP treatment was applied to synthetic dairy and meat effluents. Microbial inactivation showed treatment time dependence with significant reduction in microbial populations within 120 s, and to undetectable levels after 300 s. Post treatment retention time emerged as critical control parameter which promoted ACP bacterial inactivation efficiency. Moreover, ACP treatment for 20 min achieved significant reduction (≥2 Log 10 ) in Bacillus megaterium endospores in wastewater effluent. Acute aquatic toxicity was assessed using two fish cell lines (PLHC-1 and RTG-2) and a crustacean model (Daphnia magna). Untreated effluents were toxic to the aquatic models, however, plasma treatment limited the toxic effects. Differing sensitivities were observed to ACP treated effluents across the different test bio-assays in the following order: PLHC-1 > RTG-2 ≥ D. magna; with greater sensitivity retained to plasma treated meat effluent than dairy effluent. The toxic effects were dependent on concentration and treatment time of the ACP treated effluent; with 30% cytotoxicity in D. magna and fish cells observed after 24 h of exposure to ACP treated effluent for concentrations up to 5%. The findings suggest the need to employ wider variety of aquatic organisms for better understanding and complete toxicity evaluation of long-term effects. The study demonstrates the potential to tailor ACP system parameters to control pertinent microbial targets (mono/poly-microbial, vegetative or spore form) found in complex and nutritious wastewater effluents whilst maintaining a safe eco-toxicity profile for aquatic species. Copyright © 2018 Elsevier B.V. All rights reserved.

Awareness of Emerging Wireless Technologies: Ad-hoc and Personal Area Networks Standards and Emerging Technologies (Sensibilisation a l’emergence des technologies sans fil: technologies emergeantes et normes de reseaux personnels et ad-hoc)

DTIC Science & Technology

2007-04-01

for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data...Control Organization NRL Navy Research Laboratory nrtPS Non-real- time Polling Services OFDM Orthogonal frequency division multiplex OFDMA...Routeur IDentifier RTG RTO Task Group RTO Research & Technology Organization rtPS Real- time Polling Services SC Single-carrier modulation

Toward Intelligent Autonomous Agents for Cyber Defense: Report of the 2017 Workshop by the North Atlantic Treaty Organization (NATO) Research Group IST-152 RTG

DTIC Science & Technology

2018-04-18

Significant research is currently conducted on dynamic learning and threat detection. However, this work is held back by gaps in validation methods ...and network path rotation (e.g., Stream Splitting MTD). Agents can also employ various cyber-deception methods , including direct observation hiding...ARL-SR-0395 ● APR 2018 US Army Research Laboratory Toward Intelligent Autonomous Agents for Cyber Defense: Report of the 2017

Toward Intelligent Autonomous Agents for Cyber Defense: Report of the 2017 Workshop by the North Atlantic Treaty Organization (NATO) Research Group IST-152-RTG

DTIC Science & Technology

2018-04-01

Significant research is currently conducted on dynamic learning and threat detection. However, this work is held back by gaps in validation methods ...and network path rotation (e.g., Stream Splitting MTD). Agents can also employ various cyber-deception methods , including direct observation hiding...ARL-SR-0395 ● APR 2018 US Army Research Laboratory Toward Intelligent Autonomous Agents for Cyber Defense: Report of the 2017

Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.

PubMed

Swindell, William R; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P; Voorhees, John J; Elder, James T; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P; DiGiovanni, John; Pittelkow, Mark R; Ward, Nicole L; Gudjonsson, Johann E

2011-04-04

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.

Optimizing mouse models of neurodegenerative disorders: are therapeutics in sight?

PubMed

Lutz, Cathleen M; Osborne, Melissa A

2013-01-01

The genomic and biologic conservation between mice and humans, along with our increasing ability to manipulate the mouse genome, places the mouse as a premier model for deciphering disease mechanisms and testing potential new therapies. Despite these advantages, mouse models of neurodegenerative disease are sometimes difficult to generate and can present challenges that must be carefully addressed when used for preclinical studies. For those models that do exist, the standardization and optimization of the models is a critical step in ensuring success in both basic research and preclinical use. This review looks back on the history of model development for neurodegenerative diseases and highlights the key strategies that have been learned in order to improve the design, development and use of mouse models in the study of neurodegenerative disease.

Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

PubMed Central

von Scheidt, Moritz; Zhao, Yuqi; Kurt, Zeyneb; Pan, Calvin; Zeng, Lingyao; Yang, Xia; Schunkert, Heribert; Lusis, Aldons J.

2017-01-01

Most of the biological understanding of mechanisms underlying coronary artery disease (CAD) derives from studies of mouse models. The identification of multiple CAD loci and strong candidate genes in large human genome-wide association studies (GWAS) presented an opportunity to examine the relevance of mouse models for the human disease. We comprehensively reviewed the mouse literature, including 827 literature-derived genes, and compared it to human data. First, we observed striking concordance of risk factors for atherosclerosis in mice and humans. Second, there was highly significant overlap of mouse genes with human genes identified by GWAS. In particular, of the 46 genes with strong association signals in CAD-GWAS that were studied in mouse models all but one exhibited consistent effects on atherosclerosis-related phenotypes. Third, we compared 178 CAD-associated pathways derived from human GWAS with 263 from mouse studies and observed that over 50% were consistent between both species. PMID:27916529

Genetically engineered mouse models for studying inflammatory bowel disease.

PubMed

Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko

2016-01-01

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mouse Tumor Biology (MTB): a database of mouse models for human cancer.

PubMed

Bult, Carol J; Krupke, Debra M; Begley, Dale A; Richardson, Joel E; Neuhauser, Steven B; Sundberg, John P; Eppig, Janan T

2015-01-01

The Mouse Tumor Biology (MTB; http://tumor.informatics.jax.org) database is a unique online compendium of mouse models for human cancer. MTB provides online access to expertly curated information on diverse mouse models for human cancer and interfaces for searching and visualizing data associated with these models. The information in MTB is designed to facilitate the selection of strains for cancer research and is a platform for mining data on tumor development and patterns of metastases. MTB curators acquire data through manual curation of peer-reviewed scientific literature and from direct submissions by researchers. Data in MTB are also obtained from other bioinformatics resources including PathBase, the Gene Expression Omnibus and ArrayExpress. Recent enhancements to MTB improve the association between mouse models and human genes commonly mutated in a variety of cancers as identified in large-scale cancer genomics studies, provide new interfaces for exploring regions of the mouse genome associated with cancer phenotypes and incorporate data and information related to Patient-Derived Xenograft models of human cancers. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

The latest animal models of ovarian cancer for novel drug discovery.

PubMed

Magnotti, Elizabeth; Marasco, Wayne A

2018-03-01

Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer. This article focuses on advances in the development of orthotopic and patient-derived tumor xenograft (PDX) mouse models of ovarian cancer and discusses current humanized mouse models of ovarian cancer. Expert opinion: The authors suggest that humanized mouse models of ovarian cancer will provide new insight into the role of the human immune system in combating and augmenting ovarian cancer and aid in the development of novel therapeutics. Development of humanized mouse models will take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains that are actively being derived.

How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

PubMed Central

Politi, Katerina; Pao, William

2011-01-01

Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review. PMID:21263096

Integrating model behavior, optimization, and sensitivity/uncertainty analysis: overview and application of the MOUSE software toolbox

USDA-ARS?s Scientific Manuscript database

This paper provides an overview of the Model Optimization, Uncertainty, and SEnsitivity Analysis (MOUSE) software application, an open-source, Java-based toolbox of visual and numerical analysis components for the evaluation of environmental models. MOUSE is based on the OPTAS model calibration syst...

The SMILE Soft X-ray Imager (SXI) CCD design and development

NASA Astrophysics Data System (ADS)

Soman, M. R.; Hall, D. J.; Holland, A. D.; Burgon, R.; Buggey, T.; Skottfelt, J.; Sembay, S.; Drumm, P.; Thornhill, J.; Read, A.; Sykes, J.; Walton, D.; Branduardi-Raymont, G.; Kennedy, T.; Raab, W.; Verhoeve, P.; Agnolon, D.; Woffinden, C.

2018-01-01

SMILE, the Solar wind Magnetosphere Ionosphere Link Explorer, is a joint science mission between the European Space Agency and the Chinese Academy of Sciences. The spacecraft will be uniquely equipped to study the interaction between the Earth's magnetosphere-ionosphere system and the solar wind on a global scale. SMILE's instruments will explore this science through imaging of the solar wind charge exchange soft X-ray emission from the dayside magnetosheath, simultaneous imaging of the UV northern aurora and in-situ monitoring of the solar wind and magnetosheath plasma and magnetic field conditions. The Soft X-ray Imager (SXI) is the instrument being designed to observe X-ray photons emitted by the solar wind charge exchange process at photon energies between 200 eV and 2000 eV . X-rays will be collected using a focal plane array of two custom-designed CCDs, each consisting of 18 μm square pixels in a 4510 by 4510 array. SMILE will be placed in a highly elliptical polar orbit, passing in and out of the Earth's radiation belts every 48 hours. Radiation damage accumulated in the CCDs during the mission's nominal 3-year lifetime will degrade their performance (such as through decreases in charge transfer efficiency), negatively impacting the instrument's ability to detect low energy X-rays incident on the regions of the CCD image area furthest from the detector outputs. The design of the SMILE-SXI CCDs is presented here, including features and operating methods for mitigating the effects of radiation damage and expected end of life CCD performance. Measurements with a PLATO device that has not been designed for soft X-ray signal levels indicate a temperature-dependent transfer efficiency performance varying between 5×10-5 and 9×10-4 at expected End of Life for 5.9 keV photons, giving an initial set of measurements from which to extrapolate the performance of the SXI CCDs.

Disrupting the male germ line to find infertility and contraception targets.

PubMed

Archambeault, Denise R; Matzuk, Martin M

2014-05-01

Genetically-manipulated mouse models have become indispensible for broadening our understanding of genes and pathways related to male germ cell development. Until suitable in vitro systems for studying spermatogenesis are perfected, in vivo models will remain the gold standard for inquiry into testicular function. Here, we discuss exciting advances that are allowing researchers faster, easier, and more customizable access to their mouse models of interest. Specifically, the trans-NIH Knockout Mouse Project (KOMP) is working to generate knockout mouse models of every gene in the mouse genome. The related Knockout Mouse Phenotyping Program (KOMP2) is performing systematic phenotypic analysis of this genome-wide collection of knockout mice, including fertility screening. Together, these programs will not only uncover new genes involved in male germ cell development but also provide the research community with the mouse models necessary for further investigations. In addition to KOMP/KOMP2, another promising development in the field of mouse models is the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-Cas technology. Utilizing 20 nucleotide guide sequences, CRISPR/Cas has the potential to introduce sequence-specific insertions, deletions, and point mutations to produce null, conditional, activated, or reporter-tagged alleles. CRISPR/Cas can also successfully target multiple genes in a single experimental step, forgoing the multiple generations of breeding traditionally required to produce mouse models with deletions, insertions, or mutations in multiple genes. In addition, CRISPR/Cas can be used to create mouse models carrying variants identical to those identified in infertile human patients, providing the opportunity to explore the effects of such mutations in an in vivo system. Both the KOMP/KOMP2 projects and the CRISPR/Cas system provide powerful, accessible genetic approaches to the study of male germ cell development in the mouse. A more complete understanding of male germ cell biology is critical for the identification of novel targets for potential non-hormonal contraceptive intervention. Copyright © 2014. Published by Elsevier Masson SAS.

Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

PubMed Central

Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

2011-01-01

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

The Prestige oil spill: a laboratory study about the toxicity of the water-soluble fraction of the fuel oil.

PubMed

Navas, José M; Babín, Mar; Casado, Susana; Fernández, Carlos; Tarazona, José V

2006-07-01

The Prestige oil spill caused severe effects on the coastal fauna and flora due to direct contact of organisms with the fuel oil. However, the water soluble fraction (WSF) of the fuel oil can also provoke deleterious effects in the long term and even in regions not directly affected by the spill. Our objective was to determine the toxicity of the WSF using a battery of laboratory toxicity tests. To obtain a WSF in the laboratory, a sample of the spilled fuel was mixed with adequate medium, sonicated, agitated and filtered. No cytotoxic effects were detected in RTG-2 cells exposed to the WSF. In an algae growth inhibition test (OECD test guideline 201) the WSF did not affect the growth of Chlorella vulgaris. Furthermore, acute and reproductive toxicity tests (OECD test guideline 202) carried out using Daphnia magna did not indicate any deleterious effect of the WSF. In a bioassay designed in our laboratory, D. magna were fed with algae previously exposed to the fuel, but no toxic effects were detected. However, the WSF was able to induce a dose-dependent increase of ethoxyresorufin-O-deethylase activity in RTG-2 cells, indicating the presence of chemicals that could cause sub-lethal effects to organisms. After chemical analyses it was established that the final total quantity of polyaromatic hydrocarbons dissolved in medium was approximately 70 ng/ml. These low concentrations explain the observed lack of toxicity.

Nuclear space power safety and facility guidelines study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehlman, W.F.

1995-09-11

This report addresses safety guidelines for space nuclear reactor power missions and was prepared by The Johns Hopkins University Applied Physics Laboratory (JHU/APL) under a Department of Energy grant, DE-FG01-94NE32180 dated 27 September 1994. This grant was based on a proposal submitted by the JHU/APL in response to an {open_quotes}Invitation for Proposals Designed to Support Federal Agencies and Commercial Interests in Meeting Special Power and Propulsion Needs for Future Space Missions{close_quotes}. The United States has not launched a nuclear reactor since SNAP 10A in April 1965 although many Radioisotope Thermoelectric Generators (RTGs) have been launched. An RTG powered system ismore » planned for launch as part of the Cassini mission to Saturn in 1997. Recently the Ballistic Missile Defense Office (BMDO) sponsored the Nuclear Electric Propulsion Space Test Program (NEPSTP) which was to demonstrate and evaluate the Russian-built TOPAZ II nuclear reactor as a power source in space. As of late 1993 the flight portion of this program was canceled but work to investigate the attributes of the reactor were continued but at a reduced level. While the future of space nuclear power systems is uncertain there are potential space missions which would require space nuclear power systems. The differences between space nuclear power systems and RTG devices are sufficient that safety and facility requirements warrant a review in the context of the unique features of a space nuclear reactor power system.« less

[Effect of topical application of a recombinant adenovirus carrying promyelocytic leukemia gene in a psoriasis-like mouse model].

PubMed

Wang, Qiongyu; Zhang, Aijun; Ma, Huiqun; Wang, Shijie; Ma, Yunyun; Zou, Xingwei; Li, Ruilian

2013-03-01

To investigate the effects of topical treatment with adenovirus-mediated promyelocytic leukemia gene (PML) gene in a psoriasis-like mouse model. The effect of adenovirus-mediated PML gene on the granular layer of mouse tail scale epidermis and epithelial mitosis were observed on longitudinal histological sections prepared from the tail skin and vaginal epithelium of the mice. Adenovirus-mediated PML gene significantly inhibited mitosis of mouse vaginal epithelial cells and promoted the formation of granular layer in mouse tail scale epidermis. The therapeutic effect of PML gene in the psoriasis-like mouse model may be associated with increased granular cells and suppressed epidemic cell proliferation.

Generation of transgenic mouse model using PTTG as an oncogene.

PubMed

Kakar, Sham S; Kakar, Cohin

2015-01-01

The close physiological similarity between the mouse and human has provided tools to understanding the biological function of particular genes in vivo by introduction or deletion of a gene of interest. Using a mouse as a model has provided a wealth of resources, knowledge, and technology, helping scientists to understand the biological functions, translocation, trafficking, and interaction of a candidate gene with other intracellular molecules, transcriptional regulation, posttranslational modification, and discovery of novel signaling pathways for a particular gene. Most importantly, the generation of the mouse model for a specific human disease has provided a powerful tool to understand the etiology of a disease and discovery of novel therapeutics. This chapter describes in detail the step-by-step generation of the transgenic mouse model, which can be helpful in guiding new investigators in developing successful models. For practical purposes, we will describe the generation of a mouse model using pituitary tumor transforming gene (PTTG) as the candidate gene of interest.

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Reevaluating the Potential of Mouse Models for the Human Immune System.

PubMed

Jameson, Stephen C; Masopust, David

2018-04-02

Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans. Alternative approaches are discussed that may extend the use of the mouse model for preclinical studies. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Mouse Models in Bone Marrow Transplantation and Adoptive Cellular Therapy

PubMed Central

Arber, Caroline; Brenner, Malcolm K.; Reddy, Pavan

2014-01-01

Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID:24216170

Centralized mouse repositories.

PubMed

Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

2012-10-01

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

Centralized Mouse Repositories

PubMed Central

Donahue, Leah Rae; de Angelis, Martin Hrabe; Hagn, Michael; Franklin, Craig; Lloyd, K. C. Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T.

2013-01-01

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world. PMID:22945696

Short Pulse Switches for Airborne High Power Supplies

DTIC Science & Technology

1973-10-01

4120 4130 4140 4150 4160 417 0 4180 4190 4195 «00 4ßl0 4620 «25 «30 «35 «38 «40 «50 «60 4480 4500C 4510C 5000 5010 45...IF(NTIM.GE.31)GO TO 66 GO TO 7 132 ***** i»a *i innithriinii ■F»’,»«"»W"II’III1|^-P ■’■I1 "’ "»UIP«». .- 4130 6R KCYC-KCYC*! 4140 IF...flow lato acci»ulator lB3/a«o U3/ sae 1 q1 • Inlet flow to actuator ln J/aac 221 . ri ■rf-iiTiii^aWilifrÜttli Aifctrfi i I w WM

Molecular Indicators of Stress-Induced Neuroinflammation in a Mouse Model Simulating Features of Post-Traumatic Stress Disorder (Open Access)

DTIC Science & Technology

2017-05-23

OPEN ORIGINAL ARTICLE Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post -traumatic stress disorder... post -traumatic stress disorder (PTSD). The model involved exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse for 5...revealed that neurogenesis and synaptic plasticity pathways were activated during the early responses but were inhibited after the later post -trauma

Genetic characterization and improved genotyping of the dysferlin-deficient mouse strain Dysf (tm1Kcam).

PubMed

Wiktorowicz, Tatiana; Kinter, Jochen; Kobuke, Kazuhiro; Campbell, Kevin P; Sinnreich, Michael

2015-01-01

Mouse models of dysferlinopathies are valuable tools with which to investigate the pathomechanisms underlying these diseases and to test novel therapeutic strategies. One such mouse model is the Dysf (tm1Kcam) strain, which was generated using a targeting vector to replace a 12-kb region of the dysferlin gene and which features a progressive muscular dystrophy. A prerequisite for successful animal studies using genetic mouse models is an accurate genotyping protocol. Unfortunately, the lack of robustness of currently available genotyping protocols for the Dysf (tm1Kcam) mouse has prevented efficient colony management. Initial attempts to improve the genotyping protocol based on the published genomic structure failed. These difficulties led us to analyze the targeted locus of the dysferlin gene of the Dysf (tm1Kcam) mouse in greater detail. In this study we resequenced and analyzed the targeted locus of the Dysf (tm1Kcam) mouse and developed a novel PCR protocol for genotyping. We found that instead of a deletion, the dysferlin locus in the Dysf (tm1Kcam) mouse carries a targeted insertion. This genetic characterization enabled us to establish a reliable method for genotyping of the Dysf (tm1Kcam) mouse, and thus has made efficient colony management possible. Our work will make the Dysf (tm1Kcam) mouse model more attractive for animal studies of dysferlinopathies.

Mouse models of neurodegenerative diseases: criteria and general methodology.

PubMed

Janus, Christopher; Welzl, Hans

2010-01-01

The major symptom of Alzheimer's disease is rapidly progressing dementia, coinciding with the formation of amyloid and tau deposits in the central nervous system, and neuronal death. At present familial cases of dementias provide the most promising foundation for modelling neurodegeneration. We describe the mnemonic and other major behavioral symptoms of tauopathies, briefly outline the genetics underlying familiar cases and discuss the arising implications for modelling the disease in mostly transgenic mouse lines. We then depict to what degree the most recent mouse models replicate pathological and cognitive characteristics observed in patients.There is no universally valid behavioral test battery to evaluate mouse models. The selection of individual tests depends on the behavioral and/or memory system in focus, the type of a model and how well it replicates the pathology of a disease and the amount of control over the genetic background of the mouse model. However it is possible to provide guidelines and criteria for modelling the neurodegeneration, setting up the experiments and choosing relevant tests. One should not adopt a "one (trans)gene, one disease" interpretation, but should try to understand how the mouse genome copes with the protein expression of the transgene in question. Further, it is not possible to recommend some mouse models over others since each model is valuable within its own constraints, and the way experiments are performed often reflects the idiosyncratic reality of specific laboratories. Our purpose is to improve bridging molecular and behavioural approaches in translational research.

Direct comparison of the pharmacodynamics of four antifungal drugs in a mouse model of disseminated candidiasis using microbiological assays of serum drug concentrations.

PubMed

Maki, Katsuyuki; Holmes, Ann R; Watabe, Etsuko; Iguchi, Yumi; Matsumoto, Satoru; Ikeda, Fumiaki; Tawara, Shuichi; Mutoh, Seitaro

2007-01-01

The aim of this study was to compare the pharmacodynamics of the azole antifungal drugs fluconazole, itraconazole and ketoconazole, and the polyene antifungal amphotericin B, in a mouse model of disseminated Candida albicans infection. In order to directly compare effective serum concentrations of these antifungals, drug concentrations were assayed microbiologically by measuring inhibition of C. albicans mycelial growth (mMIC) in a mouse serum-based assay (serum antifungal titer). Efficacy in the mouse infection model was determined using an organ-based (kidney burden) endpoint. For all four drugs, the serum antifungal titers, 8 hr after administration of single doses of drugs at a range of drug concentrations, correlated closely with C. albicans kidney fungal burden in the mouse model. The results showed that determining serum antifungal titer may be used to accurately represent kidney fungal burden in a mouse model of disseminated candidiasis and allowed direct comparison of the pharmacodynamics of differing classes of antifungal drugs.

Mouse Models as Tools to Identify Genetic Pathways for Retinal Degeneration, as Exemplified by Leber's Congenital Amaurosis.

PubMed

Chang, Bo

2016-01-01

Leber's congenital amaurosis (LCA) is an inherited retinal degenerative disease characterized by severe loss of vision in the first year of life. In addition to early vision loss, a variety of other eye-related abnormalities including roving eye movements, deep-set eyes, and sensitivity to bright light also occur with this disease. Many animal models of LCA are available and the study them has led to a better understanding of the pathology of the disease, and has led to the development of therapeutic strategies aimed at curing or slowing down LCA. Mouse models, with their well-developed genetics and similarity to human physiology and anatomy, serve as powerful tools with which to investigate the etiology of human LCA. Such mice provide reproducible, experimental systems for elucidating pathways of normal development, function, designing strategies and testing compounds for translational research and gene-based therapies aimed at delaying the diseases progression. In this chapter, I describe tools used in the discovery and evaluation of mouse models of LCA including a Phoenix Image-Guided Optical Coherence Tomography (OCT) and a Diagnosys Espion Visual Electrophysiology System. Three mouse models are described, the rd3 mouse model for LCA12 and LCA1, the rd12 mouse model for LCA2, and the rd16 mouse model for LCA10.

Differences in Pathogenesis for Salmonella enterica serovar Typhimurium in the Mouse Versus the Swine Model Identify Bacterial Gene Products Required for Systemic but not Gastrointestinal Disease

USDA-ARS?s Scientific Manuscript database

Over the last several decades, the mouse model of Typhoid fever has been an extremely productive model to investigate Salmonella enterica serovar Typhimurium pathogenesis. The mouse is the paradigm for investigating systemic disease due to infection by Salmonella; however, the swine model of gastro...

[Compression fracture of a fragile lumbar vertebrae as a cause of low back pain].

PubMed

Ostojić, Zdenko; Ostojić, Ljerka; Pehar, Zoran; Ceramida, Meliha; Letica, Ludvih

2002-01-01

The patient felt sharp back lumbal pain while lifting heavy object in flexion position of the back. Rtg showed compressive fracture of L2. MRI showed secondary posttraumatic edema around compressive fracture of the body of L2. The compressive fracture was caused by intracorporal haemangiome of L2. After six months we had spontaneous sanation of heamgiome. Regarding to the therapy only electromagnetotherapy was used as well as programme of kinezitherapy given according to the condition of the body of L2.

The Science Behind 'The Martian' - Staying Warm on Mars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wham, Bob; Ulrich, George

Set in the not-too-distant future, “The Martian” is the story of an astronaut stranded on Mars who has to rely on his own wit and ingenuity to survive the planet’s hostile conditions. If Mark Watney’s mission were real, Oak Ridge National Laboratory would be playing a vital role in his survival, as it would be the sole source of the Plutonium-238 needed for the RTG, as well as the fuel’s containment material in the form of iridium clad vent sets.

