Sample records for f344 gpt delta

  1. Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats.

    PubMed

    Fujioka, Masaki; Gi, Min; Kawachi, Satoko; Tatsumi, Kumiko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

    2016-11-01

    Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA V ) is a major urinary metabolite of sodium arsenite (iAs III ) and induces urinary bladder cancers in rats. DMA V and iAs III are negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMA V and iAs III in rat urinary bladder epithelium and liver using gpt delta F344 rats. Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0, 92mg/L DMA V , or 87mg/L iAs III (each 50mg/L As) for 13weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection (gpt assay) and deletion mutations are identified in the red/gam genes by Spi - selection (Spi - assay). Results of the gpt and Spi - assays showed that DMA V and iAs III had no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMA V and iAs III are not mutagenic in urinary bladder epithelium or liver in rats. Copyright © 2016. Published by Elsevier B.V.

  2. Absence of in vivo genotoxicity of 3-monochloropropane-1,2-diol and associated fatty acid esters in a 4-week comprehensive toxicity study using F344 gpt delta rats.

    PubMed

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Horibata, Katsuyoshi; Ishii, Yuji; Umemura, Takashi; Honma, Masamitsu; Nohmi, Takehiko; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-07-01

    3-Monochloropropane-1,2-diol (3-MCPD) is regarded as a rat renal and testicular carcinogen and has been classified as a possible human carcinogen (group 2B) by International Agency for Research on Cancer. This is potentially of great importance given that esters of this compound have recently found to be generated in many foods and food ingredients as a result of food processing. There have been a few reports about their toxicity, although we have recently found that the toxicity profile of 3-MCPD esters was similar to that of 3-MCPD in a rat 13-week repeated dose study, except for the acute renal toxicity seen in 3-MCPD-treated females. In the present study, to examine in vivo genotoxicity we administered equimolar doses of 3-MCPD or 3-MCPD fatty acid esters (palmitate diester, palmitate monoester and oleate diester) to 6-week-old male F344 gpt delta rats carrying a reporter transgene for 4 weeks by intragastric administration. In vivo micronucleus, Pig-a mutation and gpt assays were performed, as well as investigations of major toxicological parameters including histopathological features. As one result, the relative kidney weights of the 3-MCPD and all three ester groups were significantly increased compared with the vehicle control group. However, the frequency of micronucleated reticulocytes and Pig-a mutant red blood cells did not differ among groups. Moreover, no changes were observed in mutant frequencies of gpt and red/gam (Spi(-)) genes in the kidney and the testis of 3-MCPD and 3-MCPD-fatty-acid-esters-treated rats. In histopathological analyses, no treatment related changes were observed, except for decrease of eosinophilic bodies in the kidneys of all treated groups. These results suggest that 3-MCPD and its fatty acid esters are not in vivo genotoxins, although they may exert renal toxicity. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e

  3. Tissue-specific and time-dependent clonal expansion of ENU-induced mutant cells in gpt delta mice.

    PubMed

    Nakayama, Takafumi; Sawai, Tomoko; Masuda, Ikuko; Kaneko, Shinya; Yamauchi, Kazumi; Blyth, Benjamin J; Shimada, Yoshiya; Tachibana, Akira; Kakinuma, Shizuko

    2017-10-01

    DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment. The gpt mutations were passengers of the mutant cell of origin and its daughter cells and thus could be used as neutral markers of clones that arose and persisted in the tissues. Female B6C3F1 mice exposed for 1 month to 200 ppm ENU in the drinking water developed early thymic lymphomas and late liver and lung tumors. To assay gpt mutations, we sampled the thymus, liver, lung, and small intestine of female gpt delta mice at 3 days, 4 weeks, and 8 weeks after the end of ENU exposure. Our results reveal that, in all four tissues, the ENU-induced gpt mutations persisted for weeks after the end of mutagen exposure. Clonal expansion of mutant cells was observed in the thymus and small intestine, with the thymus showing larger clone sizes. These results indicate that the clearance of mutant cells and the potential for clonal expansion during normal tissue growth depends on tissue type and that these factors may affect the sensitivity of different tissues to carcinogenesis. Environ. Mol. Mutagen. 58:592-606, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Orally administered glycidol and its fatty acid esters as well as 3-MCPD fatty acid esters are metabolized to 3-MCPD in the F344 rat.

    PubMed

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Akagi, Jun-ichi; Fujiwara, Satoshi; Ochiai, Ryosuke; Tsujino, Kazushige; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2015-12-01

    IARC has classified glycidol and 3-monochloropropane-1,2-diol (3-MCPD) as group 2A and 2B, respectively. Their esters are generated in foodstuffs during processing and there are concerns that they may be hydrolyzed to the carcinogenic forms in vivo. Thus, we conducted two studies. In the first, we administered glycidol and 3-MCPD and associated esters (glycidol oleate: GO, glycidol linoleate: GL, 3-MCPD dipalmitate: CDP, 3-MCPD monopalmitate: CMP, 3-MCPD dioleate: CDO) to male F344 rats by single oral gavage. After 30 min, 3-MCPD was detected in serum from all groups. Glycidol was detected in serum from the rats given glycidol or GL and CDP and CDO in serum from rats given these compounds. In the second, we examined if metabolism occurs on simple reaction with rat intestinal contents (gastric, duodenal and cecal contents) from male F344 gpt delta rats. Newly produced 3-MCPD was detected in all gut contents incubated with the three 3-MCPD fatty acid esters and in gastric and duodenal contents incubated with glycidol and in duodenal and cecal contents incubated with GO. Although our observation was performed at 1 time point, the results showed that not only 3-MCPD esters but also glycidol and glycidol esters are metabolized into 3-MCPD in the rat. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

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

    van Bruggen, M.C.; van den Broek, M.F.; van den Berg, W.B.

    1991-09-01

    Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 ratsmore » reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation.« less

  6. The legacy of the F344 rat as a cancer bioassay model (a retrospective summary of three common F344 rat neoplasms)

    PubMed Central

    Maronpot, Robert R.; Nyska, Abraham; Foreman, Jennifer E.; Ramot, Yuval

    2016-01-01

    Abstract The Fischer 344 (F344) rat was used by the National Toxicology Program (NTP) for over 5 decades for toxicity and carcinogenicity studies. However, in 2006, the NTP decided to switch to a different rat stock due largely to high background control incidences of Leydig cell tumors (LCTs) and mononuclear cell leukemia (MNCL), also known as large granular lymphocytic (LGL) leukemia. In the current review, we aim (1) to provide a summary of NTP bioassays with treatment-associated effects involving MNCL and LCTs in addition to male F344-specific tunica vaginalis mesothelioma (TVM); (2) to describe important pathobiological differences between these F344 rat tumor responses and similar target tissue-tumor response in humans; and (3) to present the NTP reasons for switching away from the F344 rat. We show that due to the highly variable background incidence of F344 MNCL, more reliance on historical control data than is usual for most tumor responses is warranted to evaluate potential effect of any chemical treatment in this rat strain. The high spontaneous incidence of LCTs in the testes of male F344 rats has made this tumor endpoint of little practical use in identifying potential testicular carcinogenic responses. TVM responses in F344 rats have a biological plausible relationship to LCTs unlike TVM in humans. Given their high spontaneous background incidence and species-specific biology, we contend that MNCL and LCT, along with TVM responses, in F344 rat carcinogenicity studies are inappropriate tumor types for human health risk assessment and lack relevance in predicting human carcinogenicity. PMID:27278595

  7. Air puff-induced 22-kHz calls in F344 rats.

    PubMed

    Inagaki, Hideaki; Sato, Jun

    2016-03-01

    Air puff-induced ultrasonic vocalizations in adult rats, termed "22-kHz calls," have been applied as a useful animal model to develop psychoneurological and psychopharmacological studies focusing on human aversive affective disorders. To date, all previous studies on air puff-induced 22-kHz calls have used outbred rats. Furthermore, newly developed gene targeting technologies, which are essential for further advancement of biomedical experiments using air puff-induced 22-kHz calls, have enabled the production of genetically modified rats using inbred rat strains. Therefore, we considered it necessary to assess air puff-induced 22-kHz calls in inbred rats. In this study, we assessed differences in air puff-induced 22-kHz calls between inbred F344 rats and outbred Wistar rats. Male F344 rats displayed similar total (summed) duration of air puff-induced 22 kHz vocalizations to that of male Wistar rats, however, Wistar rats emitted fewer calls of longer duration, while F344 rats emitted higher number of vocalizations of shorter duration. Additionally, female F344 rats emitted fewer air puff-induced 22-kHz calls than did males, thus confirming the existence of a sex difference that was previously reported for outbred Wistar rats. The results of this study could confirm the reliability of air puff stimulus for induction of a similar amount of emissions of 22-kHz calls in different rat strains, enabling the use of air puff-induced 22-kHz calls in inbred F344 rats and derived genetically modified animals in future studies concerning human aversive affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO THE MALE F344/N RAT AND B6C3F, MOUSE

    EPA Science Inventory

    CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO THE MALE F344/N RAT AND B6C3F1 MOUSE.

    Bromodichloromethane (BDCM) has been shown to produce kidney and large bowel tumors in both male and female F344/N rats, kidney tumors in male B6C3F 1 mice and ...

  9. Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice

    PubMed Central

    Chai, Y; Calaf, G M; Zhou, H; Ghandhi, S A; Elliston, C D; Wen, G; Nohmi, T; Amundson, S A; Hei, T K

    2013-01-01

    Background: Although radiation-induced bystander effects have been confirmed using a variety of endpoints, the mechanism(s) underlying these effects are not well understood, especially for in vivo study. Methods: A 1-cm2 area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays, and changes in out-of-field lung and liver were observed. Results: Compared with sham-treated controls, the Spi− mutation frequency increased 2.4-fold in non-targeted lung tissues at 24 h after partial body irradiation (PBIR). Consistent with dramatic Cyclooxygenase 2 (COX-2) induction in the non-targeted bronchial epithelial cells, increasing levels of prostaglandin, together with 8-hydroxydeoxyguanosine, in the out-of-field lung tissues were observed after PBIR. In addition, DNA double-strand breaks and apoptosis were induced in bystander lung tissues after PBIR. Conclusion: The PBIR induces DNA damage and mutagenesis in non-targeted lung tissues, especially in bronchial epithelial cells, and COX-2 has an essential role in bystander mutagenesis. PMID:23321513

  10. Carcinogenicity of acrylamide in B6C3F(1) mice and F344/N rats from a 2-year drinking water exposure.

    PubMed

    Beland, Frederick A; Mellick, Paul W; Olson, Greg R; Mendoza, Maria C B; Marques, M Matilde; Doerge, Daniel R

    2013-01-01

    Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F(1) mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F(1) mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F(1) mice. Male B6C3F(1) mice also had a significantly increased incidence of forestomach tumors, while female B6C3F(1) mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide. Published by Elsevier Ltd.

  11. Whole-Genome Sequences of DA and F344 Rats with Different Susceptibilities to Arthritis, Autoimmunity, Inflammation and Cancer

    PubMed Central

    Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A.; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S.

    2013-01-01

    DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease. PMID:23695301

  12. Whole-genome sequences of DA and F344 rats with different susceptibilities to arthritis, autoimmunity, inflammation and cancer.

    PubMed

    Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S

    2013-08-01

    DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease.

  13. Nucleic acids encoding plant glutamine phenylpyruvate transaminase (GPT) and uses thereof

    DOEpatents

    Unkefer, Pat J.; Anderson, Penelope S.; Knight, Thomas J.

    2016-03-29

    Glutamine phenylpyruvate transaminase (GPT) proteins, nucleic acid molecules encoding GPT proteins, and uses thereof are disclosed. Provided herein are various GPT proteins and GPT gene coding sequences isolated from a number of plant species. As disclosed herein, GPT proteins share remarkable structural similarity within plant species, and are active in catalyzing the synthesis of 2-hydroxy-5-oxoproline (2-oxoglutaramate), a powerful signal metabolite which regulates the function of a large number of genes involved in the photosynthesis apparatus, carbon fixation and nitrogen metabolism.

  14. CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS.

    EPA Science Inventory

    Carbonyl sulfide (COS) is an intermediate in the production of pesticides and herbicides, and is a metabolite of the neurotoxicant carbon disulfide. The potential neurotoxicity of inhaled COS was investigated in F344 rats. Male rats were exposed to 0, 75, 150, 300, or 600 ppm COS...

  15. A mouse model for the cystic fibrosis delta F508 mutation.

    PubMed Central

    van Doorninck, J H; French, P J; Verbeek, E; Peters, R H; Morreau, H; Bijman, J; Scholte, B J

    1995-01-01

    Most cystic fibrosis (CF) patients produce a mutant form (delta F508) of the cystic fibrosis transmembrane conductance regulator (CFTR), which is not properly processed in normal cells but is active as a chloride channel in several experimental systems. We used a double homologous recombination ('Hit and Run') procedure to generate a mouse model for the delta F508 mutation. Targeted embryonic stem (ES) cells (Hit clones) were found; of these either 80 or 20% of the clones had lost the delta F508 mutation, depending on the distance between the linearization site in the targeting construct and the delta F508 mutation. Correctly targeted clones underwent a second selection step resulting in ES cell clones (Run clones) heterozygous for the delta F508 mutation with an efficiency of 2-7%. Chimeric mice were generated and offspring homozygous for the delta F508 mutation showed electrophysiological abnormalities in nasal epithelium, gallbladder and in the intestine, and histological abnormalities in the intestine, typical of CF. Our data suggest that the delta F508 mice have residual delta F508 CFTR activity which would explain the mild pathology of the delta F508 mice. The delta F508 mouse may provide a useful model for the study of the processing defect of delta F508 CFTR and for the development of novel therapeutic approaches based on circumvention of the processing block. Images PMID:7556083

  16. FORMALDEHYDE-INDUCED GENE EXPRESSION IN F344 RAT NASAL RESPIRATORY EPITHELIUM.

    EPA Science Inventory

    Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium

    ABSTRACT

    Formaldehyde, an occupational and environmental toxicant used extensively in the manufacturing of many household and personal use products, is known to induce squamous cell carci...

  17. Thermostatted delta f

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

    Krommes, J.A.

    2000-01-18

    The delta f simulation method is revisited. Statistical coarse-graining is used to rigorously derive the equation for the fluctuation delta f in the particle distribution. It is argued that completely collisionless simulation is incompatible with the achievement of true statistically steady states with nonzero turbulent fluxes because the variance of the particle weights w grows with time. To ensure such steady states, it is shown that for dynamically collisionless situations a generalized thermostat or W-stat may be used in lieu of a full collision operator to absorb the flow of entropy to unresolved fine scales in velocity space. The simplestmore » W-stat can be implemented as a self-consistently determined, time-dependent damping applied to w. A precise kinematic analogy to thermostatted nonequilibrium molecular dynamics (NEMD) is pointed out, and the justification of W-stats for simulations of turbulence is discussed. An extrapolation procedure is proposed such that the long-time, steady-state, collisionless flux can be deduced from several short W-statted runs with large effective collisionality, and a numerical demonstration is given.« less

  18. Tanshinone IIA promotes the proliferation of WB-F344 hepatic oval cells via Wnt/β-catenin signaling

    PubMed Central

    ZE, XINGYU; JIA, JIDONG; LI, XINMIN; YOU, HONG; ZHAO, XINYAN; ZHANG, DONG; WANG, BAOEN

    2016-01-01

    Tanshinone IIA (TSA) is a widely used traditional Chinese medicine, which has been demonstrated to protect damaged liver cells and is currently administered in the treatment of liver fibrosis. Liver precursor cells, also termed oval cells, are key in the repair of liver tissues following injury. However, whether TSA improves the function of liver cells and protects the liver from injury by enhancing the growth and proliferation of hepatic oval cells remains to be elucidated. In the present study, low to moderate concentrations of TSA were observed to stimulate proliferation, did not induce apoptosis in WB-F344 rat hepatic oval cells and the increased expression levels of β-catenin. WB-F344 cells were treated with various concentrations of TSA (0–80 µg/ml) for 24, 48, 72 and 96 h. Cell proliferation was measured using a Cell Counting kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine assay and a carboxyfluorescein diacetate succinimidyl ester (CFSE) assay. The CCK-8 assay demonstrated that treatment of WB-F344 cells with 20–40 µg/ml TSA for up to 72 h significantly increased proliferation. Similar results were observed in the subsequent EdU and CFSE assays. Furthermore, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated that 20–40 µg/ml TSA treatment for up to 96 h did not induce apoptosis of the WB-F344 cells. Notably, the results of western blot, immunofluorescence and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that treatment of the WB-F344 cells with 20–40 µg/ml TSA for up to 72 h significantly increased the expression levels of β-catenin. These data indicated that TSA at concentrations between 20 and 40 µg/ml may induce WB-F344 cell proliferation by activating the canonical Wnt signaling pathway. The results of the present study suggest that TSA may be a useful natural agent to enhance repair and regeneration of the injured liver, and improve liver regeneration

  19. Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

    USDA-ARS?s Scientific Manuscript database

    The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-gl...

  20. Hydrogen peroxide stimulates cell motile activity through LPA receptor-3 in liver epithelial WB-F344 cells

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

    Shibata, Ayano; Tanabe, Eriko; Inoue, Serina

    2013-04-12

    Highlights: •Hydrogen peroxide stimulates cell motility of WB-F344 cells. •LPA{sub 3} is induced by hydrogen peroxide in WB-F344 cells. •Cell motility by hydrogen peroxide is inhibited in LPA{sub 3} knockdown cells. •LPA signaling is involved in cell migration by hydrogen peroxide. -- Abstract: Hydrogen peroxide which is one of reactive oxygen species (ROS) mediates a variety of biological responses, including cell proliferation and migration. In the present study, we investigated whether lysophosphatidic acid (LPA) signaling is involved in cell motile activity stimulated by hydrogen peroxide. The rat liver epithelial WB-F344 cells were treated with hydrogen peroxide at 0.1 or 1more » μM for 48 h. In cell motility assays, hydrogen peroxide treated cells showed significantly high cell motile activity, compared with untreated cells. To measure the expression levels of LPA receptor genes, quantitative real time RT-PCR analysis was performed. The expressions of LPA receptor-3 (Lpar3) in hydrogen peroxide treated cells were significantly higher than those in control cells, but not Lpar1 and Lpar2 genes. Next, to assess the effect of LPA{sub 3} on cell motile activity, the Lpar3 knockdown cells from WB-F344 cells were also treated with hydrogen peroxide. The cell motile activity of the knockdown cells was not stimulated by hydrogen peroxide. Moreover, in liver cancer cells, hydrogen peroxide significantly activated cell motility of Lpar3-expressing cells, but not Lpar3-unexpressing cells. These results suggest that LPA signaling via LPA{sub 3} may be mainly involved in cell motile activity of WB-F344 cells stimulated by hydrogen peroxide.« less

  1. Thermostatted {delta}f

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

    Krommes, J.A.

    1999-05-01

    The {delta}f simulation method is revisited. Statistical coarse graining is used to rigorously derive the equation for the fluctuation {delta}f in the particle distribution. It is argued that completely collisionless simulation is incompatible with the achievement of true statistically steady states with nonzero turbulent fluxes because the variance {ital W} of the particle weights {ital w} grows with time. To ensure such steady states, it is shown that for dynamically collisionless situations a generalized thermostat or {open_quotes}{ital W} stat{close_quotes} may be used in lieu of a full collision operator to absorb the flow of entropy to unresolved fine scales inmore » velocity space. The simplest {ital W} stat can be implemented as a self-consistently determined, time-dependent damping applied to {ital w}. A precise kinematic analogy to thermostatted nonequilibrium molecular dynamics is pointed out, and the justification of {ital W} stats for simulations of turbulence is discussed. An extrapolation procedure is proposed such that the long-time, steady-state, collisionless flux can be deduced from several short {ital W}-statted runs with large effective collisionality, and a numerical demonstration is given. {copyright} {ital 1999 American Institute of Physics.}« less

  2. Anxiety-like behavior as an early endophenotype in the TgF344-AD rat model of Alzheimer's disease.

    PubMed

    Pentkowski, Nathan S; Berkowitz, Laura E; Thompson, Shannon M; Drake, Emma N; Olguin, Carlos R; Clark, Benjamin J

    2018-01-01

    Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Induction of HSP70 promotes DeltaF508 CFTR trafficking.

    PubMed

    Choo-Kang, L R; Zeitlin, P L

    2001-07-01

    The DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) is a temperature-sensitive trafficking mutant that is detected as an immature 160-kDa form (band B) in gel electrophoresis. The goal of this study was to test the hypothesis that HSP70, a member of the 70-kDa heat shock protein family, promotes DeltaF508 CFTR processing to the mature 180-kDa form (band C). Both pharmacological and genetic techniques were used to induce HSP70. IB3-1 cells were treated with sodium 4-phenylbutyrate (4PBA) to promote maturation of DeltaF508 CFTR to band C. A dose-dependent increase in band C and total cellular HSP70 was observed. Under these conditions, HSP70-CFTR complexes were increased and 70-kDa heat shock cognate protein-CFTR complexes were decreased. Increased DeltaF508 CFTR maturation was also seen after transfection with an HSP70 expression plasmid and exposure to glutamine, an inducer of HSP70. With immunofluorescence techniques, the increased appearance of CFTR band C correlated with CFTR distribution beyond the perinuclear regions. These data suggest that induction of HSP70 promotes DeltaF508 CFTR maturation and trafficking.

  4. Systemic functional expression of N-acetyltransferase polymorphism in the F344 Nat2 congenic rat

    PubMed Central

    Hein, David W.; Bendaly, Jean; Neale, Jason R.; Doll, Mark A.

    2008-01-01

    Rat lines congenic for the rat N-acetyltransferase 2 [(RAT)Nat2] gene were constructed and characterized. F344 (homozygous Nat2 rapid) males were mated to WKY (homozygous Nat2 slow) females to produce heterozygous F1. F1 females were then backcrossed to F344 males. Heterozygous acetylator female progeny from this and each successive backcross were identified by rat Nat2 genotyping and mated with F344 rapid acetylator males. Following ten generations of backcross mating, heterozygous acetylator brother/sister progeny were mated to produce the homozgygous rapid and slow acetylator Nat2 congenic rat lines. p-Aminobenzoic acid (selective for rat NAT2) and 4-aminobiphenyl N-acetyltransferase activities were expressed in all tissues examined (liver, lung, esophagus, stomach, small intestine, colon, pancreas, kidney, skin, leukocytes, and urinary bladder in male and female rats and in breast of female and prostate of male rats). NAT2 expression in rat extrahepatic tissues was much higher than in liver. In each tissue, activities were Nat2-genotype dependent, with highest levels in homozygous rapid acetylators, intermediate levels in heterozygous acetylators, and lowest in homozygous slow acetylators. Sulfamethazine (selective for rat NAT1) N-acetyltransferase activities were observed in all tissues examined in both male and female rats except for breast (females), bladder and leukocytes. In each tissue, the activity was Nat2-genotype independent, with similar levels in homozygous rapid, heterozygous, and homozygous slow acetylators. These congenic rat lines are useful to investigate the role of NAT2 genetic polymorphism in susceptibility to cancers related to arylamine carcinogen exposures. PMID:18799801

  5. CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO MALE F344/N RATS AND B6C3F1 MICE

    EPA Science Inventory

    A life-time exposure study was conducted to assess the carcinogenicity of bromodichloromethane (BDCM) administered in the drinking water to male F344/N rats and B6C3F1 mice. Mouse: Target concentrations of BDCM (dissolved in deionized water containing 0.25% emulphor) were 0.05, ...

  6. Opiate-agonist induced taste aversion learning in the Fischer 344 and Lewis inbred rat strains: evidence for differential mu opioid receptor activation.

    PubMed

    Davis, Catherine M; Rice, Kenner C; Riley, Anthony L

    2009-10-01

    The Fischer 344 (F344) and Lewis (LEW) inbred rat strains react differently to morphine in a number of behavioral and physiological preparations, including the acquisition of aversions induced by this compound. The present experiment tested the ability of various compounds with relative selectivity at kappa, delta and mu receptor subtypes to assess the relative roles of these subtypes in mediating the differential aversive effects of morphine in the two strains. In the assessment of the role of the kappa receptor in morphine-induced aversions, animals in both strains were given access to saccharin followed by varying doses of the kappa agonist (-)-U50,488H (0.0, 0.28, 0.90 and 1.60 mg/kg). Although (-)-U50,488H induced aversions in both strains, no strain differences emerged. A separate subset of subjects was trained with the selective delta opioid agonist, SNC80 (0.0, 5.6, 10.0 and 18.0 mg/kg), and again although SNC80 induced aversions, there were no strain differences. Finally, a third subset of subjects was trained with heroin (0.0, 3.2, 5.6 and 10.0 mg/kg), a compound with activity at all three opiate receptor subtypes. Although heroin induced aversions in both strains, the aversions were significantly greater in the F344 strain, suggesting that differential activation of the mu opioid receptor likely mediates the reported strain differences in morphine-induced aversion learning. These data were discussed in terms of strain differences in opioid system functioning and the implications of such differences for other morphine-induced behavioral effects reported in F344 and LEW rats.

  7. Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats

    PubMed Central

    Boudreau, Mary D.

    2013-01-01

    Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species. Based upon this observation, 2-year drinking water studies were conducted to assess the carcinogenic potential of an Aloe vera whole-leaf extract when administered to F344/N rats (48 per sex per group) at 0.5, 1, and 1.5%, and B6C3F1 mice (48 per sex per group) at 1, 2, and 3%. Compared with controls, survival was decreased in the 1.5% dose group of female rats. Treatment-related neoplasms and nonneoplastic lesions in both species were confined primarily to the large intestine. Incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and ascending and transverse colon were significantly higher than controls in male and female rats in the 1 and 1.5% dose groups. There were no neoplasms of the large intestine in mice or in the 0 or 0.5% dose groups of rats. Increased incidences of mucosa hyperplasia of the large intestine were observed in F344/N rats, and increased incidences of goblet cell hyperplasia of the large intestine occurred in B6C3F1 mice. These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats. PMID:22968693

  8. ESTIMATING CHLOROFORM BIOTRANSFORMATION IN F-344 RAT LIVER USING IN VITRO TECHNIQUES AND PHARMACOKINETIC MODELING

    EPA Science Inventory

    ESTIMATING CHLOROFORM BIOTRANSFORMATION IN F-344 RAT LIVER USING IN VITRO TECHNIQUES AND PHARMACOKINETIC MODELING

    Linskey, C.F.1, Harrison, R.A.2., Zhao, G.3., Barton, H.A., Lipscomb, J.C4., and Evans, M.V2., 1UNC, ESE, Chapel Hill, NC ; 2USEPA, ORD, NHEERL, RTP, NC; 3 UN...

  9. Use of micro-positron emission tomography with (18)F-fallypride to measure the levels of dopamine receptor-D2 and (18)F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 rats.

    PubMed

    Li, Ping; Gui, Songbai; Cao, Lei; Gao, Hua; Bai, Jiwei; Li, Chuzhong; Zhang, Yazhuo

    2016-01-01

    Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with (18)F-fallypride and (18)F-fluorodeoxyglucose ((18)F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17β-estradiol for 8 weeks. The growth of tumors was monitored by the small-animal magnetic resonance imaging and micro-PET. A series of molecular biological experiments were also performed 4 and 6 weeks after pump implantation. The micro-PET molecular imaging with (18)F-fallypride revealed a decreased expression of DRD2 in F344 rat prolactinoma models, but the micro-PET molecular imaging with (18)F-FDG presented an increased uptake in the prolactinoma compared with the pituitary gland. A decreasing trend of levels of DRD2 in F344 rat prolactinoma models was also detected by molecular biological experiments. From this, we can conclude that micro-PET with (18)F-fallypride and (18)F-FDG can be used to assess tumorigenesis of the prolactinomas in vivo and molecular imaging detection of DRD2 level in prolactinoma may be an indication of treatment effect in the animal experiment.

  10. Maternal environment alters social interactive traits but not open-field behavior in Fischer 344 rats.

    PubMed

    Yamamuro, Yutaka

    2008-10-01

    Although it is recognized that the genetic background governs behavioral phenotypes, environmental factors also play a critical role in the development of various behavioral processes. The maternal environment has a major impact on pups, and the cross-fostering procedure is used to determine the influence of early life experiences. The present study examined the influence of maternal environment on behavioral traits in inbred Fischer 344 (F344) rats. F344/DuCrlCrlj and Wistar (Crlj:WI) pups were fostered from postnatal day 1 as follows: Wistar pups raised by Wistar dams, F344 raised by Wistar, Wistar raised by F344, and F344 raised by F344. At 10 weeks of age, rats were randomly assigned to an open-field test and social interaction test. In the open-field test, irrespective of the rearing conditions, the activity during the first 1 min was significantly lower in F344 rats than in Wistar rats. Latency to the onset of movement showed no difference between groups. In the social interaction test, the recognition performance during the first 1 min in F344 raised by F344 was significantly shorter than that in the other groups. The onset of recognition to a novel social partner in F344 raised by F344 was significantly delayed, and the delay disappeared upon cross-fostering by Wistar dams. These results raise the possibility that the behavioral phenotype of F344 rats results from the interplay of genetic factors and maternal environment during early life, and that F344 rats are a strain with high susceptibility to rearing conditions for the formation of their emotionality.

  11. TOXICITY OF TETRYL (N-METHYL-N,2,4,6-TETRANITROANILINE) IN F344 RATS

    EPA Science Inventory

    The toxicity of tetryl (N-methyl-N,2,4,6-tetranitroaniline) in male and female F344 rats was evaluated after adminstration in the diet for 14 or 90 days. The 14-day study diet concentrations used were 0, 500, 1250, 2000, 2500, and 5000 ppm; the 90-day study diet concentrations we...

  12. DICHLOROACETIC ACID (DCA) INHIBITS PROLIFERATION AND APOPTOSIS IN NORMAL HEPATOCYTES OF MALE F344 RATS

    EPA Science Inventory

    Dichloroacetic acid (DCA} inhibits proliferation and apoptosis in nonnal hepatocytes of
    male F344 rats.

    Large segments of the population are chronically exposed to dichloroacetic acid (DCA}: DCA is a by product of the chlorine disinfection of drinking water, a metab...

  13. GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.

    PubMed

    Hengel, H; Keimer, R; Deigendesch, W; Rieß, A; Marzouqa, H; Zaidan, J; Bauer, P; Schöls, L

    2018-06-07

    Various genetic defects can cause intellectual and developmental disabilities (IDD). Often IDD is a symptom of a more complex neurodevelopmental or neurodegenerative syndrome. Identifying syndromic patterns is substantive for diagnostics and for understanding the pathomechanism of a disease. Recessive GPT2 mutations have recently been associated with IDD in four families. Here, we report a novel recessive GPT2 stop mutation p.Gln24* causing a complex IDD phenotype in a homozygous state in five patients from two consanguineous Arab families. By compiling clinical information of these individuals and previously described GPT2 patients a recognizable neurodevelopmental and potentially neurodegenerative phenotype can be assigned consisting of intellectual disability, pyramidal tract affection with spastic paraplegia, microcephaly and frequently epilepsy. Due to the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Hydrogen peroxide stimulates cell motile activity through LPA receptor-3 in liver epithelial WB-F344 cells.