A unified model of the excitability of mouse sensory and motor axons.

PubMed

Makker, Preet G S; Matamala, José Manuel; Park, Susanna B; Lees, Justin G; Kiernan, Matthew C; Burke, David; Moalem-Taylor, Gila; Howells, James

2018-06-19

Non-invasive nerve excitability techniques have provided valuable insight into the understanding of neurological disorders. The widespread use of mice in translational research on peripheral nerve disorders and by pharmaceutical companies during drug development requires valid and reliable models that can be compared to humans. This study established a novel experimental protocol that enables comparative assessment of the excitability properties of motor and sensory axons at the same site in mouse caudal nerve, compared the mouse data to data for motor and sensory axons in human median nerve at the wrist, and constructed a mathematical model of the excitability of mouse axons. In a separate study, ischaemia was employed as an experimental manoeuvre to test the translational utility of this preparation. The patterns of mouse sensory and motor excitability were qualitatively similar to human studies under normal and ischaemic conditions. The most conspicuous differences between mouse and human studies were observed in the recovery cycle and the response to hyperpolarization. Modelling showed that an increase in temperature in mouse axons could account for most of the differences in the recovery cycle. The modelling also suggested a larger hyperpolarization-activated conductance in mouse axons. The kinetics of this conductance appeared to be much slower raising the possibility that an additional or different hyperpolarization-activated cyclic-nucleotide gated (HCN) channel isoform underlies the accommodation to hyperpolarization in mouse axons. Given a possible difference in HCN isoforms, caution should be exercised in extrapolating from studies of mouse motor and sensory axons to human nerve disorders. This article is protected by copyright. All rights reserved.

Rapamycin improves sociability in the BTBR T(+)Itpr3(tf)/J mouse model of autism spectrum disorders.

PubMed

Burket, Jessica A; Benson, Andrew D; Tang, Amy H; Deutsch, Stephen I

2014-01-01

Overactivation of the mammalian target of rapamycin (mTOR) has been implicated in the pathogenesis of syndromic forms of autism spectrum disorders (ASDs), such as tuberous sclerosis complex, neurofibromatosis 1, and fragile X syndrome. Administration of mTORC1 (mTOR complex 1) inhibitors (e.g. rapamycin) in syndromic mouse models of ASDs improved behavior, cognition, and neuropathology. However, since only a minority of ASDs are due to the effects of single genes (∼10%), there is a need to explore inhibition of mTOR activity in mouse models that may be more relevant to the majority of nonsyndromic presentations, such as the genetically inbred BTBR T(+)Itpr3(tf)/J (BTBR) mouse model of ASDs. BTBR mice have social impairment and exhibit increased stereotypic behavior. In prior work, d-cycloserine, a partial glycineB site agonist that targets the N-methyl-d-aspartate (NMDA) receptor, was shown to improve sociability in both Balb/c and BTBR mouse models of ASDs. Importantly, NMDA receptor activation regulates mTOR signaling activity. The current study investigated the ability of rapamycin (10mg/kg, i.p.×four days), an mTORC1 inhibitor, to improve sociability and stereotypic behavior in BTBR mice. Using a standard paradigm to assess mouse social behavior, rapamycin improved several measures of sociability in the BTBR mouse, suggesting that mTOR overactivation represents a therapeutic target that mediates or contributes to impaired sociability in the BTBR mouse model of ASDs. Interestingly, there was no effect of rapamycin on stereotypic behaviors in this mouse model. Copyright © 2013 Elsevier Inc. All rights reserved.

In Vivo Hyperthermic Stress Model: An Easy Tool to Study the Effects of Oxidative Stress on Neuronal Tau Functionality in Mouse Brain.

PubMed

Chauderlier, Alban; Delattre, Lucie; Buée, Luc; Galas, Marie-Christine

2017-01-01

Oxidative damage is an early event in neurodegenerative disorders such as Alzheimer disease. To increase oxidative stress in AD-related mouse models is essential to study early mechanisms involved in the physiopathology of these diseases. In this chapter, we describe an experimental mouse model of transient and acute hyperthermic stress to induce in vivo an increase of oxidative stress in the brain of any kind of wild-type or transgenic mouse.

Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor.

PubMed

Panda, Dibyendu Kumar; Goltzman, David; Karaplis, Andrew C

2012-12-15

The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and β-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition.

Quantitative Comparison of Dense-Core Amyloid Plaque Accumulation in Amyloid-β Protein Precursor Transgenic Mice.

PubMed

Liu, Peng; Reichl, John H; Rao, Eshaan R; McNellis, Brittany M; Huang, Eric S; Hemmy, Laura S; Forster, Colleen L; Kuskowski, Michael A; Borchelt, David R; Vassar, Robert; Ashe, Karen H; Zahs, Kathleen R

2017-01-01

There exist several dozen lines of transgenic mice that express human amyloid-β protein precursor (AβPP) with Alzheimer's disease (AD)-linked mutations. AβPP transgenic mouse lines differ in the types and amounts of Aβ that they generate and in their spatiotemporal patterns of expression of Aβ assemblies, providing a toolkit to study Aβ amyloidosis and the influence of Aβ aggregation on brain function. More complete quantitative descriptions of the types of Aβ assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how Aβ toxicity in mice relates to the pathogenesis of AD. Here, we provide a direct quantitative comparison of amyloid plaque burdens and plaque sizes in four lines of AβPP transgenic mice. We measured the fraction of cortex and hippocampus occupied by dense-core plaques, visualized by staining with Thioflavin S, in mice from young adulthood through advanced age. We found that the plaque burdens among the transgenic lines varied by an order of magnitude: at 15 months of age, the oldest age studied, the median cortical plaque burden in 5XFAD mice was already ∼4.5 times that of 21-month-old Tg2576 mice and ∼15 times that of 21-24-month-old rTg9191 mice. Plaque-size distributions changed across the lifespan in a line- and region-dependent manner. We also compared the dense-core plaque burdens in the mice to those measured in a set of pathologically-confirmed AD cases from the Nun Study. Cortical plaque burdens in Tg2576, APPSwePS1ΔE9, and 5XFAD mice eventually far exceeded those measured in the human cohort.

Quantitative Comparison of Dense-Core Amyloid Plaque Accumulation in Amyloid-β Precursor Protein Transgenic Mice

PubMed Central

Liu, Peng; Reichl, John H.; Rao, Eshaan R.; McNellis, Brittany M.; Huang, Eric S.; Hemmy, Laura S.; Forster, Colleen L.; Kuskowski, Michael A.; Borchelt, David R.; Vassar, Robert; Ashe, Karen H.; Zahs, Kathleen R.

2016-01-01

There exist several dozen lines of transgenic mice that express human amyloid-β precursor protein (AβPP) with Alzheimer’s disease (AD)-linked mutations. AβPP transgenic mouse lines differ in the types and amounts of Aβ that they generate and in their spatiotemporal patterns of expression of Aβ assemblies, providing a toolkit to study Aβ amyloidosis and the influence of Aβ aggregation on brain function. More complete quantitative descriptions of the types of Aβ assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how Aβ toxicity in mice relates to the pathogenesis of AD. Here, we provide a direct quantitative comparison of amyloid plaque burdens and plaque sizes in four lines of AβPP transgenic mice. We measured the fraction of cortex and hippocampus occupied by dense-core plaques, visualized by staining with Thioflavin S, in mice from young adulthood through advanced age. We found that the plaque burdens among the transgenic lines varied by an order of magnitude: at 15 months of age, the oldest age studied, the median cortical plaque burden in 5XFAD mice was already ~4.5 times that of 21-month Tg2576 mice and ~15 times that of 21–24-month rTg9191 mice. Plaque-size distributions changed across the lifespan in a line- and region-dependent manner. We also compared the dense-core plaque burdens in the mice to those measured in a set of pathologically-confirmed AD cases from the Nun Study. Cortical plaque burdens in Tg2576, APPSwePS1ΔE9, and 5XFAD mice eventually far exceeded those measured in the human cohort. PMID:28059792

Implementation of a manual for working with wobbler mice and criteria for discontinuation of the experiment.

PubMed

Ott, Bastian; Dahlke, Carolin; Meller, Karl; Napirei, Markus; Schmitt-John, Thomas; Brand-Saberi, Beate; Theiss, Carsten; Saberi, Darius

2015-07-01

Mouse breeding is of importance to a whole range of medical and biological research. There are many known mouse models for motor neuron diseases. However, it must be kept in mind that especially mouse models for amyotrophic lateral sclerosis develop severe symptoms causing intense stress. This article is designed to summarize conscientious work with the wobbler mouse, a model for the sporadic form of amyotrophic lateral sclerosis. This mouse model is characterized by a degeneration of α-motor-neurons leading to head tremor, loss of body weight and rapidly progressive paralysis. Although this mouse model has been known since 1956, there are no guidelines for breeding wobbler mice. Due to the lack of such guidelines the present study tries to close this gap and implements a manual for further studies. It includes the whole workflow in regard to wobbler mice from breeding and animal care taking, genotyping and phenotype analysis, but also gives some examples for the use of various neuronal tissues for histological investigation. Beside the progress in research a second aim should always be the enhancement of mouse welfare and reduction of stress for the laboratory animals. Copyright © 2015 Elsevier GmbH. All rights reserved.

Rational Design of Mouse Models for Cancer Research.

PubMed

Landgraf, Marietta; McGovern, Jacqui A; Friedl, Peter; Hutmacher, Dietmar W

2018-03-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models. Nevertheless, most preclinical studies in mice suffer from insufficient predictive value when compared with cancer biology and therapy response of human patients. We propose an innovative strategy to improve the predictive power of preclinical cancer models. Combining (i) genomic, tissue engineering and regenerative medicine approaches for rational design of mouse models with (ii) rapid prototyping and computational benchmarking against human clinical data will enable fast and nonbiased validation of newly generated models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Review of DoD Malaria Research Programs,

DTIC Science & Technology

1992-05-01

the irraliated sporozoite vaccine. Work in the mouse model system and then extrapolate to human malarias. Study naturally acquired immune ...recombinant vaccines. Work simultaneously in the mouse model system and with human malarias. 3. Identify targets and mechanisms of protective immunity not...multivalent vaccines that attack these same targets. 3. Working again in the mouse model, non- human primate model, andI human systems we

Animal models for prenatal gene therapy: rodent models for prenatal gene therapy.

PubMed

Roybal, Jessica L; Endo, Masayuki; Buckley, Suzanne M K; Herbert, Bronwen R; Waddington, Simon N; Flake, Alan W

2012-01-01

Fetal gene transfer has been studied in various animal models, including rabbits, guinea pigs, cats, dogs, and nonhuman primate; however, the most common model is the rodent, particularly the mouse. There are numerous advantages to mouse models, including a short gestation time of around 20 days, large litter size usually of more than six pups, ease of colony maintenance due to the small physical size, and the relatively low expense of doing so. Moreover, the mouse genome is well defined, there are many transgenic models particularly of human monogenetic disorders, and mouse-specific biological reagents are readily available. One criticism has been that it is difficult to perform procedures on the fetal mouse with suitable accuracy. Over the past decade, accumulation of technical expertise and development of technology such as high-frequency ultrasound have permitted accurate vector delivery to organs and tissues. Here, we describe our experiences of gene transfer to the fetal mouse with and without ultrasound guidance from mid to late gestation. Depending upon the vector type, the route of delivery and the age of the fetus, specific or widespread gene transfer can be achieved, making fetal mice excellent models for exploratory biodistribution studies.

Treatment of d-galactose induced mouse aging with Lycium barbarum polysaccharides and its mechanism study.

PubMed

Tang, Tao; He, Bixiu

2013-01-01

We evaluated the effects of Lycium barbarum polysaccharides LBP) on D-galactose aging model mouse, and explored its possible mechanism. Kunming mice were randomly divided into the control group, the model group, the high-dose LBP group, and the low-dose LBP group. Except the control group, D-galactose was used for modelling. The drug was administrated when modelling. Mouse behavioural, learning and memory changes were observed, and the contents of lipid peroxidation (LPO), lipofuscin (LF) and monoamine oxidase B (MAO-B) in mouse brain tissue and the weight of immune organs were measured after 6 weeks. Compared with the control group, mouse weight gain in the model group reduced significantly. Compared with model group, after mice drank LBP, the times of electric shock was less than aging mice (in which, the high-dose LBP group, P<0.05), and electric shock incubation period was longer (P<0.01). On Day 45 after modelling and drug administration, the contents of LPO, LF and MAO-B in mouse brain tissue in the model group increased significantly, while those in the drug administration groups decreased significantly. The thymus index in the aging model group decreased significantly; the thymus index and the spleen index in the high-dose LBP group and the low-dose LBP group rebounded significantly (P<0.01). We concluded that LBP has an anti-aging effect on D-galactose induced aging model mouse, and its mechanism may be related with the alleviation of glucose metabolism disorder and the resistance of the generation of lipid peroxide and other substances, which damage cell membrane lipid.

Mutagenicity testing with transgenic mice. Part II: Comparison with the mouse spot test

PubMed Central

Wahnschaffe, Ulrich; Bitsch, Annette; Kielhorn, Janet; Mangelsdorf, Inge

2005-01-01

The mouse spot test, an in vivo mutation assay, has been used to assess a number of chemicals. It is at present the only in vivo mammalian test system capable of detecting somatic gene mutations according to OECD guidelines (OECD guideline 484). It is however rather insensitive, animal consuming and expensive type of test. More recently several assays using transgenic animals have been developed. From data in the literature, the present study compares the results of in vivo testing of over twenty chemicals using the mouse spot test and compares them with results from the two transgenic mouse models with the best data base available, the lacI model (commercially available as the Big Blue® mouse), and the lacZ model (commercially available as the Muta™ Mouse). There was agreement in the results from the majority of substances. No differences were found in the predictability of the transgenic animal assays and the mouse spot test for carcinogenicity. However, from the limited data available, it seems that the transgenic mouse assay has several advantages over the mouse spot test and may be a suitable test system replacing the mouse spot test for detection of gene but not chromosome mutations in vivo. PMID:15676065

The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

PubMed

Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

2015-01-01

The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology

PubMed Central

Martinez‐Barbera, Juan Pedro

2017-01-01

Abstract Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ‐specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. PMID:28414891

Mouse neuroblastoma cell based model and the effect of epileptic events on calcium oscillations and neural spikes

NASA Astrophysics Data System (ADS)

Kim, Suhwan; Baek, Juyeong; Jung, Unsang; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-05-01

Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

Characterization of Pu-238 heat source granule containment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson Ii, P D; Thronas, D L; Romero, J P

2008-01-01

The Milliwatt Radioisotopic Thermoelectric Generator (RTG) provides power for permissive-action links. These nuclear batteries convert thermal energy to electrical energy using a doped silicon-germanium thermopile. The thermal energy is provided by a heat source made of {sup 238}Pu, in the form of {sup 238}PuO{sub 2} granules. The granules are contained in 3 layers of encapsulation. A thin T-111 liner surrounds the {sup 238}PuO{sub 2} granules and protects the second layer (strength member) from exposure to the fuel granules. The T-111 strength member contains the fuel under impact condition. An outer clad of Hastelloy-C protects the T-111 from oxygen embrittlement. Themore » T-111 strength member is considered the critical component in this {sup 238}PuO{sub 2} containment system. Any compromise in the strength member is something that needs to be characterized. Consequently, the T-111 strength member is characterized upon it's decommissioning through Scanning Electron Microscopy (SEM), and Metallography. SEM is used in Secondary Electron mode to reveal possible grain boundary deformation and/or cracking in the region of the strength member weld. Deformation and cracking uncovered by SEM are further characterized by Metallography. Metallography sections are mounted and polished, observed using optical microscopy, then documented in the form of photomicrographs. SEM may further be used to examine polished Metallography mounts to characterize elements using the SEM mode of Energy Dispersive X-ray Spectroscopy (EDS). This paper describes the characterization of the metallurgical condition of decommissioned RTG heat sources.« less

Individualized supervised resistance training during nebulization in adults with cystic fibrosis.

PubMed

Shaw, Ina; Kinsey, Janine E; Richards, Roxanne; Shaw, Brandon S

2016-01-01

Since dyspnea limits exercise adherence and intensity in cystic fibrosis (CF) patients, engaging in resistance training (RT), which causes less dyspnea than other exercise modalities, while using nebulizers could not only overcome this barrier, but also enhance long-term adaptations to treatment. The objective of this study was to examine the effects of RT during nebulization on spirometry, anthropometry, chest wall excursion, respiratory muscle strength and health-related quality of life (HRQOL). Fourteen male and female CF patients were assigned to a four-week, 20-minute, 5-day per week proof-of-concept RT group (RTG) (n=7) or non-exercising control group (CON) (n=7), with 3 CON patients later dropping out of the study. Patients performed whole body exercises for 3 sets of 10 reps using resistance bands, since such bands have previously demonstrated a greater effect on functional exercise capacity than conventional RT in lung patients. The RTG displayed significant (p≤0.05) increases in FEV 1 , FEV 1 /FVC, latissimusdorsi strength, pectoralis major clavicular portion strength, pectoralis major sternocostal portion strength and emotional and digestion HRQOL domains, while decreasing pectoralis minor strength on the left and social, body image and respiration HRQOL domains. This small scale proof-of-concept investigation demonstrates the multiple and simultaneous benefits of RT during nebulization in CF patients. The improvements in pulmonary measures are particularly promising especially since this study only made use of a four-week experimental period. This study provides an important alternative, time-saving treatment for the CF patient that does not add to the treatment burden of CF patients.

Effects of two programs of exercise on body composition of adolescents with Down syndrome

PubMed Central

Seron, Bruna Barboza; Silva, Renan Alvarenga C.; Greguol, Márcia

2014-01-01

Objective: To investigate the effects of a 12 week aerobic and resistance exercise on body composition of adolescents with Down syndrome. Methods: A quasi-experimental study with 41 adolescents with Down syndrome, aged 15.5±2.7 years, divided into three groups: Aerobic Training Group (ATG; n=16), Resisted Training Group (RTG; n=15) and Control Group (CG; n=10). There were two types of training: aerobic, with intensity of 50-70% of the heart rate reserve 3 times/week, and resisted, with intensity of 12 maximum repetitions 2 times week. Both trainings were applied during a 12-week period. The percentage of fat evaluation was performed using plethysmography with Bod Pod(r) equipment. Waist circumference (WC), body weight and height were also measured. Paired t-test was used to compare variables before and after the exercise program. Results: The percentage of body fat did not change significantly for both groups that participated in the training intervention. However, CG showed a significant increase in this variable (31.3±7.2 versus 34.0±7.9). On the other hand, body mass index (BMI) and WC were significantly reduced for ATG (BMI: 27.0±4.4 and 26.5±4.2; WC: 87.3±11.1 and 86.2±9.7), while RTG and GC showed no differences in these variables. Conclusions: The aerobic and resisted training programs maintained body fat levels. ATG significantly reduced BMI and WC measures. Individuals who did not attend the training intervention increased their percentage of fat. PMID:24676196

Dynamics of circulating gamma delta T cell activity in an immunocompetent mouse model of high-grade glioma

USDA-ARS?s Scientific Manuscript database

Human gamma delta T cells are potent effectors against glioma cell lines in vitro and in human/mouse xenograft models of glioblastoma, however, this effect has not been investigated in an immunocompetent mouse model. In this report, we established GL261 intracranial gliomas in syngeneic WT C57BL/6 m...

Lack of species-specific difference in pulmonary function when using mouse versus human plasma in a mouse model of hemorrhagic shock.

PubMed

Peng, Zhanglong; Pati, Shibani; Fontaine, Magali J; Hall, Kelly; Herrera, Anthony V; Kozar, Rosemary A

2016-11-01

Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared with lactated Ringer's solution. As our long-term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy. Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure (MAP) of 35 ± 5 mm Hg followed by resuscitation at 1× shed blood using either mouse fresh frozen plasma (FFP), human FFP, or human lyophilized plasma. Mean arterial pressure was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were killed, and lungs collected for analysis. There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared with human FFP or human lyophilized plasma. However, despite these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability, or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining; however, myeloperoxidase immunostaining revealed no significant differences in between groups. The study of human plasma in a mouse model of hemorrhagic shock is feasible but does reveal some differences compared with mouse plasma-based resuscitation in physiologic measures such as MAP postresuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic shock and resuscitation.

In vivo quantitative bioluminescence tomography using heterogeneous and homogeneous mouse models.

PubMed

Liu, Junting; Wang, Yabin; Qu, Xiaochao; Li, Xiangsi; Ma, Xiaopeng; Han, Runqiang; Hu, Zhenhua; Chen, Xueli; Sun, Dongdong; Zhang, Rongqing; Chen, Duofang; Chen, Dan; Chen, Xiaoyuan; Liang, Jimin; Cao, Feng; Tian, Jie

2010-06-07

Bioluminescence tomography (BLT) is a new optical molecular imaging modality, which can monitor both physiological and pathological processes by using bioluminescent light-emitting probes in small living animal. Especially, this technology possesses great potential in drug development, early detection, and therapy monitoring in preclinical settings. In the present study, we developed a dual modality BLT prototype system with Micro-computed tomography (MicroCT) registration approach, and improved the quantitative reconstruction algorithm based on adaptive hp finite element method (hp-FEM). Detailed comparisons of source reconstruction between the heterogeneous and homogeneous mouse models were performed. The models include mice with implanted luminescence source and tumor-bearing mice with firefly luciferase report gene. Our data suggest that the reconstruction based on heterogeneous mouse model is more accurate in localization and quantification than the homogeneous mouse model with appropriate optical parameters and that BLT allows super-early tumor detection in vivo based on tomographic reconstruction of heterogeneous mouse model signal.

Of Mice and Men: Comparative Analysis of Neuro-Inflammatory Mechanisms in Human and Mouse Using Cause-and-Effect Models.

PubMed

Kodamullil, Alpha Tom; Iyappan, Anandhi; Karki, Reagon; Madan, Sumit; Younesi, Erfan; Hofmann-Apitius, Martin

2017-01-01

Perturbance in inflammatory pathways have been identified as one of the major factors which leads to neurodegenerative diseases (NDD). Owing to the limited access of human brain tissues and the immense complexity of the brain, animal models, specifically mouse models, play a key role in advancing the NDD field. However, many of these mouse models fail to reproduce the clinical manifestations and end points of the disease. NDD drugs, which passed the efficacy test in mice, were repeatedly not successful in clinical trials. There are numerous studies which are supporting and opposing the applicability of mouse models in neuroinflammation and NDD. In this paper, we assessed to what extend a mouse can mimic the cellular and molecular interactions in humans at a mechanism level. Based on our mechanistic modeling approach, we investigate the failure of a neuroinflammation targeted drug in the late phases of clinical trials based on the comparative analyses between the two species.

NCI Mouse Repository | FNLCR Staging

Cancer.gov

The NCI Mouse Repository is an NCI-funded resource for mouse cancer models and associated strains. The repository makes strains available to all members of the scientific community (academic, non-profit, and commercial). NCI Mouse Repository strains

An extended Kalman filter for mouse tracking.

PubMed

Choi, Hongjun; Kim, Mingi; Lee, Onseok

2018-05-19

Animal tracking is an important tool for observing behavior, which is useful in various research areas. Animal specimens can be tracked using dynamic models and observation models that require several types of data. Tracking mouse has several barriers due to the physical characteristics of the mouse, their unpredictable movement, and cluttered environments. Therefore, we propose a reliable method that uses a detection stage and a tracking stage to successfully track mouse. The detection stage detects the surface area of the mouse skin, and the tracking stage implements an extended Kalman filter to estimate the state variables of a nonlinear model. The changes in the overall shape of the mouse are tracked using an oval-shaped tracking model to estimate the parameters for the ellipse. An experiment is conducted to demonstrate the performance of the proposed tracking algorithm using six video images showing various types of movement, and the ground truth values for synthetic images are compared to the values generated by the tracking algorithm. A conventional manual tracking method is also applied to compare across eight experimenters. Furthermore, the effectiveness of the proposed tracking method is also demonstrated by applying the tracking algorithm with actual images of mouse. Graphical abstract.

TEMPORAL EVOLUTION OF THE VELA PULSAR’S PULSE PROFILE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palfreyman, J. L.; Dickey, J. M.; Ellingsen, S. P.

The mechanisms of emission and changes in rotation frequency (“glitching”) of the Vela pulsar (J0835−4510) are not well understood. Further insight into these mechanisms can be achieved by long-term studies of integrated pulse width, timing residuals, and bright-pulse rates. We have undertaken an intensive observing campaign of Vela and collected over 6000 hr of single-pulse data. The data shows that the pulse width changes with time, including marked jumps in width after micro-glitches (frequency changes). The abundance of bright pulses also changes after some micro-glitches, but not all. The secular changes in pulse width have three possible cyclic periods thatmore » match with X-ray periodicities of a helical jet that are interpreted as free precession.« less

Terrestrial and marine records of climatic and environmental changes during the Pliocene in subtropical Florida

USGS Publications Warehouse

Willard, D.A.; Cronin, T. M.; Ishman, S.E.; Litwin, R.J.

1993-01-01

Pollen, ostracode, and benthic foraminifer assemblages deposited during sea-level highstands in subtropical Florida record a climate change during the period 4.5-1.0 Ma. Before 3.5 Ma, open-shelf marine faunas and pollen assemblages with abundant Pinus, Quercus, Fagus, Carya, and nonarboreal pollen were present, indicating cooler conditions than today. From ~3.5 to 1.0 Ma, marine and terrestrial records indicate warmer conditions, similar to those existing in south Florida today. Combined with evidence for much warmer than modern conditions at high latitudes, these data suggest that increased poleward oceanic heat transport, possibly related to the emergence of the Central American isthmus between ~3.5 and 2.5 Ma, was a major influence on mid-Pliocene warmth. -Authors

A Ti-V-based bcc phase alloy for use as metal hydride electrode with high discharge capacity

NASA Astrophysics Data System (ADS)

Yu, X. B.; Wu, Z.; Xia, B. J.; Xu, N. X.

2004-07-01

The electrochemical characteristics of single bcc phase Ti-30V-15Cr-15Mn alloy were investigated. It was demonstrated that the single bcc phase alloy has high electrochemical discharge performance at high temperature. Its discharge capacity is closely related with temperature and discharge current. The first discharge capacities of 580-814 mAh g-1 of the alloy powder were obtained at discharge current of 45-10 mA g-1 in 6 M KOH solution at 353 K. Although the electrochemical cycle life of the alloy is unsatisfactory at present, it opens up prospects for developing a new hydrogen storage alloy with high hydrogen capacity for use as high performance metal hydride electrodes in rechargeable Ni-MH battery.

A Ti-V-based bcc phase alloy for use as metal hydride electrode with high discharge capacity.

PubMed

Yu, X B; Wu, Z; Xia, B J; Xu, N X

2004-07-08

The electrochemical characteristics of single bcc phase Ti-30V-15Cr-15Mn alloy were investigated. It was demonstrated that the single bcc phase alloy has high electrochemical discharge performance at high temperature. Its discharge capacity is closely related with temperature and discharge current. The first discharge capacities of 580-814 mAh g(-1) of the alloy powder were obtained at discharge current of 45-10 mA g(-1) in 6 M KOH solution at 353 K. Although the electrochemical cycle life of the alloy is unsatisfactory at present, it opens up prospects for developing a new hydrogen storage alloy with high hydrogen capacity for use as high performance metal hydride electrodes in rechargeable Ni-MH battery.

Mouse Models for Down Syndrome-Associated Developmental Cognitive Disabilities

PubMed Central

Liu, Chunhong; Belichenko, Pavel V.; Zhang, Li; Fu, Dawei; Kleschevnikov, Alexander M.; Baldini, Antonio; Antonarakis, Stylianos E.; Mobley, William C.; Yu, Y. Eugene

2011-01-01

Down syndrome (DS) is mainly caused by the presence of an extra copy of human chromosome 21 (Hsa21) and is a leading genetic cause for developmental cognitive disabilities in humans. The mouse is a premier model organism for DS because the regions on Hsa21 are syntenically conserved with three regions in the mouse genome, which are located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. With the advance of chromosomal manipulation technologies, new mouse mutants have been generated to mimic DS at both the genotypic and phenotypic levels. Further mouse-based molecular genetic studies in the future may lead to the unraveling of the mechanisms underlying DS-associated developmental cognitive disabilities, which would lay the groundwork for developing effective treatments for this phenotypic manifestation. In this review, we will discuss recent progress and future challenges in modeling DS-associated developmental cognitive disability in mice with an emphasis on hippocampus-related phenotypes. PMID:21865664

Methods in Molecular Biology Mouse Genetics: Methods and Protocols | Center for Cancer Research

Cancer.gov

Mouse Genetics: Methods and Protocols provides selected mouse genetic techniques and their application in modeling varieties of human diseases. The chapters are mainly focused on the generation of different transgenic mice to accomplish the manipulation of genes of interest, tracing cell lineages, and modeling human diseases.

Use of mouse models to study the mechanisms and consequences of RBC clearance

PubMed Central

Hod, E. A.; Arinsburg, S. A.; Francis, R. O.; Hendrickson, J. E.; Zimring, J. C.; Spitalnik, S. L.

2013-01-01

Mice provide tractable animal models for studying the pathophysiology of various human disorders. This review discusses the use of mouse models for understanding red-blood-cell (RBC) clearance. These models provide important insights into the pathophysiology of various clinically relevant entities, such as autoimmune haemolytic anaemia, haemolytic transfusion reactions, other complications of RBC transfusions and immunomodulation by Rh immune globulin therapy. Mouse models of both antibody- and non-antibody-mediated RBC clearance are reviewed. Approaches for exploring unanswered questions in transfusion medicine using these models are also discussed. PMID:20345515

Generation Of A Mouse Model For Schwannomatosis

DTIC Science & Technology

2010-09-01

TITLE: Generation of a Mouse Model for Schwannomatosis PRINCIPAL INVESTIGATOR: Long-Sheng Chang, Ph.D. CONTRACTING ORGANIZATION: The...Annual 3. DATES COVERED (From - To) 1 Sep 2009 - 31 Aug 2010 4. TITLE AND SUBTITLE Generation of a Mouse Model for Schwannomatosis 5a. CONTRACT...hypothesis involving inactivation of both the INI1/SNF5 and NF2 tumor suppressor genes in the formation of schwannomatosis -associated tumors. To

Mouse Genome Database: From sequence to phenotypes and disease models

PubMed Central

Richardson, Joel E.; Kadin, James A.; Smith, Cynthia L.; Blake, Judith A.; Bult, Carol J.

2015-01-01

Summary The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here, we describe the data acquisition process, specifics about MGD's key data areas, methods to access and query MGD data, and outreach and user help facilities. genesis 53:458–473, 2015. © 2015 The Authors. Genesis Published by Wiley Periodicals, Inc. PMID:26150326

Establishing a laboratory animal model from a transgenic animal: RasH2 mice as a model for carcinogenicity studies in regulatory science.

PubMed

Urano, K; Tamaoki, N; Nomura, T

2012-01-01

Transgenic animal models have been used in small numbers in gene function studies in vivo for a period of time, but more recently, the use of a single transgenic animal model has been approved as a second species, 6-month alternative (to the routine 2-year, 2-animal model) used in short-term carcinogenicity studies for generating regulatory application data of new drugs. This article addresses many of the issues associated with the creation and use of one of these transgenic models, the rasH2 mouse, for regulatory science. The discussion includes strategies for mass producing mice with the same stable phenotype, including constructing the transgene, choosing a founder mouse, and controlling both the transgene and background genes; strategies for developing the model for regulatory science, including measurements of carcinogen susceptibility, stability of a large-scale production system, and monitoring for uniform carcinogenicity responses; and finally, efficient use of the transgenic animal model on study. Approximately 20% of mouse carcinogenicity studies for new drug applications in the United States currently use transgenic models, typically the rasH2 mouse. The rasH2 mouse could contribute to animal welfare by reducing the numbers of animals used as well as reducing the cost of carcinogenicity studies. A better understanding of the advantages and disadvantages of the transgenic rasH2 mouse will result in greater and more efficient use of this animal model in the future.

NCI Mouse Repository | Frederick National Laboratory for Cancer Research

Cancer.gov

The NCI Mouse Repository is an NCI-funded resource for mouse cancer models and associated strains. The repository makes strains available to all members of the scientific community (academic, non-profit, and commercial). NCI Mouse Repository strains

Therapeutic effects of autologous lymphocytes activated with trastuzumab for xenograft mouse models of human breast cancer.

PubMed

Nakagawa, Shinichiro; Matsuoka, Yusuke; Ichihara, Hideaki; Yoshida, Hitoji; Yoshida, Kenshi; Ueoka, Ryuichi

2013-01-01

Trastuzumab (TTZ) is molecular targeted drug used for metastatic breast cancer patients overexpressing human epidermal growth factor receptor 2 (HER2). Therapeutic effects of lymphocytes activated with TTZ (TTZ-LAK) using xenograft mouse models of human breast cancer (MDA-MB-453) cells were examined in vivo. Remarkable reduction of tumor volume in a xenograft mouse models intravenously treated with TTZ-LAK cells after the subcutaneously inoculated of MDA-MB-453 cells was verified in vivo. The migration of TTZ-LAK cells in tumor of mouse models subcutaneously inoculated MDA-MB-453 cells was observed on the basis of histological analysis using immunostaining with CD-3. Induction of apoptosis in tumor of xenograft mice treated with TTZ-LAK cells was observed in micrographs using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. It was noteworthy that the therapeutic effects of TTZ-LAK cells along with apoptosis were obtained for xenograft mouse models of human breast tumor in vivo.

Thermal Analysis of Step 2 GPHS for Next Generation Radioisotope Power Source Missions

NASA Astrophysics Data System (ADS)

Pantano, David R.; Hill, Dennis H.

2005-02-01

The Step 2 General Purpose Heat Source (GPHS) is a slightly larger and more robust version of the heritage GPHS modules flown on previous Radioisotope Thermoelectric Generator (RTG) missions like Galileo, Ulysses, and Cassini. The Step 2 GPHS is to be used in future small radioisotope power sources, such as the Stirling Radioisotope Generator (SRG110) and the Multi-Mission Radioisotope Thermoelectric Generator (MMRTG). New features include an additional central web of Fine Weave Pierced Fabric (FWPF) graphite in the aeroshell between the two Graphite Impact Shells (GIS) to improve accidental reentry and impact survivability and an additional 0.1-inch of thickness to the aeroshell broad faces to improve ablation protection. This paper details the creation of the thermal model using Thermal Desktop and AutoCAD interfaces and provides comparisons of the model to results of previous thermal analysis models of the heritage GPHS. The results of the analysis show an anticipated decrease in total thermal gradient from the aeroshell to the iridium clads compared to the heritage results. In addition, the Step 2 thermal model is investigated under typical SRG110 boundary conditions, with cover gas and gravity environments included where applicable, to provide preliminary guidance for design of the generator. Results show that the temperatures of the components inside the GPHS remain within accepted design limits during all envisioned mission phases.

Disposable Multi-Sensor Unattended Ground Sensor Systems for Detecting Personnel (Systemes de detection multi-capteurs terrestres autonome destines a detecter du personnel)

DTIC Science & Technology

2015-02-01

du personnel » (SET-158 RTG) identifient et accèdent aux technologies potentielles de détection des personnes, qui améliorent la sécurité par...croissante de systèmes de détection à distance, qui soient robustes et de haute performance afin d’assurer la surveillance et l’acquisition des ...les caméras basse et haute résolution. Dans la seconde phase, des approches de phénoménologie des capteurs et de traitement du

Management of Heat and Cold Stress -- Guidance to NATO Medical Personnel (Gestion des contraintes thermiques (chaleur et froid) Conseils aux personnels medicaux de I’OTAN)

DTIC Science & Technology

2013-12-01

de la performance de leurs troupes; b) d’importants écarts scientifiques / de capacités existent en ce qui concerne la susceptibilité, le... La HFM/RTG-187 avait pour but de : a) comparer et évaluer les ressources techniques qui sont actuellement utilisées pour un « système de gestion des ...d’une doctrine et de programmes d’enseignement intégrés pour la gestion des risques thermiques afin de garantir le maintien

The Science Behind 'The Martian' - Staying Warm on Mars

ScienceCinema

Wham, Bob; Ulrich, George

2018-06-21

Set in the not-too-distant future, “The Martian” is the story of an astronaut stranded on Mars who has to rely on his own wit and ingenuity to survive the planet’s hostile conditions. If Mark Watney’s mission were real, Oak Ridge National Laboratory would be playing a vital role in his survival, as it would be the sole source of the Plutonium-238 needed for the RTG, as well as the fuel’s containment material in the form of iridium clad vent sets.

Design, fabricate, and provide engineering support for radiosotope thermoelectric generators for NASA'S CRHF and CASSINI missions

NASA Astrophysics Data System (ADS)

The technical progress achieved during the period 11 January through 31 March 1991 on Contract DE-AC03-91SF18852.000 Radioisotope Thermoelectric Generators and ancillary activities is described. The system contract consists of the following tasks: (1) Spacecraft Integration and Liaison; (2) Engineering Support; (3) Safety; (4) Qualify Unicouple Fabrication; (5) ETG Fabrication, Assembly and Test; (6) GSE; (7) RTG Shipping and Launch Support; (8) Designs, Reviews, and Mission Applications; (9) Project Management, Quality Assurance and Reliability; and (10) CAGO Acquisition (Capital Funds). The progress achieved is broken down into these tasks.

Generation of a neuro-specific microarray reveals novel differentially expressed noncoding RNAs in mouse models for neurodegenerative diseases.

PubMed

Gstir, Ronald; Schafferer, Simon; Scheideler, Marcel; Misslinger, Matthias; Griehl, Matthias; Daschil, Nina; Humpel, Christian; Obermair, Gerald J; Schmuckermair, Claudia; Striessnig, Joerg; Flucher, Bernhard E; Hüttenhofer, Alexander

2014-12-01

We have generated a novel, neuro-specific ncRNA microarray, covering 1472 ncRNA species, to investigate their expression in different mouse models for central nervous system diseases. Thereby, we analyzed ncRNA expression in two mouse models with impaired calcium channel activity, implicated in Epilepsy or Parkinson's disease, respectively, as well as in a mouse model mimicking pathophysiological aspects of Alzheimer's disease. We identified well over a hundred differentially expressed ncRNAs, either from known classes of ncRNAs, such as miRNAs or snoRNAs or which represented entirely novel ncRNA species. Several differentially expressed ncRNAs in the calcium channel mouse models were assigned as miRNAs and target genes involved in calcium signaling, thus suggesting feedback regulation of miRNAs by calcium signaling. In the Alzheimer mouse model, we identified two snoRNAs, whose expression was deregulated prior to amyloid plaque formation. Interestingly, the presence of snoRNAs could be detected in cerebral spine fluid samples in humans, thus potentially serving as early diagnostic markers for Alzheimer's disease. In addition to known ncRNAs species, we also identified 63 differentially expressed, entirely novel ncRNA candidates, located in intronic or intergenic regions of the mouse genome, genomic locations, which previously have been shown to harbor the majority of functional ncRNAs. © 2014 Gstir et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

PDX-1 Is a Therapeutic Target for Pancreatic Cancer, Insulinoma and Islet Neoplasia Using a Novel RNA Interference Platform

PubMed Central

Liu, Shi-He; Rao, Donald D.; Nemunaitis, John; Senzer, Neil; Zhou, Guisheng; Dawson, David; Gingras, Marie-Claude; Wang, Zhaohui; Gibbs, Richard; Norman, Michael; Templeton, Nancy S.; DeMayo, Francesco J.; O'Malley, Bert; Sanchez, Robbi; Fisher, William E.; Brunicardi, F. Charles

2012-01-01

Pancreatic and duodenal homeobox-1 (PDX-1) is a transcription factor that regulates insulin expression and islet maintenance in the adult pancreas. Our recent studies demonstrate that PDX-1 is an oncogene for pancreatic cancer and is overexpressed in pancreatic cancer. The purpose of this study was to demonstrate that PDX-1 is a therapeutic target for both hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Immunohistochemistry of human pancreatic and islet neoplasia specimens revealed marked PDX-1 overexpression, suggesting PDX-1 as a “drugable” target within these diseases. To do so, a novel RNA interference effector platform, bifunctional shRNAPDX-1, was developed and studied in mouse and human cell lines as well as in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Systemic delivery of bi-shRNAhumanPDX-1 lipoplexes resulted in marked reduction of tumor volume and improved survival in a human pancreatic cancer xenograft mouse model. bi-shRNAmousePDX-1 lipoplexes prevented death from hyperinsulinemia and hypoglycemia in an insulinoma mouse model. shRNAmousePDX-1 lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of islet neoplasia. PDX-1 was overexpressed in pancreatic neuroendocrine tumors and nesidioblastosis. These data demonstrate that PDX-1 RNAi therapy controls hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia, therefore, PDX-1 is a potential therapeutic target for these pancreatic diseases. PMID:22905092

A Comparison of the Performance Capabilities of Radioisotope Energy Conversion Systems, Betavoltaic Cells, and other Nuclear Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinfelds, Eric V; Prelas, Mark A.; Sudarshan, Loyalka K.

2006-07-01

In this paper we compare the potential performance capabilities of several types of nuclear batteries to the Radioisotope Thermocouple Generators (RTG's) currently in use. There have been theoretical evaluations of, and some experimental testing of, several types of nuclear batteries including Radioisotope Energy Conversion Systems (RECS), Direct Energy Conversion (DEC) systems, and Betavoltaic Power Cells (BPC's). It has been theoretically shown, and to some extent experimentally demonstrated, that RECS, capacitive DEC systems, and possibly BPC's are all potentially capable of efficiencies well above the 9% maximum efficiency demonstrated to date in RTG's customized for deep space probe applications. Even thoughmore » RTG's have proven their reliability and have respectable power to mass ratios, it is desirable to attain efficiencies of at least 25% in typical applications. High fuel efficiency is needed to minimize the quantities of radioisotopic or nuclear fuels in the systems, to maximize power to mass ratios, and to minimize housing requirements. It has been shown that RECS can attain electric power generation efficiencies greater than 18% for devices which use Sr-90 fuel and where the accompanying material is less than roughly twice the mass of the Sr-90 fuel. Other radioisotopic fuels such as Pu-238 or Kr-85 can also be placed into RECS in order to attain efficiencies over 18%. With the likely exception of one fuel investigated by the authors, all of the promising candidates for RECS fuels can attain electric power to mass ratios greater than 15 W kg{sup -1}. It has been claimed recently [1] that the efficiency of tritium-fueled BPC's can be as high as 25%. While this is impressive and tritium has the benefit of being a 'soft' radioisotopic fuel, the silicon wafer that holds the tritium would have to be considerably more massive than the tritium contained within it and immediately adjacent to the wafer. Considering realistic mass requirements for the presence of silicon in the bulk of the wafer, a tritium cell would thus be limited to power to mass ratios <3 W kg{sup -1}. Even RECS designs with more energetic fuels and higher shielding burdens can attain >3 W kg{sup -1} and efficiencies exceeding 20%. Capacitive DEC systems can also offer significant benefits. With larger fuel quantities and larger dimensions, DEC systems can attain power efficiencies >50%. For small nuclear batteries of low or medium power, RECS appear highly desirable since the efficiency of a RECS does not vary with the amount of fuel present nor does it vary with temperature to any significant degree. (authors)« less

Reduced tillage and cover crops as a strategy for mitigating atmospheric CO2 increase through soil organic carbon sequestration in dry Mediterranean agroecosystems.

NASA Astrophysics Data System (ADS)

Almagro, María; Garcia-Franco, Noelia; de Vente, Joris; Boix-Fayos, Carolina; Díaz-Pereira, Elvira; Martínez-Mena, María

2016-04-01

The implementation of sustainable land management (SLM) practices in semiarid Mediterranean agroecosystems can be beneficial to maintain or enhance levels of soil organic carbon and mitigate current atmospheric CO2 increase. In this study, we assess the effects of different tillage treatments (conventional tillage (CT), reduced tillage (RT), reduced tillage combined with green manure (RTG), and no tillage (NT)) on soil CO2 efflux, aggregation and organic carbon stabilization in two semiarid organic rainfed almond (Prunus dulcis Mill., var. Ferragnes) orchards located in SE Spain Soil CO2 efflux, temperature and moisture were measured monthly between May 2012 and December 2014 (site 1), and between February 2013 and December 2014 (site 2). In site 1, soil CO2 efflux rates were also measured immediately following winter and spring tillage operations. Aboveground biomass inputs were estimated at the end of the growing season in each tillage treatment. Soil samples (0-15 cm) were collected in the rows between the trees (n=4) in October 2012. Four aggregate size classes were distinguished by sieving (large and small macroaggregates, free microaggregates, and free silt plus clay fraction), and the microaggregates occluded within macroaggregates (SMm) were isolated. Soil CO2efflux rates in all tillage treatments varied significantly during the year, following changes during the autumn, winter and early spring, or changes in soil moisture during late spring and summer. Repeated measures analyses of variance revealed that there were no significant differences in soil CO2 efflux between tillage treatments throughout the study period at both sites. Average annual values of C lost by soil respiration were slightly but not significantly higher under RT and RTG treatments (492 g C-CO2 m-2 yr-1) than under NT treatment (405 g C-CO2 m-2 yr-1) in site 1, while slightly but not significantly lower values were observed under RT and RTG treatments (468 and 439 g C-CO2 m-2 yr-1, respectively) than under CT treatment (399 g C-CO2 m-2 yr-1) in site 2. Tillage operations had a rapid but short-lived effect on soil CO2 efflux rates, with no significant influence on the annual soil CO2 emissions. The larger amounts of plant biomass incorporated into soil annually in the reduced tillage treatments compared to the conventional tillage treatment promoted soil aggregation and the physico-chemical soil organic carbon stabilization while soil CO2 emissions did not significantly increase. According to our results, reduced-tillage is strongly recommended as a beneficial SLM strategy for mitigating atmospheric CO2 increase through soil carbon sequestration and stabilization in semiarid Mediterranean agroecosystems.

Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

DTIC Science & Technology

2009-07-01

Microbiology. All Rights Reserved. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever Kelly L. Warfield,* Steven B...mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV...cause severe hemorrhagic fevers in humans and non- human primates (27). The incubation time is estimated to be 3 to 21 days, with human case fatality

Producing a Mouse Model to Explore the Linkages Between Tocopherol Biology and Prostate Cancer

DTIC Science & Technology

2005-07-01

Edwards, Prostate cancer and supplementation with alpha-tocopherol and beta -carotene: incidence and mortality in a controlled trial. J Natl Cancer ...1-0153 TITLE: Producing a Mouse Model to Explore the Linkages Between Tocopherol Biology and Prostate Cancer ...TITLE AND SUBTITLE Producing a Mouse Model to Explore the Linkages Between Tocopherol 5a. CONTRACT NUMBER Biology and Prostate Cancer 5b. GRANT

Synergistic Action of FOXP3 and TSC1 Pathways During Tumor Progression

DTIC Science & Technology

2015-10-01

invasive carcinoma and, ultimately, metastatic disease [1-3]. Mouse models of PIN (mPIN) generated by a single- mutant gene in prostate do not progress...downstream target) is sufficient to significantly reduce the initiation of prostate cancer in the Pten conditional knockout mouse model [19-21...the possibility that these two genetic hits cooperate to promote tumor progression, and mouse models show that this cooperation accelerates

Designing Mouse Behavioral Tasks Relevant to Autistic-Like Behaviors

ERIC Educational Resources Information Center

Crawley, Jacqueline N.

2004-01-01

The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e.,…

Behavioral phenotypes of genetic mouse models of autism

PubMed Central

Kazdoba, T. M.; Leach, P. T.; Crawley, J. N.

2016-01-01

More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. PMID:26403076

Defining the role of polyamines in colon carcinogenesis using mouse models

PubMed Central

Ignatenko, Natalia A.; Gerner, Eugene W.; Besselsen, David G.

2011-01-01

Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM) models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min) mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention. PMID:21712957

Targeting Cancer Protein Profiles with Split-Enzyme Reporter Fragments to Achieve Chemical Resolution for Molecular Imaging

DTIC Science & Technology

2013-08-01

We next tested the utility of the construct to accumulate in tumors expressing EGFR using an orthotopic mouse model for brain tumors. Glioma cells...filament tumor marker, identified implanted cells within the orthotopic mouse model which were of human origin, i.e. Gli36Δ5 cells, and demonstrated that...forward into in vivo animal tumor model studies. • In vivo imaging of EGFR targeted-complex in orthotopic mouse model of brain tumor. • Ex vivo validation

Genetically engineered mouse models of melanoma.

PubMed

Pérez-Guijarro, Eva; Day, Chi-Ping; Merlino, Glenn; Zaidi, M Raza

2017-06-01

Melanoma is a complex disease that exhibits highly heterogeneous etiological, histopathological, and genetic features, as well as therapeutic responses. Genetically engineered mouse (GEM) models provide powerful tools to unravel the molecular mechanisms critical for melanoma development and drug resistance. Here, we expound briefly the basis of the mouse modeling design, the available technology for genetic engineering, and the aspects influencing the use of GEMs to model melanoma. Furthermore, we describe in detail the currently available GEM models of melanoma. Cancer 2017;123:2089-103. © 2017 American Cancer Society. © 2017 American Cancer Society.

CRISPR-Mediated Knockout of Cybb in NSG Mice Establishes a Model of Chronic Granulomatous Disease for Human Stem-Cell Gene Therapy Transplants.