    PubMed

    Shibata, Ayano; Tanabe, Eriko; Inoue, Serina; Kitayoshi, Misaho; Okimoto, Souta; Hirane, Miku; Araki, Mutsumi; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

    2013-04-12

    Hydrogen peroxide which is one of reactive oxygen species (ROS) mediates a variety of biological responses, including cell proliferation and migration. In the present study, we investigated whether lysophosphatidic acid (LPA) signaling is involved in cell motile activity stimulated by hydrogen peroxide. The rat liver epithelial WB-F344 cells were treated with hydrogen peroxide at 0.1 or 1 μM for 48 h. In cell motility assays, hydrogen peroxide treated cells showed significantly high cell motile activity, compared with untreated cells. To measure the expression levels of LPA receptor genes, quantitative real time RT-PCR analysis was performed. The expressions of LPA receptor-3 (Lpar3) in hydrogen peroxide treated cells were significantly higher than those in control cells, but not Lpar1 and Lpar2 genes. Next, to assess the effect of LPA3 on cell motile activity, the Lpar3 knockdown cells from WB-F344 cells were also treated with hydrogen peroxide. The cell motile activity of the knockdown cells was not stimulated by hydrogen peroxide. Moreover, in liver cancer cells, hydrogen peroxide significantly activated cell motility of Lpar3-expressing cells, but not Lpar3-unexpressing cells. These results suggest that LPA signaling via LPA3 may be mainly involved in cell motile activity of WB-F344 cells stimulated by hydrogen peroxide. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT

    EPA Science Inventory

    EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.

    S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive T...

  16. APOPTOSIS AND PROLIFERATION DURING DICHLOROACETIC ACID (DCA) INDUCED HEPTACELLULAR CARCINOGENESIS IN THE F344 MALE RAT

    EPA Science Inventory

    Apoptosis and Proliferation During DicWoroacetic Acid (DCA) Induced Hepatocellular
    Carcinogenesis in the F344 Male Rat

    Chlorine, introduced into public drinking \\\\'ater supplies for disinfection, can react with organic compounds in surface waters to form toxic by-prod...

  17. Differences in the metabolism and disposition of inhaled (3H)benzene by F344/N rats and B6C3F1 mice

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

    Sabourin, P.J.; Bechtold, W.E.; Birnbaum, L.S.

    1988-06-15

    Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3F1 mice which might be responsible for this increased susceptibility. Metabolites of benzene in blood, liver, lung, and bone marrow were measured during and following a 6-hr 50 ppm exposure to benzene vapor. Hydroquinone glucuronide, hydroquinone, and muconic acid, which reflect pathways leading to potential toxic metabolites of benzene,more » were present in much greater concentrations in the mouse than in rat tissues. Phenylsulfate, a detoxified metabolite, and an unknown water-soluble metabolite were present in approximately equal concentrations in these two species. These results indicate that the proportion of benzene metabolized via pathways leading to the formation of potentially toxic metabolites as opposed to detoxification pathways was much higher in B6C3F1 mice than in F344 rats, which may explain the higher susceptibility of mice to benzene-induced hematotoxicity and carcinogenicity.« less

  18. Thermodynamic properties of {Delta}H{sub f 298}{degree}, S{sub 298}{degree}, and C{sub p}(T) for 2-fluoro-2-methylpropane, {Delta}H{sub f 298}{degree} of fluorinated ethanes, and group additivity for fluoroalkanes

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

    Yamada, Takahiro; Bozzelli, J.W.

    1999-09-09

    G2(MP2) composite calculations are performed to obtain thermodynamic properties ({Delta}H{sub f 298}{degree}, S{sub 298}{degree} and C{sub p}(T)'s) of 2-fluoro-2-methylpropane. {Delta}H{sub f 298}{degree} is calculated from the G2(MP2) calculated enthalpy of reaction ({Delta}H{sub rxn 298}{degree}) and use of isodesmic reactions. Standard entropy (S{sub 298}{degree} in cal/(mol{center{underscore}dot}K)) and heat capacities (C{sub p}(T)'s in cal/(mol{center{underscore}dot}K)) are calculated using the rigid-rotor--harmonic-oscillator approximation with direct integration over energy levels of the intermolecular rotation potential energy curve. These thermodynamic properties are used to estimate data for the C/C3/F group. Enthalpies of formation ({Delta}H{sub f 298}{degree} in kcal/mol) for 1,2-difluoroethane ({minus}102.7), 1,1,2-trifluoroethane ({minus}156.9), 1,1,2,2- and 1,1,1,2-tetrafluoroethane (209.6more » and 213.3), and pentafluoroethane ({minus}264.1), are calculated using total energies obtained from G2(MP2) composite ab initio methods. Isodesmic reactions with existing literature values of {Delta}H{sub f 298}{degree} for ethane, 1-fluoroethane, 1,1-difjuoroethane and 1,1,1-trifluoroethane are used. Fluorine/fluorine interaction terms, F/F, 2F/F, 3F/F, 2F/2F, and 3F/2F, where ``/'' indicates interaction for alkane compounds, for {Delta}H{sub f 298}{degree} are reevaluated based on {Delta}H{sub f 298}{degree} of the above five fluoroethanes. Thermodynamic properties ({Delta}H{sub f 298}{degree}, S{sub 298}{degree} and C{sub p}(T)'s (300 {le} T/K {le} 1500)) for fluorinated carbon groups, C/C3F, C/C2/F/H, C/C2/F2, are calculated using data from ab initio methods and existing literature data. Fluorine-methyl (alkyl) group additivity corrections for gauche interactions are also evaluated.« less

  19. SERUM HORMONE CHARACTERIZATION AND EXOGENEOUS HORMONE RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT

    EPA Science Inventory

    SERUM HORMONE CHARACTERIZATION AND EXOGENEOUS HORMONE RESCUE OF BROMODICHLOROMETHANE-INDUCED
    PREGNANCY LOSS IN THE F344 RAT
    Susan R. Bielmeier*, Deborah S. Best^, and Michael G. Narotsky^

    ABSTRACT
    Previously, we demonstrated that bromodichloromethane (BDCM), a d...

  20. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT

    EPA Science Inventory

    EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.

    S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive T...

  1. PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS

    EPA Science Inventory

    PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS
    Bielmeier1, S.R., D.S. Best2, and M.G. Narotsky2; 1University of North Carolina at Chapel Hill, Curriculum in Toxicology, 2Reproductive Toxicology Division, U.S. Enviro...

  2. Genotoxicity of Styrene–Acrylonitrile Trimer in Brain, Liver, and Blood Cells of Weanling F344 Rats

    PubMed Central

    Hobbs, Cheryl A.; Chhabra, Rajendra S.; Recio, Leslie; Streicker, Michael; Witt, Kristine L.

    2012-01-01

    Styrene–acrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P < 0.0001) in MN-RET were measured in both male and female rats administered SAN Trimer. The RET population was reduced in high dose male rats, suggesting chemical-related bone marrow toxicity. Results of the Comet assay showed significant, dose-related increases in DNA damage in brain cells of male (P < 0.0074) and female (P < 0.0001) rats; increased levels of DNA damage were also measured in liver cells and leukocytes of treated rats. Chemical-related cytotoxicity was not indicated in any of the tissues examined for DNA damage. The results of this subacute MN/Comet assay indicate induction of significant genetic damage in multiple tissues of weanling F344 male and female rats after oral exposure to SAN Trimer. PMID:22351108

  3. Aspartate Aminotransferase (AST/GOT) and Alanine Aminotransferase (ALT/GPT) Detection Techniques

    PubMed Central

    Huang, Xing-Jiu; Choi, Yang-Kyu; Im, Hyung-Soon; Yarimaga, Oktay; Yoon, Euisik; Kim, Hak-Sung

    2006-01-01

    The levels of aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) in serum can help people diagnose body tissues especially the heart and the liver are injured or not. This article provides a comprehensive review of research activities that concentrate on AST/GOT and ALT/GPT detection techniques due to their clinical importance. The detection techniques include colorimetric, spectrophotometric, chemiluminescence, chromatography, fluorescence and UV absorbance, radiochemical, and electrochemical techniques. We devote the most attention on experimental principle. In some methods a few representative devices and important conclusions are presented.

  4. RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT BY EXOGENOUS PROGESTERONE AND HCG

    EPA Science Inventory

    Rescue of bromodichloromethane-induced pregnancy loss in the F344 rat by exogenous progesterone and hCG.

    Susan R. Bielmeier1, Deborah S. Best2 and Michael G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive Toxico...

  5. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT DURING PREGNANCY

    EPA Science Inventory

    Effects of Bromodichloromethane (BDCM) on Ex Vivo Luteal Function In the Pregnant F344 Rat

    Susan R. Bielmeier1, Ashley S. Murr2, Deborah S. Best2, Jerome M. Goldman2, and Michael G. Narotsky2

    1Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC 27599,...

  6. USE OF qRTPCR TO IDENTIFY POTENTIAL BIOMARKERS OF BROMATE EXPOSURE IN F344 MALE RAT KIDNEYS

    EPA Science Inventory

    Potassium bromate (KBrO3) is a drinking water disinfection by-product that is nephrotoxic and carcinogenic. To identify potential biomarkers of carcinogenicity, male F344 rats were chronically exposed to a carcinogenic dose (400mg/l) of KBrO3 in their drinking water. Kidneys were...

  7. Pattern Specificity in the Effect of Prior [delta]f on Auditory Stream Segregation

    ERIC Educational Resources Information Center

    Snyder, Joel S.; Weintraub, David M.

    2011-01-01

    During repeating sequences of low (A) and high (B) tones, perception of two separate streams ("streaming") increases with greater frequency separation ([delta]f) between the A and B tones; in contrast, a prior context with large [delta]f results in less streaming during a subsequent test pattern. The purpose of the present study was to…

  8. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

    PubMed Central

    Ouyang, Qing; Nakayama, Tojo; Baytas, Ozan; Davidson, Shawn M.; Yang, Chendong; Schmidt, Michael; Lizarraga, Sofia B.; Mishra, Sasmita; EI-Quessny, Malak; Niaz, Saima; Gul Butt, Mirrat; Imran Murtaza, Syed; Javed, Afzal; Chaudhry, Haroon Rashid; Vaughan, Dylan J.; Hill, R. Sean; Partlow, Jennifer N.; Yoo, Seung-Yun; Lam, Anh-Thu N.; Nasir, Ramzi; Al-Saffar, Muna; Barkovich, A. James; Schwede, Matthew; Nagpal, Shailender; Rajab, Anna; DeBerardinis, Ralph J.; Housman, David E.; Mochida, Ganeshwaran H.; Morrow, Eric M.

    2016-01-01

    Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms. PMID:27601654

  9. The Integration of Delta Prime (f)in a Multidimensional Space

    NASA Technical Reports Server (NTRS)

    Farassat, F.

    1999-01-01

    Consideration is given to the thickness noise term of the Ffowcs Williams-Hawkings equation when the time derivative is taken explicitly. An interpretation is presented of the integral I = function phi(x)delta-prime(f) dx, where it is initially assumed that the absolute value of Del-f is not equal to 1 on the surface f = 0.

  10. Propiverine-induced accumulation of nuclear and cytosolic protein in F344 rat kidneys: Isolation and identification of the accumulating protein

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

    Dietrich, D.R.; Heussner, A.H.; O'Brien, E.

    2008-12-15

    Male and female F344 rats but not B6C3F1 mice exposed for 104 weeks to propiverine hydrochloride (1-methylpiperid-4-yl 2,2-diphenyl-2-(1-propoxy)acetate hydrochloride), used for treatment of patients with neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), presented with an accumulation of proteins in the cytosol and nuclei of renal proximal tubule epithelial cells, yet despite this, no increased renal tumor incidence was observed. In order to provide an improved interpretation of these findings and a better basis for human health risk assessment, male and female F344 rats were exposed for 16 weeks to 1000 ppm propiverine in the diet, the accumulating protein wasmore » isolated from the kidneys via cytosolic and nuclear preparations or laser-capture microdissection and analyzed using molecular weight determination and mass spectrometry. The accumulating protein was found to be D-amino acid oxidase (DAAO), an enzyme involved in amino and fatty acid metabolism. Subsequent reanalysis of kidney homogenate and nuclear samples as well as tissue sections using western blot and DAAO-immunohistochemistry, confirmed the presence and localization of DAAO in propiverine-treated male and female F344 rats. The accumulation of DAAO only in rats, and the limited similarity of rat DAAO with other species, including humans, suggests a rat-specific mechanism underlying the drug-induced renal DAAO accumulation with little relevance for patients chronically treated with propiverine.« less

  11. Metabolic Rate Constants for Hydroquinone in F344 Rat and Human Liver Isolated Hepatocytes: Application to a PBPK model.

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

    Poet, Torka S.; Wu, Hong; English, J C.

    2004-11-15

    Hydroquinone (HQ) is an important industrial chemical that also occurs naturally in foods and in the leaves and bark of a number of plant species. Exposure of laboratory animals to HQ may result in a species-, sex-, and strain-specific nephrotoxicity. The sensitivity of male F344 vs. female F344 and Sprague-Dawley rats or B6C3F1 mice appears to be related to differences in the rates of formation and further metabolism of key nephrotoxic metabolites. Metabolic rate constants for the conversion of HQ through several metabolic steps to the mono-glutathione conjugate and subsequent detoxification via mercapturic acid were measured in suspension cultures ofmore » hepatocytes isolated from male F344 rats and humans. An in vitro mathematic kinetic model was used to analyze each metabolic step by simultaneously fitting the disappearance of each substrate and the appearance of subsequent metabolites. An iterative, nested approach was used whereby downstream metabolites were considered first and the model was constrained by the requirement that rate constants determined during analysis of individual metabolic steps must also satisfy the complete, integrated metabolism scheme, including competitive pathways. The results from this study indicated that the overall capacity for metabolism of HQ and its mono-glutathione conjugate is greater in hepatocytes from humans than those isolated from rats, suggesting a greater capacity for detoxification of the glutathione conjugates. Metabolic rate constants were applied to an existing physiologically based pharmacokinetic model and the model was used to predict total glutathione metabolites produced in the liver. The results showed that body burdens of these metabolites will be much higher in rats than humans.« less

  12. Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR.

    PubMed

    Rubenstein, R C; Zeitlin, P L

    2000-02-01

    The most common mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), DeltaF508, is a trafficking mutant that has prolonged associations with molecular chaperones and is rapidly degraded, at least in part by the ubiquitin-proteasome system. Sodium 4-phenylbutyrate (4PBA) improves DeltaF508-CFTR trafficking and function in vitro in cystic fibrosis epithelial cells and in vivo. To further understand the mechanism of action of 4PBA, we tested the hypothesis that 4PBA modulates the targeting of DeltaF508-CFTR for ubiquitination and degradation by reducing the expression of Hsc70 in cystic fibrosis epithelial cells. IB3-1 cells (genotype DeltaF508/W1282X) that were treated with 0.05-5 mM 4PBA for 2 days in culture demonstrated a dose-dependent reduction in Hsc70 protein immunoreactivity and mRNA levels. Immunoprecipitation with Hsc70-specific antiserum demonstrated that Hsc70 and CFTR associated under control conditions and that treatment with 4PBA reduced these complexes. Levels of immunoreactive Hsp40, Hdj2, Hsp70, Hsp90, and calnexin were unaffected by 4PBA treatment. These data suggest that 4PBA may improve DeltaF508-CFTR trafficking by allowing a greater proportion of mutant CFTR to escape association with Hsc70.

  13. Toxicology and carcinogenesis studies of methylphenidate hydrochloride (Cas No. 298-59-9) in F344/N rats and B6C3F1 mice (feed studies). Technical report series

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

    NONE

    1995-07-01

    Toxicology and carcinogenicity studies were conducted by administration of methylphenidate hydrochloride in feed to groups of 70 F344/N rats of each sex at doses of 0, 100, 500, or 1,0000 ppm and to groups of 70 B6C3F1 mice of each sex at doses of 0, 50, 250, or 500 ppm. Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of methylphenidate hydrochloride in male or female F344/N rats receiving 100, 500, or 1,000 ppm. There was some evidence of carcinogenic activity in male and female B6C3F1 mice, based on the occurrence of hepatocellular neoplasms.more » Treatment of female rats with methylphenidate hydrochloride was associated with a decrease in the incidence of mammary gland fibroadenomas. Administration of methylphenidate hydrochloride to male and female mice resulted in increased incidence of eosinophilic foci in the liver.« less

  14. Ocular changes in TgF344-AD rat model of Alzheimer's disease.

    PubMed

    Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V; Girman, Sergey; Ross-Cisneros, Fred N; Sadun, Alfredo A; Svendsen, Clive N; Cohen, Robert M; Wang, Shaomei

    2014-01-29

    Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response and luminance threshold recording from the superior colliculus. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was observed further in human AD retina. Along with Ab deposition, the inflammatory response was manifested by microglial recruitment and complement activation. Further studies are needed to elucidate the significance and mechanisms of these pathological changes [corrected].

  15. Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

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

    Rice, Kevin M.; Manne, Nandini D. P. K.; Gadde, Murali K.

    Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNiamore » (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.« less

  16. Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

    DOE PAGES

    Rice, Kevin M.; Manne, Nandini D. P. K.; Gadde, Murali K.; ...

    2015-03-28

    Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNiamore » (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.« less

  17. Differential establishment and maintenance of oral ethanol reinforced behavior in Lewis and Fischer 344 inbred rat strains.

    PubMed

    Suzuki, T; George, F R; Meisch, R A

    1988-04-01

    Oral ethanol self-administration was investigated systematically in two inbred strains of rats, Fischer 344 CDF (F-344)/CRLBR (F344) and Lewis LEW/CRLBR (LEW). For both strains ethanol maintained higher response rates and was consumed in larger volumes than the water vehicle. In addition, blood ethanol levels increased with increases in ethanol concentration. However, LEW rats drank substantially more ethanol than F344 rats. The typical inverted U-shaped function between ethanol concentration and number of deliveries was observed for the LEW rats, whereas for the F344 rats much smaller differences were seen between ethanol and water maintained responding. For the LEW strain, as the fixed-ratio size was increased, the number of responses increased almost in direct proportion to the fixed-ratio size increase, so that at least at the lower fixed-ratio values the rats were obtaining similar numbers of deliveries at different fixed-ratio sizes. However, a decrease in ethanol deliveries and blood ethanol levels was observed at higher fixed-ratio sizes. Similar results were obtained in F344 rats, but the amount of responding was lower and less consistent. LEW rats showed significantly higher response rates, numbers of ethanol deliveries and blood ethanol levels. Ethanol-induced behavioral activation also was observed in LEW rats, but not in F344 rats. These results support the conclusion that ethanol serves as a strong positive reinforcer for LEW rats and as a weak positive reinforcer for F344 rats, and that genotype is a determinant of the degree to which ethanol functions as a reinforcer.

  18. EFFECTS OF BROMODICHLOROMETHANE ON EX VIVO AND IN VITRO LUTEAL FUNCTION AND BROMODICHLOROMETHANE TISSUE DOSIMETRY IN THE PREGNANT F344 RAT

    EPA Science Inventory

    Bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss, i.e. full-litter resorption, in F344 rats when treated during the luteinizing hormone (LH)-dependent period. This effect is associated with reduced maternal serum progesterone (P) and LH...

  19. Convair F-106B Delta Dart Prepares for a Flight

    NASA Image and Video Library

    1969-05-21

    National Aeronautics and Space Administration (NASA) pilot Cliff Crabbs and the flight operations crew prepare a Convair F-106B Delta Dart for a flight from the Lewis Research Center in Cleveland, Ohio. NASA acquired the aircraft three years earlier to investigate noise-reducing inlet and nozzle designs for the supersonic transport engine program. Two General Electric J85 engines were installed underneath the aircraft’s delta wings to simulate the general shape of the supersonic transport’s engines. One of the engines was modified with experimental inlet or nozzle configurations. The unmodified engine was used for comparison. Most F-106B flights were flown in a 200-mile path over the lake between Buffalo and Sandusky, known as the Lake Erie Corridor. The 1100-miles per hour flight took only 11 minutes at an altitude of 30,000 feet. The aircraft almost always returned with a depleted fuel supply so a Visual Flight Rules operation was required. Following the crash of another jet fighter at Lewis in July 1969, the F-106s were stationed at Selfridge Air Force Base in Michigan. NASA pilots flew transport planes each morning to the base before commencing the F-106B missions.

  20. Serum Glutamic-Oxaloacetic Transaminase (GOT) and Glutamic-Pyruvic Transaminase (GPT) Levels in Children and Adolescents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

    2010-01-01

    The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or…

  1. Lack of carcinogenicity of lyophilized Agaricus blazei Murill in a F344 rat two year bioassay.

    PubMed

    Lee, I P; Kang, B H; Roh, J K; Kim, J R

    2008-01-01

    The Brazilian mushroom Agaricus blazei Murill has antimutagenic, antioxidant, immunostimulatory and antitumorigenic activities, and is increasingly consumed as a health food worldwide. We undertook the present study to evaluate the chronic toxicity and oncogenicity of A. blazei Murill in F344 rats. To establish a no-observed-adverse-effect level (NOAEL), four treatment groups of 100 rats each (50 males and 50 females) were fed a powder diet containing lyophilized A. blazei aqueous extract at 0, 6250, 12,500, and 25,000 ppm for up to 2 years. During this period, there was no remarkable change in mean body weight, body weight gain, hematologic or serum chemistry parameters, or absolute or relative organ weights in control or treatment groups. Mortality in male treatment groups (26%, 16%, and 30%), however, was significantly lower than in controls (48%). Histopathological studies showed no increased incidence of tumors in any treatment group, and total tumor incidence across all groups was comparable to historical data. In conclusion, an A. blazei Murill lyophilized powder diet even at 25,000 ppm (1176 mg/kgb x w x /day for male rats and 1518 mg/kgb.w./day for female rats) resulted in no remarkable carcinogenic effects in F344 rats over a 2-year period. Therefore, the dietary NOAEL is 25,000 ppm.

  2. Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in children and adolescents with intellectual disabilities.

    PubMed

    Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

    2010-01-01

    The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3-21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value (R(2)=0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value (R(2)=0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

  3. Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water.

    PubMed

    Cullen, John M; Ward, Jerrold M; Thompson, Chad M

    2016-02-01

    Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. © The Author(s) 2015.

  4. Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water

    PubMed Central

    Cullen, John M.; Ward, Jerrold M.

    2015-01-01

    Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. PMID:26538584

  5. Lewis and Fischer 344 rats as a model for genetic differences in spatial learning and memory: Cocaine effects.

    PubMed

    Fole, Alberto; Miguéns, Miguel; Morales, Lidia; González-Martín, Carmen; Ambrosio, Emilio; Del Olmo, Nuria

    2017-06-02

    Lewis (LEW) and Fischer 344 (F344) rats are considered a model of genetic vulnerability to drug addiction. We previously showed important differences in spatial learning and memory between them, but in contrast with previous experiments demonstrating cocaine-induced enhanced learning in Morris water maze (MWM) highly demanding tasks, the eight-arm radial maze (RAM) performance was not modified either in LEW or F344 rats after chronic cocaine treatment. In the present work, chronically cocaine-treated LEW and F344 adult rats have been evaluated in learning and memory performance using the Y-maze, two RAM protocols that differ in difficulty, and a reversal protocol that tests cognitive flexibility. After one of the RAM protocols, we quantified dendritic spine density in hippocampal CA1 neurons and compared it to animals treated with cocaine but not submitted to RAM. LEW cocaine treated rats showed a better performance in the Y maze than their saline counterparts, an effect that was not evident in the F344 strain. F344 rats significantly took more time to learn the RAM task and made a greater number of errors than LEW animals in both protocols tested, whereas cocaine treatment induced deleterious effects in learning and memory in the highly difficult protocol. Moreover, hippocampal spine density was cocaine-modulated in LEW animals whereas no effects were found in F344 rats. We propose that differences in addictive-like behavior between LEW and F344 rats could be related to differences in hippocampal learning and memory processes that could be on the basis of individual vulnerability to cocaine addiction. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Toxicology and carcinogenesis studies of acrylamide (CASRN 79-06-1) in F344/N rats and B6C3F1 mice (feed and drinking water studies).

    PubMed

    2012-07-01

    Acrylamide, a water-soluble α,β-unsaturated amide, is a contaminant in baked and fried starchy foods, including french fries, potato chips, and bread, as a result of Maillard reactions involving asparagine and reducing sugars. Additional sources of acrylamide exposure include cigarettes, laboratory procedures involving polyacrylamide gels, and various occupations (e.g, monomer production and polymerization processes). Acrylamide is carcinogenic in experimental animals. To obtain data for developing quantitative risk assessments for dietary exposures to acrylamide, the Food and Drug Administration nominated acrylamide for an in-depth toxicological evaluation by the National Toxicology Program. As part of this evaluation, male and female B6C3F1/Nctr (C57BL/6N x C3H/HeN MTV-) mice and male and female F344/N Nctr rats were exposed to acrylamide (at least 99.4% pure) in drinking water for 2 years. 2-WEEK STUDY IN RATS: Groups of four male and four female F344/N rats were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM acrylamide in the drinking water (0, 10, 25, 50, 100, 250, or 500 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, 185, or 370 mg acrylamide per kg diet for 14 days. One male rat administered 7.03 mM acrylamide in the drinking water died on day 14. Male and female rats receiving 7.03 mM acrylamide weighed 56% and 64% of controls, respectively. Male and female rats fed 370 mg acrylamide per kg diet weighed 74% and 83% of controls, respectively. Female rats receiving 3.52 mM acrylamide in drinking water and male rats fed 185 mg acrylamide per kg diet weighed 85% and 89% of controls, respectively. Rats receiving 7.03 mM acrylamide in drinking water or 370 mg acrylamide per kg diet exhibited hind-leg paralysis on day 14. Mild to moderate dilatation of the urinary bladder was observed in all rats given 370 mg acrylamide per kg diet, and in three of four male rats and all four female rats given 7.03 mM acrylamide in drinking water, and in one of four male

  7. Effects of amphetamine on striatal dopamine release, open-field activity, and play in Fischer 344 and Sprague-Dawley rats.

    PubMed

    Siviy, Stephen M; McDowell, Lana S; Eck, Samantha R; Turano, Alexandra; Akopian, Garnik; Walsh, John P

    2015-12-01

    Previous work from our laboratories has shown that juvenile Fischer 344 (F344) rats are less playful than other strains and also appear to be compromised in dopamine (DA) functioning. To determine whether the dysfunctional play in this strain is associated with deficits in the handling and delivery of vesicular DA, the following experiments assessed the extent to which F344 rats are differentially sensitive to the effects of amphetamine. When exposed to amphetamine, striatal slices obtained from F344 rats showed a small increase in unstimulated DA release when compared with slices from Sprague-Dawley rats; they also showed a more rapid high K+-mediated release of DA. These data provide tentative support for the hypothesis that F344 rats have a higher concentration of cytoplasmic DA than Sprague-Dawley rats. When rats were tested for activity in an open field, F344 rats presented a pattern of results that was consistent with either an enhanced response to amphetamine (3 mg/kg) or a more rapid release of DA (10 mg/kg). Although there was some indication that amphetamine had a dose-dependent differential effect on play in the two strains, play in F344 rats was not enhanced to any degree by amphetamine. Although these results are not consistent with our working hypothesis that F344 rats are less playful because of a deficit in vesicular release of DA, they still suggest that this strain may be a useful model for better understanding the role of DA in social behavior during the juvenile period.

  8. [Changes in index-F and index-delta 4P in normal pregnancy, labor and the puerperium].

    PubMed

    Kamada, T

    1984-04-01

    Index-F and index-delta 4P (cortisol and progesterone which are not bound to corticosteroid-binding globulin (CBG) in the umbilical cord vein and the maternal blood were determined during pregnancy, at delivery and puerperium. Index-F and index-delta 4P were calculated as the total cortisol or total progesterone X% unbound to CBG divided by 100. The level of index-F showed a gradual rise during pregnancy, and in late pregnancy reached about 1.5 times as high as that of non-pregnant women, whereas the total cortisol level was about 3.3 times. Near delivery, index-F was almost completely stable, but at delivery, it increased suddenly in proportion to the rise in the total cortisol level. This rise is probably due to stress. In the umbilical cord vein blood, the level of index-F was 1.5 times higher than that in the maternal plasma before delivery; however the total cortisol level was lower than that of the maternal plasma. The levels of both index-delta 4P and total progesterone showed a gradual increase during pregnancy in parallel, and each value in late pregnancy was about 4.5 to 4.9 times that of early pregnant women. At or near delivery, the level of index-delta 4P was almost stable and no decrease occurred. In the umbilical cord vein plasma, the levels of index-delta 4P and total progesterone were extremely high. However, the meaning of these results isn't clear.

  9. TRIBROMOMETHANE EXPOSURE AND DIETARY FOLATE DEFICIENCY IN THE FORMATION OF ABERRANT CRYPT FOCI IN THE COLONS OF F344/N RATS

    EPA Science Inventory

    TRIBROMOMETHANE EXPOSURE AND DIETARY FOLATE DEFICIENCY IN THE FORMATION OF ABERRANT CRYPT FOCI IN THE COLONS OF F344/N RATS

    David R. Geter', Tanya M. Moore', Michael H. George', Steve R. Kilburn', Gloria Huggins-Clark', James W. Allen', and Anthony B. DeAngelo' 'National H...

  10. THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

    EPA Science Inventory

    The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats

    Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-
    Mendel rat when administered either by corn oil gavage or in drin...

  11. Effects of Benzo(a)pyrene on Intra-testicular Function in F-344 Rats

    PubMed Central

    Archibong, Anthony E.; Ramesh, Aramandla; Niaz, Mohammad S.; Brooks, Cynthia M.; Roberson, Shannon I.; Lunstra, Donald D.

    2008-01-01

    The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 (F-344) rats to inhaled benzo(a)pyrene (BaP), a ubiquitous environmental toxicant present in cigarette smoke, automobile exhaust fumes and industrial emissions. Rats were assigned randomly to a treatment or control group. Treatment consisted of exposure of rats via nose-only inhalation to 75μg BaP/m3, 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately on day 60 of exposures (time 0) and subsequently at 24, 48, and 72 hours, to assess the effect of exposures to BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Mean testis weight, total weight of tubules and total tubular length per paired testes were reduced 33% (P< 0.025), 27% (P < 0.01) and 39%, respectively in exposed rats (P < 0.01) compared with UNC rats. The number of homogenization-resistant spermatids was significantly reduced in BaP-exposed versus UNC rats. Plasma testosterone and intra-testicular testosterone (ITT) concentrations were significantly decreased by BaP compared with those of UNC rats. The decreases in circulating plasma testosterone were accompanied by concomitant increases in plasma LH concentrations in BaP-exposed versus control rats (P < 0.05). These data suggest that 60 days exposure to inhaled BaP contribute to reduced testicular endocrine and spermatogenic functions in exposed rats. PMID:18441403

  12. [Effect of selenium deficiency on the F344 inbred line offspring rats' neuro-behavior, ability of learning and memory].