PubMed

Sweeney, Colin L; Choi, Uimook; Liu, Chengyu; Koontz, Sherry; Ha, Seung-Kwon; Malech, Harry L

2017-07-01

Chronic granulomatous disease (CGD) is characterized by defects in the production of microbicidal reactive oxygen species (ROS) by phagocytes. Testing of gene and cell therapies for the treatment of CGD in human hematopoietic cells requires preclinical transplant models. The use of the lymphocyte-deficient NOD.Cg-Prkdc scid Il2rg tm1Wjl/ SzJ (NSG) mouse strain for human hematopoietic cell xenografts to test CGD therapies is complicated by the presence of functional mouse granulocytes capable of producing ROS for subsequent bacterial and fungal killing. To establish a phagocyte-defective mouse model of X-linked CGD (X-CGD) in NSG mice, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 was utilized for targeted knockout of mouse Cybb on the X-chromosome by microinjection of NSG mouse zygotes with Cas9 mRNA and CRISPR single-guide RNA targeting Cybb exon 1 or exon 3. This resulted in a high incidence of indel formation at the CRISPR target site, with all mice exhibiting deletions in at least one Cybb allele based on sequence analysis of tail snip DNA. A female mouse heterozygous for a 235-bp deletion in Cybb exon 1 was bred to an NSG male to establish the X-CGD NSG mouse strain, NSG.Cybb[KO]. Resulting male offspring with the 235 bp deletion were found to be defective for production of ROS by neutrophils and other phagocytes, and demonstrated increased susceptibility to spontaneous bacterial and fungal infections with granulomatous inflammation. The establishment of the phagocyte-defective NSG.Cybb[KO] mouse model enables the in vivo assessment of gene and cell therapy strategies for treating CGD in human hematopoietic cell transplants without obfuscation by functional mouse phagocytes, and may also be useful for modeling other phagocyte disorders in humanized NSG mouse xenografts.

Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.

PubMed

Apps, John Richard; Martinez-Barbera, Juan Pedro

2017-05-01

Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

PubMed Central

Kerr, Abigail L.; Tennant, Kelly A.

2014-01-01

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models. PMID:25045916

A comparison of some organizational characteristics of the mouse central retina and the human macula.

PubMed

Volland, Stefanie; Esteve-Rudd, Julian; Hoo, Juyea; Yee, Claudine; Williams, David S

2015-01-01

Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

A Genetically Engineered Mouse Model of Neuroblastoma Driven by Mutated ALK and MYCN

DTIC Science & Technology

2014-09-01

AWARD NUMBER: W81XWH-13-1-0220 TITLE: A Genetically Engineered Mouse Model of Neuroblastoma ...CONTRACT NUMBER A Genetically Engineered Mouse Model of Neuroblastoma Driven by Mutated ALK and MYCN 5b. GRANT NUMBER W81XWH-13-1-0220 5c...common ALK mutations in neuroblastoma , F1174L and R1275Q. We have determined that in tumors cells expressing mutated ALK, different downstream

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2014-10-01

AD_________________ Award Number: W81XWH-13-1-0325 TITLE: Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using ...Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING ORGANIZATION ...Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER W81XWH-13-1-0325 Carcinoma Using Genetically Engineered Mouse Models and 5b

Behavioural phenotyping assays for mouse models of autism

PubMed Central

Silverman, Jill L.; Yang, Mu; Lord, Catherine; Crawley, Jacqueline N.

2011-01-01

Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100–150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of austism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders. PMID:20559336

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webb, Carol F., E-mail: carol-webb@omrf.org; Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights:more » • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.« less

Mouse phenotyping.

PubMed

Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

2011-02-01

Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

Human androgen deficiency: insights gained from androgen receptor knockout mouse models

PubMed Central

Rana, Kesha; Davey, Rachel A; Zajac, Jeffrey D

2014-01-01

The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor (AR) through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout (ARKO) models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype. PMID:24480924

Modelling clinical systemic lupus erythematosus: similarities, differences and success stories

PubMed Central

Celhar, Teja

2017-01-01

Abstract Mouse models of SLE have been indispensable tools to study disease pathogenesis, to identify genetic susceptibility loci and targets for drug development, and for preclinical testing of novel therapeutics. Recent insights into immunological mechanisms of disease progression have boosted a revival in SLE drug development. Despite promising results in mouse studies, many novel drugs have failed to meet clinical end points. This is probably because of the complexity of the disease, which is driven by polygenic predisposition and diverse environmental factors, resulting in a heterogeneous clinical presentation. Each mouse model recapitulates limited aspects of lupus, especially in terms of the mechanism underlying disease progression. The main mouse models have been fairly successful for the evaluation of broad-acting immunosuppressants. However, the advent of targeted therapeutics calls for a selection of the most appropriate model(s) for testing and, ultimately, identification of patients who will be most likely to respond. PMID:28013204

Mouse Models of Gastric Cancer

PubMed Central

Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

Phenotyping male infertility in the mouse: how to get the most out of a 'non-performer'.

PubMed

Borg, Claire L; Wolski, Katja M; Gibbs, Gerard M; O'Bryan, Moira K

2010-01-01

Functional male gametes are produced through complex processes that take place within the testis, epididymis and female reproductive tract. A breakdown at any of these phases can result in male infertility. The production of mutant mouse models often yields an unexpected male infertility phenotype. It is with this in mind that the current review has been written. The review aims to act as a guide to the 'non-reproductive biologist' to facilitate a systematic analysis of sterile or subfertile mice and to assist in extracting the maximum amount of information from each model. This is a review of the original literature on defects in the processes that take a mouse spermatogonial stem cell through to a fully functional spermatozoon, which result in male infertility. Based on literature searches and personal experience, we have outlined a step-by-step strategy for the analysis of an infertile male mouse line. A wide range of methods can be used to define the phenotype of an infertile male mouse. These methods range from histological methods such as electron microscopy and immunohistochemistry, to hormone analyses and methods to assess sperm maturation status and functional competence. With the increased rate of genetically modified mouse production, the generation of mouse models with unexpected male infertility is increasing. This manuscript will help to ensure that the maximum amount of information is obtained from each mouse model and, by extension, will facilitate the knowledge of both normal fertility processes and the causes of human infertility.

A surgical approach appropriate for targeted cochlear gene therapy in the mouse.

PubMed

Jero, J; Tseng, C J; Mhatre, A N; Lalwani, A K

2001-01-01

Therapeutic manipulations of the mammalian cochlea, including cochlear gene transfer, have been predominantly studied using the guinea pig as the experimental model. With the significant developments in mouse genomics and the availability of mutant strains of mice with well-characterized hearing loss, the mouse justifiably will be the preferred animal model for therapeutic manipulations. However, the potential advantages of the mouse model have not been fully realized due to the surgical difficulty of accessing its small cochlea. This study describes a ventral approach, instead of the routinely used postauricular approach in other rodents, for accessing the mouse middle and inner ear, and its application in cochlear gene transfer. This ventral approach enabled rapid and direct delivery of liposome-transgene complex to the mouse inner ear while avoiding blood loss, facial nerve morbidity, and mortality. Transgene expression at 3 days was detected in Reissner's membrane, spiral limbus, spiral ligament, and spiral ganglion cells, in a pattern similar to that previously described in the guinea pig. The successful access and delivery of material to the mouse cochlea and the replication of gene expression seen in the guinea pig demonstrated in this study should promote the use of the mouse in future studies investigating targeted cochlear therapy.

Behavioral phenotypes of genetic mouse models of autism.

PubMed

Kazdoba, T M; Leach, P T; Crawley, J N

2016-01-01

More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Using Genetic Mouse Models to Gain Insight into Glaucoma: Past Results and Future Possibilities

PubMed Central

Fernandes, Kimberly A.; Harder, Jeffrey M.; Williams, Pete A.; Rausch, Rebecca L.; Kiernan, Amy E.; Nair, K. Saidas; Anderson, Michael G.; John, Simon W.; Howell, Gareth R.; Libby, Richard T.

2015-01-01

While all forms of glaucoma are characterized by a specific pattern of retinal ganglion cell death, they are clinically divided into several distinct subclasses, including normal tension glaucoma, primary open angle glaucoma, congenital glaucoma, and secondary glaucoma. For each type of glaucoma there are likely numerous molecular pathways that control susceptibility to the disease. Given this complexity, a single animal model will never precisely model all aspects of all the different types of human glaucoma. Therefore, multiple animal models have been utilized to study glaucoma but more are needed. Because of the powerful genetic tools available to use in the laboratory mouse, it has proven to be a highly useful mammalian system for studying the pathophysiology of human disease. The similarity between human and mouse eyes coupled with the ability to use a combination of advanced cell biological and genetic tools in mice have led to a large increase in the number of studies using mice to model specific glaucoma phenotypes. Over the last decade, numerous new mouse models and genetic tools have emerged, providing important insight into the cell biology and genetics of glaucoma. In this review, we describe available mouse genetic models that can be used to study glaucoma-relevant disease/pathobiology. Furthermore, we discuss how these models have been used to gain insights into ocular hypertension (a major risk factor for glaucoma) and glaucomatous retinal ganglion cell death. Finally, the potential for developing new mouse models and using advanced genetic tools and resources for studying glaucoma are discussed. PMID:26116903

Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field

PubMed Central

Hunsaker, Michael R.

2013-01-01

It has become increasingly important that the field of behavioral genetics identifies not only the gross behavioral phenotypes associated with a given mutation, but also the behavioral endophenotypes that scale with the dosage of the particular mutation being studied. Over the past few years, studies evaluating the effects of the polymorphic CGG trinucleotide repeat on the FMR1 gene underlying Fragile X-Associated Disorders have reported preliminary evidence for a behavioral endophenotype in human Fragile X Premutation carrier populations as well as the CGG knock-in (KI) mouse model. More recently, the behavioral experiments used to test the CGG KI mouse model have been extended to the Fmr1 knock-out (KO) mouse model. When combined, these data provide compelling evidence for a clear neurocognitive endophenotype in the mouse models of Fragile X-Associated Disorders such that behavioral deficits scale predictably with genetic dosage. Similarly, it appears that the CGG KI mouse effectively models the histopathology in Fragile X-Associated Disorders across CGG repeats well into the full mutation range, resulting in a reliable histopathological endophenotype. These endophenotypes may influence future research directions into treatment strategies for not only Fragile X Syndrome, but also the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). PMID:24627796

Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model.

PubMed

Zhang, Haiyun; Sun, Dejun; Li, Defu; Zheng, Zeguang; Xu, Jingyi; Liang, Xue; Zhang, Chenting; Wang, Sheng; Wang, Jian; Lu, Wenju

2018-05-15

Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.

A Deep Space Power System Option Based on Synergistic Power Conversion Technologies

NASA Technical Reports Server (NTRS)

Schreiber, Jeffrey G.

2000-01-01

Deep space science missions have typically used radioisotope thermoelectric generator (RTG) power systems. The RTG power system has proven itself to be a rugged and highly reliable power system over many missions, however the thermal-to-electric conversion technology used was approximately 5% efficient. While the relatively low efficiency has some benefits in terms of system integration, there are compelling reasons why a more efficient conversion system should be pursued. The cost savings alone that are available as a result of the reduced isotope inventory are significant. The Advanced Radioisotope Power System (ARPS) project was established to fulfill this goal. Although it was not part of the ARPS project, Stirling conversion technology is being demonstrated with a low level of funding by both NASA and DOE. A power system with Stirling convertors. although intended for use with an isotope heat source. can be combined with other advanced technologies to provide a novel power system for deep space missions. An inflatable primary concentrator would be used in combination with a refractive secondary concentrator (RSC) as the heat source to power the system. The inflatable technology as a structure has made great progress for a variety of potential applications such as communications reflectors, radiators and solar arrays. The RSC has been pursued for use in solar thermal propulsion applications, and it's unique properties allow some advantageous system trades to be made. The power system proposed would completely eliminate the isotope heat source and could potentially provide power for science missions to planets as distant as Uranus. This paper will present the background and developmental status of the technologies and will then describe the power system being proposed.

Thermal Expansion Studies of Selected High Temperature Thermoelectric Materials

NASA Technical Reports Server (NTRS)

Ravi, Vilupanur; Firdosy, Samad; Caillat, Thierry; Brandon, Erik; Van Der Walde, Keith; Maricic, Lina; Sayir, Ali

2008-01-01

Radioisotope thermoelectric generators (RTGs) generate electrical power by converting the heat released from the nuclear decay of radioactive isotopes (typically plutonium-238) into electricity using a thermoelectric converter. RTGs have been successfully used to power a number of space missions and have demonstrated their reliability over an extended period of time (tens of years) and are compact, rugged, radiation resistant, scalable, and produce no noise, vibration or torque during operation. System conversion efficiency for state-of-practice RTGs is about 6% and specific power less than or equal to 5.1 W/kg. Higher specific power would result in more on-board power for the same RTG mass, or less RTG mass for the same on-board power. The Jet Propulsion Laboratory has been leading, under the advanced thermoelectric converter (ATEC) project, the development of new high-temperature thermoelectric materials and components for integration into advanced, more efficient RTGs. Thermoelectric materials investigated to date include skutterudites, the Yb14MnSb11 compound, and SiGe alloys. The development of long-lived thermoelectric couples based on some of these materials has been initiated and is assisted by a thermo-mechanical stress analysis to ensure that all stresses under both fabrication and operation conditions will be within yield limits for those materials. Several physical parameters are needed as input to this analysis. Among those parameters, the coefficient of thermal expansion (CTE) is critically important. Thermal expansion coefficient measurements of several thermoelectric materials under consideration for ATEC are described in this paper. The stress response at the interfaces in material stacks subjected to changes in temperature is discussed, drawing on work from the literature and project-specific tools developed here. The degree of CTE mismatch and the associated effect on the formation of stress is highlighted.

A Rover Concept for Exploring the Surface of Titan

NASA Astrophysics Data System (ADS)

Balint, T. S.; Shirley, J. H.; Schriener, T. M.

2005-12-01

Titan is one of the premier targets for future in-situ exploration in the outer solar system, as unique "pre-biotic" organic chemical processes may be presently occurring at its surface. A mission to the surface of Titan is not as technically difficult as one to Europa; Titan's atmosphere allows for aerobraking descents, the radiation environment is not a mission-critical factor, and the organic materials we want to sample should be widely distributed (and easily accessible). The recent Titan landing by the Huygens Probe has focused considerable scientific interest on this remarkable body, and future missions to Titan are under consideration. We evaluated a Titan Rover mission concept that would have the capability to survive on Titan's surface for a period of 3 terrestrial years. This long mission lifetime is enabled by employing a radioisotope power system (RPS). To minimize costs and use as much flight heritage as possible, we began by assuming that system masses, dimensions, and instrumentation would be comparable to those of the Mars Surface Lander (MSL). We found that a rover configuration with a 110 W (electric) power system and four 1.5 m diameter inflatable wheels could potentially enable traverse distances up to ~500 km, depending on science and mission requirements, surface environments, and the capability of the autonomous navigation system employed. Direct to Earth communication would simplify the mission by removing the need for a relay orbiter. We will describe our strawman instrument payload and rover subsystems. Trades between the potentially available RPS systems (RTG, Advanced RTG, TPV, SRG, Advanced Stirling and Brayton RPSs) will be outlined. While many possible approaches exist for Titan in-situ exploration, the Titan rover concept presented here could provide a scientifically interesting and programmatically affordable solution.

Composite membranes for alkaline electrolysis based on polysulfone and mineral fillers

NASA Astrophysics Data System (ADS)

Burnat, Dariusz; Schlupp, Meike; Wichser, Adrian; Lothenbach, Barbara; Gorbar, Michal; Züttel, Andreas; Vogt, Ulrich F.

2015-09-01

Mineral-based membranes for high temperature alkaline electrolysis were developed by a phase inversion process with polysulfone as binder. The long-term stability of new mineral fillers: wollastonite, forsterite and barite was assessed by 8000 h-long leaching experiments (5.5 M KOH, 85 °C) combined with thermodynamic modelling. Barite has released only 6.22 10-4 M of Ba ions into the electrolyte and was selected as promising filler material, due to its excellent stability. Barite-based membranes, prepared by the phase inversion process, were further studied. The resistivity of these membranes in 5.5 M KOH was investigated as a function of membrane thickness and total porosity, hydrodynamic porosity as well as gas purities determined by conducting electrolysis at ambient conditions. It was found that a dense top layer resulting from the phase inversion process, shows resistivity values up to 451.0 ± 22 Ω cm, which is two orders of magnitude higher than a porous bulk membrane microstructure (3.89 Ω cm). Developed membranes provided hydrogen purity of 99.83 at 200 mA cm-2, which is comparable to previously used chrysotile membranes and higher than commercial state-of-the-art Zirfon 500utp membrane. These cost-effective polysulfone - barite membranes are promising candidates as asbestos replacement for commercial applications.

Modeling bladder cancer in mice: opportunities and challenges

PubMed Central

Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

2015-01-01

The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

Development and function of human innate immune cells in a humanized mouse model.

PubMed

Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

2014-04-01

Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

Development and function of human innate immune cells in a humanized mouse model

PubMed Central

Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V.; Teichmann, Lino L.; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A. Karolina; Manz, Markus G.; Flavell, Richard A.

2014-01-01

Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models are unable to support development of human innate immune cells, including myeloid cells and NK cells. Here we describe a mouse strain, called MI(S)TRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked in to their respective mouse loci. The human cytokines support the development and function of monocytes/macrophages and natural killer cells derived from human fetal liver or adult CD34+ progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MI(S)TRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology. PMID:24633240

Effect of electroacupuncture on brain-derived neurotrophic factor mRNA expression in mouse hippocampus following cerebral ischemia-reperfusion injury.

PubMed

Zhao, Jianxin; Xu, Huazhou; Tian, Yuanxiang; Hu, Manxiang; Xiao, Hongling

2013-04-01

This work aims to observe the effects of electroacupuncture on brain-derived neurotrophic factor (BDNF) mRNA expression in mouse hippocampus following cerebral ischemia-reperfusion injury. The models of mouse cerebral ischemia-reperfusion injury were established. A total of 96 healthy mice were randomly assigned into 4 groups, namely, the sham surgery, model, model + electroacupuncture, and mode + hydergine groups. Mice in the model + electroacupuncture group were treated through electroacupuncture at the Shenshu (BL 23), Geshu (BL 17), and Baihui (GV 20) acupoints. Mice in the model+hydergine group were intragastrically administered with hydergine (0.77 mg/kg(-1) x day(-1)). The levels of BDNF mRNA expressions in the hippocampus were ana lyzed through a semi-quantitative reverse transcription-polymerase chain reaction assay on days 1 and 7 after the surgeries. BDNF mRNA expressions in the mouse hippocampus of the model group on days 1 and 7 after the surgery were higher than those of the sham surgery group (both P < 0.01). On days 1 and 7 of the electroacupuncture treatment, BDNF mRNA expression in the mouse hippocampus of the model + electroacupuncture group was significantly elevated compared with the model group (both P < 0.01) or the model + hydergine group (both P < 0.01). On days 1 and 7 of the hydergine treatment, BDNF mRNA expression in the mouse hippocampus of the model + hydergine group tended to increase compared with the model group; however, statistical significance was not achieved (both P > 0.05). Electroacupuncture treatment enhances endogenous BDNF expression, which may improve the survival environment for intracerebral neurons and inhibit the apoptosis of hippocampal cells.

Intramyocardial Injection of siRNAs Can Efficiently Establish Myocardial Tissue-Specific Renalase Knockdown Mouse Model.

PubMed

Huang, Kun; Liu, Ju; Zhang, Hui; Wang, Jiliang; Li, Huili

2016-01-01

Ischaemia/reperfusion (I/R) injury will cause additional death of cardiomyocytes in ischaemic heart disease. Recent studies revealed that renalase was involved in the I/R injury. So, the myocardial tissue-specific knockdown mouse models were needed for the investigations of renalase. To establish the mouse models, intramyocardial injection of siRNAs targeting renalase was performed in mice. The wild distribution and high transfection efficiency of the siRNAs were approved. And the renalase expression was efficiently suppressed in myocardial tissue. Compared with the high cost, time consumption, and genetic compensation risk of the Cre/loxP technology, RNA interference (RNAi) technology is much cheaper and less time-consuming. Among the RNAi technologies, injection of siRNAs is safer than virus. And considering the properties of the I/R injury mouse models, the efficiency and durability of injection with siRNAs are acceptable for the studies. Altogether, intramyocardial injection of siRNAs targeting renalase is an economical, safe, and efficient method to establish myocardial tissue-specific renalase knockdown mouse models.

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary.

PubMed

Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B; Blankson, Joel N; Burnett, John C; Casares, Sofia; Garcia, J Victor; Hasenkrug, Kim J; Kashanchi, Fatah; Kitchen, Scott G; Klein, Florian; Kumar, Priti; Luster, Andrew D; Poluektova, Larisa Y; Rao, Mangala; Sanders-Beer, Brigitte E; Shultz, Leonard D; Zack, Jerome A

2016-02-01

The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting.

Oral recombinant human or mouse lactoferrin reduces Mycobacterium tuberculosis TDM induced granulomatous lung pathology.

PubMed

Hwang, Shen-An; Kruzel, Marian L; Actor, Jeffrey K

2017-02-01

Trehalose 6'6-dimycolate (TDM) is the most abundant glycolipid on the cell wall of Mycobacterium tuberculosis (MTB). TDM is capable of inducing granulomatous pathology in mouse models that resembles those induced by MTB infection. Using the acute TDM model, this work investigates the effect of recombinant human and mouse lactoferrin to reduce granulomatous pathology. C57BL/6 mice were injected intravenously with TDM at a dose of 25 μg·mouse -1 . At day 4 and 6, recombinant human or mouse lactoferrin (1 mg·(100 μL) -1 ·mouse -1 ) were delivered by gavage. At day 7 after TDM injection, mice were evaluated for lung pathology, cytokine production, and leukocyte populations. Mice given human or mouse lactoferrin had reduced production of IL-12p40 in their lungs. Mouse lactoferrin increased IL-6 and KC (CXCL1) in lung tissue. Increased numbers of macrophages were observed in TDM-injected mice given human or mouse lactoferrin. Granulomatous pathology, composed of mainly migrated leukocytes, was visually reduced in mice that received human or mouse lactoferrin. Quantitation of granulomatous pathology demonstrated a significant decrease in mice given human or mouse lactoferrin compared with TDM control mice. This report is the first to directly compare the immune modulatory effects of both heterologous recombinant human and homologous mouse lactoferrin on the development of TDM-induced granulomas.

Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

NASA Astrophysics Data System (ADS)

Kim, Suhwan; Jung, Unsang; Baek, Juyoung; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-01-01

Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.

Nutrient input through submarine groundwater discharge in two major Chinese estuaries: the Pearl River Estuary and the Changjiang River Estuary

NASA Astrophysics Data System (ADS)

Liu, Jianan; Du, Jinzhou; Wu, Ying; Liu, Sumei

2018-04-01

In this study, we used a 224Ra mass balance model to evaluate the importance of submarine groundwater discharge (SGD) for the budgets of biogenic elements in two major Chinese estuaries: the Pearl River Estuary (PRE) and the Changjiang River Estuary (CRE). The apparent water age in the PRE was estimated to be 4.8 ± 1.1 days in the dry season and 1.8 ± 0.6 days in the wet season using a physical model based on the tidal prism. In the dry season, the water age in the CRE was estimated to be 11.7 ± 3.0 days using the 224Ra/223Ra activities ratios apparent age model. By applying the 224Ra mass balance model, we obtained calculations of the SGD flow in the PRE of (4.5-10) × 108 m3 d-1 (0.23-0.50 m3 m-2 d-1) and (1.2-2.7) × 108 m3 d-1 (0.06-0.14 m3 m-2 d-1) in the dry season and wet season, respectively, and the estimated SGD flux was (4.6-11) × 109 m3 d-1 (0.18-0.45 m3 m-2 d-1) in the dry season of the CRE. In comparison with the nutrient fluxes from the rivers, the SGD-derived nutrient fluxes may play a vital role in controlling the nutrient budgets and stoichiometry in the study areas. The large amount of dissolved inorganic nitrogen and phosphorus fluxes together with high N: P ratios into the PRE and CRE would potentially contribute to eutrophication and the occurrence of red tides along the adjacent waters.

High-fertility phenotypes: two outbred mouse models exhibit substantially different molecular and physiological strategies warranting improved fertility.

PubMed

Langhammer, Martina; Michaelis, Marten; Hoeflich, Andreas; Sobczak, Alexander; Schoen, Jennifer; Weitzel, Joachim M

2014-01-01

Animal models are valuable tools in fertility research. Worldwide, there are more than 400 transgenic or knockout mouse models available showing a reproductive phenotype; almost all of them exhibit an infertile or at least subfertile phenotype. By contrast, animal models revealing an improved fertility phenotype are barely described. This article summarizes data on two outbred mouse models exhibiting a 'high-fertility' phenotype. These mouse lines were generated via selection over a time period of more than 40 years and 161 generations. During this selection period, the number of offspring per litter and the total birth weight of the entire litter nearly doubled. Concomitantly with the increased fertility phenotype, several endocrine parameters (e.g. serum testosterone concentrations in male animals), physiological parameters (e.g. body weight, accelerated puberty, and life expectancy), and behavioral parameters (e.g. behavior in an open field and endurance fitness on a treadmill) were altered. We demonstrate that the two independently bred high-fertility mouse lines warranted their improved fertility phenotype using different molecular and physiological strategies. The fertility lines display female- as well as male-specific characteristics. These genetically heterogeneous mouse models provide new insights into molecular and cellular mechanisms that enhance fertility. In view of decreasing fertility in men, these models will therefore be a precious information source for human reproductive medicine. Translated abstract A German translation of abstract is freely available at http://www.reproduction-online.org/content/147/4/427/suppl/DC1.