    PubMed

    Hong, Liang-Li; Tian, Dong-Ping; Su, Min; Shen, Xiu-Na; Gao, Yuxia

    2006-01-01

    To establish the selenium (Se) deficient animal model on F344 inbred line rats and observe the effects of a long-term Se-deficiency on the offspring's neuro-behavior, abilities of learning and memory. Feeding F344 inbred line rats on Se-deficient diet to establish Se-deficient animal model. For the offspring, the body weight, physiological indexes nervous reflections for growth and development were monitored during the early postnatal period. The Se-deficient diet contained less than 0.01 mg/kg and the glutathione peroxidase (GSH-Px) activity in blood of the Se-deficient group rats is lower than the Se-normal group after feeding on Se-deficient diet for 4 weeks. For the offspring, the birth weight and the body weight of Se-deficient group were obviously lower than the Se-normal group before weaning. Se-deficient offspring rats differed from Se-normal controls in lower scores in surface righting reflex (RR) test at postnatal 4th day after delivery, cliff avoidance test at postnatal 7th day and auditory acuity trial at postnatal 10th day respectively. But these differences disappear after a few days in the same tests. In addition, no significant differences between two groups in suspending test and walking ability test at postnatal 12th and 14th day. In open field test, Se-deficient male offspring stayed less time in the middle grid and moved less. In Morris water maze test, the Se-deficient offspring spent more time to find the hidden platform at the 6th and 9th training tests in the place navigation trial. Furthermore, the Se-deficient group spent less time in target quadrant when giving the spatial probe trial. A Se-deficient animal model have been established on F344 inbred line rats successfully. A long-term Se deficiency could retard the development of the offspring in uterus and after delivery. Se deficiency also decreased the offspring's abilities of spatial learning and memory in Morris water maze test and resulted in the male offspring's nervousness to new

  13. CHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The chronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 (F344) rats was evaluated by feeding a diet containing 0, 5, 60 and 300 ppm of TNB for 2 years. The calculated average TNB intake over 2 years for males and females was 0.22, 2.64, 13.44 and 0.23,...

  14. AN ADDITIVE EFFECT OF A MIXTURE OF AMMONIUM PERCHLORATE AND SODIUM CHLORATE ON PITUTARY-THYROID AXIS IN MALE F-344 RATS

    EPA Science Inventory

    An Additive Effect of a Mixture of Ammonium Perchlorate
    and Sodium Chlorate on Pitutary-Thyroid Axis in Male F-344 Rats

    Moazzam A. Khan 1,2,, 3Suzanne E. Fenton. 2Adam E. Swank, ZGeremy W. Knapp, 2Susan D.
    Hester, and 2Douglas C. Wolf. 1NRC, 2Environmental Carcinog...

  15. Comparative disposition of (R)-(+)-pulegone in B6C3F1 mice and F344 rats.

    PubMed

    Chen, L-J; Lebetkin, E H; Burka, L T

    2003-07-01

    Pulegone is a monoterpene ketone that is usually associated with the herb pennyroyal but is also found in the essential oils from many other mint species. It is the major constituent of pennyroyal oil. Pennyroyal is used as a flavoring and fragrance and as an herbal medicine to induce menstruation and abortion. A disposition study of 14C-pulegone in B6C3F1 mice and F344 rats has been conducted at doses from 0.8 to 80 mg/kg. Mice excrete 85 to 100% of the dose in 24 h. Rats excrete only 59 to 81% of the administered radioactivity in the same time, primarily in urine and feces, with a trace in respired air. Consequently, tissue concentrations are lower in mice than in rats. Male rats tend to have higher tissue concentrations, especially in kidney, than female rats have, but this sex difference is not seen in mice. The residual radioactivity at 24 h demonstrates potential for accumulation of pulegone-derived material in several tissues following multiple doses. The metabolic profile is complex in both species, with at least three pathways involving hydroxylation, reduction, or conjugation with glutathione as first steps. Mercapturic acid pathway metabolites were detected in bile in mice and both bile and urine in rats.

  16. THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO THIHALOMETHANE MIXTURES IN THE DRINKING WATER

    EPA Science Inventory


    THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N
    RATS EXPOSED TO TRIHALOMETHANE MIXTURES IN THE DRINKING WATER

    The trihalomethanes (THM), bromoform (TBM) and bromodichloromethane (BDCM), administered by corn oil gavage were found to increase large...

  17. Dimethylarsinic acid in drinking water changed the morphology but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats

    EPA Science Inventory

    Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In laboratory animals, it is dimethylarsinic acid [DMA(V)], a major arsenic metabolite in the urine of inorganic arsenic-exposed people, that increases transitional cell carcinoma, namely in F344 r...

  18. Disposition and pharmacokinetics of phenethyl isothiocyanate and 6-phenylhexyl isothiocyanate in F344 rats.

    PubMed

    Conaway, C C; Jiao, D; Kohri, T; Liebes, L; Chung, F L

    1999-01-01

    Naturally occurring phenethyl isothiocyanate (PEITC) and its synthetic homolog 6-phenylhexyl isothiocyanate (PHITC) are both effective inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumor development in A/J mice and F344 rats. To help explain why PHITC is considerably more efficacious than PEITC in chemopreventive potency, comparative disposition and pharmacokinetics data for male F344 rats were obtained after a single gavage dose of 50 micromol/kg (3.71 microCi/micromol) [14C]PEITC or 50 micromol/kg (6.59 microCi/micromol) [14C]PHITC in corn oil. After [14C]PEITC dosing, whole blood 14C peaked at 2.9 h, with an elimination half-life (T1/2e) of 21.7 h; blood 14C from [14C]PHITC-treated rats peaked at 8.9 h, with an T1/2e of 20.5 h. In lungs, the target organ, the T1/2e for [14C]PHITC and its labeled metabolites were more than twice that for [14C]PEITC and its labeled metabolites. The effective dose (area under the concentration-time curve) for 14C from PHITC was greater than 2.5 times the area under the concentration-time curve of 14C from PEITC in liver, lungs, and several other tissues. During 48 h, approximately 16.5% of the administered dose of [14C]PHITC was expired as [14C]CO2, more than 100 times the [14C]CO2 expired by rats treated with [14C]PEITC. In rats given [14C]PEITC, 88.7 +/- 2.2% and 9.9 +/- 1.9% of the dose appeared in the urine and feces, respectively, during 48 h; however, rats given [14C]PHITC excreted 7.2 +/- 0.8% of the dose of 14C in urine and 47.4 +/- 14.0% in the feces. Higher effective doses of PHITC in the lungs and other organs may be the basis, in part, for its greater potency as a chemopreventive agent.

  19. Carcinogenicity of bromodichloromethane administered in drinking water to Male F344/N Rats and B6C3F1 mice.

    PubMed

    George, Michael H; Olson, Greg R; Doerfler, Donald; Moore, Tanya; Kilburn, Steve; DeAngelo, Anthony B

    2002-01-01

    A life-time exposure study was conducted to assess the carcinogenicity of bromodichloromethane (BDCM) administered in the drinking water to male F344/N rats and B6C3F(1) mice. In mouse, the calculated mean daily BDCM concentrations (measured concentrations corrected for on-cage loss of chemical) were 0.06, 0.28 and 0.49 g/l. Time-weighted water consumption of 135, 97, and 89 ml/kg/day resulted in mean daily doses of 8.1, 27.2, and 43.4 mg BDCM/kg/day. No changes in feed consumption, final body weight, or survival were observed. Kidney weights were significantly depressed at 27.2 and 43.4 mg BDCM/kg/day. There was no increase in neoplasia in the liver, kidney, spleen, testis, bladder, sections along the alimentary tract, excised lesions, or at any other organ site. In rat, the corrected mean daily BDCM concentrations were 0.06, 0.33, and 0.62 g/l. Time-weighted water consumption of 65, 63, and 59 ml/kg/day yielded 3.9, 20.6 and 36.3 mg BDCM/kg/day. No alterations in feed consumption, body weight gain, and survival were seen. Kidney weight was significantly depressed in the 36.3-mg/kg/day treatment group. There was a significantly enhanced prevalence and multiplicity of hepatocellular adenomas at 3.9 mg BDCM/kg/day (15.5% and 0.16/animal vs. 2.2% and 0.02/animal for the control). Hepatocellular carcinomas increased from 2.2% and 0.02/animal for the control and 3.9 mg BDCM/kg/day to 8.3% and 0.10/animal at 20.6 mg BDCM/kg/day. The combined neoplasms were enhanced at 3.9 and 20.6 mg BDCM/kg/day. Liver neoplasia was depressed to the control value at 36.3 mg BDCM/kg. The prevalence of basophilic and clear cell, but not eosinophilic cells, altered foci of cells declined with increasing dose. BDCM did not increase cancer in the large bowel, renal tubules, or in any of the other tissues examined. Renal tubular hyperplasia was observed at 36.3 mg BDCM/kg (15.8% vs. 8.7% for the control group). Under the conditions of the study, BDCM in the drinking water was not carcinogenic

  20. PERSISTENT SUPPRESSION OF CONTACT HYPERSENSITIVITY, AND ALTERED T-CELL PARAMETERS IN F344 RATS EXPOSED PERINATALLY TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

    EPA Science Inventory

    Abstract
    The outcome of perinatal low-level TCDD exposure on the T cell-mediated contact hypersensitivity response (CHS) in adult F344 rats was investigated. Suppression of the 2,4- dinitrofluorobenzene (DNFB)-specific contact hypersensitivity reponse occurred in mature off...

  1. Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats

    PubMed Central

    Matthews, Jessica L.; Schultz, Irvin R.; Easterling, Michael R.; Melnick, Ronald L.

    2010-01-01

    A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite α-halocarboxymethylglutathione (αH1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibrated with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical- and species-specific parameters. PMID:20045428

  2. Carcinogenicity of 4-methoxyphenol and 4-methylcatechol in F344 rats.

    PubMed

    Asakawa, E; Hirose, M; Hagiwara, A; Takahashi, S; Ito, N

    1994-01-02

    The carcinogenic potentials of 4-methoxyphenol (4-MP) and 4-methylcatechol (4-MC), phenolic compounds which are structurally similar to the known forestomach carcinogen BHA and the glandular stomach carcinogen catechol respectively, and cause considerably enhanced cell proliferation and cytotoxicities in rat forestomach and/or glandular stomach epithelium, were examined in male and female F344 rats. Groups of 30 male and female animals were administered diets containing 2% 4-MP or 2% 4-MC for 104 weeks. Histopathological findings in the 4-MP case included atypical hyperplasias (male, 67%, female, 37%), papillomas (50%, 23%) and squamous-cell carcinomas (77%, 20%) in the forestomach. 4-MC induced forestomach papillomas (70%, 93%) and squamous-cell carcinomas (53%, 37%), also glandular stomach submucosal hyperplasias (90%, 93%), adenomas (100%, 100%) and adenocarcinomas (57%, 47%), with ulceration or erosion. The degree of differentiation of the squamous-cell carcinomas induced by 4-MP was less than with 4-MC. The present study demonstrated unequivocal forestomach carcinogenicity for 4-MP and forestomach and glandular stomach carcinogenicity for 4-MC, with cytotoxicity and cell proliferation both appearing as important factors for these non-genotoxic carcinogens.

  3. VMF3/GPT3: refined discrete and empirical troposphere mapping functions

    NASA Astrophysics Data System (ADS)

    Landskron, Daniel; Böhm, Johannes

    2018-04-01

    Incorrect modeling of troposphere delays is one of the major error sources for space geodetic techniques such as Global Navigation Satellite Systems (GNSS) or Very Long Baseline Interferometry (VLBI). Over the years, many approaches have been devised which aim at mapping the delay of radio waves from zenith direction down to the observed elevation angle, so-called mapping functions. This paper contains a new approach intended to refine the currently most important discrete mapping function, the Vienna Mapping Functions 1 (VMF1), which is successively referred to as Vienna Mapping Functions 3 (VMF3). It is designed in such a way as to eliminate shortcomings in the empirical coefficients b and c and in the tuning for the specific elevation angle of 3°. Ray-traced delays of the ray-tracer RADIATE serve as the basis for the calculation of new mapping function coefficients. Comparisons of modeled slant delays demonstrate the ability of VMF3 to approximate the underlying ray-traced delays more accurately than VMF1 does, in particular at low elevation angles. In other words, when requiring highest precision, VMF3 is to be preferable to VMF1. Aside from revising the discrete form of mapping functions, we also present a new empirical model named Global Pressure and Temperature 3 (GPT3) on a 5°× 5° as well as a 1°× 1° global grid, which is generally based on the same data. Its main components are hydrostatic and wet empirical mapping function coefficients derived from special averaging techniques of the respective (discrete) VMF3 data. In addition, GPT3 also contains a set of meteorological quantities which are adopted as they stand from their predecessor, Global Pressure and Temperature 2 wet. Thus, GPT3 represents a very comprehensive troposphere model which can be used for a series of geodetic as well as meteorological and climatological purposes and is fully consistent with VMF3.

  4. THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS

    EPA Science Inventory

    THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS.

    Abstract:

    The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (D...

  5. Photosynthetic acclimation of WS and WS-gpt2 in Arabidopsis thaliana under fluctuating natural light condition

    NASA Astrophysics Data System (ADS)

    Pa'ee, Furzani; Johnson, Giles

    2017-10-01

    Photoacclimation is a process by which photosynthetic capacity is regulated in response to environmental adjustments in terms of light regime. Photoacclimation is essential in determining the photosynthetic capacity to optimize light use and to avoid potentially damaging effects. Previous work in our laboratory has identified a gene, gpt2 (At1g61800) that is essential for plants to acclimate to an increase and decrease of growth irradiance, separately. To investigate the photoacclimation ability towards fluctuating natural light condition in Arabidopsis thaliana, photosynthetic capacity was measured in plants of the accession Wassileskija (WS) and in plants lacking expression of the gene At1g61800 (WS-gpt2). The experiment was carried out over a time span from early Autumn to early Spring season in 2010-2011 and 2011-2012. The seedlings were grown in an unheated greenhouse in Manchester, UK without supplementary lighting. Gas exchange measurements and chlorophyll content estimation were performed on WS and WS-gpt2 and it showed that both sets of plants were able to acclimate to fluctuating natural light condition. Therefore, it is suggested that the mechanisms of acclimation in a separate growth light condition is mechanistically distinct than the mechanism under fluctuating natural light condition.

  6. VEHICLE AND MODE OF ADMINISTRATION EFFECTS ON THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO BROMODICHLOROMETHANE

    EPA Science Inventory

    Vehicle and Mode of Administration Effects on the Induction of Aberrant Crypt Foci in the Colons of Male F344/N Rats Exposed to Bromodichloromethane.

    David R. Geter, Michael H. George, Tanya M. Moore, Steve Kilburn, Gloria Huggins-Clark, and Anthony B. DeAngelo. Submited ...

  7. Cystic fibrosis in the Basque country: high frequency of mutation delta F508 in patients of Basque origin.

    PubMed Central

    Casals, T; Vázquez, C; Lázaro, C; Girbau, E; Giménez, F J; Estivill, X

    1992-01-01

    The Basque population is one of the oldest populations of Europe. It has been suggested that the Basques arose from a population established in western Europe during the late Paleolithic Age. The Basque language (Euskera) is a supposedly pre-Indo-European language that originates from the first settlers of Europe. The variable distribution of the major cystic fibrosis (CF) mutation (delta F508 deletion) in Europe, with higher frequencies of the mutation in northern Europe and lower frequencies in southern Europe, has suggested that the delta F508 mutation was spread by early farmers migrating from the Middle East during the Neolithic period. We have studied 45 CF families from the Basque Country, where the incidence of CF is approximately 1/4,500. The birthplaces of the parents and grandparents have been traced and are distributed according to their origin as Basque or Mixed Basque. The frequency of the delta F508 mutation in the chromosomes of Basque origin is 87%, compared with 58% in those of Mixed Basque origin. The analysis of haplotypes, both with markers closely linked to the CF gene and with intragenic markers, suggests that the delta F508 mutation was not spread by the Indo-European invasions but was already present in Europe more than 10,000 years ago, during the Paleolithic period. PMID:1370875

  8. Synthesis of a potent and selective (18)F-labeled delta-opioid receptor antagonist derived from the Dmt-Tic pharmacophore for positron emission tomography imaging.

    PubMed

    Ryu, Eun Kyoung; Wu, Zhanhong; Chen, Kai; Lazarus, Lawrence H; Marczak, Ewa D; Sasaki, Yusuke; Ambo, Akihiro; Salvadori, Severo; Ren, Chuancheng; Zhao, Heng; Balboni, Gianfranco; Chen, Xiaoyuan

    2008-03-27

    Identification and pharmacological characterization of two new selective delta-opioid receptor antagonists, derived from the Dmt-Tic pharmacophore, of potential utility in positron emission tomography (PET) imaging are described. On the basis of its high delta selectivity, H-Dmt-Tic--Lys(Z)-OH (reference compound 1) is a useful starting point for the synthesis of (18)F-labeled compounds prepared by the coupling of N-succinimidyl 4-[ (18)F]fluorobenzoate ([(18)F]SFB) with Boc-Dmt-Tic--Lys(Z)-OH under slightly basic conditions at 37 degrees C for 15 min, deprotection with TFA, and HPLC purification. The total synthesis time was 120 min, and the decay-corrected radiochemical yield of [(18)F]- 1 was about 25-30% ( n = 5) starting from [(18)F]SFB ( n = 5) with an effective specific activity about 46 GBq/micromol. In vitro autoradiography studies showed prominent uptake of [ (18)F]- 1 in the striatum and cortex with significant blocking by 1 and UFP-501 (selective delta-opioid receptor antagonist), suggesting high specific binding of [(18)F]- 1 to delta-opioid receptors. Noninvasive microPET imaging studies revealed the absence of [(18)F]- 1 in rat brain, since it fails to cross the blood-brain barrier. This study demonstrates the suitability of [ (18)F]- 1 for imaging peripheral delta-opioid receptors.

  9. Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats

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

    Matthews, Jessica L., E-mail: Jessica_Matthews@sra.co; Schultz, Irvin R., E-mail: irv.schultz@pnl.go; Easterling, Michael R., E-mail: Michael_Easterling@sra.co

    A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite alpha-halocarboxymethylglutathione (alphaH1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibratedmore » with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical-and species-specific parameters.« less

  10. NTP toxicology and carcinogenesis studies of decalin (CAS No. 91-17-8) in F344/N rats and B6C3F(1) mice and a toxicology study of decalin in male NBR rats (inhalation studies).

    PubMed

    2005-01-01

    Decalin is used as an industrial solvent for naphthalene, fats, resins, oils, and waxes. It is also used as a substitute for turpentine in lacquers, paints, and varnishes; as a solvent and stabilizer for shoe polishes and floor waxes; and as a constituent of motor fuels and lubricants. Other applications include use as a paint thinner and remover, a patent fuel in stoves, a high-density fuel in submarine-launched cruise missile systems, and in stain removal and cleaning machinery. Decalin was nominated for study by the National Cancer Institute because of its chemical structure, its potential for consumer exposure, and a lack of adequate testing of the chemical. Male and female F344/N rats and B6C3F(1) mice were exposed to decalin (greater than 99% pure) by inhalation for 2 weeks, 3 months, or 2 years. Groups of male NBR rats were exposed to decalin for 2 weeks. Male NBR rats do not produce alpha2u-globulin; the NBR rats were included to study the relationship of alpha2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. 2-WEEK STUDIES IN RATS: Groups of five male and five female F344/N rats and five male NBR rats were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 16 days. All rats survived to the end of the study, and mean body weights of exposed groups were similar to those of the chamber controls. Renal toxicity studies were performed in male F344/N and NBR rats. The numbers of labeled cells and the labeling indices in the left kidney of 200 and 400 ppm F344/N male rats were significantly greater than those in the chamber controls. The alpha2u-globulin/soluble protein ratios were significantly increased in all exposed groups of F344/N rats. Liver weights of male F344/N and NBR rats exposed to 100 ppm or greater were significantly increased, as were those of all exposed groups of females. Kidney weights of male F344/N rats

  11. Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.

    PubMed

    Zlotnik, Alexander; Tsesis, Svetlana; Gruenbaum, Benjamin Fredrick; Ohayon, Sharon; Gruenbaum, Shaun Evan; Boyko, Matthew; Sheiner, Eyal; Brotfain, Evgeny; Shapira, Yoram; Teichberg, Vivian Itzhak

    2012-09-01

    Excess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. 10 ml of venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10 ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). Fetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (p<0.001). The difference in GPT levels between maternal and fetal serum was not statistically significant. There was no difference in fetal glutamate, GOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, p<0.01) and arterial (R=0.33, p<0.05) fetal blood. This study demonstrated that higher baseline concentrations of blood glutamate are present in fetal blood compared with maternal blood, and this was associated with elevated GOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

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

    Gamboa da Costa, Gonçalo, E-mail: goncalo.gamboa@fda.hhs.gov; Jacob, Cristina C.; Von Tungeln, Linda S.

    The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats weremore » fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.« less

  13. In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR.

    PubMed Central

    Rubenstein, R C; Egan, M E; Zeitlin, P L

    1997-01-01

    The most common cystic fibrosis transmembrane conductance regulator mutation, delta F508-CFTR, is a partially functional chloride channel that is retained in the endoplasmic reticulum and degraded. We hypothesize that a known transcriptional regulator, sodium 4-phenylbutyrate (4PBA), will enable a greater fraction of delta F508-CFTR to escape degradation and appear at the cell surface. Primary cultures of nasal polyp epithelia from CF patients (delta F508 homozygous or heterozygous), or the CF bronchial epithelial cell line IB3-1 (delta F508/W1282X) were exposed to 4PBA for up to 7 d in culture. 4PBA treatment at concentrations of 0.1 and 2 mM resulted in the restoration of forskolin-activated chloride secretion. Protein kinase A-activated, linear, 10 pS chloride channels appeared at the plasma membrane of IB3-1 cells at the tested concentration of 2.5 mM. Treatment of IB3-1 cells with 0.1-1 mM 4PBA and primary nasal epithelia with 5 mM 4PBA also resulted in the appearance of higher molecular mass forms of CFTR consistent with addition and modification of oligosaccharides in the Golgi apparatus, as detected by immunoblotting of whole cell lysates with anti-CFTR antisera. Immunocytochemistry in CF epithelial cells treated with 4PBA was consistent with increasing amounts of delta F508-CFTR. These data indicate that 4PBA is a promising pharmacologic agent for inducing correction of the CF phenotype in CF patients carrying the delta F508 mutation. PMID:9366560

  14. In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR.

    PubMed

    Rubenstein, R C; Egan, M E; Zeitlin, P L

    1997-11-15

    The most common cystic fibrosis transmembrane conductance regulator mutation, delta F508-CFTR, is a partially functional chloride channel that is retained in the endoplasmic reticulum and degraded. We hypothesize that a known transcriptional regulator, sodium 4-phenylbutyrate (4PBA), will enable a greater fraction of delta F508-CFTR to escape degradation and appear at the cell surface. Primary cultures of nasal polyp epithelia from CF patients (delta F508 homozygous or heterozygous), or the CF bronchial epithelial cell line IB3-1 (delta F508/W1282X) were exposed to 4PBA for up to 7 d in culture. 4PBA treatment at concentrations of 0.1 and 2 mM resulted in the restoration of forskolin-activated chloride secretion. Protein kinase A-activated, linear, 10 pS chloride channels appeared at the plasma membrane of IB3-1 cells at the tested concentration of 2.5 mM. Treatment of IB3-1 cells with 0.1-1 mM 4PBA and primary nasal epithelia with 5 mM 4PBA also resulted in the appearance of higher molecular mass forms of CFTR consistent with addition and modification of oligosaccharides in the Golgi apparatus, as detected by immunoblotting of whole cell lysates with anti-CFTR antisera. Immunocytochemistry in CF epithelial cells treated with 4PBA was consistent with increasing amounts of delta F508-CFTR. These data indicate that 4PBA is a promising pharmacologic agent for inducing correction of the CF phenotype in CF patients carrying the delta F508 mutation.

  15. Chronic Carcinogenicity Study of Gasoline Vapor Condensate (GVC) and GVC Containing Methyl Tertiary-Butyl Ether in F344 Rats

    PubMed Central

    Benson, Janet M.; Gigliotti, Andrew P.; March, Thomas H.; Barr, Edward B.; Tibbetts, Brad M.; Skipper, Betty J.; Clark, Charles R.; Twerdok, Lorraine

    2011-01-01

    Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m3 for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints. PMID:21432714

  16. Chronic carcinogenicity study of gasoline vapor condensate (GVC) and GVC containing methyl tertiary-butyl ether in F344 rats.

    PubMed

    Benson, Janet M; Gigliotti, Andrew P; March, Thomas H; Barr, Edward B; Tibbetts, Brad M; Skipper, Betty J; Clark, Charles R; Twerdok, Lorraine

    2011-01-01

    Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m³ for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints.

  17. A comparative study of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in the saliva of diabetic and normal patients.

    PubMed

    Verma, M; Metgud, R; Madhusudan, A S; Verma, N; Saxena, M; Soni, A

    2014-10-01

    Diabetes has been reported to affect salivary glands adversely in humans and experimental models. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) are salivary enzymes that also are widely distributed in animal tissues. We determined GOT and GPT levels in saliva samples of 100 type 1 and 30 type 2 diabetic patients using reflectance spectrophotometry and compared them to 30 age and sex matched healthy controls. Statistically significant differences were observed in the mean values of GOT and GPT in type 1 diabetics compared to type 2 and control groups. Significantly higher GOT levels were found in the 1-20 year age group of type 1 diabetics. Our findings suggest that salivary gland damage is due to the same immunological attack that affects pancreatic β cells and results in type 1 diabetes.

  18. General Electric 32-Spoke Nozzle on the Convair F-106B Delta Dart

    NASA Image and Video Library

    1971-03-21

    National Aeronautics and Space Administration (NASA) Convair F-106B Delta Dart with a 32-spoke nozzle installed on its General Electric J85 test engine. Lewis acquired a Delta Dart fighter in 1966 to study the components for propulsion systems that could be applied to supersonic transport aircraft at transonic speeds. The F-106B was modified with two General Electric J85-13 engines under its wings to study these components. The original test plan was expanded to include the study of boattail drag, noise reduction, and inlets. From February to July 1971 the modified F-106B was used to study different ejector nozzles. Researchers conducted both acoustic and aerodynamic tests on the ground and in flight. Several models were created to test different suppression methods. NASA Lewis’ conical nozzle was used as the baseline configuration. Flightline and sideline microphones were set up on the ground. The F-106B would idle its own engine and buzz the recording station from an altitude of 300 feet at Mach 0.4 with the test engines firing. Researchers found that the suppression of the perceived noise level was usually lower during flight than the researchers had statistically predicted. The 64 and 32-spoke nozzles performed well in actual flight, but the others nozzles tended to negatively affect the engine’s performance. Different speeds or angles- -of-attack sometimes changed the noise levels. In the end, no general conclusions could be applied to all the nozzles.

  19. Convair F-106B Delta Dart with Research Engines

    NASA Image and Video Library

    1969-08-21

    A Convair F-106B Delta Dart rolls to the right to reveal the two research engines installed under its wings by the National Aeronautics and Space Administration (NASA) Lewis Research Center. Lewis acquired the aircraft in October of 1966 to study inlet and nozzle designs for the supersonic transport engine program. Two General Electric J85 engines were mounted beneath the F-106B’s wings and operated from Mach 1 to 1.5. The right wing always carried reference nozzle for which the performance was known. Six supersonic nozzle variations and two inlets were tested on the left engine. The designs had already been studied in the Lewis wind tunnels, but those tests were limited by shock waves in the tunnels. Most F-106B flights were flown in a 200-mile path over the lake between Buffalo and Sandusky, known as the Lake Erie Corridor. The 1100-mile-per-hour flight took only 11 minutes at an altitude of 30,000 feet. The aircraft almost always returned with a depleted fuel supply so a Visual Flight Rules operation was required. Following the crash of another jet fighter at Lewis in July 1969, the F-106s were stationed at Selfridge Air Force Base in Michigan. NASA pilots flew transport planes each morning to the base before commencing the F-106B missions. After the supersonic transport program was cancelled, the F-106B was used as a test bed for additional engine exhaust nozzle configurations. The F-106B was also used to test inlet configurations for the noise reduction program.

  20. Noni (Morinda citrifolia L.) fruit juice reverses age-related decline in neural-immune interactions in the spleens of old F344 rats.

    PubMed

    Pratap, Uday P; Hima, Lalgi; Priyanka, Hannah P; ThyagaRajan, Srinivasan

    2017-02-23

    Various parts of the tropical plant, Morinda citrifolia L. (Noni), have been widely used in traditional medicine in South and Southeast Asia for several centuries. The therapeutic effects of the noni are believed to be mediated through several phytochemicals such as anthraquinones, iridoid, fatty acid glycosides, alcohols, etc. The aim of the study is to investigate the effects of Morinda citrifolia fruit juice (noni fruit juice; NFJ) on neural-immune interactions through the involvement of intracellular signaling pathways both in vitro and in vivo in the splenic lymphocytes of young and old male F344 rats. In the in vitro study, splenocytes from young and old F344 rats were isolated and treated with 0.0001-1% concentrations of NFJ for a period of 24h, while in the in vivo study, old F344 rats were orally administered (5ml/kg body weight) with NFJ (5%, 10% and 20%) twice daily for 60 days. After the treatment period, concanavalin A (Con A)-induced lymphocyte proliferation, cytokines (IL-2, IFN-γ, IL-6, and TNF-α) production, expression of tyrosine hydroxylase (p-TH), nerve growth factor (NGF), m-TOR, IκB-α, p-NF-κB (p50 and p65), p-ERK, p-Akt, p-CREB and lipid peroxidation, protein carbonyl formation, nitric oxide (NO) production were examined in the splenocytes. In vitro NFJ incubation of splenic lymphocytes increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and expression of p-ERK, p-Akt, and p-CREB in young and old rats. In vivo treatment of old rats with NFJ increased lymphoproliferation, IL-2 and IFN-γ production, the expression of p-TH, NGF, and NO production, and suppressed IL-6 production, lipid peroxidation, protein carbonyl formation, and the expression of IκB-α and p-NF-κB (p50) in the splenocytes. Taken together, these results suggest that Morinda citrifolia fruit juice enhanced neural-immune interactions and cell survival pathways while inhibiting inflammatory processes that may be useful in the treatment of age

  1. Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.

    PubMed

    Reddy, B S; Furuya, K; Lowenfels, A

    1984-07-01

    The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.

  2. 14 CFR 34.4 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false [Reserved] 34.4 Section 34.4 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT FUEL VENTING AND EXHAUST EMISSION REQUIREMENTS FOR TURBINE ENGINE POWERED AIRPLANES General Provisions § 34.4 [Reserved] ...