Ultrasonic vocalizations: a tool for behavioural phenotyping of mouse models of neurodevelopmental disorders

PubMed Central

Scattoni, Maria Luisa; Crawley, Jacqueline; Ricceri, Laura

2009-01-01

In neonatal mice ultrasonic vocalizations have been studied both as an early communicative behavior of the pup-mother dyad and as a sign of an aversive affective state. Adult mice of both sexes produce complex ultrasonic vocalization patterns in different experimental/social contexts. All these vocalizations are becoming an increasingly valuable assay for behavioral phenotyping throughout the mouse life-span and alterations of the ultrasound patterns have been reported in several mouse models of neurodevelopmental disorders. Here we also show that the modulation of vocalizations by maternal cues (maternal potentiation paradigm) – originally identified and investigated in rats - can be measured in C57Bl/6 mouse pups with appropriate modifications of the rat protocol and can likely be applied to mouse behavioral phenotyping. In addition we suggest that a detailed qualitative evaluation of neonatal calls together with analysis of adult mouse vocalization patterns in both sexes in social settings, may lead to a greater understanding of the communication value of vocalizations in mice. Importantly, both neonatal and adult USV altered patterns can be determined during the behavioural phenotyping of mouse models of human neurodevelopmental and neuropsychiatric disorders, starting from those in which deficits in communication are a primary symptom. PMID:18771687

Strain-compensated infrared photodetector and photodetector array

DOEpatents

Kim, Jin K; Hawkins, Samuel D; Klem, John F; Cich, Michael J

2013-05-28

A photodetector is disclosed for the detection of infrared light with a long cutoff wavelength in the range of about 4.5-10 microns. The photodetector, which can be formed on a semiconductor substrate as an nBn device, has a light absorbing region which includes InAsSb light-absorbing layers and tensile-strained layers interspersed between the InAsSb light-absorbing layers. The tensile-strained layers can be formed from GaAs, InAs, InGaAs or a combination of these III-V compound semiconductor materials. A barrier layer in the photodetector can be formed from AlAsSb or AlGaAsSb; and a contact layer in the photodetector can be formed from InAs, GaSb or InAsSb. The photodetector is useful as an individual device, or to form a focal plane array.

A Comparison of Some Organizational Characteristics of the Mouse Central Retina and the Human Macula

PubMed Central

Hoo, Juyea; Yee, Claudine; Williams, David S.

2015-01-01

Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch’s membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch’s membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident. PMID:25923208

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Ying; Adachi, Hiroaki, E-mail: hadachi-ns@umin.org; Department of Neurology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555

Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ)-encoding tract within the androgen receptor (AR) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. Hepatocyte growth factor (HGF) is a polypeptide growth factor which has neuroprotective properties. To investigate whether HGF overexpression can affect disease progression in a mouse model of SBMA, we crossed SBMA transgenic model mice expressing an AR gene with anmore » expanded CAG repeat with mice overexpressing HGF. Here, we report that high expression of HGF induces Akt phosphorylation and modestly ameliorated motor symptoms in an SBMA transgenic mouse model treated with or without castration. These findings suggest that HGF overexpression can provide a potential therapeutic avenue as a combination therapy with disease-modifying therapies in SBMA. - Highlights: • HGF overexpression ameliorates the motor phenotypes of the SBMA mouse model. • HGF overexpression induces Akt phosphorylation in the SBMA mouse model. • This is the first report of combination therapy in a mouse model of polyQ diseases.« less

Defining the optimal animal model for translational research using gene set enrichment analysis.

PubMed

Weidner, Christopher; Steinfath, Matthias; Opitz, Elisa; Oelgeschläger, Michael; Schönfelder, Gilbert

2016-08-01

The mouse is the main model organism used to study the functions of human genes because most biological processes in the mouse are highly conserved in humans. Recent reports that compared identical transcriptomic datasets of human inflammatory diseases with datasets from mouse models using traditional gene-to-gene comparison techniques resulted in contradictory conclusions regarding the relevance of animal models for translational research. To reduce susceptibility to biased interpretation, all genes of interest for the biological question under investigation should be considered. Thus, standardized approaches for systematic data analysis are needed. We analyzed the same datasets using gene set enrichment analysis focusing on pathways assigned to inflammatory processes in either humans or mice. The analyses revealed a moderate overlap between all human and mouse datasets, with average positive and negative predictive values of 48 and 57% significant correlations. Subgroups of the septic mouse models (i.e., Staphylococcus aureus injection) correlated very well with most human studies. These findings support the applicability of targeted strategies to identify the optimal animal model and protocol to improve the success of translational research. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Transgenic and gene knockout mice in gastric cancer research

PubMed Central

Jiang, Yannan; Yu, Yingyan

2017-01-01

Mouse models are useful tool for carcinogenic study. They will greatly enrich the understanding of pathogenesis and molecular mechanisms for gastric cancer. However, only few of mice could develop gastric cancer spontaneously. With the development and improvement of gene transfer technology, investigators created a variety of transgenic and knockout/knockin mouse models of gastric cancer, such as INS-GAS mice and gastrin knockout mice. Combined with helicobacter infection and carcinogens treatment, these transgenic/knockout/knockin mice developed precancerous or cancerous lesions, which are proper for gene function study or experimental therapy. Here we review the progression of genetically engineered mouse models on gastric cancer research, and emphasize the effects of chemical carcinogens or infectious factors on carcinogenesis of genetically modified mouse. We also emphasize the histological examination on mouse stomach. We expect to provide researchers with some inspirations on this field. PMID:27713138

A Mouse Model to Investigate Postmenopausal Biology as an Etiology of Ovarian Cancer Risk

DTIC Science & Technology

2006-11-01

Wv mice and genetic alterations such as p53, pten, or p27kip1, which are found in human ovarian cancer. 2. Body: Research Progress In the first year...press (Yang et al., Am. J. Pathology 2007). To collaborate with the mouse model study, we have also examined human ovaries obtained from prophylactic...results in the coming years. Xu, Xiangxi, Ph.D. 8 3. Key Research Accomplishments (1) Further verify the relevance of the Wv mouse model to human

The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

DTIC Science & Technology

2015-02-01

cell lines, and mouse models . c) In vivo tumorigenesis and metastasis assays. Milestones: Identify whether ArhGAP11A and RacGAP1 can promote tumor growth...also upregulated in basal (C3(I)-Tag) but not luminal (MMTV-Neu) genetically- engineered mouse models (Fig. 1B). At the protein level, RacGAP1 was...hypothesis that these RhoGAPs are indeed playing an oncogenic role in these cells. Human Tumors Mouse Model Tumors Normal Luminal A Basal-like Normal

A Physiologically Based Kinetic Model of Rat and Mouse Gestation: Disposition of a Weak Acid

EPA Science Inventory

A physiologically based toxicokinetic model of gestation in the rat mouse has been developed. The model is superimposed on the normal growth curve for nonpregnant females. It describes the entire gestation period including organogenesis. The model consists of uterus, mammary tiss...

Priceless GEMMs: genetically engineered mouse models for colorectal cancer drug development.

PubMed

Roper, Jatin; Hung, Kenneth E

2012-08-01

To establish effective drug development for colorectal cancer (CRC), preclinical models that are robust surrogates for human disease are crucial. Mouse models are an attractive platform because of their relatively low cost, short life span, and ease of use. There are two main categories of mouse CRC models: xenografts derived from implantation of CRC cells or tumors in immunodeficient mice; and genetically engineered mouse models (GEMMs) derived from modification of human cancer predisposition genes, resulting in spontaneous tumor formation. Here, we review xenografts and GEMMs and focus on their potential application in translational research. Furthermore, we describe newer GEMMs for sporadic CRC that are particularly suitable for drug testing. Finally, we discuss recent advances in small-animal imaging, such as optical colonoscopy, which allow in vivo assessment of tumors. With the increasing sophistication of GEMMs, our preclinical armamentarium provides new hope for the ongoing war against CRC. Copyright © 2012. Published by Elsevier Ltd.

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer.

PubMed

Betzler, Alexander M; Kochall, Susan; Blickensdörfer, Linda; Garcia, Sebastian A; Thepkaysone, May-Linn; Nanduri, Lahiri K; Muders, Michael H; Weitz, Jürgen; Reissfelder, Christoph; Schölch, Sebastian

2017-07-06

Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Genetically engineered mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in large organs such as the colon in which only a single tumor is desired. As a result, an immunocompetent, genetically engineered mouse model of colorectal cancer was developed which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor development is initiated by surgical, segmental infection of the distal colon with adeno-cre virus in compound conditionally mutant mice. The tumors can be easily detected and monitored via colonoscopy. We here describe the surgical technique of segmental adeno-cre infection of the colon, the surveillance of the tumor via high-resolution colonoscopy and present the resulting colorectal tumors.

Advanced Controller for the Free-Piston Stirling Convertor

NASA Technical Reports Server (NTRS)

Gerber, Scott S.; Jamison, Mike; Roth, Mary Ellen; Regan, Timothy F.

2004-01-01

The free-piston Stirling power convertor is being considered as an advanced power conversion technology to be used for future NASA deep space missions requiring long life radioisotope power systems. This technology has a conversion efficiency of over 25%, which is significantly higher than the efficiency of the Radioisotope Thermal-electric Generators (RTG) now in use. The NASA Glenn Research Center has long been recognized as a leader in Stirling technology and is responsible for the development of advanced technologies that are intended to significantly improve key characteristics of the Stirling convertor. The advanced technologies identified for development also consider the requirements of potential future missions and the new capabilities that have become available in the associated technical areas. One of the key areas identified for technology development is the engine controller. To support this activity, an advanced controller is being developed for the Stirling power convertor. This controller utilizes active power factor correction electronics and microcontroller-based controls. The object of this paper is to present an overview of the advanced controller concept with modeling, simulation and hardware test data.

Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of Down Syndrome

PubMed Central

Goodliffe, Joseph W.; Olmos-Serrano, Jose Luis; Aziz, Nadine M.; Pennings, Jeroen L.A.; Guedj, Faycal; Bianchi, Diana W.

2016-01-01

Studies in humans with Down syndrome (DS) show that alterations in fetal brain development are followed by postnatal deficits in neuronal numbers, synaptic plasticity, and cognitive and motor function. This same progression is replicated in several mouse models of DS. Dp(16)1Yey/+ (hereafter called Dp16) is a recently developed mouse model of DS in which the entire region of mouse chromosome 16 that is homologous to human chromosome 21 has been triplicated. As such, Dp16 mice may more closely reproduce neurodevelopmental changes occurring in humans with DS. Here, we present the first comprehensive cellular and behavioral study of the Dp16 forebrain from embryonic to adult stages. Unexpectedly, our results demonstrate that Dp16 mice do not have prenatal brain defects previously reported in human fetal neocortex and in the developing forebrains of other mouse models, including microcephaly, reduced neurogenesis, and abnormal cell proliferation. Nevertheless, we found impairments in postnatal developmental milestones, fewer inhibitory forebrain neurons, and deficits in motor and cognitive performance in Dp16 mice. Therefore, although this new model does not express prenatal morphological phenotypes associated with DS, abnormalities in the postnatal period appear sufficient to produce significant cognitive deficits in Dp16. SIGNIFICANCE STATEMENT Down syndrome (DS) leads to intellectual disability. Several mouse models have increased our understanding of the neuropathology of DS and are currently being used to test therapeutic strategies. A new mouse model that contains an expanded number of DS-related genes, known as Dp(16)1Yey/+ (Dp16), has been generated recently. We sought to determine whether the extended triplication creates a better phenocopy of DS-related brain pathologies. We measured embryonic development, forebrain maturation, and perinatal/adult behavior and revealed an absence of prenatal phenotypes in Dp16 fetal brain, but specific cellular and behavioral deficits after the first 2 postnatal weeks. These results uncover important differences in prenatal phenotype between Dp16 animals and humans with DS and other DS mouse models. PMID:26961948

Use of a highly sensitive strand-specific quantitative PCR to identify abortive replication in the mouse model of respiratory syncytial virus disease

PubMed Central

2010-01-01

Background The BALB/c mouse is commonly used to study RSV infection and disease. However, despite the many advantages of this well-characterised model, the inoculum is large, viral replication is restricted and only a very small amount of virus can be recovered from infected animals. A key question in this model is the fate of the administered virus. Is replication really being measured or is the model measuring the survival of the virus over time? To answer these questions we developed a highly sensitive strand-specific quantitative PCR (QPCR) able to accurately quantify the amount of RSV replication in the BALB/c mouse lung, allowing characterisation of RSV negative and positive strand RNA dynamics. Results In the mouse lung, no increase in RSV genome was seen above the background of the original inoculum whilst only a limited transient increase (< 1 log) in positive strand, replicative intermediate (RI) RNA occurred. This RNA did however persist at detectable levels for 59 days post infection. As expected, ribavirin therapy reduced levels of infectious virus and RI RNA in the mouse lung. However, whilst Palivizumab therapy was also able to reduce levels of infectious virus, it failed to prevent production of intracellular RI RNA. A comparison of RSV RNA kinetics in human (A549) and mouse (KLN205) cell lines demonstrated that RSV replication was also severely delayed and impaired in vitro in the mouse cells. Conclusions This is the first time that such a sensitive strand-specific QPCR technique has been to the RSV mouse system. We have accurately quantified the restricted and abortive nature of RSV replication in the mouse. Further in vitro studies in human and mouse cells suggest this restricted replication is due at least in part to species-specific host cell-viral interactions. PMID:20860795

Establishment of mouse neuron and microglial cell co-cultured models and its action mechanism.

PubMed

Zhang, Bo; Yang, Yunfeng; Tang, Jun; Tao, Yihao; Jiang, Bing; Chen, Zhi; Feng, Hua; Yang, Liming; Zhu, Gang

2017-06-27

The objective of this study is to establish a co-culture model of mouse neurons and microglial cells, and to analyze the mechanism of action of oxygen glucose deprivation (OGD) and transient oxygen glucose deprivation (tOGD) preconditioning cell models. Mouse primary neurons and BV2 microglial cells were successfully cultured, and the OGD and tOGD models were also established. In the co-culture of mouse primary neurons and microglial cells, the cell number of tOGD mouse neurons and microglial cells was larger than the OGD cell number, observed by a microscope. CCK-8 assay result showed that at 1h after treatment, the OD value in the control group is lower compared to all the other three groups (P < 0.05). The treatment group exhibited the highest OD value among the four groups. The results observed at 5h were consistent with the results at 1 h. Flow cytometry results showed that at 1h after treatment the apoptosis percentages is higher in the control group compared to other three groups (P < 0.05). Mouse brain tissues were collected and primary neurons cells were cultured. In the meantime mouse BV2 microglia cells were cultured. Two types of cells were co-cultured, and OGD and tOGD cell models were established. There were four groups in the experiment: control group (OGD), treatment group (tOGD+OGD), placebo group (tOGD+OGD+saline) and minocycline intervention group (tOGD+OGD+minocycline). CCK-8 kit was used to detect cell viability and flow cytometry was used to detect apoptosis. In this study, mouse primary neurons and microglial cells were co-cultured. The OGD and tOGD models were established successfully. tOGD was able to effectively protect neurons and microglial cells from damage, and inhibit the apoptosis caused by oxygen glucose deprivation.

Actinic keratosis modelling in mice: A translational study

PubMed Central

Vandenberghe, Isabelle; Cartron, Valérie; Cèbe, Patrick; Blanchet, Jean-Christophe; Sibaud, Vincent; Guilbaud, Nicolas; Audoly, Laurent; Lamant, Laurence; Kruczynski, Anna

2017-01-01

Background Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. Objectives Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. Methods Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. Results An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®. Conclusion These data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease. PMID:28662116

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

PubMed

Dougherty, John P; Wolff, Brian S; Cullen, Mary J; Saligan, Leorey N; Gershengorn, Marvin C

2017-10-01

Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH 1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans. Published by Elsevier Ltd.

MR images of mouse brain using clinical 3T MR scanner and 4CH-Mouse coil

NASA Astrophysics Data System (ADS)

Lim, Soo Mee; Park, Eun Mi; Lyoo, In Kyoon; Lee, Junghyun; Han, Bo Mi; Lee, Jeong Kyong; Lee, Su Bin

2015-07-01

Objectives: Although small-bore high-field magnets are useful for research in small rodent models,this technology, however, has not been easily accessible to most researchers. This current study, thus,tried to evaluate the usability of 4CH-Mouse coil (Philips Healthcare, Best, the Netherlands) forpreclinical investigations in clinical 3T MR scan environment. We evaluated the effects of ischemicpreconditioning (IP) in the mouse stroke model with clinical 3T MR scanner and 4CH-Mouse coil. Materials and Methods: Experiments were performed on male C57BL/6 mice that either received the IP or sham operation (control). Three different MR sequences including diffusion weighted images (DWI), T2-weighted images (T2WI), and fluid attenuated inversion recovery (FLAIR) were performed on the mouse brains following 24, 72 hours of middle cerebral artery occlusion (MCAO) and analyzed for infarct lesions. Results: The images showed that the IP-treated mouse brains had significantly smaller infarct volumes compared to the control group. Of the MR sequences employed, the T2WI showed the highest level of correlations with postmortem infarct volume measurements. Conclusions: The clinical 3T MR scanner turned out to have a solid potential as a practical tool for imaging small animal brains. MR sequences including DWI, T2WI, FLAIR were obtained with acceptable resolution and in a reasonable time constraint in evaluating a mouse stroke model brain.

Mutagenicity testing with transgenic mice. Part I: Comparison with the mouse bone marrow micronucleus test

PubMed Central

Wahnschaffe, U; Bitsch, A; Kielhorn, J; Mangelsdorf, I

2005-01-01

As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue® mouse, and the lacZ model; commercially available as the Muta™Mouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects. PMID:15655069

Small space reactor power systems for unmanned solar system exploration missions

NASA Technical Reports Server (NTRS)

Bloomfield, Harvey S.

1987-01-01

A preliminary feasibility study of the application of small nuclear reactor space power systems to the Mariner Mark II Cassini spacecraft/mission was conducted. The purpose of the study was to identify and assess the technology and performance issues associated with the reactor power system/spacecraft/mission integration. The Cassini mission was selected because study of the Saturn system was identified as a high priority outer planet exploration objective. Reactor power systems applied to this mission were evaluated for two different uses. First, a very small 1 kWe reactor power system was used as an RTG replacement for the nominal spacecraft mission science payload power requirements while still retaining the spacecraft's usual bipropellant chemical propulsion system. The second use of reactor power involved the additional replacement of the chemical propulsion system with a small reactor power system and an electric propulsion system. The study also provides an examination of potential applications for the additional power available for scientific data collection. The reactor power system characteristics utilized in the study were based on a parametric mass model that was developed specifically for these low power applications. The model was generated following a neutronic safety and operational feasibility assessment of six small reactor concepts solicited from U.S. industry. This assessment provided the validation of reactor safety for all mission phases and generatad the reactor mass and dimensional data needed for the system mass model.

In vivo characterization of a bigenic fluorescent mouse model of Alzheimer's disease with neurodegeneration.

PubMed

Crowe, Sarah E; Ellis-Davies, Graham C R

2013-07-01

The loss of cognitive function in Alzheimer's disease (AD) patients is strongly correlated with the loss of neurons in various regions of the brain. We have created a new fluorescent bigenic mouse model of AD by crossing "H-line" yellow fluorescent protein (YFP) mice with the 5xFAD mouse model, which we call the 5XY mouse model. The 5xFAD mouse has been shown to have significant loss of L5 pyramidal neurons by 12 months of age. These neurons are transgenically labeled with YFP in the 5XY mouse, which enable longitudinal imaging of structural changes. In the 5XY mice, we observed an appearance of axonal dystrophies, with two distinct morphologies in the early stages of the disease progression. Simple swelling dystrophies are transient in nature and are not directly associated with amyloid plaques. Rosette dystrophies are more complex structures that remained stable throughout all imaging sessions, and always surrounded an amyloid plaque. Plaque growth was followed over 4 weeks, and significant growth was seen between weekly imaging sessions. In addition to axonal dystrophy appearance and plaque growth, we were able to follow spine stability in 4-month old 5XY mice, which revealed no significant loss of spines. 5XY mice also showed a striking shrinkage of the neocortex at older ages (12-14 months). The 5XY mouse model may be a valuable tool for studying specific events in the degeneration of the neocortex, and may suggest new avenues for therapeutic intervention. Copyright © 2013 Wiley Periodicals, Inc.

Technique Selectively Represses Immune System

MedlinePlus

... from attacking myelin in a mouse model of multiple sclerosis. Dr David Furness, Wellcome Images. All rights reserved ... devised a way to successfully treat symptoms resembling multiple sclerosis in a mouse model. With further development, the ...

Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome.

PubMed

Wu, Chaomin; Evans, Colin E; Dai, Zhiyu; Huang, Xiaojia; Zhang, Xianming; Jin, Hua; Hu, Guochang; Song, Yuanlin; Zhao, You-Yang

2017-01-01

Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans. Furthermore, current mouse models of ARDS do not recapitulate certain prominent aspects of the pathogenesis of ARDS in humans. In this study, we developed an improved endotoxemic mouse model of ARDS resembling many features of clinical ARDS including extended courses of injury and recovery as well as development of fibrosis following i.p. injection of lipopolysaccharide (LPS) to corn oil-preloaded mice. Compared with mice receiving LPS alone, those receiving corn oil and LPS exhibited extended course of lung injury and repair that occurred over a period of >2 weeks instead of 3-5days. Importantly, LPS challenge of corn oil-preloaded mice resulted in pulmonary fibrosis during the repair phase as often seen in ARDS patients. In summary, this simple novel mouse model of ARDS could represent a valuable experimental tool to elucidate mechanisms that regulate lung injury and repair in ARDS patients.

Endometrial apoptosis and neutrophil infiltration during menstruation exhibits spatial and temporal dynamics that are recapitulated in a mouse model.

PubMed

Armstrong, Gregory M; Maybin, Jacqueline A; Murray, Alison A; Nicol, Moira; Walker, Catherine; Saunders, Philippa T K; Rossi, Adriano G; Critchley, Hilary O D

2017-12-12

Menstruation is characterised by synchronous shedding and restoration of tissue integrity. An in vivo model of menstruation is required to investigate mechanisms responsible for regulation of menstrual physiology and to investigate common pathologies such as heavy menstrual bleeding (HMB). We hypothesised that our mouse model of simulated menstruation would recapitulate the spatial and temporal changes in the inflammatory microenvironment of human menses. Three regulatory events were investigated: cell death (apoptosis), neutrophil influx and cytokine/chemokine expression. Well-characterised endometrial tissues from women were compared with uteri from a mouse model (tissue recovered 0, 4, 8, 24 and 48 h after removal of a progesterone-secreting pellet). Immunohistochemistry for cleaved caspase-3 (CC3) revealed significantly increased staining in human endometrium from late secretory and menstrual phases. In mice, CC3 was significantly increased at 8 and 24 h post-progesterone-withdrawal. Elastase + human neutrophils were maximal during menstruation; Ly6G + mouse neutrophils were maximal at 24 h. Human endometrial and mouse uterine cytokine/chemokine mRNA concentrations were significantly increased during menstrual phase and 24 h post-progesterone-withdrawal respectively. Data from dated human samples revealed time-dependent changes in endometrial apoptosis preceding neutrophil influx and cytokine/chemokine induction during active menstruation. These dynamic changes were recapitulated in the mouse model of menstruation, validating its use in menstrual research.

KSC-97PC1068

NASA Image and Video Library

1997-07-18

Jet Propulsion Laboratory (JPL) workers Dan Maynard and John Shuping prepare to install a radioisotope thermoelectric generator (RTG) on the Cassini spacecraft in the Payload Hazardous Servicing Facility (PHSF). The three RTGs which will provide electrical power to Cassini on its mission to the Saturnian system are undergoing mechanical and electrical verification testing in the PHSF. RTGs use heat from the natural decay of plutonium to generate electric power. The generators enable spacecraft to operate far from the Sun where solar power systems are not feasible. The Cassini mission is scheduled for an Oct. 6 launch aboard a Titan IVB/Centaur expendable launch vehicle. Cassini is built and managed for NASA by JPL

Power Supplies for Space Systems Quality Assurance by Sandia Laboratories

DOE R&D Accomplishments Database

Hannigan, R. L.; Harnar, R. R.