  3. 14 CFR 34.4 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false [Reserved] 34.4 Section 34.4 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT FUEL VENTING AND EXHAUST EMISSION REQUIREMENTS FOR TURBINE ENGINE POWERED AIRPLANES General Provisions § 34.4 [Reserved] ...

  4. 14 CFR 34.4 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false [Reserved] 34.4 Section 34.4 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT FUEL VENTING AND EXHAUST EMISSION REQUIREMENTS FOR TURBINE ENGINE POWERED AIRPLANES General Provisions § 34.4 [Reserved] ...

  5. 14 CFR 34.4 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false [Reserved] 34.4 Section 34.4 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT FUEL VENTING AND EXHAUST EMISSION REQUIREMENTS FOR TURBINE ENGINE POWERED AIRPLANES General Provisions § 34.4 [Reserved] ...

  6. 32 CFR 344.2 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Applicability. 344.2 Section 344.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.2 Applicability. This part...

  7. 32 CFR 344.2 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Applicability. 344.2 Section 344.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.2 Applicability. This part...

  8. 32 CFR 344.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Definitions. 344.3 Section 344.3 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.3 Definitions. (a) Reserve...

  9. 32 CFR 344.6 - Authorities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Authorities. 344.6 Section 344.6 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.6 Authorities. The ASD(RA) is...

  10. 32 CFR 344.6 - Authorities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Authorities. 344.6 Section 344.6 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.6 Authorities. The ASD(RA) is...

  11. 16 CFR 3.44 - Record.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Record. 3.44 Section 3.44 Commercial... ADJUDICATIVE PROCEEDINGS Hearings § 3.44 Record. (a) Reporting and transcription. Hearings shall be... Administrative Law Judge, and the original transcript shall be a part of the record and the sole official...

  12. 45 CFR 3.44 - Solicitation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Solicitation. 3.44 Section 3.44 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE Facilities and Grounds § 3.44 Solicitation. It shall be unlawful for a...

  13. 45 CFR 3.44 - Solicitation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Solicitation. 3.44 Section 3.44 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE Facilities and Grounds § 3.44 Solicitation. It shall be unlawful for a...

  14. 45 CFR 3.44 - Solicitation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Solicitation. 3.44 Section 3.44 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE Facilities and Grounds § 3.44 Solicitation. It shall be unlawful for a...

  15. 45 CFR 3.44 - Solicitation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Solicitation. 3.44 Section 3.44 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE Facilities and Grounds § 3.44 Solicitation. It shall be unlawful for a...

  16. 45 CFR 3.44 - Solicitation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Solicitation. 3.44 Section 3.44 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE Facilities and Grounds § 3.44 Solicitation. It shall be unlawful for a...

  17. 21 CFR 344.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Definitions. 344.3 Section 344.3 Food and Drugs... TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE General Provisions § 344.3 Definitions. As used... external ear canal that aids in the removal of excessive earwax. (c) Water-clogged ears. The retention of...

  18. Comparative pharmacokinetic and disposition studies of [1-14C]1-eicosanylcyclohexane, a surrogate mineral hydrocarbon, in female Fischer-344 and Sprague-Dawley rats.

    PubMed

    Halladay, Jason S; Mackerer, Carl R; Twerdok, Lorraine E; Sipes, I Glenn

    2002-12-01

    White oils or waxes [mineral hydrocarbons (MHCs)] with substantial levels of saturated hydrocarbons in the range of C18 to C32 have produced hepatic microgranulomas and lymph node microgranulomas (also referred to as histiocytosis) after repeated administration to female Fischer-344 (F-344) rats. Female Sprague-Dawley (S-D) rats are less sensitive to these MHC-induced hepatic and lymph node effects. Studies reported herein characterized the pharmacokinetics and disposition of a representative C-26 MHC, [1-(14)C]1-eicosanylcyclohexane ([(14)C]EICO), in these two rat strains. Female F-344 and S-D rats were administered by oral gavage either a high (1.80 g/kg) or a low (0.18 g/kg) dose of MHC in olive oil (1:4, v/v) containing [(14)C]EICO as a tracer. Blood, urine, feces, liver, and mesenteric lymph nodes (MLNs) were analyzed for [(14)C]EICO and (14)C-metabolites. After the high dose, F-344 rats had a higher blood C(max) of [(14)C]EICO, a longer time to C(max), and a greater area under the systemic blood concentration-time curve from zero to time infinity compared with S-D rats. After the low dose, F-344 rats displayed a unique triphasic blood concentration-time profile, meaning two distinct C(max) values were observed. Fecal excretion was the major route of [(14)C]EICO elimination for both rat strains (70-92% of the dose). S-D rats eliminated the majority of [(14)C]EICO metabolites recovered in the urine by 16 h (8-17% of the dose), whereas F-344 rats did not excrete the same amount until 72 to 96 h. Beyond 24 h, a greater level of [(14)C]EICO was recovered in livers of F-344 rats; at 96 h, 3 and 0.1% of the dose was retained in livers of F-344 and S-D rats, respectively. The major urinary metabolites of EICO in both rat strains were identified as 12-cyclohexyldodecanoic acid and 10-cyclohexyldecanoic acid. Based on the pharmacokinetic parameters and disposition profiles, the data indicate inherent strain differences in the total systemic exposure, rate of metabolism

  19. Disposition of [14C]N,N-dimethyl-p-toluidine in F344 rats and B6C3F1 mice.

    PubMed

    Dix, Kelly J; Ghanbari, Katayoon; Hedtke-Weber, Briana M

    2007-05-15

    N,N-Dimethyl-p-toluidine (DMPT) is used as a polymerization accelerator, in industrial glues, and as an intermediate in dye and pesticide synthesis. There is potential for human exposure to DMPT. The disposition of oral and intravenous (i.v.) doses of [14C]DMPT in F344 rats and B6C3F1 mice was investigated. A single i.v. (2.5 mg/kg) or oral (2.5, 25, or 250 mg/kg) dose of [14C]DMPT (1-25 microCi) was administered in an aqueous vehicle to male rats and mice. The 25-mg/kg oral dose was administered to females to investigate possible gender differences in disposition. However, no striking gender differences were observed. Since toxicity studies conducted elsewhere used a corn oil vehicle, the 250-mg/kg oral dose also was administered in corn oil to male rats; disposition was not dependent on vehicle. Excreta (through 24 h) and tissues collected at sacrifice were analyzed for total radioactivity. Dose-dependent differences in toxicity and disposition were observed. Toxicity at the 250-mg/kg oral dose to male mice was consistent with acute renal failure. At the same dose, male rats exhibited clinical signs of toxicity through 12 h but were clinically normal by 24 h. At lower oral doses, [14C]DMPT-derived radioactivity was well absorbed and rapidly excreted, primarily in urine.

  20. Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice after Chronic Oral Exposure

    PubMed Central

    Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Collins, Bradley J.; Travlos, Gregory S.; Witt, Kristine L.; Melnick, Ronald L.; Abdo, Kamal M.; Malarkey, David E.; Hooth, Michelle J.

    2009-01-01

    Background Hexavalent chromium [Cr(VI)] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI). Objective We characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents. Methods The National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice. Results Cr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice. Conclusions Cr(VI) was carcinogenic after administration in drinking water to male and female rats and mice. PMID:19479012

  1. Nonlinear Delta-f Simulations of Collective Effects in Intense Charged Particle Beams

    NASA Astrophysics Data System (ADS)

    Qin, Hong

    2002-11-01

    A nonlinear delta-f particle simulation method based on the Vlasov-Maxwell equations has been recently developed to study collective processes in high-intensity beams, where space-charge and magnetic self-field effects play a critical role in determining the nonlinear beam dynamics. Implemented in the Beam Equilibrium, Stability and Transport (BEST) code, the nonlinear delta-f method provides a low-noise and self-consistent tool for simulating collective interactions and nonlinear dynamics of high-intensity beams in modern and next- generation accelerators and storage rings, such as the Spallation Neutron Source, and heavy ion fusion drivers. Simulation results for the electron-proton two-stream instability in the Proton Storage Ring (PSR) experiment at Los Alamos National Laboratory agree well with experimental observations. Large-scale parallel simulations have also been carried out for the ion-electron two-stream instability in the very high-intensity heavy ion beams envisioned for heavy ion fusion applications. In both cases, the simulation results indicate that the dominant two-stream instability has a dipole-mode (hose-like) structure and can be stabilized by a modest axial momentum spread of the beam particles of less than 0.25collective processes in high-intensity beams, such as anisotropy-driven instabilities, collective eigenmode excitations for perturbations about stable beam equilibria, and the Darwin model for fully electromagnetic perturbations will also be discussed.

  2. NTP technical report on toxicity studies of cadmium oxide (Cas No. 1306-19-0) administered by inhalation to F344/N rats and B6C3f1 mice. Toxicity report series

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

    NONE

    1995-03-01

    Three thousand tons of cadmium are imported or produced annually in the United States, and approximately 90% of this is cadmium oxide. Cadmium oxide is used in batteries, electroplating baths, pigments, plastics, synthetic products, and a variety of other materials. Cadmium oxide was nominated for study by the National Cancer Institute because of its widespread use and to obtain toxicity and carcinogenicity information. This report describes toxicity studies of cadmium oxide aerosol in F344/N rats and B6C3F1 mice, including sperm motility and vaginal cytology evaluations, and developmental toxicity studies of cadmium oxide aerosol in Sprague-Dawley rats and Swiss (CD-1) mice.more » Genetic toxicology studies were done in Salmonella typhimurium and B6C3F1 mice erythrocytes.« less

  3. Convair F-106B Delta Dart with Air Sampling Equipment

    NASA Image and Video Library

    1974-04-21

    The National Aeronautics and Space Administration (NASA) Lewis Research Center’s Convair F-106B Delta Dart equipped with air sampling equipment in the mid-1970s. NASA Lewis created and managed the Global Air Sampling Program (GASP) in 1972 in partnership with several airline companies. NASA researchers used the airliners’ Boeing 747 aircraft to gather air samples to determine the amount of pollution present in the stratosphere. Private companies developed the air sampling equipment for the GASP program, and Lewis created a particle collector. The collector was flight tested on NASA Lewis’ F-106B in the summer of 1973. The sampling equipment was automatically operated once the proper altitude was achieved. The sampling instruments collected dust particles in the air so their chemical composition could be analyzed. The equipment analyzed one second’s worth of data at a time. The researchers also monitored carbon monoxide, monozide, ozone, and water vapor. The 747 flights began in December 1974 and soon included four airlines flying routes all over the globe. The F-106B augmented the airline data with sampling of its own, seen here. It gathered samples throughout this period from locations such as New Mexico, Texas, Michigan, and Ohio. In July 1977 the F-106B flew eight GASP flights in nine days over Alaska to supplement the earlier data gathered by the airlines.

  4. Comparison of the Effects of Hexavalent Chromium in the Alimentary Canal of F344 Rats and B6C3F1 Mice Following Exposure in Drinking Water: Implications for Carcinogenic Modes of Action

    PubMed Central

    Thompson, Chad M.; Proctor, Deborah M.; Suh, Mina; Haws, Laurie C.; Hébert, Charles D.; Mann, Jill F.; Shertzer, Howard G.; Hixon, J. Gregory; Harris, Mark A.

    2012-01-01

    Exposure to high concentrations of hexavalent chromium (Cr[VI]) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1–182 mg/l Cr(VI), administered as 0.3–520 mg/l sodium dichromate dihydrate. Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines, and iron status suggest potential contributions from other factors as well. PMID:22011396

  5. Comparison of the effects of hexavalent chromium in the alimentary canal of F344 rats and B6C3F1 mice following exposure in drinking water: implications for carcinogenic modes of action.

    PubMed

    Thompson, Chad M; Proctor, Deborah M; Suh, Mina; Haws, Laurie C; Hébert, Charles D; Mann, Jill F; Shertzer, Howard G; Hixon, J Gregory; Harris, Mark A

    2012-01-01

    Exposure to high concentrations of hexavalent chromium (Cr[VI]) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1-182 mg/l Cr(VI), administered as 0.3-520 mg/l sodium dichromate dihydrate. Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines, and iron status suggest potential contributions from other factors as well.

  6. 7 CFR 1210.344 - Operating reserve.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Operating reserve. 1210.344 Section 1210.344 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... PROMOTION PLAN Watermelon Research and Promotion Plan Expenses and Assessments § 1210.344 Operating reserve...

  7. Chemoprevention of azoxymethane-induced colon cancer by ascorbylpalmitate, carbenoxolone, dimethylfumarate and p-methoxyphenol in male F344 rats.

    PubMed

    Rao, C V; Rivenson, A; Kelloff, G J; Reddy, B S

    1995-01-01

    The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarate (DMF) and p-methoxyphenol (p-MP) administrated in the diet before and during initiation and postinitiation phases of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD levels of AP, CBX, DMF and p-MP were determined in male F344 rats and found to be 5000 1500, 1000 and 1000 ppm, respectively, in modified AIN-76A diet. Based on these MTD values, 40 and 80% MTD levels of each agent was tested for their efficacy in color carcinogenesis. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A diet or diets containing 40 and 80% MTD levels of each AP, CBX, DMF and p-MP. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of AOM at a dose rate of 15 mg/kg body weight/week. All groups were continued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. The results indicate that dietary administration of 40% MTD of AP significantly inhibited multiplicities (tumor/animal) of noninvasive and total (invasive plus noninvasive) adenocarcinoma of the colon (P < 0.05) and 80% MTD of AP significantly inhibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary CBX at 40 and 80% MTD levels suppressed the incidence and multiplicities of invasive and total adenocarcinomas (P < 0.05 to 0.001) whereas 40 and 80% MTD of DMF and p-MP had significantly inhibited invasive adenocarcinoma incidence and multiplicity (P < 0.05 to 0.001). However, DMF and p-MP had no significant effect on noninvasive and total adenocarcinoma incidence and multiplicity (P > 0.05). These results suggest that AP and CBX possess potential

  8. DIMETHYLARSINIC ACID ALTERS EXPRESSION OF OXIDATIVE STRESS AND DNA REPAIR GENES IN A DOSE DEPENDENT MANNER IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS.

    EPA Science Inventory

    Dose-dependent alteration of oxidative stress and DNA repair gene expression by Dimethylarsinic acid [DMA(V)] in transitional epithelium of urinary bladder from female F344 rats.
    Arsenic (As) is a major concern as millions of people are at risk from drinking arsenic contaminat...

  9. 42 CFR 34.4 - Medical notifications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Medical notifications. 34.4 Section 34.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS MEDICAL EXAMINATION OF ALIENS § 34.4 Medical notifications. (a) Medical examiners shall issue medical...

  10. 42 CFR 34.4 - Medical notifications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Medical notifications. 34.4 Section 34.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS MEDICAL EXAMINATION OF ALIENS § 34.4 Medical notifications. (a) Medical examiners shall issue medical...

  11. 42 CFR 34.4 - Medical notifications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Medical notifications. 34.4 Section 34.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS MEDICAL EXAMINATION OF ALIENS § 34.4 Medical notifications. (a) Medical examiners shall issue medical...

  12. 42 CFR 34.4 - Medical notifications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Medical notifications. 34.4 Section 34.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS MEDICAL EXAMINATION OF ALIENS § 34.4 Medical notifications. (a) Medical examiners shall issue medical...

  13. COMPARATIVE IMMUNOSUPPRESSION OF VARIOUS GLYCOL ETHERS ORALLY ADMINISTERED TO FISCHER 344 RATS

    EPA Science Inventory

    Oral dosing of adult rats F344 rats with the glycol ether 2-methoxyethanol (ME) or its principal metabolite 2-methoxyacetic acid (MAA) results in the suppression of the primary plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP_LPS). n the present study,...

  14. 31 CFR 29.344 - Survivor benefits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Survivor benefits. 29.344 Section 29.344 Money and Finance: Treasury Office of the Secretary of the Treasury FEDERAL BENEFIT PAYMENTS UNDER CERTAIN DISTRICT OF COLUMBIA RETIREMENT PROGRAMS Split Benefits § 29.344 Survivor benefits. (a) The...

  15. 31 CFR 29.344 - Survivor benefits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Survivor benefits. 29.344 Section 29.344 Money and Finance: Treasury Office of the Secretary of the Treasury FEDERAL BENEFIT PAYMENTS UNDER CERTAIN DISTRICT OF COLUMBIA RETIREMENT PROGRAMS Split Benefits § 29.344 Survivor benefits. (a) The...

  16. Safety of purified decolorized (low anthraquinone) whole leaf Aloe vera (L) Burm. f. juice in a 3-month drinking water toxicity study in F344 rats.

    PubMed

    Shao, A; Broadmeadow, A; Goddard, G; Bejar, E; Frankos, V

    2013-07-01

    Decolorized (purified, low anthraquinone) whole leaf Aloe vera (L.) Burm. f. juice was administered at concentrations of 0%, 0.5%, 1% and 2% in the drinking water of F344Du rats for 3 months without any adverse effect. The no-observed-adverse-effect level (NOAEL) in this study was considered to be >2%w/v (>1845 mg/kg bodyweight/day for males and >2920 mg/kg bodyweight for females). The test material contained total anthraquinones at <0.1 parts per million. In the present study there was a complete absence of any histological alteration in samples from the cecum, colon (proximal, mid and distal regions). Similar concentrations of non-decolorized (unpurified, high anthraquinone) Aloe vera extracts tested in other studies have resulted in an increased incidence and severity of diarrhea and colon adenomas and carcinomas. The results of this study supports the assertion that the high levels of anthraquinone present in orally administered, non-purified whole leaf Aloe vera extract may be responsible for the adverse effects observed on the colon. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B6C3F1 mice exposed to hexavalent chromium via the drinking water.

    PubMed

    Shipkowski, Kelly A; Sheth, Christopher M; Smith, Matthew J; Hooth, Michelle J; White, Kimber L; Germolec, Dori R

    2017-12-01

    Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B 6 C 3 F 1 mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516 ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250 ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250 ppm B 6 C 3 F 1 mice and 516 ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516 ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5-7%) decreased in 250 ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on

  18. Analysis of a delta spot

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Zhang, H. Q.

    2002-05-01

    delta -groups generally develop in three different ways: eruption of a single complex active region, eruption of large satellite spots near a large older spot, or collision of spots of opposite polarity from different dipoles. In this paper, we present a rare observational result in which a delta -spot forms from rapid coalescence of two opposite magnetic features in a pre-existing delta -configuration. The white-light (WL) observations of this delta -spot in active region NOAA 9077 were performed by TRACE. The time-lapse movie of the co-aligned WL images shows that the whole active region was undergoing rapid disintegration and reconstruction on 11-17 July 2000. The preceding ({p}) and following ({f}) components of the delta -spot continue to grow in size, while the active region is in the decaying phase. Their proper motions are determined as a function of time using SOHO/MDI full-disk magnetograms. A major flare (3B/X5.7) erupted in the active region on 14 July. Initially, a relative shearing motion is visible between the {p} and {f} spots on this day. About two hours before the major flare, the shearing motion suddenly stops and the velocities change significantly. The ribbons of the flare are located just outside of the delta -configuration. An interesting finding is the sign reversal of the helicity of the {f} spot also just 2 hours before the flare. The delta -spot obviously separates after the flare. Our results clearly demonstrate that helicity reversal in magnetic features of a delta -configuration is likely to destabilize the compact structure, as well as to re-organize the magnetic field configuration, and, hence, is important for the rapid disintegration of a delta -spot during major flares. A model is presented to explain why a spot can change its chirality.

  19. Deficits in synaptic function occur at medial perforant path-dentate granule cell synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel TgF344-Alzheimer's Disease Rat Model.

    PubMed

    Smith, Lindsey A; McMahon, Lori L

    2018-02-01

    Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known. Furthermore, it is not known if specific hippocampal synapses are differentially affected by progressing AD pathology, or if synaptic deficits begin to appear at the same age in males and females in this preclinical model. Here, we investigated the time-course of synaptic changes in basal transmission, paired-pulse ratio, as an indirect measure of presynaptic release probability, long-term potentiation (LTP), and dendritic spine density at two hippocampal synapses in male and ovariectomized female TgF344-AD rats and wildtype littermates, prior to reported behavioral deficits. Decreased basal synaptic transmission begins at medial perforant path-dentate granule cell (MPP-DGC) synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d-aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1 synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC synapses in TgF344-AD rats at 6months only. Sex differences were only observed at CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age in males versus females. These are the first studies to define presymptomatic alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The time course of altered synaptic transmission mimics the spread of pathology through hippocampus in human AD and provides

  20. Assessment of the mutagenic potential of Cr(VI) in the oral mucosa of Big Blue® transgenic F344 rats.

    PubMed

    Thompson, Chad M; Young, Robert R; Suh, Mina; Dinesdurage, Harshini R; Elbekai, Reem H; Harris, Mark A; Rohr, Annette C; Proctor, Deborah M

    2015-08-01

    Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingival mucosa surrounding the upper molar teeth. To investigate whether these tumors could have resulted from a mutagenic mode of action (MOA), a transgenic mutation assay based on OECD Test Guideline 488 was conducted in Big Blue(®) TgF344 rats. The mutagenic oral carcinogen 4-nitroquinoline-1-oxide (4-NQO) served as a positive control. Mutant frequency was measured in the inner gingiva with adjacent palate, and outer gingiva with adjacent buccal tissue. Exposure to 10 ppm 4-NQO in drinking water for 28 days increased mutant frequency in the cII transgene significantly, from 39.1 ± 7.5 × 10(-6) to 688 ± 250 × 10(-6) in the gingival/buccal region, and from 49.8 ± 17.8 × 10(-6) to 1818 ± 362 × 10(-6) in the gingival/palate region. Exposure to 180 ppm Cr(VI) in drinking water for 28 days did not significantly increase the mutant frequency in the gingival/buccal (44.4 ± 25.4 × 10(-6)) or the gingival/palate (57.8 ± 9.1 × 10(-6)) regions relative to controls. These data indicate that high (∼180,000 times expected human exposure), tumorigenic concentrations of Cr(VI) did not significantly increase mutations in the gingival epithelium, and suggest that Cr(VI) does not act by a mutagenic MOA in the rat oral cavity. © 2015 Wiley Periodicals, Inc.

  1. Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

    PubMed Central

    Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei

    2014-01-01

    Purpose. Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Methods. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. Results. As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. Conclusions. Further studies are needed to elucidate the significance and mechanisms of this pathological change and luminance threshold recording from the superior colliculus. PMID:24398104

  2. HISTOPATHOLOGICAL ANALYSIS OF THE F344 RAT LUNG UPON EXPOSURE TO RETENOIC ACID, OVALBUMIN, MOLD SPORES AND CITRAL.

    PubMed

    Farah, Ibrahim O; Holt-Gray, Carlene; Cameron, Joseph A; Tucci, Michelle; Benghuzzi, Hamed

    2017-01-01

    The paradoxical role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of allergic and/or inflammatory complications in contrast to a therapeutic modality for lung pathology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function; a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2), in the reversal of retinoic acid, ovalbumin and allergic mold spore pathophysiology is also not well ascertained under an in vivo setting. Therefore, it is hypothesized that exposure of F344 lung tissues to supra-physiologic levels of retinoic acid, ovalbumin and mold spores individually or in combination with each other will lead to inflammatory tissue pathology and that Citral 1 and 2 will reverse or ameliorate the related pathological damage to lung tissues. Even though ovalbumin and retinoic acid have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this study was to evaluate the histopathological implications of such exposure in vivo. This IACUC approved in vivo study used Fischer 344 rats ( n = 80 ; 229 to 273g), which were randomly assigned to controls as well as ovalbumin and mold-sensitized treatment groups (0.80 mg/kg and 1×10 9 mold spores combined from 4 strains/100 μl intra-tracheal; all others were dosed by intra-peritoneal injection at days 1 and 7 with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent all four chemicals and mold spores treatments. Positive and negative controls for each treatment were also included in the study. Animals were housed in rat cages at the JSU Research Animal Core Facilities and were placed on a 12:12 light-dark cycle. A standard rodent diet and water access were provided ad libidum. All animals were sacrificed on day 21 and lung tissues were processed for histopathology. Slides were prepared and

  3. THE INDUCTION OF ABERRANT CRYPT FOCI (ACF) IN MALE AND FEMALE F344/N RATS BY BROMOCHLOROACETIC ACID (BCA) ADMINISTERED IN THE DRINKING WATER

    EPA Science Inventory

    The Induction of Aberrant Crypt Foci (ACF) in Male and Female F344/N Rats by Bromochloroacetic Acid (BCA) Administered in the Drinking Water.

    M.H. George1, D. Delker1, D.R. Geter1, C.Herbert2, J. Roycroft3, R. Melnick3, D.W.
    Rosenberg4, and A.B. DeAngelo1. 1USEPA, Resea...

  4. Genetic differences in NMDA and D1 receptor levels, and operant responding for food and morphine in Lewis and Fischer 344 rats.

    PubMed

    Martín, Sonsoles; Lyupina, Yulia; Crespo, José Antonio; González, Begoña; García-Lecumberri, Carmen; Ambrosio, Emilio

    2003-05-30

    Previously, we have shown that Lewis (LEW) rats acquire faster than Fischer 344 (F344) rats operant food- and morphine-reinforced tasks under fixed-ratio schedules of reinforcement. The first purpose of the present work has been to study if differences in operant responding behavior may participate in the reported differences in morphine self-administration behavior between both inbred rat strains. To this end, we have analyzed the microstructure of responding obtained under a variable-interval (VI) of food reinforcement by calculating the inter-response time (IRT) for each rat strain. LEW rats exhibited shorter IRTs than F344 rats, suggesting that LEW rats may have an inherent high or compulsive operant responding activity. When subjects of both inbred rat strains were submitted to a schedule of morphine reinforcement of high responding requirements such as progressive ratio schedules, LEW rats also reached significantly higher breaking points and final response ratio than F344 rats for i.v. morphine self-administration. Given that there are neurochemical differences between both rat strains and that glutamatergic N-methyl-D-aspartate (NMDA) and dopaminergic D(1) receptors have been involved in operant responding behavior, a second purpose of this work has been to measure basal NMDA and D(1) receptor levels in these rat strains by quantitative receptor autoradiography. Compared to F344 rats, LEW rats showed higher basal NMDA receptor levels in frontal and cingulate cortex, caudate putamen, central amygdaloid nuclei, and intermediate white layer of superior colliculus, and higher basal D(1) receptor levels in several areas of hippocampus and thalamus, and substantia nigra pars reticulata. Taken together, these results suggest that an inherent high operant responding activity of LEW rats may have a role in the previous reported faster acquisition of opiate-reinforced behavior in operant self-administration paradigms under fixed-ratio schedules of reinforcement. In

  5. 32 CFR 344.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Definitions. 344.3 Section 344.3 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL... employees), contractor staff, and host-nation support personnel. ...

  6. Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX.

    PubMed

    Andersson, C; Roomans, G M

    2000-05-01

    The cellular basis of cystic fibrosis (CF) is a defect in a cyclic adenosine monophosphate (cAMP)-activated chloride channel (CF transmembrane conductance regulator) in epithelial cells that leads to decreased chloride ion transport and impaired water transport across the cell membrane. This study investigated whether it was possible to activate the defective chloride channel in cystic fibrosis respiratory epithelial cells with 4-phenylbutyrate (4PBA), genistein and 8-cyclopentyl-1,3-dipropylxanthine (CPX). The CF bronchial epithelial cell line CFBE41o-, which expresses the deltaF508 mutation, was treated with these agents and loss of Cl-, indicating Cl- efflux, measured by X-ray microanalysis. 8-bromo-cAMP alone did not induce Cl- efflux in CFBE41o- cells, but after incubation with 4PBA a significant efflux of Cl- occurred. Stimulation of cells with a combination of genistein and cAMP also induced Cl- efflux, whereas a combination of pretreatment with 4PBA and a combined stimulation with genistein and cAMP induced an even larger Cl- efflux. Cl- efflux could also be stimulated by CPX, but this effect was not enhanced by 4PBA pretreatment. The deltaF508 mutation leads to impaired processing of the cystic fibrosis transmembrane conductance regulator. The increased efflux of chloride after 4-phenylbutyrate treatment can be explained by the fact that 4-phenylbutyrate allows the deltaF508 cystic fibrosis transmembrane conductance regulator to escape degradation and to be transported to the cell surface. Genistein and 8-cyclopentyl-1,3-dipropylxanthine act by stimulating chloride ion efflux by increasing the probability of the cystic fibrosis transmembrane conductance regulator being open. The combination of 4-phenylbutyrate and genistein may be useful in a potential pharmacological therapy for cystic fibrosis patients with the deltaF508 mutation.

  7. THE EFFECTS OF A HIGH ANIMAL FAT DIET ON THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO TRIHALOMETHANES IN THE DRINKING WATER

    EPA Science Inventory

    The Effects of a High Animal Fat Diet on the Induction of Aberrant Crypt Foci in the Colons of Male F344/N Rats Exposed to Trihalomethanes in the Drinking Water

    Abstract

    Aberrant crypt foci (ACF), identified as the putative precursor lesion in the development of co...

  8. NTP toxicity studies of dimethylaminopropyl chloride, hydrochloride (CAS No. 5407-04-5) administered by Gavage to F344/N rats and B6C3F1 mice.

    PubMed

    Abdo, Km

    2007-07-01

    Dimethylaminopropyl chloride, hydrochloride is used primarily as an industrial and research organic chemical intermediate acting as an alkylating reagent in Grignard and other types of reactions. It is also used as a pharmaceutical intermediate for the synthesis of many types of drugs, as an agricultural chemical intermediate, as a photographic chemical intermediate, and as a biochemical reagent for enzyme and other studies. Human occupational or other accidental exposure can occur by inhalation, ingestion, or skin absorption. Male and female F344/N rats and B6C3F1 mice received dimethylaminopropyl chloride, hydrochloride (greater than 99% pure) in water by gavage for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. In the 2-week toxicity studies, groups of five male and five female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg dimethylaminopropyl chloride, hydrochloride/kg body weight in deionized water by gavage, 5 days per week for 16 days. All dosed male and female rats and mice survived until the end of the 2-week study; one vehicle control female mouse died early. Mean body weights of all dosed groups of rats and mice were similar to those of the vehicle control groups. No gross or microscopic lesions were considered related to dimethylaminopropyl chloride, hydrochloride administration. In the 3-month toxicity studies, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg/kg in deionized water by gavage, 5 days per week for 3 months. One male rat in the 50 mg/kg group died during week 12 of the study, and one female mouse in the 100 mg/kg group died during week 9 and another during week 13. The final mean body weights of 50 mg/kg male rats and 50 mg/kg female mice were significantly less than those of the vehicle controls. Possible chemical-related clinical findings in rats

  9. Carcinogenicity of glycidamide in B6C3F1 mice and F344/N rats from a two-year drinking water exposure.

    PubMed

    Beland, Frederick A; Olson, Greg R; Mendoza, Maria C B; Marques, M Matilde; Doerge, Daniel R

    2015-12-01

    Acrylamide is a contaminant in baked and fried starchy foods, roasted coffee, and cigarette smoke. Previously we reported that acrylamide is a multi-organ carcinogen in B6C3F1 mice and F344/N rats, and hypothesized that acrylamide is activated to an ultimate carcinogen through metabolism to the epoxide glycidamide. We have now examined the carcinogenic effects of glycidamide administered at 0, 0.0875, 0.175, 0.35 and 0.70 mM in drinking water to the same strains of rodents for two years. In male and female mice, there were significant increases in tumors of the Harderian gland, lung, forestomach, and skin. Female mice also had an increased incidence of tumors of the mammary gland and ovary. In male and female rats, there were significant increases in thyroid gland and oral cavity neoplasms and mononuclear cell leukemia. Male rats also had increases in tumors of the epididymis/testes and heart, while female rats demonstrated increases in tumors of the mammary gland, clitoral gland, and forestomach. A similar spectrum of tumors was obtained in mice and rats administered acrylamide. These data indicate that, under the conditions of these bioassays, acrylamide is efficiently metabolized to glycidamide and that the carcinogenic activity of acrylamide is due to its conversion into glycidamide. Published by Elsevier Ltd.

  10. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

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

    Huang, Zhenlie; Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550; Ichihara, Sahoko

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins.more » Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed

  11. 18 CFR 344.1 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Applicability. 344.1 Section 344.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... thereof, for the transportation, storage, or handling of petroleum and petroleum products at reduced rates...

  12. 18 CFR 344.1 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Applicability. 344.1 Section 344.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... thereof, for the transportation, storage, or handling of petroleum and petroleum products at reduced rates...

  13. 18 CFR 344.1 - Applicability.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Applicability. 344.1 Section 344.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... thereof, for the transportation, storage, or handling of petroleum and petroleum products at reduced rates...

  14. 18 CFR 344.1 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Applicability. 344.1 Section 344.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... thereof, for the transportation, storage, or handling of petroleum and petroleum products at reduced rates...

  15. 32 CFR 344.5 - Relationships.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Relationships. 344.5 Section 344.5 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL..., direction, and control over the National Committee for Employer Support of the Guard and Reserve. (3...

  16. 32 CFR 344.5 - Relationships.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.5 Relationships. (a) In the performance of assigned functions and responsibilities, the ASD(RA) shall serve under the authority, direction... ASD(RA) on all matters related to the responsibilities and functions cited in § 344.4. ...

  17. Deuterated methoxyflurane anesthesia and renal function in Fischer 344 rats

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

    Baden, J.M.; Rice, S.A.; Mazze, R.I.

    1982-03-01

    Inorganic fluoride (F-) production and renal function were assessed in six groups of Fischer 344 rats administered either methoxyflurane (MOF) or deuterated methoxyflurane (d4-MOF). One untreated and one phenobarbital (PB)-treated group were exposed for two hours to either air, 0.5 per cent (V/v) MOF, or 0.5 per cent (v/v) d4-MOF. Serum and urinary F- and serum urea nitrogen and creatinine were measured. Urine volume and urinary F- excretion were only slightly greater among MOF than among d4-MOF exposed animals. Pretreatment with PB, however, greatly enhanced F- production in MOF-exposed animals leading to marked renal impairment but only slightly enhanced F-more » production in d4-MOF animals leading to mild renal impairment. Thus, only in PB-pretreated animals could a biologically significant difference in nephrotoxicity be demonstrated for MOF and d4-MOF.« less

  18. Amphetamine Self-Administration and Dopamine Function: Assessment of Gene x Environment Interactions in Lewis and Fischer 344 Rats

    PubMed Central

    Meyer, Andrew C.; Bardo, Michael T.

    2015-01-01

    Rationale Previous research suggests both genetic and environmental influences on substance abuse vulnerability. Objectives The current work sought to investigate the interaction of genes and environment on the acquisition of amphetamine self-administration, as well as amphetamine-stimulated dopamine (DA) release in nucleus accumbens shell using in vivo microdialysis. Methods Inbred Lewis (LEW) and Fischer (F344) rat strains were raised in either an enriched condition (EC), social condition (SC), or isolated condition (IC). Acquisition of amphetamine self-administration (0.1 mg/kg/infusion) was determined across an incrementing daily fixed ratio (FR) schedule. In a separate cohort of rats, extracellular DA and the metabolite dihydroxyphenylacetic acid (DOPAC) were measured in the nucleus accumbens shell following an acute amphetamine injection (1 mg/kg). Results “Addiction-prone” LEW had greater acquisition of amphetamine self-administration on a FR1 schedule compared to “addiction-resistant” F344 when raised in the SC environment. These genetic differences were negated in both the EC and IC environments, with enrichment buffering against self-administration and isolation enhancing self-administration in both strains. On a FR5 schedule, the isolation-induced increase in amphetamine self-administration was greater in F344 than LEW. While no group differences were obtained in extracellular DA, gene x environment differences were obtained in extracellular levels of the metabolite DOPAC. In IC rats only, LEW showed an attenuation in the amphetamine-induced decrease in DOPAC compared to F344. IC LEW rats also had an attenuated DOPAC response to amphetamine compared to EC LEW. Conclusions The current results demonstrate gene x environment interactions in amphetamine self-administration and amphetamine-induced changes in extracellular DOPAC in NAc shell. However, the behavioral and neurochemical differences were not related directly, indicating that mechanisms

  19. Assembly of the stator in Escherichia coli ATP synthase. Complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha

    PubMed Central

    Senior, Alan E.; Muharemagi, Alma; Wilke-Mounts, Susan

    2008-01-01

    Alpha subunit of Escherichia coli ATP synthase was expressed with a C-terminal 6-His tag and purified. Pure alpha was monomeric, competent in nucleotide binding, and had normal N-terminal sequence. In F1-subunit dissociation/reassociation experiments it supported full reconstitution of ATPase, and reassociated complexes were able to bind to F1-depleted membranes with restoration of ATP-driven proton pumping. Therefore interaction between the stator delta subunit and the N-terminal residue 1-22 region of alpha occurred normally when pure alpha was complexed with other F1 subunits. On the other hand, three different types of experiment showed that no interaction occurred between pure delta and isolated alpha subunit. Unlike in F1, the N-terminal region of isolated alpha was not susceptible to trypsin cleavage. Therefore, during assembly of ATP synthase, complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha. We suggest that the N-terminal 1-22 residues of alpha are sequestered in isolated alpha until released by binding of beta to alpha subunit. This prevents 1/1 delta/alpha complexes from forming, and provides a satisfactory explanation of the stoichiometry of one delta per three alpha seen in the F1 sector of ATP synthase, assuming that steric hindrance prevents binding of more than one delta to the alpha3/beta3 hexagon. The cytoplasmic fragment of the b subunit (bsol) did not bind to isolated alpha. It might also be that complexation of alpha with beta subunits is prerequisite for direct binding of stator b subunit to the F1-sector. PMID:17176112

  20. 21 CFR 344.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Definitions. 344.3 Section 344.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE... impairment. (d) Ear drying aid. A drug used in the external ear canal to help dry water-clogged ears. [51 FR...

  1. Two-week aerosol inhalation study on polyethylene glycol (PEG) 3350 in F-344 rats.

    PubMed

    Klonne, D R; Dodd, D E; Losco, P E; Troup, C M; Tyler, T R

    1989-03-01

    PEGs in the 3000 to 4000 MW range are used in many pharmaceutical and cosmetic applications; they produce little ocular or dermal irritation and have extremely low acute and subchronic toxicity by oral and dermal routes of administration. However, little information exists on the potential of aerosols of these materials to produce adverse health effects. F-344 rats were exposed to aerosols of PEG 3350 (20% w:w in water) at 0, 109, 567, or 1008 (highest attainable) mg/m3 for 6 hr/d, 5 d/wk for 2 wk. No exposure-related toxicity was found with regard to clinical signs, ophthalmology, serum chemistry, urinalysis, or gross pathology. Exposure-related effects included: a 50% increase in the neutrophil count (males only) at 1008 mg/m3; decreased body weight gain (16%) for both the 567 and 1008 mg/m3 groups (males only); absolute lung weights of both sexes were increased 10 and 18% for the 567 and 1008 mg/m3 groups, respectively. A slight increase in the number of macrophages in the alveoli was the only change observed histologically in all PEG 3350-exposed groups. Therefore, inhalation of aerosols of PEG 3350 at concentrations up to 1008 mg/m3 produced relatively little toxicity in rats, the lung was the target organ, and the no-observable-effect-level was between 109 to 567 mg/m3.

  2. Biological relevance of effects following chronic administration of octamethylcyclotetrasiloxane (D4) in Fischer 344 rats.

    PubMed

    Dekant, Wolfgang; Scialli, Anthony R; Plotzke, Kathy; Klaunig, James E

    2017-10-20

    Octamethylcyclotetrasiloxane (D4) is a cyclic siloxane primarily used as a monomer or intermediate in the production of silicone polymers resulting in potential exposure of workers, and potential low level inhalation or dermal exposure for consumers and the general public. Following a two-year inhalation toxicity study with D4 in rats, increases in uterine endometrial cystic hyperplasia and adenomas were observed at the highest concentration of D4 administered (700ppm). No other neoplasms were increased with D4 treatment. In addition, chronic inhalation exposure of rats to D4 induced changes in relative liver and kidney weights, and produced a chronic nephropathy. This manuscript examines the biological relevance and possible modes of action for the effects observed in the F344 rat following chronic inhalation exposure to D4. D4 is not genotoxic and appears to exert its effects through a nongenotoxic mode of action. An alteration in the estrous cycle in the aging F344 rat was the most likely mode of action for the observed uterine effects following chronic inhalation exposure. Data support the conclusion that D4 acts indirectly via a dopamine-like mechanism leading to alteration of the pituitary control of the estrous cycle in aging F344 rats with a decrease in progesterone and an increase in the estrogen/progesterone ratio most likely induced by a decrease in prolactin concentration. D4 also inhibited the pre-ovulatory LH surge causing a delay in ovulation, persistent follicles and thus a prolonged exposure to elevated estrogen in the adult Sprague Dawely rat. A lengthening of the estrous cycle in the F344 rat with an increase in endogenous estrogen was also induced by D4 inhalation. Although the mode of action responsible for induction of uterine adenomas in the female F344 rat has not been clearly confirmed, the subtlety of effects on the effects of D4 on cyclicity may prevent further assessment and definition of the mode of action. The occurrence of uterine

  3. Dimethylarsinic acid in drinking water changed the morphology of urinary bladder but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats.

    PubMed

    Wang, Amy; Wolf, Douglas C; Sen, Banalata; Knapp, Geremy W; Holladay, Steven D; Huckle, William R; Caceci, Thomas; Robertson, John L

    2009-06-01

    Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeared to be the main source of vacuoles in the transitional epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA polymerase beta (Polbeta), were not altered by DMA(V). These data suggested that either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA repair without affecting baseline mRNA levels of repair genes. The possibility remains that DMA(V) may lower damage-induced increases in repair gene expression or cause post-translational modification of repair enzymes.

  4. Toxicology and carcinogenesis study of styrene-acrylonitrile trimer in F344/N rats (perinatal and postnatal feed studies).

    PubMed

    2012-07-01

    Styrene-acrylonitrile trimer (SAN Trimer) is a mixture of isomers formed by the condensation of two moles of acrylonitrile and one mole of styrene and has a molecular weight of 210. The mixture is composed of two structural forms: 4-cyano-1,2,3,4-tetrahydro-a-methyl-1-naphthaleneacetonitrile (THNA, CAS No. 57964-39-3) and 4-cyano-1,2,3,4-tetrahydro-1-naphthalenepropionitrile (THNP, CAS No. 57964-40-6). The THNA form consists of four stereoisomers. [Structure:see text]. The THNP form consists of two stereoisomers. [Structure:see text]. SAN Trimer is a by-product of the production of acrylonitrile styrene plastics and is created in specific manufacturing processes for polymers of acrylonitrile and styrene. In June 1998, due to community concerns about the toxicity of SAN Trimer, it was nominated to the NTP for carcinogenicity testing by a member of Congress. Male and female F344/N rats were exposed to SAN Trimer in feed in perinatal and postnatal studies for 7 weeks, 18 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli, and in rat reticulocytes, leukocytes, liver cells, and brain cells. In vivo comet and micronucleus assays were performed in the juvenile rats. 7-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were fed diets containing 0, 250, 500, 1,000, 2,000, or 4,000 ppm SAN Trimer (equivalent to average daily doses of approximately 50, 90, 175, 270, or 410 mg SAN Trimer/kg body weight to males and 45, 90, 185, 295, or 430 mg/kg to females) for 2 weeks postweaning; the dams of these rats were fed the same concentrations of SAN Trimer from gestation day 7 until the pups were weaned. One 4,000 ppm male rat died 3 days after weaning; all other rats that started the postweaning phase survived to the end of the study. Mean body weights of 1,000, 2,000, and 4,000 ppm males and 2,000 and 4,000 ppm females were significantly less than those of the controls; weaning mean body weights were reduced in 4

  5. Noni (Morinda citrifolia L.) fruit juice delays immunosenescence in the lymphocytes in lymph nodes of old F344 rats.

    PubMed

    Pratap, Uday P; Priyanka, Hannah P; Ramanathan, Karthik R; Raman, Vishak; Hima, Lalgi; Thyagarajan, Srinivasan

    2018-05-01

    Aging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system. The medicinal properties of Morinda citrifolia L. have been widely exploited for the treatment of age-associated diseases. This study aims to investigate the in vitro and in vivo effects of noni (M. citrifolia) fruit juice (NFJ) on neuro-immunomodulation in the lymph node lymphocytes of F344 rats. Lymphocytes isolated from axillary and inguinal lymph nodes of young (3-4 months) and old (18-21 months) rats were treated in vitro with different concentrations (0.0001%, 0.01%, and 1%) of NFJ for a period of 24 h. In the in vivo study, old (16-17 months) male F344 rats were treated with 5 mL/kg body weight of 5%, 10% and 20% of NFJ, twice a day, by oral gavage, and lymph node lymphocytes were isolated after 60 d. Concanavalin A (Con A)-induced lymphocyte proliferation, interleukin-2 (IL-2) and interferon-γ (IFN-γ) production and expression of intracellular markers, such as phospho-extracellular signal-regulated kinase (p-ERK1/2), phospho-cAMP response element-binding protein, phospho-protein kinase B (p-Akt), phospho-tyrosine hydroxylase (p-TH), phospho-nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α (p-IκB-α) and phospho-nuclear factor-κB (p-NF-κB p65 and p50) were examined in the lymphocytes of lymph nodes. NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50. These results suggest that the immunostimulatory properties of NFJ are facilitated through intracellular signaling pathways involving ERK1/2, Akt and NF-κB. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

  6. 5 CFR 9701.344 - Special within-band increases.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Special within-band increases. 9701.344 Section 9701.344 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT... HUMAN RESOURCES MANAGEMENT SYSTEM Pay and Pay Administration Performance-Based Pay § 9701.344 Special...

  7. Plant delta 15N correlates with the transpiration efficiency of nitrogen acquisition in tropical trees.

    PubMed

    Cernusak, Lucas A; Winter, Klaus; Turner, Benjamin L

    2009-11-01

    Based upon considerations of a theoretical model of (15)N/(14)N fractionation during steady-state nitrate uptake from soil, we hypothesized that, for plants grown in a common soil environment, whole-plant delta(15)N (deltaP) should vary as a function of the transpiration efficiency of nitrogen acquisition (F(N)/v) and the difference between deltaP and root delta(15)N (deltaP - deltaR). We tested these hypotheses with measurements of several tropical tree and liana species. Consistent with theoretical expectations, both F(N)/v and deltaP - deltaR were significant sources of variation in deltaP, and the relationship between deltaP and F(N)/v differed between non-N(2)-fixing and N(2)-fixing species. We interpret the correlation between deltaP and F(N)/v as resulting from variation in mineral nitrogen efflux-to-influx ratios across plasma membranes of root cells. These results provide a simple explanation of variation in delta(15)N of terrestrial plants and have implications for understanding nitrogen cycling in ecosystems.

  8. 18 CFR 344.2 - Manner of submitting quotations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... quotations. 344.2 Section 344.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE INTERSTATE COMMERCE ACT FILING QUOTATIONS FOR U.S. GOVERNMENT SHIPMENTS AT REDUCED RATES § 344.2 Manner of submitting quotations. (a) The quotation or tender...

  9. Myocardial short-range force responses increase with age in F344 rats

    PubMed Central

    Mitov, Mihail I.; Holbrook, Anastasia M.; Campbell, Kenneth S.

    2009-01-01

    The mechanical properties of triton-permeabilized ventricular preparations isolated from 4, 18 and 24-month-old F344 rats were analyzed to provide information about the molecular mechanisms that lead to age-related increases in diastolic myocardial stiffness in these animals. Passive stiffness (measured in solutions with minimal free Ca2+) did not change with age. This implies that the aging-associated dysfunction is not due to changes in titin or collagen molecules. Ca2+-activated preparations exhibited a characteristic short-range force response: force rose rapidly until the muscle reached its elastic limit and less rapidly thereafter. The elastic limit increased from 0.43 ± 0.01 % l0 (where l0 is the initial muscle length) in preparations from 4-month-old animals to 0.49 ± 0.01 % l0 in preparations from 24-month-old rats (p<0.001, ANOVA). Relative short-range force was defined as the maximum force produced during the short-range response normalized to the prevailing tension. This parameter increased from 0.110 ± 0.002 to 0.142 ± 0.002 over the same age-span (p<0.001, ANOVA). Analytical gel electrophoresis showed that the maximum stiffness of the preparations during the short-range response and the relative short-range force increased (p=0.031 and p=0.005 respectively) with the relative content of slow β myosin heavy chain molecules. Elastic limit values did not correlate with myosin isoform content. Simulations based on these results suggest that attached β myosin heavy chain cross-bridges are stiffer than links formed by α myosin heads. In conclusion, elevated content of stiffer β myosin heavy chain molecules may contribute to aging-associated increases in myocardial stiffness. PMID:19007786

  10. Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

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

    Tang, Lili; Southern Yangtze University, Wuxi; Guan Hongxia

    Modulation by lycopene of aflatoxin B{sub 1} (AFB{sub 1})-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB{sub 1} (250 {mu}g/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB{sub 1} (250 {mu}g/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB{sub 1} and greatly modulated AFB{sub 1} metabolism andmore » metabolic activation. Urinary excretion of AFB{sub 1} phase 1 metabolites, AFM{sub 1}, AFQ{sub 1}, and AFP{sub 1}, was significantly decreased in lycopene-treated animals. Formation of serum AFB{sub 1}-albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p < 0.05) to 67.7% on day 15 (p < 0.001). Lycopene intervention also significantly reduced formation of AFB{sub 1}-DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p < 0.05). Levels of AFB{sub 1}-N {sup 7}-guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB{sub 1}-mecapturic acid, was significantly increased in lycopene-intervened animals. AFB{sub 1}-induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene.« less

  11. 43 CFR 34.4 - Discrimination prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Discrimination prohibited. 34.4 Section 34... DURING CONSTRUCTION AND OPERATION OF THE ALASKA NATURAL GAS TRANSPORTATION SYSTEM § 34.4 Discrimination... part applies. (b) Specific actions in which discrimination is prohibited. No person shall directly or...

  12. 43 CFR 34.4 - Discrimination prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Discrimination prohibited. 34.4 Section 34... DURING CONSTRUCTION AND OPERATION OF THE ALASKA NATURAL GAS TRANSPORTATION SYSTEM § 34.4 Discrimination... part applies. (b) Specific actions in which discrimination is prohibited. No person shall directly or...

  13. 43 CFR 34.4 - Discrimination prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Discrimination prohibited. 34.4 Section 34... DURING CONSTRUCTION AND OPERATION OF THE ALASKA NATURAL GAS TRANSPORTATION SYSTEM § 34.4 Discrimination... part applies. (b) Specific actions in which discrimination is prohibited. No person shall directly or...

  14. 31 CFR 29.344 - Survivor benefits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Survivor benefits. 29.344 Section 29.344 Money and Finance: Treasury Office of the Secretary of the Treasury FEDERAL BENEFIT PAYMENTS UNDER CERTAIN DISTRICT OF COLUMBIA RETIREMENT PROGRAMS Split Benefits Calculation of the Amount of Federal...

  15. 31 CFR 29.344 - Survivor benefits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Survivor benefits. 29.344 Section 29.344 Money and Finance: Treasury Office of the Secretary of the Treasury FEDERAL BENEFIT PAYMENTS UNDER CERTAIN DISTRICT OF COLUMBIA RETIREMENT PROGRAMS Split Benefits Calculation of the Amount of Federal...

  16. 31 CFR 29.344 - Survivor benefits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Survivor benefits. 29.344 Section 29.344 Money and Finance: Treasury Office of the Secretary of the Treasury FEDERAL BENEFIT PAYMENTS UNDER CERTAIN DISTRICT OF COLUMBIA RETIREMENT PROGRAMS Split Benefits Calculation of the Amount of Federal...

  17. Ntp report on the toxicity studies of ethylbenzene in f344/n rats and b6c3f1 mice (inhalation studies). Report for 29 March-30 June 1988

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

    Chan, P.

    1992-03-01

    Inhalation toxicology studies of ethylbenzene (99% pure) were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to ethylbenzene vapor at chamber concentrations of 0 to 1000 ppm, 6 hours per day, 5 days per week for 13 weeks. No rats or mice died during the 13-week exposure. Body weight gains were slightly lower in the high dose groups of male and female rats, but the differences were not statistically significant. Absolute and relative kidney, liver, and lung weights were increased in the exposed rats, while weight increases occurred only in the livers of exposed mice.more » No changes were observed in the evaluation of sperm or vaginal cytology in rats or mice. Ethylbenzene was not mutagenic in Salmonella and did not induce chromosomal aberrations or sister chromatid exchanges in Chinese hamster ovary (CHO) cells in vitro, though it did induce trifluorothymidine resistance in mouse lymphoma cells at the highest concentration tested. Micronuclei assays in peripheral blood of mice were negative.« less

  18. Effects of chronic cocaine treatment during adolescence in Lewis and Fischer-344 rats: Novel location recognition impairment and changes in synaptic plasticity in adulthood.

    PubMed

    Fole, A; Martin, M; Morales, L; Del Olmo, N

    2015-09-01

    The use of Lewis (LEW) together with Fischer-344 (F344) rats has been proposed as an addiction model because of the addiction behavior differences of these two strains. We have previously suggested that these differences could be related to learning and memory processes and that they depend on the genetic background of these two strains of rats. Adolescence is a period of active synaptic remodeling, plasticity and particular vulnerability to the effects of environmental insults such as drugs of abuse. We have evaluated spatial memory using novel location recognition in LEW and F344 adult rats undergoing a chronic treatment with cocaine during adolescence or adulthood. In order to study whether synaptic plasticity mechanisms were involved in the possible changes in learning after chronic cocaine treatment, we carried out electrophysiological experiments in hippocampal slices from treated animals. Our results showed that, in LEW cocaine-treated rats, hippocampal memory was only significantly impaired when the drug was administered during adolescence whereas adult administration did not produce any detrimental effect in spatial memory measured in this protocol. Moreover, F344 rats showed clear difficulties carrying out the protocol even in standard conditions, confirming the spatial memory problems observed in previous reports and demonstrating the genetic differences in spatial learning and memory. Our experiments show that the effects in behavioral experiments are related to synaptic plasticity mechanisms. Long-term depression induced by the glutamate agonist NMDA (LTD-NMDA) is partially abolished in cocaine-treated animals in hippocampal slices from LEW rats. Hippocampal LTD-NMDA is partially inhibited in F344 animals regardless of whether saline or cocaine administration, suggesting the lack of plasticity of this strain that could be related to the inability of these animals to carry out the novel object location protocol. Copyright © 2015 Elsevier Inc. All

  19. Spatial performance correlates with in vitro potentiation in young and aged Fischer 344 rats.

    PubMed

    Deupree, D L; Turner, D A; Watters, C L

    1991-07-19

    Young adult (2-4 months old) and aged (24-26 months old) Fischer 344 (F344) rats were trained for spatial behavior (locating a hidden escape platform) in a circular water maze. The aged rats showed deficits in both the acquisition and retention of the learned response. Following the behavioral training, hippocampal slices from the rats were prepared. Potentiation of CA1 extracellular, somatic field potentials was studied in vitro following either a short stimulus train (4 pulses) or a longer train (50 pulses). Slices from the aged rats showed less short-term potentiation (124.8 +/- 4.9% baseline, mean +/- S.E.M.) at 1 min following the short train in comparison to slices from the young rats (151.8 +/- 7.5%, P less than 0.05). However, following the longer train, no differences were found between the groups in the degree of either short-term (measured at 1 min after stimulation) or long-term potentiation (measured at 60 min). The amount of potentiation seen at various time points after either train correlated with the behavioral measure of retention. These results indicate that F344 rats exhibit age-related behavioral deficits, and age-related synaptic potentiation deficits in response to short stimulation trains. The correlation between the degree of potentiation (both short-term and long-term) and retention of a behavioral task adds strength to the hypothesis that potentiation mechanisms may underlie memory processes.

  20. A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function.

    PubMed

    Rubenstein, R C; Zeitlin, P L

    1998-02-01

    Sodium 4-phenylbutyrate (Buphenyl, 4PBA) is a new FDA approved drug for management of urea cycle disorders. We have previously presented data suggesting that 4PBA, at clinically achievable concentrations, induces CFTR channel function on the plasma membrane of deltaF508-expressing cystic fibrosis (CF) airway epithelial cells in vitro (Rubenstein, R. C., and P. L. Zeitlin, 1997. J. Clin. Invest. 100:2457-2463). We hypothesized that 4PBA would induce epithelial CFTR function in vivo in individuals homozygous for deltaF508-CFTR. A randomized, double-blind, placebo-controlled trial in 18 deltaF508-homozygous patients with CF was performed with the maximum approved adult dose of 4PBA, 19 grams p.o. divided t.i.d., given for 1 wk. Nasal potential difference (NPD) response patterns and sweat chloride concentrations were determined before and after study drug treatment, and 4PBA and metabolites were assayed in plasma and urine at the end of study drug treatment. Subjects in the 4PBA group demonstrated small, but statistically significant improvements of the NPD response to perfusion of an isoproterenol/amiloride/chloride-free solution; this measure reflects epithelial CFTR function and is highly discriminatory between patients with and without CF. Subjects who had received 4PBA did not demonstrate significantly reduced sweat chloride concentrations or alterations in the amiloride-sensitive NPD. Side effects due to drug therapy were minimal and comparable in the two groups. These data are consistent with 4PBA therapy inducing CFTR function in the nasal epithelia of deltaF508-homozygous CF patients.

  1. CFTR DeltaF508 mutation detection from dried blood samples in the first trimester of pregnancy: a possible routine prenatal screening strategy for cystic fibrosis?

    PubMed

    Konialis, Christopher P; Hagnefelt, Birgitta; Kazamia, Constantina; Karapanou, Sophia; Pangalos, Constantinos

    2007-01-01

    The implementation and evaluation of a proposed wide-scale prenatal screening strategy, based on DNA isolated from dried blood spots in the first trimester of pregnancy, for the early detection of pregnancies at risk for cystic fibrosis (CF). The screening was performed in conjunction with routine biochemical marker screening for Down's syndrome risk in the first trimester of pregnancy. DNA was isolated from 1,233 dried blood spots and analyzed for the presence of the CF transmembrane regulator DeltaF508 mutation. Women carriers were offered and accepted the option for additional full testing of their partners in order to assess the risk for the fetus. All 1,233 samples were successfully analyzed, identifying 23 DeltaF508 carriers, corresponding to a DeltaF508 carrier rate of approximately 1/55 (1.8%). All partners of the women carriers were further tested without revealing any need for further prenatal testing in this group. This study reveals the relatively high frequency of the DeltaF508 CF mutation in the Greek population. More importantly, we demonstrate that the proposed prenatal screening strategy, based on the ease and cost-effectiveness of the analysis for the detection of a single common mutation, can be considered as a feasible and practical approach for wide-scale prenatal screening for CF, following the sequential model. It is applied early on in pregnancy, allowing for the timely management of families at risk for the corresponding genetic disorders. Finally, it can easily be extended to include screening for other common genetic disorders in specific population groups.

  2. 45 CFR 34.4 - Allowable claims.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the claimant to save human life or government property. (4) Property used for the benefit of the... 45 Public Welfare 1 2011-10-01 2011-10-01 false Allowable claims. 34.4 Section 34.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CLAIMS FILED UNDER THE MILITARY PERSONNEL AND...

  3. 45 CFR 34.4 - Allowable claims.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the claimant to save human life or government property. (4) Property used for the benefit of the... 45 Public Welfare 1 2010-10-01 2010-10-01 false Allowable claims. 34.4 Section 34.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CLAIMS FILED UNDER THE MILITARY PERSONNEL AND...

  4. NTP toxicology and carcinogenesis studies of chromium picolinate monohydrate (CAS No. 27882-76-4) in F344/N rats and B6C3F1 mice (feed studies).

    PubMed

    2010-06-01

    Chromium picolinate monohydrate is the commercially available form of chromium picolinate. Chromium picolinate is one of a number of compounds that contain chromium in the trivalent state (Cr III), which is the predominant form of chromium in nature. Humans ingest Cr III in food and dietary supplements. The major uses of Cr III in the chemical and manufacturing industries include production of chromium pigments and leather tanning. Chromium picolinate was nominated by the National Cancer Institute and a private individual for testing based on the potential for widespread consumer exposure from use as a dietary supplement. Male and female F344/N rats and B6C3F1 mice were exposed to chromium picolinate monohydrate (95% to 96% pure) in feed for 3 months or 2 years. Genetic toxicology studies with chromium picolinate monohydrate were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. Genetic toxicology studies with chromium picolinate were conducted in S. typhimurium and rat bone marrow cells. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were fed diets containing 0, 80, 240, 2,000, 10,000, or 50,000 ppm chromium picolinate monohydrate (equivalent to average daily doses of approximately 7, 20, 160, 800, and 4,240 mg chromium picolinate monohydrate/kg body weight to males and 6, 20, 160, 780, and 4,250 mg/kg to females) for 14 weeks. All rats survived to the end of the study. Mean body weights and feed consumption of all exposed groups of males and females were similar to those of the control groups throughout the study. No exposure-related lesions occurred in males or females. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were fed diets containing 0, 80, 240, 2,000, 10,000, or 50,000 ppm chromium picolinate monohydrate (equivalent to average daily doses of approximately 17, 50, 450, 2,300, and 11,900 mg chromium picolinate monohydrate/kg body weight to males and 14, 40, 370, 1,775, and 9,140 mg/kg to females) for 14

  5. Plekhs1 and Prdx3 are candidate genes responsible for mild hyperglycemia associated with obesity in a new animal model of F344-fa-nidd6 rat.