1976-07-01

The Sandia Laboratories` participation in Quality Assurance programs for Radioisotopic Thermoelectric Generators which have been used in space systems over the past 10 years is summarized. Basic elements of this QA program are briefly described and recognition of assistance from other Sandia organizations is included. Descriptions of the various systems for which Sandia has had the QA responsibility are presented, including SNAP 19 (Nimbus, Pioneer, Viking), SNAP 27 (Apollo), Transit, Multi Hundred Watt (LES 8/9 and MJS), and a new program, High Performance Generator Mod 3. The outlook for Sandia participation in RTG programs for the next several years is noted.

Performance testing of thermoelectric generators including Voyager and LES 8/9 flight results

NASA Technical Reports Server (NTRS)

Garvey, L.; Stapfer, G.

1979-01-01

Several thermoelectric generators ranging in output power from 0.5 to 155 W have been completed or are undergoing testing at JPL. These generators represent a wide range of technologies, using Bi2Te3, PbTe and SiGe thermoelectric materials. Several of these generators are of a developmental type, such as HPG S/N2, and others are representative of Transit and Multi-Hundred Watt (MHW) Technology. Representative flight performance data of LES 8/9 and Voyager RTG's are presented and compared with the DEGRA computer program based on the data observed from tests of SiGe couples, modules and MHW generators.

Mars rover 1988 concepts

NASA Technical Reports Server (NTRS)

Pivirotto, Donna Shirley; Penn, Thomas J.; Dias, William C.

1989-01-01

Results of FY88 studies of a sample-collecting Mars rover are presented. A variety of rover concepts are discussed which include different technical approaches to rover functions. The performance of rovers with different levels of automation is described and compared to the science requirement for 20 to 40 km to be traversed on the Martian surface and for 100 rock and soil samples to be collected. The analysis shows that a considerable amount of automation in roving and sampling is required to meet this requirement. Additional performance evaluation shows that advanced RTG's producing 500 W and 350 WHr of battery storage are needed to supply the rover.

KSC-05pd2542

NASA Image and Video Library

2005-12-01

KENNEDY SPACE CENTER, FLA. - Inside NASA Kennedy Space Center’s Payload Hazardous Servicing Facility, workers push the newly arrived third stage, or upper stage for the New Horizons spacecraft, into position for uncovering. The third stage is a Boeing STAR 48 solid-propellant kick motor. The Atlas V is the launch vehicle for NASA’s New Horizons spacecraft, scheduled to launch from Cape Canaveral Air Force Station, Fla., during a 35-day window that opens Jan. 11 and fly through the Pluto system as early as summer 2015. New Horizons will be powered by a single radioisotope thermoelectric generator (RTG), provided by the Department of Energy, which will be installed shortly before launch.

KSC-05pd2539

NASA Image and Video Library

2005-12-01

KENNEDY SPACE CENTER, FLA. - Before dawn, the third stage, or upper stage for the New Horizons spacecraft, arrives at NASA Kennedy Space Center’s Payload Hazardous Servicing Facility. The third stage is a Boeing STAR 48 solid-propellant kick motor. The Atlas V is the launch vehicle for NASA’s New Horizons spacecraft, scheduled to launch from Cape Canaveral Air Force Station, Fla., during a 35-day window that opens Jan. 11 and fly through the Pluto system as early as summer 2015. New Horizons will be powered by a single radioisotope thermoelectric generator (RTG), provided by the Department of Energy, which will be installed shortly before launch.

KSC-05pd2541

NASA Image and Video Library

2005-12-01

KENNEDY SPACE CENTER, FLA. - The third stage, or upper stage for the New Horizons spacecraft, is moved toward the open door of NASA Kennedy Space Center’s Payload Hazardous Servicing Facility. The third stage is a Boeing STAR 48 solid-propellant kick motor. The Atlas V is the launch vehicle for NASA’s New Horizons spacecraft, scheduled to launch from Cape Canaveral Air Force Station, Fla., during a 35-day window that opens Jan. 11 and fly through the Pluto system as early as summer 2015. New Horizons will be powered by a single radioisotope thermoelectric generator (RTG), provided by the Department of Energy, which will be installed shortly before launch.

KSC-05pd2540

NASA Image and Video Library

2005-12-01

KENNEDY SPACE CENTER, FLA. - The third stage, or upper stage for the New Horizons spacecraft, is moved toward the open door of NASA Kennedy Space Center’s Payload Hazardous Servicing Facility. The third stage is a Boeing STAR 48 solid-propellant kick motor. The Atlas V is the launch vehicle for NASA’s New Horizons spacecraft, scheduled to launch from Cape Canaveral Air Force Station, Fla., during a 35-day window that opens Jan. 11 and fly through the Pluto system as early as summer 2015. New Horizons will be powered by a single radioisotope thermoelectric generator (RTG), provided by the Department of Energy, which will be installed shortly before launch.

KSC-05pd2543

NASA Image and Video Library

2005-12-01

KENNEDY SPACE CENTER, FLA. - Inside NASA Kennedy Space Center’s Payload Hazardous Servicing Facility, workers remove the protective cover from around the newly arrived third stage, or upper stage for the New Horizons spacecraft. The third stage is a Boeing STAR 48 solid-propellant kick motor. The Atlas V is the launch vehicle for NASA’s New Horizons spacecraft, scheduled to launch from Cape Canaveral Air Force Station, Fla., during a 35-day window that opens Jan. 11 and fly through the Pluto system as early as summer 2015. New Horizons will be powered by a single radioisotope thermoelectric generator (RTG), provided by the Department of Energy, which will be installed shortly before launch.

Space Science

NASA Image and Video Library

1997-07-18

Jet Propulsion Research Lab (JPL) workers use a borescope to verify the pressure relief device bellow's integrity on a radioisotope thermoelectric generator (RTG) that has been installed on the Cassini spacecraft in the Payload Hazardous Servicing Facility. The activity is part of the mechanical and electrical verification testing of RTGs during prelaunch processing. RTGs use heat from the natural decay of plutonium to generate electrical power. The three RTGs on Cassini will enable the spacecraft to operate far from the Sun where solar power systems are not feasible. They will provide electrical power to Cassini on it seven year trip to the Saturnian system and during its four year mission at Saturn.

The STR/ort mouse model of spontaneous osteoarthritis - an update.

PubMed

Staines, K A; Poulet, B; Wentworth, D N; Pitsillides, A A

2017-06-01

Osteoarthritis is a degenerative joint disease and a world-wide healthcare burden. Characterized by cartilage degradation, subchondral bone thickening and osteophyte formation, osteoarthritis inflicts much pain and suffering, for which there are currently no disease-modifying treatments available. Mouse models of osteoarthritis are proving critical in advancing our understanding of the underpinning molecular mechanisms. The STR/ort mouse is a well-recognized model which develops a natural form of osteoarthritis very similar to the human disease. In this Review we discuss the use of the STR/ort mouse in understanding this multifactorial disease with an emphasis on recent advances in its genetics and its bone, endochondral and immune phenotypes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mouse brain magnetic resonance microscopy: Applications in Alzheimer disease.

PubMed

Lin, Lan; Fu, Zhenrong; Xu, Xiaoting; Wu, Shuicai

2015-05-01

Over the past two decades, various Alzheimer's disease (AD) trangenetic mice models harboring genes with mutation known to cause familial AD have been created. Today, high-resolution magnetic resonance microscopy (MRM) technology is being widely used in the study of AD mouse models. It has greatly facilitated and advanced our knowledge of AD. In this review, most of the attention is paid to fundamental of MRM, the construction of standard mouse MRM brain template and atlas, the detection of amyloid plaques, following up on brain atrophy and the future applications of MRM in transgenic AD mice. It is believed that future testing of potential drugs in mouse models with MRM will greatly improve the predictability of drug effect in preclinical trials. © 2015 Wiley Periodicals, Inc.

Better Utilization of Mouse Models of Neurodegenerative Diseases in Preclinical Studies: From the Bench to the Clinic.

PubMed

Janus, Christopher; Hernandez, Carolina; deLelys, Victoria; Roder, Hanno; Welzl, Hans

2016-01-01

The major symptom of Alzheimer's disease is dementia progressing with age. Its clinical diagnosis is preceded by a long prodromal period of brain pathology that encompasses both formation of extracellular amyloid and intraneuronal tau deposits in the brain and widespread neuronal death. At present, familial cases of dementia provide the most promising foundation for modeling neurodegenerative tauopathies, a group of heterogeneous disorders characterized by prominent intracellular accumulation of hyperphosphorylated tau protein. In this chapter, we describe major behavioral hallmarks of tauopathies, briefly outline the genetics underlying familial cases, and discuss the arising implications for modeling the disease in transgenic mouse systems. The selection of tests performed to evaluate the phenotype of a model should be guided by the key behavioral hallmarks that characterize human disorder and their homology to mouse cognitive systems. We attempt to provide general guidelines and establish criteria for modeling dementia in a mouse; however, interpretations of obtained results should avoid a reductionist "one gene, one disease" explanation of model characteristics. Rather, the focus should be directed to the question of how the mouse genome can cope with the over-expression of the protein coded by transgene(s). While each model is valuable within its own constraints and the experiments performed are guided by specific hypotheses, we seek to expand upon their methodology by offering guidance spanning from issues of mouse husbandry to choices of behavioral tests and routes of drug administration that might increase the external validity of studies and consequently optimize the translational aspect of preclinical research.

Rodent models of congenital and hereditary cataract in man.

PubMed

Tripathi, B J; Tripathi, R C; Borisuth, N S; Dhaliwal, R; Dhaliwal, D

1991-01-01

Because the organogenesis and physiology of the lens are essentially similar in various mammals, an understanding of the etiology and pathogenesis of the formation of cataract in an animal model will enhance our knowledge of cataractogenesis in man. In this review, we summarize the background, etiology, and pathogenesis of cataracts that occur in rodents. The main advantages of using rodent mutants include the well-researched genetics of the animals and the comparative ease of breeding of large litters. Numerous rodent models of congenital and hereditary cataracts have been studied extensively. In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain. The rat models include BUdR, ICR, Sprague-Dawley, and Wistar rats, the spontaneously hypertensive rat (SHR), the John Rapp inbred strain of Dahl salt-sensitive rat, as well as WBN/Kob, Royal College of Surgeons (RCS), and Brown-Norway rats. Other proposed models for the study of hereditary cataract include the degu and the guinea pig. Because of the ease of making clinical observations in vivo and the subsequent availability of the intact lens for laboratory analyses at different stages of cataract formation, these animals provide excellent models for clinicopathologic correlations, for monitoring of the natural history of the aging process and of metabolic defects, as well as for investigations on the effect of cataract-modulating agents and drugs, including the prospect of gene therapy.

Mouse Genome Informatics (MGI) Is the International Resource for Information on the Laboratory Mouse.

PubMed

Law, MeiYee; Shaw, David R

2018-01-01

Mouse Genome Informatics (MGI, http://www.informatics.jax.org/ ) web resources provide free access to meticulously curated information about the laboratory mouse. MGI's primary goal is to help researchers investigate the genetic foundations of human diseases by translating information from mouse phenotypes and disease models studies to human systems. MGI provides comprehensive phenotypes for over 50,000 mutant alleles in mice and provides experimental model descriptions for over 1500 human diseases. Curated data from scientific publications are integrated with those from high-throughput phenotyping and gene expression centers. Data are standardized using defined, hierarchical vocabularies such as the Mammalian Phenotype (MP) Ontology, Mouse Developmental Anatomy and the Gene Ontologies (GO). This chapter introduces you to Gene and Allele Detail pages and provides step-by-step instructions for simple searches and those that take advantage of the breadth of MGI data integration.

Differential biological effects of dehydroepiandrosterone (DHEA) between mouse (B16F10) and human melanoma (BLM) cell lines.

PubMed

Joshi, Kumud; Hassan, Sherif S; Ramaraj, Pandurangan

2017-01-01

Dehydroepiandrosterone (DHEA) is a weak androgen and had been shown to have anti-cancer, anti-adipogenic and anti-inflammatory effects on mouse and other rodent models, but not on humans, suggesting a systemic level difference between mouse and human. Our previous study on DHEA biological functions involving a variety of cell lines, suggested that the functional differences between mouse and human existed even at the cellular level. Hence, using mouse and human melanoma cell models, in-vitro effects of DHEA on cell growth, mechanism of cell death and mechanism of DHEA action were studied. Results indicated a differential biological effects of DHEA between mouse and human melanoma cell lines. These in-vitro studies also suggested that the differential biological effects observed between these two cell lines could be due to the difference in the way DHEA was processed or metabolized inside the cell.

Current State of Animal (Mouse) Modeling in Melanoma Research.

PubMed

Kuzu, Omer F; Nguyen, Felix D; Noory, Mohammad A; Sharma, Arati

2015-01-01

Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

Identification of novel mRNAs and lncRNAs associated with mouse experimental colitis and human inflammatory bowel disease.

PubMed

Rankin, Carl Robert; Theodorou, Evangelos; Law, Ivy Ka Man; Rowe, Lorraine; Kokkotou, Efi; Pekow, Joel; Wang, Jiafang; Martin, Martin G; Pothoulakis, Charalabos; Padua, David Miguel

2018-06-28

Inflammatory bowel disease (IBD) is a complex disorder that is associated with significant morbidity. While many recent advances have been made with new diagnostic and therapeutic tools, a deeper understanding of its basic pathophysiology is needed to continue this trend towards improving treatments. By utilizing an unbiased, high-throughput transcriptomic analysis of two well-established mouse models of colitis, we set out to uncover novel coding and non-coding RNAs that are differentially expressed in the setting of colonic inflammation. RNA-seq analysis was performed using colonic tissue from two mouse models of colitis, a dextran sodium sulfate induced model and a genetic-induced model in mice lacking IL-10. We identified 81 coding RNAs that were commonly altered in both experimental models. Of these coding RNAs, 12 of the human orthologs were differentially expressed in a transcriptomic analysis of IBD patients. Interestingly, 5 of the 12 of human differentially expressed genes have not been previously identified as IBD-associated genes, including ubiquitin D. Our analysis also identified 15 non-coding RNAs that were differentially expressed in either mouse model. Surprisingly, only three non-coding RNAs were commonly dysregulated in both of these models. The discovery of these new coding and non-coding RNAs expands our transcriptional knowledge of mouse models of IBD and offers additional targets to deepen our understanding of the pathophysiology of IBD.

A Dynamic Simulation of Musculoskeletal Function in the Mouse Hindlimb During Trotting Locomotion

PubMed Central

Charles, James P.; Cappellari, Ornella; Hutchinson, John R.

2018-01-01

Mice are often used as animal models of various human neuromuscular diseases, and analysis of these models often requires detailed gait analysis. However, little is known of the dynamics of the mouse musculoskeletal system during locomotion. In this study, we used computer optimization procedures to create a simulation of trotting in a mouse, using a previously developed mouse hindlimb musculoskeletal model in conjunction with new experimental data, allowing muscle forces, activation patterns, and levels of mechanical work to be estimated. Analyzing musculotendon unit (MTU) mechanical work throughout the stride allowed a deeper understanding of their respective functions, with the rectus femoris MTU dominating the generation of positive and negative mechanical work during the swing and stance phases. This analysis also tested previous functional inferences of the mouse hindlimb made from anatomical data alone, such as the existence of a proximo-distal gradient of muscle function, thought to reflect adaptations for energy-efficient locomotion. The results do not strongly support the presence of this gradient within the mouse musculoskeletal system, particularly given relatively high negative net work output from the ankle plantarflexor MTUs, although more detailed simulations could test this further. This modeling analysis lays a foundation for future studies of the control of vertebrate movement through the development of neuromechanical simulations. PMID:29868576

Additive interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and clobazam in the mouse maximal electroshock-induced tonic seizure model--an isobolographic analysis for parallel dose-response relationship curves.

PubMed

Andres-Mach, Marta; Haratym-Maj, Agnieszka; Zagaja, Mirosław; Luszczki, Jarogniew J

2014-01-01

The aim of this study was to characterize the anticonvulsant effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ) in combination with clobazam (CLB) in the mouse maximal electroshock-induced seizure (MES) model. The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the mouse MES model was determined using an isobolographic analysis for parallel dose-response relationship curves. Electroconvulsions were produced in albino Swiss mice by a current (sine wave, 25 mA, 500 V, 50 Hz, 0.2-second stimulus duration) delivered via auricular electrodes by a Hugo Sachs generator. There was an additive effect of the combination of 1-MeTHIQ with CLB (at the fixed ratios of 1:3, 1:1 and 3:1) in the mouse MES-induced tonic seizure model. The additive interaction of the combination of 1-MeTHIQ with CLB (at fixed-ratios of 1:3, 1:1 and 3:1) in the mouse MES model seems to be pharmacodynamic in nature and worth of considering in further clinical practice. © 2014 S. Karger AG, Basel.

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID “Meet the Experts” 2015 Workshop Summary

PubMed Central

Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B.; Blankson, Joel N.; Burnett, John C.; Casares, Sofia; Garcia, J. Victor; Hasenkrug, Kim J.; Kitchen, Scott G.; Klein, Florian; Kumar, Priti; Luster, Andrew D.; Poluektova, Larisa Y.; Rao, Mangala; Shultz, Leonard D.; Zack, Jerome A.

2016-01-01

Abstract The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chainnull (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting. PMID:26670361

Behavioral assays with mouse models of Alzheimer’s disease: practical considerations and guidelines

PubMed Central

Puzzo, Daniela; Lee, Linda; Palmeri, Agostino; Calabrese, Giorgio; Arancio, Ottavio

2014-01-01

In Alzheimer’s disease (AD) basic research and drug discovery, mouse models are essential resources for uncovering biological mechanisms, validating molecular targets and screening potential compounds. Both transgenic and non-genetically modified mouse models enable access to different types of AD-like pathology in vivo. Although there is a wealth of genetic and biochemical studies on proposed AD pathogenic pathways, as a disease that centrally features cognitive failure, the ultimate readout for any interventions should be measures of learning and memory. This is particularly important given the lack of knowledge on disease etiology – assessment by cognitive assays offers the advantage of targeting relevant memory systems without requiring assumptions about pathogenesis. A multitude of behavioral assays are available for assessing cognitive functioning in mouse models, including ones specific for hippocampal-dependent learning and memory. Here we review the basics of available transgenic and non-transgenic AD mouse models and detail three well-established behavioral tasks commonly used for testing hippocampal-dependent cognition in mice – contextual fear conditioning, radial arm water maze and Morris water maze. In particular, we discuss the practical considerations, requirements and caveats of these behavioral testing paradigms. PMID:24462904

Icotinib inhibits EGFR signaling and alleviates psoriasis-like symptoms in animal models.

PubMed

Tan, Fenlai; Yang, Guiqun; Wang, Yanping; Chen, Haibo; Yu, Bo; Li, He; Guo, Jing; Huang, Xiaoling; Deng, Yifang; Yu, Pengxia; Ding, Lieming

2018-02-01

To investigate the effects of icotinib hydrochloride and a derivative cream on epidermal growth factor receptor (EGFR) signaling and within animal psoriasis models, respectively. The effect of icotinib on EGFR signaling was examined in HaCaT cells, while its effect on angiogenesis was tested in chick embryo chorioallantoic membranes (CAM). The effectiveness of icotinib in treating psoriasis was tested in three psoriasis models, including diethylstilbestrol-treated mouse vaginal epithelial cells, mouse tail granular cell layer formation, and propranolol-induced psoriasis-like features in guinea pig ear skin. Icotinib treatment blocked EGFR signaling and reduced HaCaT cell viability as well as suppressed CAM angiogenesis. Topical application of icotinib ameliorated psoriasis-like histological characteristics in mouse and guinea pig psoriasis models. Icotinib also significantly inhibited mouse vaginal epithelium mitosis, promoted mouse tail squamous epidermal granular layer formation, and reduced the thickness of the horny layer in propranolol treated auricular dorsal surface of guinea pig. We conclude that icotinib can effectively inhibit psoriasis in animal models. Future clinical studies should be conducted to explore the therapeutic effects of icotinb in humans. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Pathogenicity of swine influenza viruses possessing an avian or swine-origin PB2 polymerase gene evaluated in mouse and pig models.

PubMed

Ma, Wenjun; Lager, Kelly M; Li, Xi; Janke, Bruce H; Mosier, Derek A; Painter, Laura E; Ulery, Eva S; Ma, Jingqun; Lekcharoensuk, Porntippa; Webby, Richard J; Richt, Jürgen A

2011-02-05

PB2 627K is a determinant of influenza host range and contributes to the pathogenicity of human-, avian-, and mouse-adapted influenza viruses in the mouse model. Here we used mouse and pig models to analyze the contribution of a swine-origin and avian-origin PB2 carrying either 627K or 627E in the background of the classical swine H1N1 (A/Swine/Iowa/15/30; 1930) virus. The results showed PB2 627K is crucial for virulence in the mouse model, independent of whether PB2 is derived from an avian or swine influenza virus (SIV). In the pig model, PB2 627E decreases pathogenicity of the classical 1930 SIV when it contains the swine-origin PB2, but not when it possesses the avian-origin PB2. Our study suggests the pathogenicity of SIVs with different PB2 genes and mutation of codon 627 in mice does not correlate with the pathogenicity of the same SIVs in the natural host, the pig. Copyright © 2010 Elsevier Inc. All rights reserved.

An Immunocompetent Mouse Model of Zika Virus Infection.

PubMed

Gorman, Matthew J; Caine, Elizabeth A; Zaitsev, Konstantin; Begley, Matthew C; Weger-Lucarelli, James; Uccellini, Melissa B; Tripathi, Shashank; Morrison, Juliet; Yount, Boyd L; Dinnon, Kenneth H; Rückert, Claudia; Young, Michael C; Zhu, Zhe; Robertson, Shelly J; McNally, Kristin L; Ye, Jing; Cao, Bin; Mysorekar, Indira U; Ebel, Gregory D; Baric, Ralph S; Best, Sonja M; Artyomov, Maxim N; Garcia-Sastre, Adolfo; Diamond, Michael S

2018-05-09

Progress toward understanding Zika virus (ZIKV) pathogenesis is hindered by lack of immunocompetent small animal models, in part because ZIKV fails to effectively antagonize Stat2-dependent interferon (IFN) responses in mice. To address this limitation, we first passaged an African ZIKV strain (ZIKV-Dak-41525) through Rag1 -/- mice to obtain a mouse-adapted virus (ZIKV-Dak-MA) that was more virulent than ZIKV-Dak-41525 in mice treated with an anti-Ifnar1 antibody. A G18R substitution in NS4B was the genetic basis for the increased replication, and resulted in decreased IFN-β production, diminished IFN-stimulated gene expression, and the greater brain infection observed with ZIKV-Dak-MA. To generate a fully immunocompetent mouse model of ZIKV infection, human STAT2 was introduced into the mouse Stat2 locus (hSTAT2 KI). Subcutaneous inoculation of pregnant hSTAT2 KI mice with ZIKV-Dak-MA resulted in spread to the placenta and fetal brain. An immunocompetent mouse model of ZIKV infection may prove valuable for evaluating countermeasures to limit disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Histologic scoring of gastritis and gastric cancer in mouse models.

PubMed

Rogers, Arlin B

2012-01-01

Histopathology is a defining endpoint in mouse models of experimental gastritis and gastric adenocarcinoma. Presented here is an overview of the histology of gastritis and gastric cancer in mice experimentally infected with Helicobacter pylori or H. felis. A modular histopathologic scoring scheme is provided that incorporates relevant disease-associated changes. Whereas the guide uses Helicobacter infection as the prototype challenge, features may be applied to chemical and genetically engineered mouse models of stomach cancer as well. Specific criteria included in the combined gastric histologic activity index (HAI) include inflammation, epithelial defects, oxyntic atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia or neoplasia. Representative photomicrographs accompany descriptions for each lesion grade. Differentiation of genuine tumor invasion from pseudoinvasion is highlighted. A brief comparison of normal rodent versus human stomach anatomy and physiology is accompanied by an introduction to mouse-specific lesions including mucous metaplasia and eosinophilic droplets (hyalinosis). In conjunction with qualified pathology support, this guide is intended to assist research scientists, postdoctoral fellows, graduate students, and medical professionals from affiliated disciplines in the interpretation and histologic grading of chronic gastritis and gastric carcinoma in mouse models.

Astonishing advances in mouse genetic tools for biomedical research.