    PubMed

    Kotoh, Jun; Sasaki, Daiki; Matsumoto, Kozo; Maeda, Akihiko

    2016-12-01

    Type 2 diabetes is a polygenic disease and characterized by hyperglycemia and insulin resistance, and it is strongly associated with obesity. However, the mechanism by which obesity contributes to onset of type 2 diabetes is not well understood. We generated rat strains with a hyperglycemic quantitative trait locus (QTL) derived from the Otsuka Long-Evans Tokushima Fatty rat and a fa/fa (Lepr -/- ) locus derived from the Zucker Fatty rat. Phenotypes for plasma glucose, and insulin levels were measured, and RNA and protein levels were determined using reverse transcription quantitative PCR and Western blot analyses, respectively. Compared with the obese control strain F344-fa (Lepr -/- ), plasma glucose levels of the obese F344-fa-nidd6 (Lepr -/- and Nidd6/of) significantly increased, and plasma insulin levels significantly decreased. These phenotypes were not observed in the lean strains, suggesting that the Nidd6/of locus harbors a diabetogenic gene associated with obesity. We measured the expression of 41 genes in the Nidd6/of QTL region of each strain and found that the mRNA expression levels of the two genes significantly differed between the obese strains. The two genes, pleckstrin homology domain-containing, family S member 1 (Plechs1) and peroxiredoxin III (Prdx3), were differentially expressed only in the obese rats, suggesting that these two genes are involved in the mild elevation of blood glucose levels and insulin resistance in obesity.

  6. NTP technical report on comparative toxicity and carcinogenicity studies of o-nitrotoluene and o-toluidine hydrochloride. (Cas Nos. 88-72-2 and 636-21-5) administered in feed to male f344/n rats

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

    Elwell, M.R.

    1996-03-01

    ;Contents: Introduction (Physical and Chemical Properties, Production, Use, and Exposure, Disposition and Metabolism, Toxicity, Study Rationale and Design); Materials and Methods (Procurement and Characterization of 0-Nitroluene and o-Toluidine Hydrochloride, Preparation and Analysis of Dose Formulations, Preparation of Antibiotic Mixture, Toxicity Study Designs, Statistical Methods, Quality Assurance); Results (26-Week Feed Studies in Male F344/N Rats).

  7. Negligible Colon Cancer Risk from Food-Borne Acrylamide Exposure in Male F344 Rats and Nude (nu/nu) Mice-Bearing Human Colon Tumor Xenografts

    PubMed Central

    Raju, Jayadev; Roberts, Jennifer; Sondagar, Chandni; Kapal, Kamla; Aziz, Syed A.; Caldwell, Don; Mehta, Rekha

    2013-01-01

    Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a “complete carcinogen”, but acts as a “co-carcinogen” by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters. PMID:24040114

  8. Amphetamine self-administration and dopamine function: assessment of gene × environment interactions in Lewis and Fischer 344 rats.

    PubMed

    Meyer, Andrew C; Bardo, Michael T

    2015-07-01

    Previous research suggests both genetic and environmental influences on substance abuse vulnerability. The current work sought to investigate the interaction of genes and environment on the acquisition of amphetamine self-administration as well as amphetamine-stimulated dopamine (DA) release in nucleus accumbens shell using in vivo microdialysis. Inbred Lewis (LEW) and Fischer (F344) rat strains were raised in either an enriched condition (EC), social condition (SC), or isolated condition (IC). Acquisition of amphetamine self-administration (0.1 mg/kg/infusion) was determined across an incrementing daily fixed ratio (FR) schedule. In a separate cohort of rats, extracellular DA and the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the nucleus accumbens shell following an acute amphetamine injection (1 mg/kg). "Addiction-prone" LEW rats had greater acquisition of amphetamine self-administration on a FR1 schedule compared to "addiction-resistant" F344 rats when raised in the SC environment. These genetic differences were negated in both the EC and IC environments, with enrichment buffering against self-administration and isolation enhancing self-administration in both strains. On a FR5 schedule, the isolation-induced increase in amphetamine self-administration was greater in F344 than LEW rats. While no group differences were obtained in extracellular DA, gene × environment differences were obtained in extracellular levels of the metabolite DOPAC. In IC rats only, LEW rats showed attenuation in the amphetamine-induced decrease in DOPAC compared to F344 rats. IC LEW rats also had an attenuated DOPAC response to amphetamine compared to EC LEW rats. The current results demonstrate gene × environment interactions in amphetamine self-administration and amphetamine-induced changes in extracellular DOPAC in nucleus accumbens (NAc) shell. However, the behavioral and neurochemical differences were not related directly, indicating that

  9. 40 CFR 61.344 - Standards: Surface impoundments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 9 2012-07-01 2012-07-01 false Standards: Surface impoundments. 61.344 Section 61.344 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Benzene...

  10. 40 CFR 61.344 - Standards: Surface impoundments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Standards: Surface impoundments. 61.344 Section 61.344 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Benzene...

  11. The RCA-F/Delta launch

    NASA Technical Reports Server (NTRS)

    1983-01-01

    The Delta 3924 launch vehicle configuration which incorporates the extended long tank Thor booster, nine Castor 4 strap-on motors, the AJ-118 second stage and the TE 364-4 third stage is to place into a synchronous transfer orbit, the second in a series of high-traffic capacity, 24 transponder communications satellites. Three days after launch, the satellite's apogee kick motor circularizes the orbit at geosynchronous altitude of 19,300 NM above the equator at approximately 128 degrees W longitude. The satellite can service commercial and government voice, digital and video communications requirements between Alaska and CONUS. The communications payload, mission requirements and spacecraft systems and subsystems are described.

  12. Chronic toxicity and carcinogenicity studies of chromium picolinate monohydrate administered in feed to F344/N rats and B6C3F1 mice for 2 years.

    PubMed

    Stout, M D; Nyska, A; Collins, B J; Witt, K L; Kissling, G E; Malarkey, D E; Hooth, M J

    2009-04-01

    Trivalent chromium (Cr(III)) has been proposed to be an essential element, which may increase sensitivity to insulin and thus participate in carbohydrate and lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and in dietary supplements taken for weight loss and antidiabetic effects. Chromium picolinate (CP), a widely used supplement, contains Cr(III) chelated with three molecules of picolinic acid and was formulated in an attempt to improve the absorption of Cr(III). In order to examine the potential for CP to induce chronic toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations of 0, 2000, 10,000 or 50,000 ppm for 2 years; exposure concentrations were selected following review of the data from NTP 3-month toxicity studies. Exposure to CPM did not induce biologically significant changes in survival, body weight, feed consumption, or non-neoplastic lesions in rats or mice. In male rats, a statistically significant increase in the incidence of preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM was not carcinogenic to female rats or to male or female mice.

  13. Chronic Toxicity and Carcinogenicity Studies of Chromium Picolinate Monohydrate Administered in Feed to F344/N Rats and B6C3F1 Mice for 2 Years

    PubMed Central

    Stout, M.D.; Nyska, A.; Collins, B.J.; Witt, K.L.; Kissling, G.E.; Malarkey, D.E.; Hooth, M.J.

    2009-01-01

    Trivalent chromium (Cr(III)) has been proposed to be an essential element, which may increase sensitivity to insulin and thus participate in carbohydrate and lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and in dietary supplements taken for weight loss and antidiabetic effects. Chromium picolinate (CP), a widely used supplement, contains Cr(III) chelated with three molecules of picolinic acid and was formulated in an attempt to improve the absorption of Cr(III). In order to examine the potential for CP to induce chronic toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations of 0, 2,000, 10,000 or 50,000 ppm for 2 years; exposure concentrations were selected following review of the data from NTP 3-month toxicity studies. Exposure to CPM did not induce biologically significant changes in survival, body weight, feed consumption, or non-neoplastic lesions in rats or mice. In male rats, a statistically significant increase in the incidence of preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM was not carcinogenic to female rats or to male or female mice. PMID:19166900

  14. 5 CFR 9901.344 - Other performance payments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Other performance payments. 9901.344... SECURITY PERSONNEL SYSTEM (NSPS) Pay and Pay Administration Performance-Based Pay § 9901.344 Other performance payments. (a) The decision to grant other performance payouts, including the amount of such...

  15. Disposition and metabolism of 2-bromo-4,6-dinitroaniline in the male F344 rat

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

    Chopade, H.M.; Matthews, H.B.

    1986-01-01

    The disposition of (/sup 14/C)-2-bromo-4,6-dinitroaniline (BDNA) was studied in male F344 rats following oral or intravenous (iv) administration. The gastrointestinal absorption of BDNA was nearly complete and was not affected by dose in the range (10-100 ..mu..mol/kg body weight) studied. Following either oral or iv administration, BDNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue. Clearance of (/sup 14/C)BDNA-derived radioactivity from various tissues was rapid and was best described by two-component decay curves. The whole-body half-life of BDNA was approximately 7 h. Within 72 h, clearance of (/sup 14/C)BDNA-derived radioactivity from the bodymore » was 98% complete. (/sup 14/C)BDNA was rapidly cleared by metabolism to 13 metabolites, which were excreted in urine (62%) and feces (33%). Most (66%) of the urinary radioactivity was excreted in the form of sulfate conjugates of two metabolites of BDNA; excretion of unmetabolized BDNA was minimal (less than 2%). Biliary excretion of (/sup 14/C)BDNA was significant; however, some of this BDNA-derived radioactivity underwent enterohepatic circulation and was subsequently excreted in urine. Results of this study indicate that, if metabolism is a detoxification process, the rapid metabolism and excretion of this compound should minimize the likelihood of chronic toxicity from repeated exposure to BDNA beyond that predicted by data from acute or short-term exposures.« less

  16. A novel isoflavone, ME-344, targets the cytoskeleton in acute myeloid leukemia

    PubMed Central

    Jeyaraju, Danny V.; Hurren, Rose; Wang, Xiaoming; MacLean, Neil; Gronda, Marcela; Shamas-Din, Aisha; Minden, Mark D.; Giaever, Guri; Schimmer, Aaron D.

    2016-01-01

    The isoflavone ME-344 is a potent anti-cancer agent with preclinical and clinical efficacy in solid tumors. Yet, the mechanism of action of ME-344 has not been fully defined and the preclinical efficacy in leukemia has not been established. Therefore, we investigated the anti-leukemic properties and mechanism of action of ME-344. In a panel of 7 leukemia cell lines, ME-344 was cytotoxic with an IC50 in the range of 70–260 nM. In addition, ME-344 was cytotoxic to primary AML patient samples over normal hematopoietic cells. In an OCI-AML2 xenograft model, ME-344 reduced tumor growth by up to 95% of control without evidence of toxicity. Mechanistically, ME-344 increased mitochondrial ROS generation in leukemic cells. However, antioxidant treatment did not rescue cell death, suggesting that ME-344 had additional targets beyond the mitochondria. We demonstrated that ME-344 inhibited tubulin polymerization by interacting with tubulin near the colchicine-binding site. Furthermore, inhibition of tubulin polymerization was functionally important for ME-344 induced death. Finally, we showed that ME-344 synergizes with vinblastine in leukemia cells. Thus, our study demonstrates that ME-344 displays preclinical efficacy in leukemia through a mechanism at least partly related to targeting tubulin polymerization. PMID:27391350

  17. A novel isoflavone, ME-344, targets the cytoskeleton in acute myeloid leukemia.

    PubMed

    Jeyaraju, Danny V; Hurren, Rose; Wang, Xiaoming; MacLean, Neil; Gronda, Marcela; Shamas-Din, Aisha; Minden, Mark D; Giaever, Guri; Schimmer, Aaron D

    2016-08-02

    The isoflavone ME-344 is a potent anti-cancer agent with preclinical and clinical efficacy in solid tumors. Yet, the mechanism of action of ME-344 has not been fully defined and the preclinical efficacy in leukemia has not been established. Therefore, we investigated the anti-leukemic properties and mechanism of action of ME-344. In a panel of 7 leukemia cell lines, ME-344 was cytotoxic with an IC50 in the range of 70-260 nM. In addition, ME-344 was cytotoxic to primary AML patient samples over normal hematopoietic cells. In an OCI-AML2 xenograft model, ME-344 reduced tumor growth by up to 95% of control without evidence of toxicity. Mechanistically, ME-344 increased mitochondrial ROS generation in leukemic cells. However, antioxidant treatment did not rescue cell death, suggesting that ME-344 had additional targets beyond the mitochondria. We demonstrated that ME-344 inhibited tubulin polymerization by interacting with tubulin near the colchicine-binding site. Furthermore, inhibition of tubulin polymerization was functionally important for ME-344 induced death. Finally, we showed that ME-344 synergizes with vinblastine in leukemia cells. Thus, our study demonstrates that ME-344 displays preclinical efficacy in leukemia through a mechanism at least partly related to targeting tubulin polymerization.

  18. Lava delta deformation as a proxy for submarine slope instability

    NASA Astrophysics Data System (ADS)

    Di Traglia, Federico; Nolesini, Teresa; Solari, Lorenzo; Ciampalini, Andrea; Frodella, William; Steri, Damiano; Allotta, Benedetto; Rindi, Andrea; Marini, Lorenzo; Monni, Niccolò; Galardi, Emanuele; Casagli, Nicola

    2018-04-01

    The instability of lava deltas is a recurrent phenomenon affecting volcanic islands, which can potentially cause secondary events such as littoral explosions (due to interactions between hot lava and seawater) and tsunamis. It has been shown that Interferometric Synthetic Aperture Radar (InSAR) is a powerful technique to forecast the collapse of newly emplaced lava deltas. This work goes further, demonstrating that the monitoring of lava deltas is a successful strategy by which to observe the long-term deformation of subaerial-submarine landslide systems on unstable volcanic flanks. In this paper, displacement measurements derived from Synthetic Aperture Radar (SAR) imagery were used to detect lava delta instability at Stromboli volcano (Italy). Recent flank eruptions (2002-2003, 2007 and 2014) affected the Sciara del Fuoco (SdF) depression, created a "stacked" lava delta, which overlies a pre-existing scar produced by a submarine-subaerial tsunamigenic landslide that occurred on 30 December 2002. Space-borne X-band COSMO-SkyMED (CSK) and C-band SENTINEL-1A (SNT) SAR data collected between February 2010 and October 2016 were processed using the SqueeSAR algorithm. The obtained ground displacement maps revealed the differential ground motion of the lava delta in both CSK and SNT datasets, identifying a stable area (characterized by less than 2 mm/y in both datasets) within the northern sector of the SdF and an unstable area (characterized by velocity fields on the order of 30 mm/y and 160 mm/y in the CSK and SNT datasets, respectively) in the central sector of the SdF. The slope stability of the offshore part of the SdF, as reconstructed based on a recently performed multibeam bathymetric survey, was evaluated using a 3D Limit Equilibrium Method (LEM). In all the simulations, Factor of Safety (F) values between 0.9 and 1.1 always characterized the submarine slope between the coastline and -250 m a.s.l. The critical surfaces for all the search volumes corresponded to

  19. Structural Insights into Clostridium perfringens Delta Toxin Pore Formation

    PubMed Central

    Huyet, Jessica; Naylor, Claire E.; Savva, Christos G.; Gibert, Maryse; Popoff, Michel R.; Basak, Ajit K.

    2013-01-01

    Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins. PMID:23805259

  20. 32 CFR 34.4 - Special award conditions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Special award conditions. 34.4 Section 34.4 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT... those provided in this part, if an applicant or recipient: (1) Has a history of poor performance; (2) Is...

  1. 32 CFR 34.4 - Special award conditions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Special award conditions. 34.4 Section 34.4 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT... those provided in this part, if an applicant or recipient: (1) Has a history of poor performance; (2) Is...

  2. 32 CFR 34.4 - Special award conditions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Special award conditions. 34.4 Section 34.4 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT... those provided in this part, if an applicant or recipient: (1) Has a history of poor performance; (2) Is...

  3. 32 CFR 34.4 - Special award conditions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Special award conditions. 34.4 Section 34.4 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT... those provided in this part, if an applicant or recipient: (1) Has a history of poor performance; (2) Is...

  4. 32 CFR 34.4 - Special award conditions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Special award conditions. 34.4 Section 34.4 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT... those provided in this part, if an applicant or recipient: (1) Has a history of poor performance; (2) Is...

  5. Effects of recharge and discharge on delta2H and delta18O composition and chloride concentration of high arsenic/fluoride groundwater from the Datong Basin, northern China.

    PubMed

    Xie, Xianjun; Wang, Yanxin; Su, Chunli; Duan, Mengyu

    2013-02-01

    To better understand the effects of recharge and discharge on the hydrogeochemistry of high levels of arsenic (As) and fluoride (F) in groundwater, environmental isotopic composition (delta2H and delta18O) and chloride (Cl) concentrations were analyzed in 29 groundwater samples collected from the Datong Basin. High arsenic groundwater samples (As > 50 micog/L) were found to be enriched in lighter isotopic composition that ranged from -92 to -78 per thousand for deuterium (delta2H) and from -12.5 to -9.9 per thousand for oxygen-18 (delta18O). High F-containing groundwater (F > 1 mg/L) was relatively enriched in heavier isotopic composition and varied from -90 to -57 per thousand and from -12.2 to -6.7 per thousand for delta2H and delta18O, respectively. High chloride concentrations and delta18O values were primarily measured in groundwater samples from the northern and southwestern portions of the study area, indicating the effect of evaporation on groundwater. The observation of relatively homogenized and low delta18O values and chloride concentrations in groundwater samples from central part of the Datong Basin might be a result of fast recharge by irrigation returns, which suggests that irrigation using arsenic-contaminated groundwater affected the occurrence of high arsenic-containing groundwater in the basin.

  6. 40 CFR 60.344 - Test methods and procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Test methods and procedures. 60.344 Section 60.344 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Lime...

  7. Toxicology and carcinogenesis studies of tetralin (CAS No. 119-64-2) in F344/N rats and B6C3F1 mice (inhalation studies).

    PubMed

    2011-04-01

    Tetralin is used as an industrial solvent primarily for naphthalene, fats, resins, oils, and waxes; as a solvent and stabilizer for shoe polishes and floor waxes; as a solvent for pesticides, rubber, asphalt, and aromatic hydrocarbons (e.g., anthracene); as a dye solvent carrier in the textile industry; as a substitute for turpentine in lacquers, paints, and varnishes; in paint thinners and as a paint remover; in alkali-resistant lacquers for cleaning printing ink from rollers and type; as a constituent of motor fuels and lubricants; for the removal of naphthalene in gas distribution systems; and as an insecticide for clothes moths. Tetralin was nominated by the National Cancer Institute for carcinogenicity and disposition studies because of its structure, high production volume, and high potential for worker and consumer exposure. Male and female F344/N rats and B6C3F1 mice were exposed to tetralin (at least 97% pure) by inhalation for 2 weeks, 3 months, or 2 years; male NCI Black Reiter (NBR) rats were exposed to tetralin by inhalation for 2 weeks. Male NBR rats do not produce 2u-globulin; the NBR rats were included to study the relationship of 2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male (F344/N and NBR) and five female (F344/N) rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 12 exposures. All rats survived to the end of the studies. The final mean body weight of female rats exposed to 120 ppm and mean body weight gains of female rats exposed to 30 ppm or greater were significantly less than those of the chamber controls. Final mean body weights of exposed groups of male NBR rats and mean body weight gains of all exposed groups of male rats were significantly less than those of the chamber controls. Dark

  8. Major carcinogenic pathways identified by gene expression analysis of peritoneal mesotheliomas following chemical treatment in F344 rats

    EPA Science Inventory

    This study was performed to characterize the gene expression profile and to identify the major carcinogenic pathways involved in rat peritoneal mesothelioma (RPM) formation following treatment of Fischer 344 rats with o-nitrotoluene (o-NT) or bromochloracetic acid (BCA). Oligo a...

  9. NTP Toxicology and Carcinogenesis Studies of Molybdenum Trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

    PubMed

    1997-04-01

    Molybdenum is an essential element for the function of nitrogenase in plants and as a cofactor for enzymes including xanthine oxidoreductase, aldehyde oxidase, and sulfide oxidase in animals. Molybdenum trioxide is used primarily as an additive to steel and corrosion-resistant alloys. It is also used as a chemical intermediate for molybdenum products; an industrial catalyst; a pigment; a crop nutrient; components of glass, ceramics, and enamels; a flame retardant for polyester and polyvinyl chloride resins; and a reagent in chemical analyses. Molybdenum trioxide was nominated by the NCI for toxicity and carcinogenicity studies as a representative inorganic molybdenum compound. The production of molybdenum trioxide is the largest of all the molybdenum compounds examined. Male and female F344/N rats and B6C3F1 mice were exposed to molybdenum trioxide (approximately 99% pure) by inhalation for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Rats were exposed for 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All rats survived to the end of the study. The final mean body weights of male rats exposed to 100 mg/m(3) and male and female rats exposed to 300 mg/m(3) were significantly lower than those of the control groups. Male rats exposed to 300 mg/m(3) lost weight during the study. There were no clinical findings related to exposure to molybdenum trioxide. No chemical-related lesions were observed. 14-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Mice were exposed 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All mice survived to the end of the study. Final mean

  10. Toxicity of inhaled methyl isocyanate in F344/N rats and B6C3F1 mice. I. Acute exposure and recovery studies.

    PubMed Central

    Bucher, J R; Gupta, B N; Adkins, B; Thompson, M; Jameson, C W; Thigpen, J E; Schwetz, B A

    1987-01-01

    Male and female F344/N rats and B6C3F1 mice were exposed to lethal and sublethal concentrations of methyl isocyanate by inhalation. Mortality, clinical signs, body and organ weights, and changes in clinical pathology and hematology were monitored immediately after 2-hr exposures and during the ensuing 3 months. Additional studies investigated the possible involvement of cyanide in the toxicity of methyl isocyanate. During exposures, signs of restlessness, lacrimation, and a reddish discharge from the nose and mouth were evident in rats and mice. Following exposures, rats and mice were dyspneic and weak. Deaths of rats and mice exposed to lethal concentrations (20 to 30 ppm) began within 15-18 hr, with males more prone to early death than females. A second wave of deaths occurred after 8 to 10 days, affecting primarily female rats and mice exposed to 20 to 30 ppm of methyl isocyanate, and male and female rats exposed to 10 ppm. Most deaths occurred during the first month following the exposures and were preceded by periods of severe respiratory distress. Body weights decreased in proportion to dose early, but then weight gain resumed in survivors at control rates. The only organ with a consistent, dose-related weight change was the lung, which was heavier throughout the studies in animals exposed to high concentrations of methyl isocyanate. No significant clinical pathology, or hematologic changes were observed in exposed rats. Blood and brain cholinesterase were not inhibited. Studies attempting to measure cyanide in the blood of methyl isocyanate-exposed rats, and attempting to affect lethality with a cyanide antidote (sodium nitrite and sodium thiosulfate) gave negative results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3622444

  11. Age-related Changes in the Fracture Resistance of Male Fischer F344 Rat Bone

    PubMed Central

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J.; Does, Mark D.; Nyman, Jeffry S.

    2015-01-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Both Raman spectroscopy and reference point indentation detected differences in tissue properties with age, though the trends did not necessarily match observations from human tissue. PMID:26610688

  12. Age-related changes in the fracture resistance of male Fischer F344 rat bone.

    PubMed

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J; Does, Mark D; Nyman, Jeffry S

    2016-02-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue. Published by Elsevier Inc.

  13. Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats.

    PubMed

    Daianu, Madelaine; Jacobs, Russell E; Weitz, Tara M; Town, Terrence C; Thompson, Paul M

    2015-01-01

    Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI) and high-angular resolution imaging (HARDI) are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI), composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm2 and applied it in transgenic Alzheimer rats (line TgF344-AD) that model the full clinico-pathological spectrum of the human disease. We studied and visualized the effects of the multiple concentric "shells" when computing three distinct anisotropy maps-fractional anisotropy (FA), generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA). We tested the added value of the multi-shell q-space sampling scheme, when reconstructing neural pathways using mathematical frameworks from DTI and q-ball imaging (QBI). We show a range of properties of HYDI, including lower apparent anisotropy when using high b-value shells in DTI-based reconstructions, and increases in apparent anisotropy in QBI-based reconstructions. Regardless of the reconstruction scheme, HYDI improves FA-, GFA- and NQA-aided tractography. HYDI may be valuable in human connectome projects and clinical research, as well as magnetic resonance research in experimental animals.

  14. 13 CFR 120.344 - Unique requirements of the EWCP.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Unique requirements of the EWCP. 120.344 Section 120.344 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS... reasonableness. International Trade Loans ...

  15. 34 CFR 303.344 - Content of an IFSP.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Content of an IFSP. 303.344 Section 303.344 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES Program and Service Component...

  16. Epistatic effects contribute to variation in BMD in Fischer 344 x Lewis F2 rats.

    PubMed

    Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

    2008-01-01

    To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F(2) progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an alpha level of 0.01. Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture.

  17. 12 CFR 344.8 - Securities trading policies and procedures.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Securities trading policies and procedures. 344.8 Section 344.8 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS... Securities trading policies and procedures. (a) Policies and procedures. Every bank effecting securities...

  18. 12 CFR 344.8 - Securities trading policies and procedures.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Securities trading policies and procedures. 344.8 Section 344.8 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS... Securities trading policies and procedures. (a) Policies and procedures. Every bank effecting securities...

  19. 12 CFR 344.8 - Securities trading policies and procedures.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Securities trading policies and procedures. 344.8 Section 344.8 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS... Securities trading policies and procedures. (a) Policies and procedures. Every bank effecting securities...

  20. 12 CFR 344.8 - Securities trading policies and procedures.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Securities trading policies and procedures. 344.8 Section 344.8 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS... Securities trading policies and procedures. (a) Policies and procedures. Every bank effecting securities...

  1. 12 CFR 344.8 - Securities trading policies and procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Securities trading policies and procedures. 344.8 Section 344.8 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS... Securities trading policies and procedures. (a) Policies and procedures. Every bank effecting securities...

  2. 7 CFR 51.344 - Size.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Apples for Processing Size § 51.344 Size. (a... buyer and seller. (c) Size is the dimension of the apples determined by the smallest opening through...

  3. 7 CFR 51.344 - Size.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Apples for Processing Size § 51.344 Size. (a... buyer and seller. (c) Size is the dimension of the apples determined by the smallest opening through...

  4. 7 CFR 51.344 - Size.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Standards for Grades of Apples for Processing Size § 51.344 Size. (a) The minimum and maximum sizes or range... the apples determined by the smallest opening through which it will pass. Application of Standards ...

  5. 7 CFR 51.344 - Size.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Standards for Grades of Apples for Processing Size § 51.344 Size. (a) The minimum and maximum sizes or range... the apples determined by the smallest opening through which it will pass. Application of Standards ...

  6. 7 CFR 51.344 - Size.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Standards for Grades of Apples for Processing Size § 51.344 Size. (a) The minimum and maximum sizes or range... the apples determined by the smallest opening through which it will pass. Application of Standards ...

  7. Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats

    NASA Technical Reports Server (NTRS)

    McDonald, R. B.; Hoban-Higgins, T. M.; Ruhe, R. C.; Fuller, C. A.; Horwitz, B. A.

    1999-01-01

    We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26 degrees C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c-fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

  8. Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats

    PubMed Central

    Daianu, Madelaine; Jacobs, Russell E.; Weitz, Tara M.; Town, Terrence C.; Thompson, Paul M.

    2015-01-01

    Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI) and high-angular resolution imaging (HARDI) are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI), composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm2 and applied it in transgenic Alzheimer rats (line TgF344-AD) that model the full clinico-pathological spectrum of the human disease. We studied and visualized the effects of the multiple concentric “shells” when computing three distinct anisotropy maps–fractional anisotropy (FA), generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA). We tested the added value of the multi-shell q-space sampling scheme, when reconstructing neural pathways using mathematical frameworks from DTI and q-ball imaging (QBI). We show a range of properties of HYDI, including lower apparent anisotropy when using high b-value shells in DTI-based reconstructions, and increases in apparent anisotropy in QBI-based reconstructions. Regardless of the reconstruction scheme, HYDI improves FA-, GFA- and NQA-aided tractography. HYDI may be valuable in human connectome projects and clinical research, as well as magnetic resonance research in experimental animals. PMID:26683657

  9. Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

    PubMed Central

    Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun

    2015-01-01

    Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1 × 106 cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. Significance This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. PMID:26315571

  10. Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats.

    PubMed

    Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun; Ra, Jeong Chan; Kim, Yun-Bae

    2015-10-01

    Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1×10(6) cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. ©AlphaMed Press.

  11. Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.

    PubMed

    Cho, Young-Man; Hasumura, Mai; Imai, Toshio; Takami, Shigeaki; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2017-07-01

    Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg -1 body weight day -1 ). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg -1 body weight day -1 ), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg -1 body weight day -1 ) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Epistatic Effects Contribute to Variation in BMD in Fischer 344 × Lewis F2 Rats

    PubMed Central

    Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

    2008-01-01

    To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. Introduction The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F2 progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Materials and Methods Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an α level of 0.01. Results and Conclusions Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture. PMID:17907919

  13. Kras, Egfr, and Tp53 Mutations in B6C3F1/N Mouse and F344/NTac Rat Alveolar/Bronchiolar Carcinomas Resulting from Chronic Inhalation Exposure to Cobalt Metal

    PubMed Central

    Hong, Hue-Hua L.; Hoenerhoff, Mark J.; Ton, Thai-Vu; Herbert, Ronald A.; Kissling, Grace E.; Hooth, Michelle J.; Behl, Mamta; Witt, Kristine L.; Smith-Roe, Stephanie L.; Sills, Robert C.; Pandiri, Arun R.

    2015-01-01

    Rodent lung tumors are morphologically similar to a subtype of human lung adenocarcinomas. The objective of this study was to evaluate Kras, Egfr and Tp53 mutations, which are relevant to human lung cancer, in cobalt metal dust (CMD) induced alveolar/bronchiolar tumors of B6C3F1/N mice and F344/NTac rats. Kras mutations were detected in 67% (mice) and 31% (rats) of CMD-induced lung tumors, and were predominantly exon 1 codon 12 G to T transversions (80% in mice and 57% in rats). Egfr mutations were detected in 17% (both mice and rats) of CMD-induced lung tumors, and were predominantly in exon 20 with 50% G to A transitions (mice and rats). Tp53 mutations were detected in 19% (mice) and 23% (rats) of CMD-induced lung tumors and were predominantly in exon 5 (mice, 69% transversions) and exon 6 (rats, all transitions). No mutations were observed for these genes in spontaneous lung tumors or normal lungs from untreated controls. Ames assays indicated that CMD is mutagenic in the absence but not in the presence of S9 mix. Thus, the mutation data (G to T transversions) and Ames assay results suggest that oxidative damage to DNA may be a contributing factor in CMD-induced pulmonary carcinogenesis in rodents. PMID:26059825

  14. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Ear drying aid active ingredient. 344.12 Section...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

  15. 21 CFR 344.10 - Earwax removal aid active ingredient.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

  16. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Ear drying aid active ingredient. 344.12 Section...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

  17. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Ear drying aid active ingredient. 344.12 Section...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

  18. 21 CFR 344.10 - Earwax removal aid active ingredient.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

  19. 21 CFR 344.10 - Earwax removal aid active ingredient.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

  20. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Ear drying aid active ingredient. 344.12 Section...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

  1. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Ear drying aid active ingredient. 344.12 Section...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

  2. 21 CFR 344.10 - Earwax removal aid active ingredient.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

  3. 21 CFR 344.10 - Earwax removal aid active ingredient.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

  4. 31 CFR 344.4 - What are Time Deposit securities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.4 What are Time Deposit securities? Time Deposit... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What are Time Deposit securities? 344...? The issuer must fix the maturity periods for Time Deposit securities, which are issued as follows: (1...

  5. 31 CFR 344.4 - What are Time Deposit securities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.4 What are Time Deposit securities? Time Deposit... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What are Time Deposit securities? 344...? The issuer must fix the maturity periods for Time Deposit securities, which are issued as follows: (1...

  6. 31 CFR 344.4 - What are Time Deposit securities?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.4 What are Time Deposit securities? Time Deposit... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false What are Time Deposit securities? 344...? The issuer must fix the maturity periods for Time Deposit securities, which are issued as follows: (1...

  7. 31 CFR 344.4 - What are Time Deposit securities?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... AND LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.4 What are Time Deposit securities? Time... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false What are Time Deposit securities? 344... periods? The issuer must fix the maturity periods for Time Deposit securities, which are issued as follows...

  8. 31 CFR 344.4 - What are Time Deposit securities?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.4 What are Time Deposit securities? Time Deposit... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false What are Time Deposit securities? 344...? The issuer must fix the maturity periods for Time Deposit securities, which are issued as follows: (1...

  9. In vivo genotoxicity of furan in F344 rats at cancer bioassay doses

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

    Ding, Wei, E-mail: Wei.Ding@fda.hhs.gov; Petibone, Dayton M.; Latendresse, John R.

    2012-06-01

    Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8 mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 andmore » 16 mg/kg. Rats were killed 3 h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity. -- Highlights: ► Furan is a potent rodent liver carcinogen and represents a human cancer risk. ► Furan induces DNA damage in rat liver at cancer bioassay doses. ► Furan induces oxidative stress, inflammation and cell proliferation in rat liver.

  10. 7 CFR 1207.344 - Operating reserve.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Expenses and Assessments § 1207.344 Operating reserve. The...

  11. 7 CFR 1207.344 - Operating reserve.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Expenses and Assessments § 1207.344 Operating reserve. The...

  12. 7 CFR 1207.344 - Operating reserve.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Expenses and Assessments § 1207.344 Operating reserve. The...

  13. 7 CFR 1207.344 - Operating reserve.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Expenses and Assessments § 1207.344 Operating reserve. The...

  14. 7 CFR 1207.344 - Operating reserve.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Expenses and Assessments § 1207.344 Operating reserve. The...

  15. NTP technical report on toxicity studies of diethanolamine (CAS No. 111-42-2) administered topically and in drinking water to F344/n rats and B6C3F1 mice. Toxicity report series

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

    Melnick, R.L.

    1992-10-01

    Diethanolamine is a high-production chemical used in cosmetics, in cutting fluids, as a dispersing agent for agricultural chemicals, and as an absorbent for acidic gases. Toxicology studies of diethanolamine were conducted in F344/N rats and B6C3F1 mice of both sexes for 2 weeks (5/sex/species/dose) and 13 weeks (10/sex/species/dose) to characterize and compare the effects of oral and dermal exposure. In addition to histopathology, evaluations included clinical pathology, urinalyses, and sperm morphology or vaginal cytology. In vitro genetic toxicity studies included assessments of mutagenicity in Salmonella typhimurium and mouse lymphoma L5178Y cells, analysis of chromosomal aberrations and sister chromatid exchange inmore » Chinese hamster ovary cells, and determination of micronuclei formed in mice during the 13 week dermal exposure study. In the 13-week drinking water study in mice, nephropathy and tubular necrosis were observed in males, and degeneration of cardiac myocytes, and hepatocellular necrosis were seen in males and females. Cytologic alteration in the submandibular salivary gland was noted in male and female mice. Hepatocyte cytologic alteration also was noted in all dosed groups of mice.« less

  16. Long-term AT1 receptor blockade improves metabolic function and provides renoprotection in Fischer-344 rats.

    PubMed

    Gilliam-Davis, Shea; Payne, Valerie S; Kasper, Sherry O; Tommasi, Ellen N; Robbins, Michael E; Diz, Debra I

    2007-09-01

    Fischer-344 (F344) rats exhibit proteinuria and insulin resistance in the absence of hypertension as they age. We determined the effects of long-term (1 yr) treatment with the angiotensin (ANG) II type 1 (AT(1)) receptor blocker L-158,809 on plasma and urinary ANG peptide levels, systolic blood pressure (SBP), and indexes of glucose metabolism in 15-mo-old male F344 rats. Young rats at 3 mo of age (n = 8) were compared with two separate groups of older rats: one control group (n = 7) and one group treated with L-158,809 (n = 6) orally (20 mg/l) for 1 yr. SBP was not different between control and treated rats but was higher in young rats. Serum leptin, insulin, and glucose levels were comparable between treated and young rats, whereas controls had higher glucose and leptin with a similar trend for insulin. Plasma ANG I and ANG II were higher in treated than untreated young or older rats, as evidence of effective AT(1) receptor blockade. Urinary ANG II and ANG-(1-7) were higher in controls compared with young animals, and treated rats failed to show age-related increases. Protein excretion was markedly lower in treated and young rats compared with control rats (young: 8 +/- 2 mg/day vs. control: 129 +/- 51 mg/day vs. treated: 9 +/- 3 mg/day, P < 0.05). Long-term AT(1) receptor blockade improves metabolic parameters and provides renoprotection. Differential regulation of systemic and intrarenal (urinary) ANG systems occurs during blockade, and suppression of the intrarenal system may contribute to reduced proteinuria. Thus, insulin resistance, renal injury, and activation of the intrarenal ANG system during early aging in normotensive animals can be averted by renin-ANG system blockade.

  17. Study of lee-side flows over conically cambered Delta wings at supersonic speeds, part 2

    NASA Technical Reports Server (NTRS)

    Wood, Richard M.; Watson, Carolyn B.

    1987-01-01

    An experimental investigation was performed in which surface pressure data, flow visualization data, and force and moment data were obtained on four conical delta wing models which differed in leading edge camber only. Wing leading edge camber was achieved through a deflection of the outboard 30% of the local wing semispan of a reference 75 deg swept flat delta wing. The four wing models have leading edge deflection angles delta sub F of 0, 5, 10, and 15 deg measured streamwise. Data for the wings with delta sub F = 10 and 15 deg showed that hinge line separation dominated the lee-side wing loading and prohibited the development of leading edge separation on the deflected portion of wing leading edge. However, data for the wing with delta sub F = 5 deg showed that at an angle of attack of 5 deg, a vortex was positioned on the deflected leading edge with reattachment at the hinge line. Flow visualization results were presented which detail the influence of Mach number, angle of attack, and camber on the lee-side flow characteristics of conically cambered delta wings. Analysis of photographic data identified the existence of 12 distinctive lee-side flow types.

  18. Wheel running improves REM sleep and attenuates stress-induced flattening of diurnal rhythms in F344 rats.

    PubMed

    Thompson, Robert S; Roller, Rachel; Greenwood, Benjamin N; Fleshner, Monika

    2016-05-01

    Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12 h light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise.

  19. Wheel Running Improves REM Sleep and Attenuates Stress-induced Flattening of Diurnal Rhythms in F344 Rats

    PubMed Central

    Thompson, Robert S.; Roller, Rachel; Greenwood, Benjamin N.; Fleshner, Monika

    2016-01-01

    Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12hr light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise. PMID:27124542

  20. Black Raspberries and Their Anthocyanin and Fiber Fractions Alter the Composition and Diversity of Gut Microbiota in F-344 Rats.

    PubMed

    Pan, Pan; Lam, Vy; Salzman, Nita; Huang, Yi-Wen; Yu, Jianhua; Zhang, Jianying; Wang, Li-Shu

    2017-01-01

    Natural compounds can alter the diversity and composition of the gut microbiome, potentially benefiting our health. We previously demonstrated chemopreventive effects of black raspberries (BRBs) in colorectal cancer, which is associated with gut dysbiosis. To investigate the effects of whole BRBs and their fractions on gut microbiota, we fed F-344 rats a control diet, 5% BRBs, the BRB anthocyanin fraction, or the BRB residue fraction for 6 weeks. Feces were collected at baseline and at weeks 3 and 6, and bacterial sequence counts were analyzed. We observed distinct patterns of microbiota from different diet groups. Beta diversity analysis suggested that all diet groups exerted time-dependent changes in the bacterial diversity. Hierarchical clustering analysis revealed that post-diet fecal microbiota was segregated from baseline fecal microbiota within each diet. It is interesting to note that fractions of BRBs induced different changes in gut bacteria compared to whole BRBs. The abundance of specific microbial species known to have anti-inflammatory effects, such as Akkermansia and Desulfovibrio, was increased by whole BRBs and their residue. Further, butyrate-producing bacteria, e.g., Anaerostipes, were increased by whole BRBs. Our results suggest that whole BRBs and their fractions alter the gut microbiota in ways that could significantly influence human health.

  1. NTP Toxicology and Carcinogenesis Studies of Dimethyl Methylphosphonate (CAS No. 756-79-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1987-11-01

    Dimethyl methylphosphonate (98% pure) is one of four chemicals nominated by the U.S. Army for toxicology and carcinogenesis studies because it was being considered for use to simulate the physical and spectroscopic (but not the biologic) properties of anticholinesterase (nerve) agents. Dimethyl methylphosphonate is also used as a flame retardant, a preignition additive for gasoline, an antifoam agent, a plasticizer and stabilizer, a textile conditioner and antistatic agent, and an additive for solvents and low-temperature hydraulic fluids. The United States produces 0.2-2 million pounds (91,000-910,000 kg) of per year. Gavage was chosen as the route of administration for all four candidate "simulants" to mimic potential exposure. Experimental Design: Dimethyl methylphosphonate was administered in corn oil by gavage to male and female F344/N rats and B6C3F1 mice in single-administration, 15-day, and 13-week studies to obtain toxicity data, to establish dose levels for the 2-year studies, and to identify target tissues. Additional studies were also performed to determine toxicity to the reproductive system of male F344/N rats and B6C3F1 mice and to study the potential for genetic damage in bacteria, mammalian cells, and Drosophila. Single-Administration Studies: In the single-administration studies, dimethyl methylphosphonate was given to rats and mice at doses up to 6,810 mg/kg body weight. No compound-related deaths were seen in male or female rats or male mice; two high dose female mice died. Rats exhibited inactivity, unsteady gait, and prostration after dosing; mice were inactive after dosing. Fifteen-Day Studies: Rats and mice received doses of 0, 1,250, 2,500, 5,000, 10,000, or 15,000 mg/kg dimethyl methylphosphonate per day. Compound-related deaths occurred in the three highest dose groups of rats and the two highest dose groups of mice. Rats receiving doses of 2,500 mg/kg or higher were inactive and at 5,000 or 10,000 mg/kg had an unsteady gait after dosing

  2. Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB-F344 cells.

    PubMed

    Hirane, Miku; Ishii, Shuhei; Tomimatsu, Ayaka; Fukushima, Kaori; Takahashi, Kaede; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

    2016-11-01

    Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA 1 to LPA 6 ) mediates a variety of cellular functions, including cell motility. In the present study, we investigated the effects of LPA receptors on cell motile activity during multi-stage hepatocarcinogenesis in rat liver epithelial WB-F344 cells treated with chemical liver carcinogens. Cells were treated with a initiator (N-nitrosodiethylamine (DEN)) and three promoters (phenobarbital (PB), okadaic acid (OA) and clofibrate) every 24 h for 2 days. Cell motile activity was elevated by DEN, correlating with Lpar3 expression. PB, OA, and clofibrate elevated Lpar1 expression and inhibited cell motile activity. To evaluate the effects of long-term treatment on cell motility, cells were treated with DEN and/or PB for at least 6 months. Lpar3 expression and cell motile activity were significantly elevated by the long-term DEN treatment with or without further PB treatment. In contrast, long-term PB treatment with or without further DEN elevated Lpar1 expression and inhibited cell motility. When the synthesis of extracellular LPA was blocked by a potent ATX inhibitor S32826 before cell motility assay, the cell motility induced by DEN and PB was markedly suppressed. These results suggest that activation of the different LPA receptors may regulate the biological functions of cells treated with chemical carcinogens. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  3. Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats

    PubMed Central

    Saha, Shyamali; Prakash, Satya

    2014-01-01

    The gut microbiota is a bacterial bioreactor whose composition is an asset for human health. However, circulating gut microbiota derived endotoxins cause metabolic endotoxemia, promoting metabolic and liver diseases. This study investigates the potential of orally delivered microencapsulated Bifidobacterium infantis ATCC 15697 to modulate the gut microbiota and reduce endotoxemia in F344 rats. The rats were gavaged daily with saline or microencapsulated B. infantis ATCC 15697. Following 38 days of supplementation, the treated rats showed a significant (P < 0.05) increase in fecal Bifidobacteria (4.34 ± 0.46 versus 2.45 ± 0.25% of total) and B. infantis (0.28 ± 0.21 versus 0.52 ± 0.12 % of total) and a significant (P < 0.05) decrease in fecal Enterobacteriaceae (0.80 ± 0.45 versus 2.83 ± 0.63% of total) compared to the saline control. In addition, supplementation with the probiotic formulation reduced fecal (10.52 ± 0.18 versus 11.29 ± 0.16 EU/mg; P = 0.01) and serum (0.33 ± 0.015 versus 0.30 ± 0.015 EU/mL; P = 0.25) endotoxins. Thus, microencapsulated B. infantis ATCC 15697 modulates the gut microbiota and reduces colonic and serum endotoxins. Future preclinical studies should investigate the potential of the novel probiotic formulation in metabolic and liver diseases. PMID:24967382

  4. NTP Toxicology and Carcinogenesis Studies of Benzyl Acetate (CAS No. 140-11-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1986-08-01

    Benzyl acetate, a water-white liquid with a pear-like odor, is a natural constituent of several essential oils and flower absolutes extracted from jasmine, hyacinth, gardenia, tuberose, ylang-ylang, cananga, and neroli. Commercial benzyl acetate, a liquid prepared synthetically from benzyl chloride, acetic acid, and triethylamine is used primarily as a component of perfumes for soaps and as a flavoring ingredient. This compound is practically insoluble in water but is miscible in alcohol and ether and soluble in benzene and chloroform. Toxicology and carcinogenesis studies of benzyl acetate (>99% pure) were conducted by administering benzyl acetate in corn oil gavage to groups of 50 male and 50 female F344/N rats at doses of 0, 250, or 500 mg/kg body weight and to groups of 50 male and 50 female B6C3F1 mice at doses of 0, 500, or 1,000 mg/kg once daily five days per week for 103 weeks. Dose selection for the 2-year study was based on mean body weight gain depression and decreased survival observed at higher doses in 13 week studies. The absence of any observable adverse effect of benzyl acetate on the survival or mean body weight gains of the rats or mice in the 2-year studies suggests that both the rats and the mice of each sex could have tolerated higher doses. An infection in the genital tract was probably responsible for the deaths of 26/35 control, 14/32 low-dose, and 8/20 high-dose female mice before the end of the study. Acinar-cell adenomas in the pancreas of male rats occurred with a positive trend (P<0.01), and the incidence in the high-dose group (37/49, 76%) was significantly (P<0.01) higher than in the vehicle controls (22/50, 40%). The incidence of these tumors in the low-dose group (27/50, 54%) was comparable to that in the gavage controls. Acinar-cell hyperplasia of the pancreas was observed in 37/50 control, 34/50 low-dose, and 36/49 high-dose male rats. No acinar-cell hyperplasia or adenoma of the pancreas was observed in female rats. The

  5. From Wine to Pineapples: Delta Company Takes on New Satellite Role

    DTIC Science & Technology

    2011-01-01

    2011 Spring / Summer edition army Space Journal 2F Delta Company Takes on New Satellite Role FROM Wine TO PineAPPLeS WAHIAWA, Hawaii – 2011 has yet...next to pineapple fields on the island of Oahu, Hawaii. Delta Company has provided network and payload control for the Defense Satellite...1. REPORT DATE 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE From Wine to Pineapples : Delta Company

  6. 45 CFR 158.344 - Secretary's discretion to hold a hearing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Secretary's discretion to hold a hearing. 158.344 Section 158.344 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH... adjustment to the MLR standard. All testimony and materials received in connection with any public hearing...

  7. 32 CFR 344.6 - Authorities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.6 Authorities. The ASD(RA) is hereby delegated authority to: (a) Act for the Secretary of Defense, in accordance with section 411 of...

  8. 32 CFR 344.6 - Authorities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.6 Authorities. The ASD(RA) is hereby delegated authority to: (a) Act for the Secretary of Defense, in accordance with section 411 of...

  9. 32 CFR 344.6 - Authorities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.6 Authorities. The ASD(RA) is hereby delegated authority to: (a) Act for the Secretary of Defense, in accordance with section 411 of...

  10. Proinflammatory effect of sodium 4-phenylbutyrate in deltaF508-cystic fibrosis transmembrane conductance regulator lung epithelial cells: involvement of extracellular signal-regulated protein kinase 1/2 and c-Jun-NH2-terminal kinase signaling.

    PubMed

    Roque, Telma; Boncoeur, Emilie; Saint-Criq, Vinciane; Bonvin, Elise; Clement, Annick; Tabary, Olivier; Jacquot, Jacky

    2008-09-01

    Sodium 4-phenylbutyrate (4-PBA) has attracted a great deal of attention in cystic fibrosis (CF) pathology due to its capacity to traffic DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR) to the cell membrane and restore CFTR chloride function at the plasma membrane of CF lung cells in vitro and in vivo. Using two different DeltaF508-CFTR lung epithelial cell lines (CFBE41o- and IB3-1 cells, characterized with DeltaF508-homozygous and heterozygous genotype, respectively) in vitro, 4-PBA induced an increase of proinflammatory cytokine interleukin (IL)-8 production in a concentration-dependent manner. This 4-PBA-induced IL-8 production was associated with a strong reduction of proteasome and nuclear factor-kappaB transcriptional activities in the two DeltaF508-CFTR lung cells either in a resting state or after tumor necrosis factor-alpha stimulation. In contrast, a strong increase of activator protein-1 transcriptional activity was observed. The inhibition of extracellular signal-regulated protein kinase 1/2 (ERK1/2) by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126) and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) and c-Jun-NH(2)-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) by anthra[1,9-cd] pyrazol-6 (2H)-one (SP600125), respectively, was associated with a reduction (2-3.5-fold) of IL-8 production in both DeltaF508-CFTR lung cell lines treated with 4-PBA. No significant change of IL-8 production was observed after an inhibition of p38 MAPK with 4-[4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-2-yl] phenol (SB202190). Therefore, we suggest that inhibition of both ERK1/2 and JNK signaling may be a means to strongly reduce 4-PBA-induced IL-8 production in combination with 4-PBA treatment to restore CFTR Cl(-) channel function in lung epithelial cells of patients with CF.

  11. Region-specific DNA synthesis in brains of F344 rats following a six-day bromodeoxyuridine infusion.

    PubMed

    Bolon, B; Dunn, C; Goldsworthy, T L

    1996-09-01

    Prolonged exposure to certain alkylating chemicals induces glial and meningeal tumours in rats, probably resulting from DNA damage to dividing neural cells. The present work evaluated DNA synthesis in the brains of untreated, young adult male F344 rats in order to define a BrdUrd infusion protocol to more adequately assess proliferation in slowly dividing neural cell populations. BrdUrd (2.5 to 160 mg/ml) was administered for 6 days via subcutaneous osmotic pumps. Clinical toxicity was not observed at any dose. The labelling index (LI; % of cells per brain area that incorporated BrdUrd) and unit length labelling index (ULLI; % of cells per meningeal length that incorporated BrdUrd) were calculated for selected regions by counting labelled neural cells in defined areas of the right hemisphere in coronal brain sections. Intensely stained cells were numerous in the cerebral subependymal layer (LI = 35.8%); scattered in cerebral white matter tracts (e.g. corpus callosum and internal capsule; LI = 6.2%) as well as cerebral (ULLI = 4.2%) and cerebellar (ULLI = 3.6%) meninges; and rare in the hippocampus (LI > 0.1%). Mildy stained cells were dispersed in the pons (LI = 2.1%), deep cerebral (LI = 1.8%) and cerebellar (LI = 1.0%) grey matter, and thalamus (LI = 0.3%). Phenotypically, BrdUrd-positive cells in neuropil were glial cell precursors and their progeny, while those associated with meninges were usually located in the superficial subarachnoid space and appeared to be fibrocytes. Using BrdUrd infusion, LI for glial precursors at these sites ranged from two- to 10-fold higher than those reported previously after a brief parenteral pulse dose. These data indicate that continuous BrdUrd infusion for 6 days by subcutaneous osmotic pump is an efficient means of labelling neural cells throughout the brain.

  12. Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

    PubMed Central

    Kalinich, John F.; Emond, Christy A.; Dalton, Thomas K.; Mog, Steven R.; Coleman, Gary D.; Kordell, Jessica E.; Miller, Alexandra C.; McClain, David E.

    2005-01-01

    Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm × 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4–5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys. PMID:15929896

  13. 21 CFR 556.344 - Ivermectin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.344 Ivermectin. (a) Acceptable daily intake (ADI). The ADI for total... tolerance is established for 22,23-dihydroavermectin B1a (marker residue) in liver (target tissue) as...

  14. 21 CFR 556.344 - Ivermectin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.344 Ivermectin. (a) Acceptable daily intake (ADI). The ADI for total... tolerance is established for 22,23-dihydroavermectin B1a (marker residue) in liver (target tissue) as...

  15. 21 CFR 556.344 - Ivermectin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.344 Ivermectin. (a) Acceptable daily intake (ADI). The ADI for total... tolerance is established for 22,23-dihydroavermectin B1a (marker residue) in liver (target tissue) as...

  16. Determination of the Chronic Mammalian Toxicological Effects of RDX: (Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5- Trinitro-1,3,5-Triazine (RDX) in the Fischer 344 Rat). Volume 1.

    DTIC Science & Technology

    1983-11-01

    content. C . An J ma Is *a Fischer 344 (F344) rats, obtained from Harlan Sprague-Dawley, Madison , WI, were used for this study. Four hundred and thirty...Seminal vesicles "Skin, abdominal Spinal cord (cervical, thoracic, lumbar ) *Spleen Sternum, Including bone marrow Stomach *Testes Thymus Thyroids...abdominal * Spinal cord (cervical, thoracic and lumbar ) Spleen Sternum Including bone marrow Stomach Tissue masses Thyroids (parathyroids) Trachea

  17. Temperature independent quantum well FET with delta channel doping

    NASA Technical Reports Server (NTRS)

    Young, P. G.; Mena, R. A.; Alterovitz, S. A.; Schacham, S. E.; Haugland, E. J.

    1992-01-01

    A temperature independent device is presented which uses a quantum well structure and delta doping within the channel. The device requires a high delta doping concentration within the channel to achieve a constant Hall mobility and carrier concentration across the temperature range 300-1.4 K. Transistors were RF tested using on-wafer probing and a constant G sub max and F sub max were measured over the temperature range 300-70 K.

  18. 31 CFR 344.5 - What other provisions apply to subscriptions for Time Deposit securities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.5 What other provisions apply to subscriptions for Time Deposit securities? (a) When is my subscription due... subscriptions for Time Deposit securities? 344.5 Section 344.5 Money and Finance: Treasury Regulations Relating...

  19. 31 CFR 344.5 - What other provisions apply to subscriptions for Time Deposit securities?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.5 What other provisions apply to subscriptions for Time Deposit securities? (a) When is my subscription due... subscriptions for Time Deposit securities? 344.5 Section 344.5 Money and Finance: Treasury Regulations Relating...

  20. 31 CFR 344.5 - What other provisions apply to subscriptions for Time Deposit securities?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.5 What other provisions apply to subscriptions for Time Deposit securities? (a) When is my subscription due... subscriptions for Time Deposit securities? 344.5 Section 344.5 Money and Finance: Treasury Regulations Relating...

  1. 31 CFR 344.5 - What other provisions apply to subscriptions for Time Deposit securities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.5 What other provisions apply to subscriptions for Time Deposit securities? (a) When is my subscription due... subscriptions for Time Deposit securities? 344.5 Section 344.5 Money and Finance: Treasury Regulations Relating...

  2. DELTAS: A new Global Delta Sustainability Initiative (Invited)

    NASA Astrophysics Data System (ADS)

    Foufoula-Georgiou, E.

    2013-12-01

    Deltas are economic and environmental hotspots, food baskets for many nations, home to a large part of the world population, and hosts of exceptional biodiversity and rich ecosystems. Deltas, being at the land-water interface, are international, regional, and local transport hubs, thus providing the basis for intense economic activities. Yet, deltas are deteriorating at an alarming rate as 'victims' of human actions (e.g. water and sediment reduction due to upstream basin development), climatic impacts (e.g. sea level rise and flooding from rivers and intense tropical storms), and local exploration (e.g. sand or aggregates, groundwater and hydrocarbon extraction). Although many efforts exist on individual deltas around the world, a comprehensive global delta sustainability initiative that promotes awareness, science integration, data and knowledge sharing, and development of decision support tools for an effective dialogue between scientists, managers and policy makers is lacking. Recently, the international scientific community proposed to establish the International Year of Deltas (IYD) to serve as the beginning of such a Global Delta Sustainability Initiative. The IYD was proposed as a year to: (1) increase awareness and attention to the value and vulnerability of deltas worldwide; (2) promote and enhance international and regional cooperation at the scientific, policy, and stakeholder level; and (3) serve as a launching pad for a 10-year committed effort to understand deltas as complex socio-ecological systems and ensure preparedness in protecting and restoring them in a rapidly changing environment. In this talk, the vision for such an international coordinated effort on delta sustainability will be presented as developed by a large number of international experts and recently funded through the Belmont Forum International Opportunities Fund. Participating countries include: U.S., France, Germany, U.K., India, Japan, Netherlands, Norway, Brazil, Bangladesh

  3. Interactions between nested sunspots. 1: The formation and breakup of a delta-type sunspot

    NASA Astrophysics Data System (ADS)

    Gaizauskas, V.; Harvey, K. L.; Proulx, M.

    1994-02-01

    We investigate a nest of sunspots in which three ordinary bipolar pairs of sunspots are aligned collinearly. The usual spreading action of the growing regions brings two spots of leading polarity together (p-p collision) and forces the leading and trailing spots of the two interior regions to overlap into a single penumbra (p-f collision), thus forming a delta-spot. We examine digitally processed images from the Ottawa River Solar Observatory of two related events inside the delta-spot 5 days after the p-f collision begins: the violent disruption of the f-umbra, and the formation in less than a day of an hydrogen-alpha filament. The evolutionary changes in shape, area, relative motions, and brightness that we measure for each spot in the elongated nest are more compatible with Parker's (1979a) hypothesis of a sunspot as a cluster of flux tubes held together by downdrafts than with the notion of a sunspot as a monolithic plug of magnetic flux. From chromospheric developments over the delta-spot, we show that a shearing motion along a polarity inversion is more effective than convergence for creating a chromospheric filament. We invoke the release of an instability, triggered by a sequence of processes lasting 1 day or more, to explain the disruption of the f-umbra in this delta-spot. We show that the sequence is initiated when the colliding p-f umbrae reach a critical separation around 3200 +/- 200 km. We present a descriptive model in which the reconnected magnetic fields block vertical transport of convective heat flux just beneath the photosphere. We observe the formation of an unusual type of penumbra adjacent to the f-polarity portion of this delta-spot just before its disruption. A tangential penumbral band grows out of disordered matter connected to the f-umbra. We present this as evidence for the extrusion of umbral magnetic flux by thermal plumes rising through a loosely bound umbra.

  4. Interactions between nested sunspots. 1: The formation and breakup of a delta-type sunspot

    NASA Technical Reports Server (NTRS)

    Gaizauskas, V.; Harvey, K. L.; Proulx, M.

    1994-01-01

    We investigate a nest of sunspots in which three ordinary bipolar pairs of sunspots are aligned collinearly. The usual spreading action of the growing regions brings two spots of leading polarity together (p-p collision) and forces the leading and trailing spots of the two interior regions to overlap inot a single penumbra (p-f collision), thus forming a delta-spot. We examine digitally processed images from the Ottawa River Solar Observatory of two related events inside the delta-spot 5 days after the p-f collision begins: the violent disruption of the f-umbra, and the formation in less than a day of an hydrogen-alpha filament. The evolutionary changes in shape, area, relative motions, and brightness that we measure for each spot in the elongated nest are more compatible with Parker's (1979a) hypothesis of a sunspot as a cluster of flux tubes held together by downdrafts than with the notion of a sunspot as a monolithic plug of magnetic flux. From chromospheric developments over the delta-spot, we show that a shearing motion along a polarity inversion is more effective than convergence for creating a chromospheric filament. We invoke the release of an instability, triggered by a sequence of processes lasting 1 day or more, to explain the disruption of the f-umbra in this delta-spot. We show that the sequence is initiated when the colliding p-f umbrae reach a critical separation around 3200 +/- 200 km. We present a descriptive model in which the reconnected magnetic fields block vertical transport of convective heat flux just beneath the photosphere. We observe the formation of an unusual type of penumbra adjacent to the f-polarity portion of this delta-spot just before its disruption. A tangential penumbral band grows out of disordered matter connected to the f-umbra. We present this as evidence for the extrusion of umbral magnetic flux by thermal plumes rising through a loosely bound umbra.

  5. NTP Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1986-04-01

    Benzene ranks 16th in production volume for chemicals produced in the United States, with approximately 9.9 billion pounds being produced in 1984, 9.1 billion pounds in 1983, and 7.8 billion pounds in 1982. This simplest aromatic chemical in used in the synthesis of styrene (polystyrene plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon), aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents), chlorobenzenes, and other products used in the production of drugs, dyes, insecticides, and plastics. Benzene, along with other light, high-octane aromatic hydrocarbons, such as toluene and xylenes, is a component of motor gasoline. Benzene is also used as a solvent, but for most applications, it has been replaced by less hazardous solvents. During the 17-week studies, groups of 10 or 15 male and female F344/N rats and B6C3F1 mice were gavaged 5 days per week with benzene in corn oil (5 ml/kg) at doses of 0 to 600 mg/kg. No benzene-related deaths occurred; in rats that received benzene, final mean body weights were 14%-22% lower compared with vehicle controls and in mice, slight dose-related reductions were observed (less than 10% differences). Doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Two-year toxicology and carcinogenesis studies of benzene (greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil (5 ml/kg) were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten additional animals in each of the 16 groups were killed at 12 months and necropsies were performed. Hematologic

  6. 31 CFR 344.5 - What other provisions apply to subscriptions for Time Deposit securities?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SERVICE U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Time Deposit Securities § 344.5 What other provisions apply to subscriptions for Time Deposit securities? (a) When is my subscription due... subscriptions for Time Deposit securities? 344.5 Section 344.5 Money and Finance: Treasury Regulations Relating...

  7. Propylene glycol monomethyl ether (PGME): inhalation toxicity and carcinogenicity in Fischer 344 rats and B6C3F1 mice.