PubMed

Kaczmarczyk, Lech; Jackson, Walker S

2015-01-01

The humble house mouse has long been a workhorse model system in biomedical research. The technology for introducing site-specific genome modifications led to Nobel Prizes for its pioneers and opened a new era of mouse genetics. However, this technology was very time-consuming and technically demanding. As a result, many investigators continued to employ easier genome manipulation methods, though resulting models can suffer from overlooked or underestimated consequences. Another breakthrough, invaluable for the molecular dissection of disease mechanisms, was the invention of high-throughput methods to measure the expression of a plethora of genes in parallel. However, the use of samples containing material from multiple cell types could obfuscate data, and thus interpretations. In this review we highlight some important issues in experimental approaches using mouse models for biomedical research. We then discuss recent technological advances in mouse genetics that are revolutionising human disease research. Mouse genomes are now easily manipulated at precise locations thanks to guided endonucleases, such as transcription activator-like effector nucleases (TALENs) or the CRISPR/Cas9 system, both also having the potential to turn the dream of human gene therapy into reality. Newly developed methods of cell type-specific isolation of transcriptomes from crude tissue homogenates, followed by detection with next generation sequencing (NGS), are vastly improving gene regulation studies. Taken together, these amazing tools simplify the creation of much more accurate mouse models of human disease, and enable the extraction of hitherto unobtainable data.

Mutational landscape of a chemically-induced mouse model of liver cancer.

PubMed

Connor, Frances; Rayner, Tim F; Aitken, Sarah J; Feig, Christine; Lukk, Margus; Santoyo-Lopez, Javier; Odom, Duncan T

2018-06-26

Carcinogen-induced mouse models of liver cancer are used extensively to study pathogenesis of the disease and have a critical role in validating candidate therapeutics. These models can recapitulate molecular and histological features of human disease. However, it is not known if the genomic alterations driving these mouse tumour genomes are comparable to those found in human tumours. Here, we provide a detailed genomic characterisation of tumours from a commonly used mouse model of hepatocellular carcinoma (HCC). We analysed whole exome sequences of liver tumours arising in mice exposed to diethylnitrosamine (DEN). DEN-initiated tumours had a high, uniform number of somatic single nucleotide variants (SNVs), with few insertions, deletions or copy number alterations, consistent with the known genotoxic action of DEN. Exposure of hepatocytes to DEN left a reproducible mutational imprint in resulting tumour exomes which we could computationally reconstruct using six known COSMIC mutational signatures. The tumours carried a high diversity of low-incidence, non-synonymous point mutations in many oncogenes and tumour suppressors, reflecting the stochastic introduction of SNVs into the hepatocyte genome by the carcinogen. We identified four recurrently mutated genes that were putative oncogenic drivers of HCC in this model. Every neoplasm carried activating hotspot mutations either in codon 61 of Hras, in codon 584 of Braf or in codon 254 of Egfr. Truncating mutations of Apc occurred in 21% of neoplasms, which were exclusively carcinomas supporting a role for deregulation of Wnt/β-catenin signalling in cancer progression. Our study provides detailed insight into the mutational landscape of tumours arising in a commonly-used carcinogen model of HCC, facilitating the future use of this model to understand the human disease. Mouse models are widely used to study the biology of cancer and to test potential therapies. Here, we have described the mutational landscape of tumours arising in a carcinogen-induced mouse model of liver cancer. Since cancer is a disease caused by genomic alterations, information about the patterns and types of mutations in the tumours in this mouse model should facilitate its use to study human liver cancer. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chip Based Magnetic Imager for Molecular Profiling of Ovarian Cancer Cells

DTIC Science & Technology

2016-12-01

2015) Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell 160:1246-1260. PMC4380877, PMID:25748654. Acknowledgement of...Weissleder R, Lee H, Zhang F, Sharp PA (2015) Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell 160:1246-1260. 5. Im H, Shao H...Lett 32(10):1229–1231. 6 of 6 | www.pnas.org/cgi/doi/10.1073/pnas.1501815112 Im et al. Resource Genome-wide CRISPR Screen in a Mouse Model of Tumor

Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer

DTIC Science & Technology

2017-12-01

AWARD NUMBER: W81XWH-13-1-0162 TITLE: Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and...DATES COVERED 15Sept2013 - 14Sept2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic...for concisely studying castration response and CRPC. However, most mice never developed significant tumors. Here, we showed that ablation of p53 in this

Mouse Models for Drug Discovery. Can New Tools and Technology Improve Translational Power?

PubMed Central

Zuberi, Aamir; Lutz, Cathleen

2016-01-01

Abstract The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology. These technological advances come at a time when cost reductions in genome sequencing have led to the identification of pathogenic mutations in patient populations, providing unprecedented opportunities in the use of mice to model human disease. The ease of genetic engineering in mice also offers a potential paradigm shift in resource sharing and the speed by which models are made available in the public domain. Predictively, the knowledge alone that a model can be quickly remade will provide relief to resources encumbered by licensing and Material Transfer Agreements. For decades, mouse strains have provided an exquisite experimental tool to study the pathophysiology of the disease and assess therapeutic options in a genetically defined system. However, a major limitation of the mouse has been the limited genetic diversity associated with common laboratory mice. This has been overcome with the recent development of the Collaborative Cross and Diversity Outbred mice. These strains provide new tools capable of replicating genetic diversity to that approaching the diversity found in human populations. The Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population. The combination of traditional and contemporary mouse genome editing tools, along with the addition of genetic diversity in new modeling systems, are synergistic and serve to make the mouse a better model for biomedical research, enhancing the potential for preclinical drug discovery and personalized medicine. PMID:28053071

Mouse Model for the Preclinical Study of Metastatic Disease | NCI Technology Transfer Center | TTC

Cancer.gov

The Laboratory of Cancer Biology and Genetics, National Cancer Institute seeks partners for collaborative research to co-develop a mouse model that shows preclinical therapeutic response of residual metastatic disease.

Role of Growth Hormone in Prostate Cancer

DTIC Science & Technology

2007-02-01

syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci USA 94:13215... Laron mouse, in which the gene coding for both GHR and GH binding protein has been disrupted or knocked out, with the C3(1)/Tag mouse, which develops...the Laron mouse). Nevertheless, the new model presented here demonstrates that the loss of GHR produced a significant reduction in the level of PIN in

Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system.

PubMed

Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

2018-03-16

Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R -/- (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat's remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome

PubMed Central

Simoes de Souza, Fabio M.; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N.; Restrepo, Diego

2011-01-01

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities. PMID:22355654

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome.

PubMed

de Souza, Fabio M Simoes; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N; Restrepo, Diego

2011-01-01

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities.

A candidate model for Angelman syndrome in the mouse.

PubMed

Cattanach, B M; Barr, J A; Beechey, C V; Martin, J; Noebels, J; Jones, J

1997-07-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are well-recognized examples of imprinting in humans. They occur most commonly with paternal and maternal 15q11-13 deletions, but also with maternal and paternal disomy. Both syndromes have also occurred more rarely in association with smaller deletions seemingly causing abnormal imprinting. A putative mouse model of PWS, occurring with maternal duplication (partial maternal disomy) for the homologous region, has been described in a previous paper but, although a second imprinting effect that could have provided a mouse model of AS was found, it appeared to be associated with a slightly different region of the chromosome. Here, we provide evidence that the same region is in fact involved and further demonstrate that animals with paternal duplication for the region exhibit characteristics of AS patients. A mouse model of AS is, therefore, strongly indicated.

Development and testing of a mouse simulated space flight model

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

1987-01-01

The development and testing of a mouse model for simulating some aspects of weightlessness that occurs during space flight, and the carrying out of immunological experiments on animals undergoing space flight is examined. The mouse model developed was an antiorthostatic, hypokinetic, hypodynamic suspension model similar to one used with rats. The study was divided into two parts. The first involved determination of which immunological parameters should be observed on animals flown during space flight or studied in the suspension model. The second involved suspending mice and determining which of those immunological parameters were altered by the suspension. Rats that were actually flown in Space Shuttle SL-3 were used to test the hypotheses.

Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models.

PubMed

Choi, Catherine H; Schoenfeld, Brian P; Bell, Aaron J; Hinchey, Joseph; Rosenfelt, Cory; Gertner, Michael J; Campbell, Sean R; Emerson, Danielle; Hinchey, Paul; Kollaros, Maria; Ferrick, Neal J; Chambers, Daniel B; Langer, Steven; Sust, Steven; Malik, Aatika; Terlizzi, Allison M; Liebelt, David A; Ferreiro, David; Sharma, Ali; Koenigsberg, Eric; Choi, Richard J; Louneva, Natalia; Arnold, Steven E; Featherstone, Robert E; Siegel, Steven J; Zukin, R Suzanne; McDonald, Thomas V; Bolduc, Francois V; Jongens, Thomas A; McBride, Sean M J

2016-01-01

Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model.

The Virtual Mouse Brain: A Computational Neuroinformatics Platform to Study Whole Mouse Brain Dynamics.

PubMed

Melozzi, Francesca; Woodman, Marmaduke M; Jirsa, Viktor K; Bernard, Christophe

2017-01-01

Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brain's structure-function relationship, necessitating the close integration of diverse neuroinformatics fields. Here we extend the open-source simulation software The Virtual Brain (TVB) to whole mouse brain network modeling based on individual diffusion magnetic resonance imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain (TVMB) to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease. TVMB enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions.

Monitoring blood-flow in the mouse cochlea using an endoscopic laser speckle contrast imaging system

PubMed Central

Yu, Sunkon; Jung, Byungjo; Choi, Jin Sil

2018-01-01

Laser speckle contrast imaging (LSCI) enables continuous high-resolution assessment of microcirculation in real-time. We applied an endoscope to LSCI to measure cochlear blood-flow in an ischemia–reperfusion mouse model. We also explored whether using xenon light in combination with LSCI facilitates visualization of anatomical position. Based on a previous preliminary study, the appropriate wavelength for penetrating the thin bony cochlea was 830 nm. A 2.7-mm-diameter endoscope was used, as appropriate for the size of the mouse cochlea. Our endoscopic LSCI system was used to illuminate the right cochlea after dissection of the mouse. We observed changes in the speckle signals when we applied the endoscopic LSCI system to the ischemia-reperfusion mouse model. The anatomical structure of the mouse cochlea and surrounding structures were clearly visible using the xenon light. The speckle signal of the cochlea was scattered, with an intensity that varied between that of the stapes (with the lowest signal), the negative control, and the stapedial artery (with the highest signal), the positive control. In the cochlear ischemia–reperfusion mouse model, the speckle signal of the cochlea decreased during the ischemic phase, and increased during the reperfusion phase, clearly reflecting cochlear blood-flow. The endoscopic LSCI system generates high-resolution images in real-time, allowing visualization of blood-flow and its changes in the mouse cochlea. Anatomical structures were clearly matched using LSCI along with visible light. PMID:29489849

Monitoring blood-flow in the mouse cochlea using an endoscopic laser speckle contrast imaging system.

PubMed

Kong, Tae Hoon; Yu, Sunkon; Jung, Byungjo; Choi, Jin Sil; Seo, Young Joon

2018-01-01

Laser speckle contrast imaging (LSCI) enables continuous high-resolution assessment of microcirculation in real-time. We applied an endoscope to LSCI to measure cochlear blood-flow in an ischemia-reperfusion mouse model. We also explored whether using xenon light in combination with LSCI facilitates visualization of anatomical position. Based on a previous preliminary study, the appropriate wavelength for penetrating the thin bony cochlea was 830 nm. A 2.7-mm-diameter endoscope was used, as appropriate for the size of the mouse cochlea. Our endoscopic LSCI system was used to illuminate the right cochlea after dissection of the mouse. We observed changes in the speckle signals when we applied the endoscopic LSCI system to the ischemia-reperfusion mouse model. The anatomical structure of the mouse cochlea and surrounding structures were clearly visible using the xenon light. The speckle signal of the cochlea was scattered, with an intensity that varied between that of the stapes (with the lowest signal), the negative control, and the stapedial artery (with the highest signal), the positive control. In the cochlear ischemia-reperfusion mouse model, the speckle signal of the cochlea decreased during the ischemic phase, and increased during the reperfusion phase, clearly reflecting cochlear blood-flow. The endoscopic LSCI system generates high-resolution images in real-time, allowing visualization of blood-flow and its changes in the mouse cochlea. Anatomical structures were clearly matched using LSCI along with visible light.

ANALYSIS OF TMEFF2 ALLOGRAFTS AND TRANSGENIC MOUSE MODELS REVEALS ROLES IN PROSTATE REGENERATION AND CANCER

PubMed Central

Corbin, JM.; Overcash, RF.; Wren, JD.; Coburn, A.; Tipton, GJ.; Ezzell, JA.; McNaughton, KK.; Fung, KM; Kosanke, SD.; Ruiz-Echevarria, MJ

2015-01-01

BACKGROUND Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. METHODS The role of TMEFF2 was examined in PCa cells using Matrigel™ cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. RESULTS Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. CONCLUSIONS Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and multifunctional role for TMEFF2 during PCa progression. PMID:26417683

Analysis of TMEFF2 allografts and transgenic mouse models reveals roles in prostate regeneration and cancer.

PubMed

Corbin, Joshua M; Overcash, Ryan F; Wren, Jonathan D; Coburn, Anita; Tipton, Greg J; Ezzell, Jennifer A; McNaughton, Kirk K; Fung, Kar-Ming; Kosanke, Stanley D; Ruiz-Echevarria, Maria J

2016-01-01

Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. The role of TMEFF2 was examined in PCa cells using Matrigel(TM) cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological, and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and multifunctional role for TMEFF2 during PCa progression. © 2015 Wiley Periodicals, Inc.

What do mouse models of muscular dystrophy tell us about the DAPC and its components?

PubMed

Whitmore, Charlotte; Morgan, Jennifer

2014-12-01

There are over 30 mouse models with mutations or inactivations in the dystrophin-associated protein complex. This complex is thought to play a crucial role in the functioning of muscle, as both a shock absorber and signalling centre, although its role in the pathogenesis of muscular dystrophy is not fully understood. The first mouse model of muscular dystrophy to be identified with a mutation in a component of the dystrophin-associated complex (dystrophin) was the mdx mouse in 1984. Here, we evaluate the key characteristics of the mdx in comparison with other mouse mutants with inactivations in DAPC components, along with key modifiers of the disease phenotype. By discussing the differences between the individual phenotypes, we show that the functioning of the DAPC and consequently its role in the pathogenesis is more complicated than perhaps currently appreciated. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration

PubMed Central

Shu, Xinhua; Luhmann, Ulrich F. O.; Aleman, Tomas S.; Barker, Susan E.; Lennon, Alan; Tulloch, Brian; Chen, Mei; Xu, Heping; Jacobson, Samuel G.; Ali, Robin; Wright, Alan F.

2011-01-01

A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse “knock-in” model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct. PMID:22110650

Live dynamic imaging and analysis of developmental cardiac defects in mouse models with optical coherence tomography

NASA Astrophysics Data System (ADS)

Lopez, Andrew L.; Wang, Shang; Garcia, Monica; Valladolid, Christian; Larin, Kirill V.; Larina, Irina V.

2015-03-01

Understanding mouse embryonic development is an invaluable resource for our interpretation of normal human embryology and congenital defects. Our research focuses on developing methods for live imaging and dynamic characterization of early embryonic development in mouse models of human diseases. Using multidisciplinary methods: optical coherence tomography (OCT), live mouse embryo manipulations and static embryo culture, molecular biology, advanced image processing and computational modeling we aim to understand developmental processes. We have developed an OCT based approach to image live early mouse embryos (E8.5 - E9.5) cultured on an imaging stage and visualize developmental events with a spatial resolution of a few micrometers (less than the size of an individual cell) and a frame rate of up to hundreds of frames per second and reconstruct cardiodynamics in 4D (3D+time). We are now using these methods to study how specific embryonic lethal mutations affect cardiac morphology and function during early development.

Scattered Dose Calculations and Measurements in a Life-Like Mouse Phantom

PubMed Central

Welch, David; Turner, Leah; Speiser, Michael; Randers-Pehrson, Gerhard; Brenner, David J.

2017-01-01

Anatomically accurate phantoms are useful tools for radiation dosimetry studies. In this work, we demonstrate the construction of a new generation of life-like mouse phantoms in which the methods have been generalized to be applicable to the fabrication of any small animal. The mouse phantoms, with built-in density inhomogeneity, exhibit different scattering behavior dependent on where the radiation is delivered. Computer models of the mouse phantoms and a small animal irradiation platform were devised in Monte Carlo N-Particle code (MCNP). A baseline test replicating the irradiation system in a computational model shows minimal differences from experimental results from 50 Gy down to 0.1 Gy. We observe excellent agreement between scattered dose measurements and simulation results from X-ray irradiations focused at either the lung or the abdomen within our phantoms. This study demonstrates the utility of our mouse phantoms as measurement tools with the goal of using our phantoms to verify complex computational models. PMID:28140787

Overview of genetically engineered mouse models of colorectal carcinoma to enable translational biology and drug development.

PubMed

Roper, Jatin; Martin, Eric S; Hung, Kenneth E

2014-06-16

Preclinical models for colorectal cancer (CRC) are critical for translational biology and drug development studies to characterize and treat this condition. Mouse models of human cancer are particularly popular because of their relatively low cost, short life span, and ease of use. Genetically engineered mouse models (GEMMs) of CRC are engineered from germline or somatic modification of critical tumor suppressor genes and/or oncogenes that drive mutations in human disease. Detailed in this overview are the salient features of several useful colorectal cancer GEMMs and their value as tools for translational biology and preclinical drug development. Copyright © 2014 John Wiley & Sons, Inc.

Application of Mouse Models to Research in Hearing and Balance.

PubMed

Ohlemiller, Kevin K; Jones, Sherri M; Johnson, Kenneth R

2016-12-01

Laboratory mice (Mus musculus) have become the major model species for inner ear research. The major uses of mice include gene discovery, characterization, and confirmation. Every application of mice is founded on assumptions about what mice represent and how the information gained may be generalized. A host of successes support the continued use of mice to understand hearing and balance. Depending on the research question, however, some mouse models and research designs will be more appropriate than others. Here, we recount some of the history and successes of the use of mice in hearing and vestibular studies and offer guidelines to those considering how to apply mouse models.

Continuous imaging of the blood vessels in tumor mouse dorsal skin window chamber model by using SD-OCT

NASA Astrophysics Data System (ADS)

Peng, Xiao; Yang, Shaozhuang; Yu, Bin; Wang, Qi; Lin, Danying; Gao, Jian; Zhang, Peiqi; Ma, Yiqun; Qu, Junle; Niu, Hanben

2016-03-01

Optical Coherence Tomography (OCT) has been widely applied into microstructure imaging of tissues or blood vessels with a series of advantages, including non-destructiveness, real-time imaging, high resolution and high sensitivity. In this study, a Spectral Domain OCT (SD-OCT) system with higher sensitivity and signal-to-noise ratio (SNR) was built up, which was used to observe the blood vessel distribution and blood flow in the dorsal skin window chamber of the nude mouse tumor model. In order to obtain comparable data, the distribution images of blood vessels were collected from the same mouse before and after tumor injection. In conclusion, in vivo blood vessel distribution images of the tumor mouse model have been continuously obtained during around two weeks.

Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes

PubMed Central

Petrosino, Jennifer M.; Heiss, Valerie J.; Maurya, Santosh K.; Kalyanasundaram, Anuradha; Periasamy, Muthu; LaFountain, Richard A.; Wilson, Jacob M.; Simonetti, Orlando P.; Ziouzenkova, Ouliana

2016-01-01

Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of novel therapeutics. PMID:26859763

Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.

PubMed

Petrosino, Jennifer M; Heiss, Valerie J; Maurya, Santosh K; Kalyanasundaram, Anuradha; Periasamy, Muthu; LaFountain, Richard A; Wilson, Jacob M; Simonetti, Orlando P; Ziouzenkova, Ouliana

2016-01-01

Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of novel therapeutics.

Bridging gaps: On the performance of airborne LiDAR to model wood mouse-habitat structure relationships in pine forests.

PubMed

Jaime-González, Carlos; Acebes, Pablo; Mateos, Ana; Mezquida, Eduardo T

2017-01-01

LiDAR technology has firmly contributed to strengthen the knowledge of habitat structure-wildlife relationships, though there is an evident bias towards flying vertebrates. To bridge this gap, we investigated and compared the performance of LiDAR and field data to model habitat preferences of wood mouse (Apodemus sylvaticus) in a Mediterranean high mountain pine forest (Pinus sylvestris). We recorded nine field and 13 LiDAR variables that were summarized by means of Principal Component Analyses (PCA). We then analyzed wood mouse's habitat preferences using three different models based on: (i) field PCs predictors, (ii) LiDAR PCs predictors; and (iii) both set of predictors in a combined model, including a variance partitioning analysis. Elevation was also included as a predictor in the three models. Our results indicate that LiDAR derived variables were better predictors than field-based variables. The model combining both data sets slightly improved the predictive power of the model. Field derived variables indicated that wood mouse was positively influenced by the gradient of increasing shrub cover and negatively affected by elevation. Regarding LiDAR data, two LiDAR PCs, i.e. gradients in canopy openness and complexity in forest vertical structure positively influenced wood mouse, although elevation interacted negatively with the complexity in vertical structure, indicating wood mouse's preferences for plots with lower elevations but with complex forest vertical structure. The combined model was similar to the LiDAR-based model and included the gradient of shrub cover measured in the field. Variance partitioning showed that LiDAR-based variables, together with elevation, were the most important predictors and that part of the variation explained by shrub cover was shared. LiDAR derived variables were good surrogates of environmental characteristics explaining habitat preferences by the wood mouse. Our LiDAR metrics represented structural features of the forest patch, such as the presence and cover of shrubs, as well as other characteristics likely including time since perturbation, food availability and predation risk. Our results suggest that LiDAR is a promising technology for further exploring habitat preferences by small mammal communities.

Ultrastructural study of Rift Valley fever virus in the mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reed, Christopher; Steele, Keith E.; Honko, Anna

Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed inmore » the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV-host interactions and further characterize the mouse model of RVF.« less

Diverse Application of Magnetic Resonance Imaging for Mouse Phenotyping

PubMed Central

Wu, Yijen L.; Lo, Cecilia W.

2017-01-01

Small animal models, particularly mouse models, of human diseases are becoming an indispensable tool for biomedical research. Studies in animal models have provided important insights into the etiology of diseases and accelerated the development of therapeutic strategies. Detailed phenotypic characterization is essential, both for the development of such animal models and mechanistic studies into disease pathogenesis and testing the efficacy of experimental therapeutics. Magnetic Resonance Imaging (MRI) is a versatile and non-invasive imaging modality with excellent penetration depth, tissue coverage, and soft tissue contrast. MRI, being a multi-modal imaging modality, together with proven imaging protocols and availability of good contrast agents, is ideally suited for phenotyping mutant mouse models. Here we describe the applications of MRI for phenotyping structural birth defects involving the brain, heart, and kidney in mice. The versatility of MRI and its ease of use are well suited to meet the rapidly increasing demands for mouse phenotyping in the coming age of functional genomics. PMID:28544650

A G542X cystic fibrosis mouse model for examining nonsense mutation directed therapies.

PubMed

McHugh, Daniel R; Steele, Miarasa S; Valerio, Dana M; Miron, Alexander; Mann, Rachel J; LePage, David F; Conlon, Ronald A; Cotton, Calvin U; Drumm, Mitchell L; Hodges, Craig A

2018-01-01

Nonsense mutations are present in 10% of patients with CF, produce a premature termination codon in CFTR mRNA causing early termination of translation, and lead to lack of CFTR function. There are no currently available animal models which contain a nonsense mutation in the endogenous Cftr locus that can be utilized to test nonsense mutation therapies. In this study, we create a CF mouse model carrying the G542X nonsense mutation in Cftr using CRISPR/Cas9 gene editing. The G542X mouse model has reduced Cftr mRNA levels, demonstrates absence of CFTR function, and displays characteristic manifestations of CF mice such as reduced growth and intestinal obstruction. Importantly, CFTR restoration is observed in G542X intestinal organoids treated with G418, an aminoglycoside with translational readthrough capabilities. The G542X mouse model provides an invaluable resource for the identification of potential therapies of CF nonsense mutations as well as the assessment of in vivo effectiveness of these potential therapies targeting nonsense mutations.

Humanized Mouse Models for the Study of Human Malaria Parasite Biology, Pathogenesis, and Immunity.

PubMed

Minkah, Nana K; Schafer, Carola; Kappe, Stefan H I

2018-01-01

Malaria parasite infection continues to inflict extensive morbidity and mortality in resource-poor countries. The insufficiently understood parasite biology, continuously evolving drug resistance and the lack of an effective vaccine necessitate intensive research on human malaria parasites that can inform the development of new intervention tools. Humanized mouse models have been greatly improved over the last decade and enable the direct study of human malaria parasites in vivo in the laboratory. Nevertheless, no small animal model developed so far is capable of maintaining the complete life cycle of Plasmodium parasites that infect humans. The ultimate goal is to develop humanized mouse systems in which a Plasmodium infection closely reproduces all stages of a parasite infection in humans, including pre-erythrocytic infection, blood stage infection and its associated pathology, transmission as well as the human immune response to infection. Here, we discuss current humanized mouse models and the future directions that should be taken to develop next-generation models for human malaria parasite research.

In utero mouse embryonic imaging with OCT for ophthalmologic research

NASA Astrophysics Data System (ADS)

Syed, Saba H.; Larina, Irina V.; Dickinson, Mary E.; Larin, Kirill V.

2011-03-01

Live imaging of an eye during embryonic development in mammalian model is important for understanding dynamic aspects of normal and abnormal eye morphogenesis. In this study, we used Swept Source Optical Coherence Tomography (SS-OCT) for live structural imaging of mouse embryonic eye through the uterine wall. The eye structure was reconstructed in mouse embryos at 13.5 to 17.5 days post coitus (dpc). Despite the limited imaging depth of OCT in turbid tissues, we were able to visualize the whole eye globe at these stages. These results suggest that live in utero OCT imaging is a useful tool to study embryonic eye development in the mouse model.

A physiologically based pharmacokinetic model for atrazine and its main metabolites in the adult male C57BL/6 mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin Zhoumeng; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602; Fisher, Jeffrey W.

Atrazine (ATR) is a chlorotriazine herbicide that is widely used and relatively persistent in the environment. In laboratory rodents, excessive exposure to ATR is detrimental to the reproductive, immune, and nervous systems. To better understand the toxicokinetics of ATR and to fill the need for a mouse model, a physiologically based pharmacokinetic (PBPK) model for ATR and its main chlorotriazine metabolites (Cl-TRIs) desethyl atrazine (DE), desisopropyl atrazine (DIP), and didealkyl atrazine (DACT) was developed for the adult male C57BL/6 mouse. Taking advantage of all relevant and recently made available mouse-specific data, a flow-limited PBPK model was constructed. The ATR andmore » DACT sub-models included blood, brain, liver, kidney, richly and slowly perfused tissue compartments, as well as plasma protein binding and red blood cell binding, whereas the DE and DIP sub-models were constructed as simple five-compartment models. The model adequately simulated plasma levels of ATR and Cl-TRIs and urinary dosimetry of Cl-TRIs at four single oral dose levels (250, 125, 25, and 5 mg/kg). Additionally, the model adequately described the dose dependency of brain and liver ATR and DACT concentrations. Cumulative urinary DACT amounts were accurately predicted across a wide dose range, suggesting the model's potential use for extrapolation to human exposures by performing reverse dosimetry. The model was validated using previously reported data for plasma ATR and DACT in mice and rats. Overall, besides being the first mouse PBPK model for ATR and its Cl-TRIs, this model, by analogy, provides insights into tissue dosimetry for rats. The model could be used in tissue dosimetry prediction and as an aid in the exposure assessment to this widely used herbicide.« less

Comparative mRNA analysis of behavioral and genetic mouse models of aggression.

PubMed

Malki, Karim; Tosto, Maria G; Pain, Oliver; Sluyter, Frans; Mineur, Yann S; Crusio, Wim E; de Boer, Sietse; Sandnabba, Kenneth N; Kesserwani, Jad; Robinson, Edward; Schalkwyk, Leonard C; Asherson, Philip

2016-04-01

Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and C57BL/6. However, these strains were not designed to study aggression despite differences in aggression-related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of aggression with those from a recent genetic mouse model aggression. The study used a discovery-replication design using two independent mRNA studies from mouse brain tissue. The discovery study identified strain (BALB/cJ and C57BL/6J) × stress (chronic mild stress or control) interactions. Probe sets differentially regulated in the discovery set were intersected with those uncovered in the replication study, which evaluated differences between high and low aggressive animals from three strains specifically bred to study aggression. Network analysis was conducted on overlapping genes uncovered across both studies. A significant overlap was found with the genetic mouse study sharing 1,916 probe sets with the stress model. Fifty-one probe sets were found to be strongly dysregulated across both studies mapping to 50 known genes. Network analysis revealed two plausible pathways including one centered on the UBC gene hub which encodes ubiquitin, a protein well-known for protein degradation, and another on P38 MAPK. Findings from this study support the stress model of aggression, which showed remarkable molecular overlap with a genetic model. The study uncovered a set of candidate genes including the Erg2 gene, which has previously been implicated in different psychopathologies. The gene networks uncovered points at a Redox pathway as potentially being implicated in aggressive related behaviors. © 2016 Wiley Periodicals, Inc.

The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice.

PubMed

Waumans, Yannick; Vliegen, Gwendolyn; Maes, Lynn; Rombouts, Miche; Declerck, Ken; Van Der Veken, Pieter; Vanden Berghe, Wim; De Meyer, Guido R Y; Schrijvers, Dorien; De Meester, Ingrid

2016-02-01

Atherosclerosis remains the leading cause of death in Western countries. Dipeptidyl peptidase (DPP) 4 has emerged as a novel target for the prevention and treatment of atherosclerosis. Family members DPP8 and 9 are abundantly present in macrophage-rich regions of atherosclerotic plaques, and DPP9 inhibition attenuates activation of human M1 macrophages in vitro. Studying this family in a mouse model for atherosclerosis would greatly advance our knowledge regarding their potential as therapeutic targets. We found that DPP4 is downregulated during mouse monocyte-to-macrophage differentiation. DPP8 and 9 expression seems relatively low in mouse monocytes and macrophages. Viability of primary mouse macrophages is unaffected by DPP4 or DPP8/9 inhibition. Importantly, DPP8/9 inhibition attenuates macrophage activation as IL-6 secretion is significantly decreased. Mouse macrophages respond similarly to DPP inhibition, compared to human macrophages. This shows that the mouse could become a valid model species for the study of DPPs as therapeutic targets in atherosclerosis.

The effect of graded monetary reward on cognitive event-related potentials and behavior in young healthy adults

PubMed Central

Goldstein, Rita Z.; Cottone, Lisa A.; Jia, Zhiru; Maloney, Thomas; Volkow, Nora D.; Squires, Nancy K.

2008-01-01

Temporal correlates of the brain circuit underlying reward processing in healthy adults remain unclear. The current study investigated the P3 and contingent negative variation (CNV) as putative reward-related temporal markers. The effect of sustained monetary reward on these event-related potentials and on behavior was assessed using a warned reaction-time paradigm in 16 young healthy subjects. Monetary reward (0, 1 and 45 cents) varied across blocks of trials. While the CNV was unaffected by money, P3 amplitude was significantly larger for 45 than the 1 and 0 cent conditions. This effect corresponded to the monotonically positive subjective ratings of interest and excitement on the task (45>1>0). These findings suggest a difference between the P3 and CNV; the P3 is sensitive to the sustained effect of relative reward value while the CNV does not vary with reward magnitude. PMID:16876894

Dyadic social interaction of C57BL/6 mice versus interaction with a toy mouse: conditioned place preference/aversion, substrain differences, and no development of a hierarchy.

PubMed

Pinheiro, Barbara S; Seidl, Simon S; Habazettl, Eva; Gruber, Bernadette E; Bregolin, Tanja; Zernig, Gerald

2016-04-01

Impaired social interaction is a hallmark symptom of many psychiatric diseases, including dependence syndromes (substance use disorders). Helping the addict reorient her/his behavior away from the drug of abuse toward social interaction would be of considerable therapeutic benefit. To study the neural basis of such a reorientation, we have developed several animal models in which the attractiveness of a dyadic (i.e. one-to-one) social interaction (DSI) can be compared directly with that of cocaine as a prototypical drug of abuse. Our models are based on the conditioned place preference (CPP) paradigm. In an ongoing effort to validate our experimental paradigms in C57BL/6 mice to make use of the plethora of transgenic models available in this genus, we found the following: (a) DSI with a live mouse produced CPP, whereas an interaction with an inanimate mouse-like object (i.e. a 'toy mouse'; toy mouse interaction) led to conditioned place aversion - but only in the Jackson substrain (C57BL/6J). (b) In the NIH substrain (C57BL/6N), both DSI and toy mouse interaction produced individual aversion in more than 50% of the tested mice. (c) Four 15 min DSI episodes did not result in the development of an observable hierarchy, that is, dominance/subordination behavior in the overwhelming majority (i.e. 30 of 32) of the tested Jackson mouse pairs. Therefore, dominance/subordination does not seem to be a confounding variable in our paradigm, at least not in C57BL/6J mice. Respective data for NIH mice were too limited to allow any conclusion. The present findings indicate that (a) DSI with a live mouse produces CPP to a greater degree than an interaction with an inanimate object resembling a mouse and that (b) certain substrain differences with respect to CPP/aversion to DSI do exist between the Jax and NIH substrain of C57BL/6 mice. These differences have to be considered when choosing a proper mouse substrain model for investigating the neural basis of DSI reward versus drug reward.

Quantitative volumetric imaging of normal, neoplastic and hyperplastic mouse prostate using ultrasound.

PubMed

Singh, Shalini; Pan, Chunliu; Wood, Ronald; Yeh, Chiuan-Ren; Yeh, Shuyuan; Sha, Kai; Krolewski, John J; Nastiuk, Kent L

2015-09-21

Genetically engineered mouse models are essential to the investigation of the molecular mechanisms underlying human prostate pathology and the effects of therapy on the diseased prostate. Serial in vivo volumetric imaging expands the scope and accuracy of experimental investigations of models of normal prostate physiology, benign prostatic hyperplasia and prostate cancer, which are otherwise limited by the anatomy of the mouse prostate. Moreover, accurate imaging of hyperplastic and tumorigenic prostates is now recognized as essential to rigorous pre-clinical trials of new therapies. Bioluminescent imaging has been widely used to determine prostate tumor size, but is semi-quantitative at best. Magnetic resonance imaging can determine prostate volume very accurately, but is expensive and has low throughput. We therefore sought to develop and implement a high throughput, low cost, and accurate serial imaging protocol for the mouse prostate. We developed a high frequency ultrasound imaging technique employing 3D reconstruction that allows rapid and precise assessment of mouse prostate volume. Wild-type mouse prostates were examined (n = 4) for reproducible baseline imaging, and treatment effects on volume were compared, and blinded data analyzed for intra- and inter-operator assessments of reproducibility by correlation and for Bland-Altman analysis. Examples of benign prostatic hyperplasia mouse model prostate (n = 2) and mouse prostate implantation of orthotopic human prostate cancer tumor and its growth (n =  ) are also demonstrated. Serial measurement volume of the mouse prostate revealed that high frequency ultrasound was very precise. Following endocrine manipulation, regression and regrowth of the prostate could be monitored with very low intra- and interobserver variability. This technique was also valuable to monitor the development of prostate growth in a model of benign prostatic hyperplasia. Additionally, we demonstrate accurate ultrasound image-guided implantation of orthotopic tumor xenografts and monitoring of subsequent tumor growth from ~10 to ~750 mm(3) volume. High frequency ultrasound imaging allows precise determination of normal, neoplastic and hyperplastic mouse prostate. Low cost and small image size allows incorporation of this imaging modality inside clean animal facilities, and thereby imaging of immunocompromised models. 3D reconstruction for volume determination is easily mastered, and both small and large relative changes in volume are accurately visualized. Ultrasound imaging does not rely on penetration of exogenous imaging agents, and so may therefore better measure poorly vascularized or necrotic diseased tissue, relative to bioluminescent imaging (IVIS). Our method is precise and reproducible with very low inter- and intra-observer variability. Because it is non-invasive, mouse models of prostatic disease states can be imaged serially, reducing inter-animal variability, and enhancing the power to detect small volume changes following therapeutic intervention.

Practical use of advanced mouse models for lung cancer.

PubMed

Safari, Roghaiyeh; Meuwissen, Ralph

2015-01-01

To date a variety of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) mouse models have been developed that mimic human lung cancer. Chemically induced or spontaneous lung cancer in susceptible inbred strains has been widely used, but the more recent genetically engineered somatic mouse models recapitulate much better the genotype-phenotype correlations found in human lung cancer. Additionally, improved orthotopic transplantation of primary human cancer tissue fragments or cells into lungs of immune-compromised mice can be valuable tools for preclinical research such as antitumor drug tests. Here we give a short overview of most somatic mouse models for lung cancer that are currently in use. We accompany each different model with a description of its practical use and application for all major lung tumor types, as well as the intratracheal injection or direct injection of fresh or freeze-thawed tumor cells or tumor cell lines into lung parenchyma of recipient mice. All here presented somatic mouse models are based on the ability to (in) activate specific alleles at a time, and in a tissue-specific cell type, of choice. This spatial-temporal controlled induction of genetic lesions allows the selective introduction of main genetic lesions in an adult mouse lung as found in human lung cancer. The resulting conditional somatic mouse models can be used as versatile powerful tools in basic lung cancer research and preclinical translational studies alike. These distinctively advanced lung cancer models permit us to investigate initiation (cell of origin) and progression of lung cancer, along with response and resistance to drug therapy. Cre/lox or FLP/frt recombinase-mediated methods are now well-used techniques to develop tissue-restricted lung cancer in mice with tumor-suppressor gene and/or oncogene (in)activation. Intranasal or intratracheal administration of engineered adenovirus-Cre or lentivirus-Cre has been optimized for introducing Cre recombinase activity into pulmonary tissues, and we discuss here the different techniques underlying these applications. Concomitant with Cre/Flp recombinase-based models are the tetracycline (Tet)-inducible bitransgenic systems in which presence or absence of doxycycline can turn the expression of a specific oncogene on or off. The use of several Tet-inducible lung cancer models for NSCLC is presented here in which the reversal of oncogene expression led to complete tumor regression and provided us with important insight of how oncogene dependence influence lung cancer survival and growth. As alternative to Tet-inducible models, we discuss the application of reversible expressed, transgenic mutant estrogen receptor (ER) fusion proteins, which are regulated via systemic tamoxifen administration. Most of the various lung cancer models can be combined through the generation of transgenic compound mice so that the use of these somatic mouse models can be even more enhanced for the study of specific molecular pathways that facilitate growth and maintenance of lung cancer. Finally, this description of the practical application and methodology of mouse models for lung cancer should be helpful in assisting researchers to make the best choices and optimal use of (existing) somatic models that suits the specific experimental needs in their study of lung cancer.

Massively Parallel Sequencing Reveals the Complex Structure of an Irradiated Human Chromosome on a Mouse Background in the Tc1 Model of Down Syndrome

PubMed Central

Clayton, Stephen; Prigmore, Elena; Langley, Elizabeth; Yang, Fengtang; Maguire, Sean; Fu, Beiyuan; Rajan, Diana; Sheppard, Olivia; Scott, Carol; Hauser, Heidi; Stephens, Philip J.; Stebbings, Lucy A.; Ng, Bee Ling; Fitzgerald, Tomas; Quail, Michael A.; Banerjee, Ruby; Rothkamm, Kai; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Carter, Nigel P.

2013-01-01

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439. PMID:23596509

eIF4E/Fmr1 double mutant mice display cognitive impairment in addition to ASD-like behaviors.

PubMed

Huynh, Thu N; Shah, Manan; Koo, So Yeon; Faraud, Kirsten S; Santini, Emanuela; Klann, Eric

2015-11-01

Autism spectrum disorder (ASD) is a group of heritable disorders with complex and unclear etiology. Classic ASD symptoms include social interaction and communication deficits as well as restricted, repetitive behaviors. In addition, ASD is often comorbid with intellectual disability. Fragile X syndrome (FXS) is the leading genetic cause of ASD, and is the most commonly inherited form of intellectual disability. Several mouse models of ASD and FXS exist, however the intellectual disability observed in ASD patients is not well modeled in mice. Using the Fmr1 knockout mouse and the eIF4E transgenic mouse, two previously characterized mouse models of fragile X syndrome and ASD, respectively, we generated the eIF4E/Fmr1 double mutant mouse. Our study shows that the eIF4E/Fmr1 double mutant mice display classic ASD behaviors, as well as cognitive dysfunction. Importantly, the learning impairments displayed by the double mutant mice spanned multiple cognitive tasks. Moreover, the eIF4E/Fmr1 double mutant mice display increased levels of basal protein synthesis. The results of our study suggest that the eIF4E/Fmr1 double mutant mouse may be a reliable model to study cognitive dysfunction in the context of ASD. Copyright © 2015 Elsevier Inc. All rights reserved.

Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice

PubMed Central

Choi, Jaesung P.; Foley, Matthew; Zhou, Zinan; Wong, Weng-Yew; Gokoolparsadh, Naveena; Arthur, J. Simon C.; Li, Dean Y.; Zheng, Xiangjian

2016-01-01

Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases. PMID:27513872

The terminator mouse: salvation for primary cell culture.

PubMed

Kabgani, Nazanin; Moeller, Marcus J

2013-11-01

The Terminator had to come back from the future already several times in an effort to bring salvation to mankind. In the present issue of Kidney International, Guo et al. brought us a novel transgenic mouse model: the terminator mouse. This highly elegant mouse may facilitate significantly the derivation of primary cultures of a specific cell type from a tissue containing multiple cell populations.

Mouse Xenograft Model for Mesothelioma | NCI Technology Transfer Center | TTC

Cancer.gov

The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas. Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.

HUPO BPP Workshop on Mouse Models for Neurodegeneration--Choosing the right models.

PubMed

Hamacher, Michael; Marcus, Katrin; Stephan, Christian; van Hall, Andre; Meyer, Helmut E

2005-09-01

The HUPO Brain Proteome Project met during the 4th Dutch Endo-Neuro-Psycho Meeting in Doorwerth, The Netherlands, on June 1, 2005, in order to discuss appropriate (mouse) models for neurodegenerative diseases as well as to conceptualise sophisticated proteomics analyses strategies. Here, the topics of the meeting are summarised.

AOM/DSS Model of Colitis-Associated Cancer

PubMed Central

Parang, Bobak; Barret, Caitlyn W.; Williams, Christopher S.

2016-01-01

Summary Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer. PMID:27246042

Magnetic resonance imaging of amyloid plaques in transgenic mouse models of Alzheimer's disease

PubMed Central

Chamberlain, Ryan; Wengenack, Thomas M.; Poduslo, Joseph F.; Garwood, Michael; Jack, Clifford R.

2011-01-01

A major objective in the treatment of Alzheimer's disease is amyloid plaque reduction. Transgenic mouse models of Alzheimer's disease provide a controlled and consistent environment for studying amyloid plaque deposition in Alzheimer's disease. Magnetic resonance imaging is an attractive tool for longitudinal studies because it offers non-invasive monitoring of amyloid plaques. Recent studies have demonstrated the ability of magnetic resonance imaging to detect individual plaques in living mice. This review discusses the mouse models, MR pulse sequences, and parameters that have been used to image plaques and how they can be optimized for future studies. PMID:21499442

Standardization of deep partial-thickness scald burns in C57BL/6 mice

PubMed Central

Medina, Jorge L; Fourcaudot, Andrea B; Sebastian, Eliza A; Shankar, Ravi; Brown, Ammon W; Leung, Kai P

2018-01-01

Mouse burn models are used to understand the wound healing process and having a reproducible model is important. The different protocols used by researchers can lead to differences in depth of partial-thickness burn wounds. Additionally, standardizing a protocol for mouse burns in the laboratory for one strain may result in substantially different results in other strains. In our current study we describe the model development of a deep partial-thickness burn in C57BL/6 mice using hot water scalding as the source of thermal injury. As part of our model development we designed a template with specifications to allow for even contact of bare mouse skin (2×3 cm) with hot water while protecting the rest of the mouse. Burn depth was evaluated with H&E, Masson’s trichrome, and TUNEL staining. Final results were validated with pathology analysis. A water temperature of 54°C with a scalding time of 20 seconds produced consistent deep partial-thickness burns with available equipment described. Other than temperature and time, factors such as template materials and cooling steps after the burn could affect the uniformity of the burns. These findings are useful to burn research by providing some key parameters essential for researchers to simplify the development of their own mouse burn models. PMID:29755839

Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

PubMed Central

Campbell, Jerry L.; Clewell, Harvey J.; Zhou, Yi-Hui; Wright, Fred A.; Guyton, Kathryn Z.

2014-01-01

Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, interindividual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data. Objectives: We evaluated the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and 1 hybrid mouse strains to calibrate and extend existing physiologically based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). We used a Bayesian population analysis of interstrain variability to quantify variability in TCE metabolism. Results: Concentration–time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation were less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production were less variable (2-fold range) than DCA production (5-fold range), although the uncertainty bounds for DCA exceeded the predicted variability. Conclusions: Population PBPK modeling of genetically diverse mouse strains can provide useful quantitative estimates of toxicokinetic population variability. When extrapolated to lower doses more relevant to environmental exposures, mouse population-derived variability estimates for TCE metabolism closely matched population variability estimates previously derived from human toxicokinetic studies with TCE, highlighting the utility of mouse interstrain metabolism studies for addressing toxicokinetic variability. Citation: Chiu WA, Campbell JL Jr, Clewell HJ III, Zhou YH, Wright FA, Guyton KZ, Rusyn I. 2014. Physiologically based pharmacokinetic (PBPK) modeling of interstrain variability in trichloroethylene metabolism in the mouse. Environ Health Perspect 122:456–463; http://dx.doi.org/10.1289/ehp.1307623 PMID:24518055

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The Genetics of Cancer Susceptibility Section in the Mouse Cancer Genetics Program at NCI is seeking a highly motivated postdoctoral researcher to identify novel genetic interactors of BRCA2 using CRISPR-based genetic screen in mouse embryonic stem cells and perform functional studies in mouse models.

Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance.

PubMed

Nygaard, Unni Cecilie; Vinje, Nina Eriksen; Samuelsen, Mari; Andreassen, Monica; Groeng, Else-Carin; Bølling, Anette Kocbach; Becher, Rune; Lovik, Martinus; Bodin, Johanna

2015-09-01

The impact of early life exposure to bisphenol A (BPA) through drinking water was investigated in mouse models of respiratory allergy, food allergy and oral tolerance. Balb/c mice were exposed to BPA (0, 10 or 100 μg/ml), and the offspring were intranasally exposed to the allergen ovalbumin (OVA). C3H/HeJ offspring were sensitized with the food allergen lupin by intragastric gavage, after exposure to BPA (0, 1, 10 or 100 μg/ml). In separate offspring, oral tolerance was induced by gavage of 5 mg lupin one week before entering the protocol for the food allergy induction. In the airway allergy model, BPA (100 μg/ml) caused increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and a trend of increased OVA-specific IgE levels. In the food allergy and tolerance models, BPA did not alter the clinical anaphylaxis or antibody responses, but induced alterations in splenocyte cytokines and decreased mouse mast cell protease (MMCP)-1 serum levels. In conclusion, early life exposure to BPA through drinking water modestly augmented allergic responses in a mouse model of airway allergy only at high doses, and not in mouse models for food allergy and tolerance. Thus, our data do not support that BPA promotes allergy development at exposure levels relevant for humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures.

PubMed

Harrill, Alison H; McAllister, Kimberly A

2017-08-15

This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene-environment interactions in human disease and to inform human health risk assessment. This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. These unique resources have the potential to be powerful tools for generating hypotheses related to gene-environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274.

A Consensus Definition of Cataplexy in Mouse Models of Narcolepsy

PubMed Central

Scammell, Thomas E.; Willie, Jon T.; Guilleminault, Christian; Siegel, Jerome M.

2009-01-01

People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of murine cataplexy. The group concluded that murine cataplexy is an abrupt episode of nuchal atonia lasting at least 10 seconds. In addition, theta activity dominates the EEG during the episode, and video recordings document immobility. To distinguish a cataplexy episode from REM sleep after a brief awakening, at least 40 seconds of wakefulness must precede the episode. Bouts of cataplexy fitting this definition are common in mice with disrupted orexin/hypocretin signaling, but these events almost never occur in wild type mice. It remains unclear whether murine cataplexy is triggered by strong emotions or whether mice remain conscious during the episodes as in people with narcolepsy. This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy. Citation: Scammell TE; Willie JT; Guilleminault C; Siegel JM. A consensus definition of cataplexy in mouse models of narcolepsy. SLEEP 2009;32(1):111-116. PMID:19189786

New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures

PubMed Central

Harrill, Alison H.

2017-01-01

Background: This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene–environment interactions in human disease and to inform human health risk assessment. Objectives: This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. Methods: This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. Discussion: These unique resources have the potential to be powerful tools for generating hypotheses related to gene–environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. Conclusions: These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274 PMID:28886592

Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer.

PubMed

Okumura, Masaki; Ichihara, Hideaki; Matsumoto, Yoko

2018-11-01

Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

Murine Models of Systemic Lupus Erythematosus

PubMed Central

Perry, Daniel; Sang, Allison; Yin, Yiming; Zheng, Ying-Yi; Morel, Laurence

2011-01-01

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder. The study of diverse mouse models of lupus has provided clues to the etiology of SLE. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci from which several candidate genes have emerged. Meanwhile, induced models of lupus have provided insight into the role of environmental factors in lupus pathogenesis as well as provided a better understanding of cellular mechanisms involved in the onset and progression of disease. The SLE-like phenotypes present in these models have also served to screen numerous potential SLE therapies. Due to the complex nature of SLE, it is necessary to understand the effect specific targeted therapies have on immune homeostasis. Furthermore, knowledge gained from mouse models will provide novel therapy targets for the treatment of SLE. PMID:21403825