    PubMed

    Spencer, Pamela J; Crissman, James W; Stott, William T; Corley, Richard A; Cieszlak, Frank S; Schumann, Alan M; Hardisty, Jerry F

    2002-01-01

    A series of inhalation studies with propylene glycol monomethyl ether (PGME) vapor were undertaken to characterize its subchronic toxicity in mice and chronic toxicity/oncogenicity in rats and mice. Groups of male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 300, 1,000, or 3,000 ppm vapor from 1 week to 2 years. Primary treatment-related effects included: initial sedation of animals exposed to 3,000 ppm and its subsequent resolution correlating with induction of hepatic mixed function oxidase activity and S-phase DNA synthesis; elevated mortality in high-exposure male rats and mice (chronic study); elevated deposition of alpha2u-globulin (alpha2U-G) and associated nephropathy and S-phase DNA synthesis in male rat kidneys; accelerated atrophy of the adrenal gland X-zone in female mice (subchronic study only); and increased occurrence and/or severity of eosinophilic foci of altered hepatocytes in male rats. No toxicologically relevant statistically significant increases in neoplasia occurred in either species. A numerical increase in the incidence of kidney adenomas occurred in intermediate-exposure male rats; however, the association with alpha2U-G nephropathy, a male rat specific effect, indicated a lack of relevance for human risk assessment.

  8. 31 CFR 344.2 - What general provisions apply to SLGS securities?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... securities? 344.2 Section 344.2 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT U.S. TREASURY SECURITIES... securities? (a) What other regulations apply to SLGS securities? SLGS securities are subject to: (1) The...

  9. 43 CFR 34.4 - Discrimination prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... DURING CONSTRUCTION AND OPERATION OF THE ALASKA NATURAL GAS TRANSPORTATION SYSTEM § 34.4 Discrimination... or bids, the designation of quantities, delivery schedules or other specifications, selection... individuals or establishments to be provided an opportunity to participate in any activity; and (ix) Selection...

  10. 43 CFR 34.4 - Discrimination prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... DURING CONSTRUCTION AND OPERATION OF THE ALASKA NATURAL GAS TRANSPORTATION SYSTEM § 34.4 Discrimination... or bids, the designation of quantities, delivery schedules or other specifications, selection... individuals or establishments to be provided an opportunity to participate in any activity; and (ix) Selection...

  11. Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring

    PubMed Central

    Lejonklou, Margareta H.; Dunder, Linda; Bladin, Emelie; Pettersson, Vendela; Rönn, Monika; Lind, Lars; Waldén, Tomas B.

    2017-01-01

    Background: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive. Objectives: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring. Methods: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to 0.5μg/kg BW/d (BPA0.5; n=21) or 50μg/kg BW/d (BPA50; n=16), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (n=26). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring. Results: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels (0.81±0.10 mmol/L compared with 0.57±0.03 mmol/L, females BPA50 p=0.04; 0.81±0.05 mmol/L compared with 0.61±0.04 mmol/L, males BPA0.5 p=0.005) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls (68.2±4.4 number of adipocytes/HPF compared with 55.9±1.5 number of adipocytes/HPF; p=0.03) and by 123% in BPA0.5 females compared with BPA50 animals (68.2±4.4 number of adipocytes/high power field (HPF) compared with 55.3±2.9 number of adipocytes/HPF; p=0.04). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals (69.9±5.1 number of adipocytes/HPF compared with 54.0±3.4 number of adipocytes/HPF; p=0.03). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed

  12. Role of UDP-Glucuronosyltransferase (UGT) 2B2 in Metabolism of Triiodothyronine: Effect of Microsomal Enzyme Inducers in Sprague Dawley and UGT2B2-Deficient Fischer 344 Rats

    PubMed Central

    Richardson, Terrilyn A.; Klaassen, Curtis D.

    2010-01-01

    Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) can impact thyroid hormone homeostasis in rodents. Increased glucuronidation can result in reduction of serum thyroid hormone and a concomitant increase in thyroid-stimulating hormone (TSH). UGT2B2 is thought to glucuronidate triiodothyronine (T3). The purposes of this study were to determine the role of UGT2B2 in T3 glucuronidation and whether increased T3 glucuronidation mediates the increased TSH observed after MEI treatment. Sprague Dawley (SD) and UGT2B2-deficient Fischer 344 (F344) rats were fed a control diet or diet containing pregnenolone-16α-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum thyroxine (T4), T3, and TSH concentrations, hepatic androsterone/T4/T3 glucuronidation, and thyroid follicular cell proliferation were determined. In both SD and F344 rats, MEI treatments decreased serum T4, whereas serum T3 was maintained (except with PCB treatment). Hepatic T4 glucuronidation increased significantly after MEI in both rat strains. Compared with the other MEI, only PCN treatment significantly increased T3 glucuronidation (281 and 497%) in both SD and UGT2B2-deficient F344 rats, respectively, and increased both serum TSH and thyroid follicular cell proliferation. These data demonstrate an association among increases in T3 glucuronidation, TSH, and follicular cell proliferation after PCN treatment, suggesting that T3 is glucuronidated by other PCN-inducible UGTs in addition to UGT2B2. These data also suggest that PCN (rather than 3-MC or PCB) promotes thyroid tumors through excessive TSH stimulation of the thyroid gland. PMID:20421340

  13. 9 CFR 317.344 - Identification of major cuts of meat products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... products. 317.344 Section 317.344 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... meat products are: Beef chuck blade roast, beef loin top loin steak, beef rib roast large end, beef round eye round steak, beef round top round steak, beef round tip roast, beef chuck arm pot roast, beef...

  14. 9 CFR 317.344 - Identification of major cuts of meat products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... products. 317.344 Section 317.344 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... meat products are: Beef chuck blade roast, beef loin top loin steak, beef rib roast large end, beef round eye round steak, beef round top round steak, beef round tip roast, beef chuck arm pot roast, beef...

  15. 9 CFR 317.344 - Identification of major cuts of meat products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... products. 317.344 Section 317.344 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... 82165, Dec. 29, 2010. The major cuts of single-ingredient, raw meat products are: Beef chuck blade roast, beef loin top loin steak, beef rib roast large end, beef round eye round steak, beef round top round...

  16. 9 CFR 317.344 - Identification of major cuts of meat products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... products. 317.344 Section 317.344 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... major cuts of single-ingredient, raw meat products are: Beef chuck blade roast, beef loin top loin steak, beef rib roast large end, beef round eye round steak, beef round top round steak, beef round tip roast...

  17. 9 CFR 317.344 - Identification of major cuts of meat products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... products. 317.344 Section 317.344 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... meat products are: Beef chuck blade roast, beef loin top loin steak, beef rib roast large end, beef round eye round steak, beef round top round steak, beef round tip roast, beef chuck arm pot roast, beef...

  18. delta-Hexachlorocyclohexane (delta-HCH)

    Integrated Risk Information System (IRIS)

    delta - Hexachlorocyclohexane ( delta - HCH ) ; CASRN 319 - 86 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Ass

  19. δ- and γ-tocopherols, but not α-tocopherol, inhibit colon carcinogenesis in azoxymethane-treated F344 rats.

    PubMed

    Guan, Fei; Li, Guangxun; Liu, Anna B; Lee, Mao-Jung; Yang, Zhihong; Chen, Yu-Kuo; Lin, Yong; Shih, Weichung; Yang, Chung S

    2012-04-01

    The cancer preventive activity of vitamin E has been extensively discussed, but the activities of specific forms of tocopherols have not received sufficient attention. Herein, we compared the activities of δ-tocopherol (δ-T), γ-T, and α-T in a colon carcinogenesis model. Male F344 rats, seven weeks old, were given two weekly subcutaneous injections of azoxymethane (AOM) each at a dose of 15 mg/kg body weight. Starting 1 week before the AOM injection, the animals were maintained on a modified AIN76A diet, or the same diet containing 0.2% of δ-T, γ-T, α-T, or a γ-T-rich mixture of tocopherols (γ-TmT), until the termination of the experiment at 8 weeks after the second AOM injection. δ-T treatment showed the strongest inhibitory effect, decreasing the numbers of aberrant crypt foci by 62%. γ-T and γ-TmT were also effective, but α-T was not. Immunohistochemical analysis showed that δ-T and γ-T treatments reduced the levels of 4-hydroxynonenal and nitrotyrosine and the expression of cyclin D1 in the colon, preserved the expression of PPAR-γ, and decreased the serum levels of prostaglandin E2 and 8-isoprostane. Supplementation with 0.2% δ-T, γ-T, or α-T increased the respective levels of tocopherols and their side-chain degradation metabolites in the serum and colon tissues. Rather high concentrations of δ-T and γ-T and their metabolites were found in colon tissues. Our study provides the first evidence for the much higher cancer preventive activity of δ-T and γ-T than α-T in a chemically induced colon carcinogenesis model. It further suggests that δ-T is more effective than γ-T. 2012 AACR

  20. δ- and γ-Tocopherols, but not α-Tocopherol, Inhibit Colon Carcinogenesis in Azoxymethane-Treated F344 Rats

    PubMed Central

    Guan, Fei; Li, Guangxun; Liu, Anna B; Lee, Mao-Jung; Yang, Zhihong; Chen, Yu-Kuo; Lin, Yong; Shih, Weichung; Yang, Chung S

    2012-01-01

    The cancer preventive activity of vitamin E has been extensively discussed, but the activities of specific forms of tocopherols have not received sufficient attention. Herein, we compared the activities of δ-tocopherol (δ-T), γ-T and α-T in a colon carcinogenesis model. Male F344 rats, 7 weeks old, were given 2 weekly subcutaneous injections of azoxymethane (AOM) each at a dose of 15 mg/kg body weight. Starting 1 week before the AOM injection, the animals were maintained on a modified AIN76A diet, or the same diet containing 0.2% of δ-T, γ-T, α-T or a γ-T-rich mixture of tocopherols (γ-TmT), until the termination of the experiment at 8 weeks after the second AOM injection. δ-T treatment showed the strongest inhibitory effect, decreasing the numbers of aberrant crypt foci by 62%. γ-T and γ-TmT were also effective, but α-T was not. Immunohistochemical analysis showed that δ-T and γ-T treatments reduced the levels of 4-hydroxynonenal and nitrotyrosine and the expression of cyclin D1 in the colon, preserved the expression of PPAR-γ, and decreased the serum levels of prostaglandin E2 and 8-isoprostane. Supplementation with 0.2% δ-T, γ-T or α-T increased the respective levels of tocopherols and their side-chain degradation metabolites in the serum and colon tissues. Rather high concentrations of δ-T and γ-T and their metabolites were found in colon tissues. Our study provides the first evidence for the much higher cancer preventive activity of δ-T and γ-T than α-T in a chemically-induced colon carcinogenesis model. It further suggests that δ-T is more effective than γ-T. PMID:22366914

  1. New science, old convictions - Texas Senate Bill 344: identifying further necessary reform in forensic science.

    PubMed

    Soni, Naina

    2015-02-01

    In June 2013, Texas Senate Bill 344 (SB 344) was signed into law after strong Innocence Project support. SB 344 has since transformed the Texan judicial landscape. Known as the 'Junk Science Writ', SB 344 enables the court to grant habeas corpus relief based on scientific evidence that '(1) was not available to be offered by a convicted person at the convicted person's trial; or (2) contradicts scientific evidence relied on by the state at trial'. Inmates, such as the 'San Antonio Four', whose convictions were based upon what is now considered 'faulty' medical and forensic testimony, have been released under SB 344. Yet, science, as a field dependent on innovation, is inherently prone to debunking the scientific and forensic methods the law has relied upon to convict individuals. This commentary identifies policy behind SB 344, how SB 344 may influence the perception of science in the courtroom, and how 'junk science' is defined and/or limited. Furthermore, this commentary concludes that to achieve justice in the legal system through habeas relief based on 'junk science', it is necessary to revitalize and standardize forensic science.

  2. The Chandra/MOST Campaign on Delta Ori A

    NASA Astrophysics Data System (ADS)

    Corcoran, Michael

    2014-11-01

    X-ray emission from massive stars is produced by shocked gas distributed throughout their unstable stellar winds. These shocks play a significant role in determining accurate stellar mass loss rates. Our current understanding of these shocks is derived from indirect indicators like line profile shapes and the f/i ratio of the He-like triplets. Here we discuss a campaign of phase-resolved Chandra grating observations and simultaneous high-precision photometry using the MOST satellite of the massive binary Delta Ori A, in an attempt to directly constrain the radial extent of the hot gas in the wind of the primary star (Delta Ori Aa) via occultation by the X-ray faint secondary (Delta Ori Ab). We present an overview of this campaign and a summary of our results.

  3. Low-dose developmental bisphenol A exposure alters fatty acid metabolism in Fischer 344 rat offspring.

    PubMed

    Dunder, Linda; Halin Lejonklou, Margareta; Lind, Lars; Risérus, Ulf; Lind, P Monica

    2018-06-06

    Bisphenol A (BPA) is an endocrine disruptor and also a suggested obesogen and metabolism-disrupting chemical. Accumulating data indicates that the fatty acid (FA) profile and their ratios in plasma and other metabolic tissues are associated with metabolic disorders. Stearoyl-CoA desaturase 1 (SCD-1) is a key regulator of lipid metabolism and its activity can be estimated by dividing the FA product by its precursor measured in blood or other tissues. The primary aim of this study was to investigate the effect of low-dose developmental BPA exposure on tissue-specific FA composition including estimated SCD-1 activity, studied in 5- and 52-week (wk)-old Fischer 344 (F344) rat offspring. Pregnant F344 rats were exposed to BPA via their drinking water corresponding to 0: [CTRL], 0.5: [BPA0.5], or 50 µg/kg BW/day: [BPA50], from gestational day 3.5 until postnatal day 22. BPA0.5 increased SCD-16 (estimated as the 16:1n-7/16:0 ratio) and SCD-18 (estimated as the 18:1n-9/18:0 ratio) indices in inguinal white adipose tissue triglycerides (iWAT-TG) and in plasma cholesterol esters (PL-CE), respectively, in 5-wk-old male offspring. In addition, BPA0.5 altered the FA composition in male offspring, e.g. by decreasing levels of the essential polyunsaturated FA linoleic acid (18:2n-6) in iWAT-and liver-TG. No differences were observed regarding the studied FAs in 52-wk-old offspring, although a slightly increased BW was observed in 52-wk-old female offspring. Low-dose developmental BPA exposure increased SCD-16 in iWAT-TG and SCD-18 in PL-CE of male offspring, which may reflect higher SCD-1 activity in these tissues. Altered desaturation activity and signs of altered FA composition are novel findings that may indicate insulin resistance in the rat offspring. These aforementioned results, together with the observed increased BW, adds to previously published data demonstrating that BPA can act as a metabolism disrupting chemical. Copyright © 2018 The Authors. Published by

  4. Tolerance of aged Fischer 344 rats against chlordecone-amplified carbon tetrachloride toxicity.

    PubMed

    Murali, B; Korrapati, M C; Warbritton, Alan; Latendresse, John R; Mehendale, Harihara M

    2004-06-01

    We have investigated the effects of chlordecone 1(CD)+CCl4 combination in adult (3 months), middle aged (14 months), and old aged (24 months) male Fischer 344 (F344) rats. After a non-toxic dietary regimen of CD (10 ppm) or normal powdered diet for 15 days, rats received a single non-toxic dose of CCl4 (100 microl/kg, i.p., 1:4 in corn oil) or corn oil (500 microl/kg, i.p.) alone on day 16. Liver injury was assessed by plasma ALT, AST, and histopathology during a time course of 0-96 h. Liver tissue repair was measured by [3H-CH3]-thymidine (3H-T) incorporation into hepatic nuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry. Hepatomicrosomal CYP2E1 protein, enzyme activity, and covalent binding of 14CCl4-derived radiolabel were measured in normal and CD fed rats. Exposure to CCl4 alone caused modest liver injury only in 14- and 24-month-old rats but neither progression of injury nor mortality. The CD+CCl4 combination led to 100% mortality in 3-month-old rats by 72 h, whereas none of the 14- and 24-month-old rats died. Both 3- and 14-month-old rats exposed to CD+Cl4 had identical liver injury up to 36 h indicating that bioactivation-mediated CCl4 injury was the same in the two age groups. Thereafter, liver injury escalated only in 3-month-old while it declined in 14-month-old rats. In 24-month-old rats initial liver injury at 6 h was similar to the 3- and 14-month-old rats and thereafter did not develop to the level of the other two age groups, recovering from injury by 96 h as in the 14-month-old rats. Neither hepatomicrosomal CYP2E1 protein nor the associated p-nitrophenol hydroxylase activity or covalent binding of 14CCl4-derived radiolabel to liver tissue differed between the age groups or diet regimens 2 h after the administration of 14CCl4. Compensatory liver tissue repair (3H-T, PCNA) was prompt and robust soon after CCl4 liver injury in the 14- and 24-month-old rats. In stark contrast, in the 3-month-old rats it failed allowing

  5. Delta Vision, Delta Voices: The Mississippi Delta Beyond 2000

    DOT National Transportation Integrated Search

    2000-05-10

    This Report has taken its guidance from a single overriding goal: To recognize the enormous natural, capital, and cultural resources of the Delta, and to enable all of the Delta's citizens to participate as full and successful partners in America's s...

  6. Prediction of Endocrine System Affectation in Fisher 344 Rats by Food Intake Exposed with Malathion, Applying Naïve Bayes Classifier and Genetic Algorithms

    PubMed Central

    Mora, Juan David Sandino; Hurtado, Darío Amaya; Sandoval, Olga Lucía Ramos

    2016-01-01

    Background: Reported cases of uncontrolled use of pesticides and its produced effects by direct or indirect exposition, represent a high risk for human health. Therefore, in this paper, it is shown the results of the development and execution of an algorithm that predicts the possible effects in endocrine system in Fisher 344 (F344) rats, occasioned by ingestion of malathion. Methods: It was referred to ToxRefDB database in which different case studies in F344 rats exposed to malathion were collected. The experimental data were processed using Naïve Bayes (NB) machine learning classifier, which was subsequently optimized using genetic algorithms (GAs). The model was executed in an application with a graphical user interface programmed in C#. Results: There was a tendency to suffer bigger alterations, increasing levels in the parathyroid gland in dosages between 4 and 5 mg/kg/day, in contrast to the thyroid gland for doses between 739 and 868 mg/kg/day. It was showed a greater resistance for females to contract effects on the endocrine system by the ingestion of malathion. Females were more susceptible to suffer alterations in the pituitary gland with exposure times between 3 and 6 months. Conclusions: The prediction model based on NB classifiers allowed to analyze all the possible combinations of the studied variables and improving its accuracy using GAs. Excepting the pituitary gland, females demonstrated better resistance to contract effects by increasing levels on the rest of endocrine system glands. PMID:27833725

  7. Prediction of Endocrine System Affectation in Fisher 344 Rats by Food Intake Exposed with Malathion, Applying Naïve Bayes Classifier and Genetic Algorithms.

    PubMed

    Mora, Juan David Sandino; Hurtado, Darío Amaya; Sandoval, Olga Lucía Ramos

    2016-01-01

    Reported cases of uncontrolled use of pesticides and its produced effects by direct or indirect exposition, represent a high risk for human health. Therefore, in this paper, it is shown the results of the development and execution of an algorithm that predicts the possible effects in endocrine system in Fisher 344 (F344) rats, occasioned by ingestion of malathion. It was referred to ToxRefDB database in which different case studies in F344 rats exposed to malathion were collected. The experimental data were processed using Naïve Bayes (NB) machine learning classifier, which was subsequently optimized using genetic algorithms (GAs). The model was executed in an application with a graphical user interface programmed in C#. There was a tendency to suffer bigger alterations, increasing levels in the parathyroid gland in dosages between 4 and 5 mg/kg/day, in contrast to the thyroid gland for doses between 739 and 868 mg/kg/day. It was showed a greater resistance for females to contract effects on the endocrine system by the ingestion of malathion. Females were more susceptible to suffer alterations in the pituitary gland with exposure times between 3 and 6 months. The prediction model based on NB classifiers allowed to analyze all the possible combinations of the studied variables and improving its accuracy using GAs. Excepting the pituitary gland, females demonstrated better resistance to contract effects by increasing levels on the rest of endocrine system glands.

  8. Liquefaction potential of Nile delta, Egypt

    NASA Astrophysics Data System (ADS)

    Fergany, Elsayed; Omar, Khaled

    2017-06-01

    Understanding how sedimentary basins respond to seismic-wave energy generated by earthquake events is a significant concern for seismic-hazard estimation and risk analysis. The main goal of this study is assessing the vulnerability index, Kg, as an indicator for liquefaction potential sites in the Nile delta basin based on the microtremor measurements. Horizontal to Vertical spectral ratio analyses (HVSR) of ambient noise data, which was conducted in 2006 at 120 sites covering the Nile delta from south to north were reprocessed using Geopsy software. HVSR factors of amplification, A, and fundamental frequency, F, were calculated and Kg was estimated for each measurement. The Kg value varies widely from south toward north delta and the potential liquefaction places were estimated. The higher vulnerability indices are associated with sites located in southern part of the Nile delta and close to the branches of Nile River. The HVSR factors were correlated with geologic setting of the Nile delta and show good correlations with the sediment thickness and subsurface stratigraphic boundaries. However, we note that sites located in areas that have greatest percentage of sand also yielded relatively high Kg values with respect to sites in areas where clay is abundant. We concluded that any earthquake with ground acceleration more than 50 gal at hard rock can cause a perceived deformation of sandy sediments and liquefaction can take place in the weak zones of Kg ≥ 20. The worst potential liquefaction zones (Kg > 30) are frequently joined to the Damietta and Rosetta Nile River branches and south Delta where relatively coarser sand exists. The HVSR technique is a very sensitive tool for lithological stratigraphy variations in two dimensions and varying liquefaction susceptibility.

  9. Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks.

    PubMed

    Morgan, Daniel L; Little, Peter B; Herr, David W; Moser, Virginia C; Collins, Bradley; Herbert, Ronald; Johnson, G Allan; Maronpot, Robert R; Harry, G Jean; Sills, Robert C

    2004-10-15

    Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N3, P4, N4, and N5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree and

  10. 5 CFR 9901.344 - Other performance payments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... RELATIONS SYSTEMS (DEPARTMENT OF DEFENSE-OFFICE OF PERSONNEL MANAGEMENT) DEPARTMENT OF DEFENSE NATIONAL SECURITY PERSONNEL SYSTEM (NSPS) Pay and Pay Administration Performance-Based Pay § 9901.344 Other... officials may make other performance payments to— (1) Reward extraordinary individual performance, as...

  11. New science, old convictions − Texas Senate Bill 344: identifying further necessary reform in forensic science

    PubMed Central

    Soni, Naina

    2015-01-01

    In June 2013, Texas Senate Bill 344 (SB 344) was signed into law after strong Innocence Project support. SB 344 has since transformed the Texan judicial landscape. Known as the ‘Junk Science Writ’, SB 344 enables the court to grant habeas corpus relief based on scientific evidence that ‘(1) was not available to be offered by a convicted person at the convicted person's trial; or (2) contradicts scientific evidence relied on by the state at trial’. Inmates, such as the ‘San Antonio Four’, whose convictions were based upon what is now considered ‘faulty’ medical and forensic testimony, have been released under SB 344. Yet, science, as a field dependent on innovation, is inherently prone to debunking the scientific and forensic methods the law has relied upon to convict individuals. This commentary identifies policy behind SB 344, how SB 344 may influence the perception of science in the courtroom, and how ‘junk science’ is defined and/or limited. Furthermore, this commentary concludes that to achieve justice in the legal system through habeas relief based on ‘junk science’, it is necessary to revitalize and standardize forensic science. PMID:27774192

  12. Electronic Structure of TlBa2CaCu2O(7-Delta)

    NASA Technical Reports Server (NTRS)

    Vasquez, R. P.; Novikov, D. L.; Freeman, A. J.; Siegal, M. P.

    1997-01-01

    The core levels of TlBa2CaCu2O(7-delta) (Tl-1212) epitaxial films have been measured with X-ray photoelectron spectroscopy (XPS). The valence electronic structure has been determined using the full-potential linear muffin-tin-orbital band-structure method and measured with XPS. The calculations show that a van Hove singularity (VHS) lies above the Fermi level (E(sub F)) for the stoichiometric compound (delta = 0.5), while for 50% oxygen vacancies in the Tl-O layer (delta = 0.5) E(sub F) is in close proximity to the VHS. Samples annealed in nitrogen (to reduce the hole overdoping by the removal of oxygen) exhibit higher core-level binding energies and a higher T(sub c), consistent with a shift of E(sub F) closer to the VHS. Comparisons are made to the core levels and valence bands of Tl2Ba2CaCu2O(8 + delta)(Tl-2212) and HgBa2CaCu2O)6 + delta) (Hg- 1212). The similarity of the Cu 2p(sub 3/2) spectra for Tl-1212 and Tl-2212 indicates that the number of Tl-O layers has little effect on the Cu-O bonding. However, the Tl-1212 and Hg-1212 Cu 2p(sub 3/2) signals exhibit differences which suggest that the replacement of T(sup 3+) with Hg(sup 2+) results in a decrease in the O 2p right arrow Cu 3d charge-transfer energy and differences in the probabilities of planar vs apical oxygen charge transfer and/or Zhang-Rice singlet-state formation. Differences between the Tl-1212 and the Tl-2212 and Hg-1212 measured valence bands are consistent with the calculated Cu 3d and (Tl,Hg) 6s/5d partial densities of states.

  13. Confirmation of Pig-a mutation in flow cytometry-identified CD48-deficient T-lymphocytes from F344 rats.

    PubMed

    Revollo, Javier; Pearce, Mason G; Petibone, Dayton M; Mittelstaedt, Roberta A; Dobrovolsky, Vasily N

    2015-05-01

    The Pig-a assay is used for monitoring somatic cell mutation in laboratory animals and humans. The assay detects haematopoietic cells deficient in glycosylphosphatidylinositol (GPI)-anchored protein surface markers using flow cytometry. However, given that synthesis of the protein markers (and the expression of their genes) is independent of the expression of the X-linked Pig-a gene and the function of its enzyme product, the deficiency of markers at the surface of the cells may be caused by a number of events (e.g. by mutation or epigenetic silencing in the marker gene itself or in any of about two dozen autosomal genes involved in the synthesis of GPI). Here we provide direct evidence that the deficiency of the GPI-anchored surface marker CD48 in rat T-cells is accompanied by mutation in the endogenous X-linked Pig-a gene. We treated male F344 rats with N-ethyl-N-nitrosourea (ENU), and established colonies from flow cytometry-identified and sorted CD48-deficient spleen T-lymphocytes. Molecular analysis confirmed that the expanded sorted cells have mutations in the Pig-a gene. The spectrum of Pig-a mutation in our model was consistent with the spectrum of ENU-induced mutation determined in other in vivo models, mostly base-pair substitutions at A:T with the mutated T on the non-transcribed strand of Pig-a genomic DNA. We also used next generation sequencing to derive a similar mutational spectrum from a pool of 64 clones developed from flow-sorted CD48-deficient lymphocytes. Our findings confirm that Pig-a assays detect what they are designed to detect-gene mutation in the Pig-a gene. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344

    PubMed Central

    Manevich, Yefim; Reyes, Leticia; Britten, Carolyn D.; Townsend, Danyelle M.

    2016-01-01

    ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug-sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. PMID:27255112

  15. Missense variations in the cystic fibrosis gene: Heteroduplex formation in the F508C mutation

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

    Macek, M. Jr.; Ladanyi, L.; Buerger, J.

    1992-11-01

    Kobayashi et al. (1990) have described missense variations in the conserved region of exon 10 of the cystic fibrosis (CF) transmembrane conductance regulator gene. In their paper, two [Delta]F508/F508C compound heterozygous individuals were reported. Clinical and epithelial physiological studies in both cases were normal, suggesting that the substitution of cysteine for phenylalanine at position 508, the F508C mutation, is benign. However, Kerem et al. reported a patient with this substitution who had typical symptoms of CF. In routine [Delta]F508 mutation screening by visualization of the 3-bp deletion on a 12% polyacrylamide gel the authors detected an abnormal heteroduplex in themore » father of a CF patient of German origin. Subsequent direct sequencing of the PCR product confirmed that this clinically normal father is a compound heterozygote for the [Delta]F508/F508C mutations. This heteroduplex is slightly different from the usual heteroduplex in [Delta]F508/F508C heteroduplex was not published, it is likely that similar cases can be overseen during the widely performed [Delta]F508 mutation screening by PAGE. Detection of more cases, such as the one presented here, together with careful, standardized clinical examination of the proband, would be valuable to verify the nature of this mutation. 4 refs., 1 fig.« less

  16. NTP technical report on the toxicity studies of Castor Oil (CAS No. 8001-79-4) in F344/N Rats and B6C3F1 Mice (Dosed Feed Studies).

    PubMed

    Irwin, R

    1992-03-01

    Castor oil is a natural oil derived from the seeds of the castor bean, Ricinus communis. It is comprised largely of triglycerides with a high ricinolin content. Toxicity studies with castor oil were performed by incorporating the material at concentrations as high as 10% in diets given to F344/N rats and B6C3F1 mice of both sexes for 13 weeks. Genetic toxicity studies also were performed and were negative for mutation induction in Salmonella typhimurium, for induction of sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells, and for induction of micronuclei in the peripheral blood erythrocytes of mice evaluated at the end of the 13-week studies. Exposure to castor oil at dietary concentrations as high as 10% in 13-week studies did not affect survival or body weight gains of rats or mice (10 per sex and dose). There were no biologically significant effects noted in hematologic analyses in rats. Mild increases in total bile acids and in serum alkaline phosphatase were noted at various times during the studies in rats receiving the higher dietary concentrations of castor oil. Liver weights were increased in male rats receiving the 10% dietary concentration and in male and female mice receiving diets containing 5% or 10% castor oil. However, there were no histopathologic lesions associated with these liver changes, nor were there any compound-related morphologic changes in any organ in rats or mice. No significant changes were noted in a screening for male reproductive endpoints, including sperm count and motility, and no changes were observed in the length of estrous cycles of rats or mice given diets containing castor oil. Thus, no significant adverse effects of castor oil administration were noted in these studies. Synonyms: Ricinus Oil, oil of Palma Christi, tangantangan oil, phorboyl, Neoloid.

  17. 32 CFR 344.4 - Responsibilities and functions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) ORGANIZATIONAL CHARTERS ASSISTANT SECRETARY OF DEFENSE FOR RESERVE AFFAIRS (ASD(RA)) § 344.4 Responsibilities and... Deputy Secretary of Defense for Reserve component matters in the Department of Defense. The ASD(RA) is... capacity, the ASD(RA) shall: (a) Develop policies, conduct analyses, provide advice, and make...

  18. Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344.

    PubMed

    Manevich, Yefim; Reyes, Leticia; Britten, Carolyn D; Townsend, Danyelle M; Tew, Kenneth D

    2016-08-01

    ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug-sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Influence of different organic fertilizers on quality parameters and the delta(15)N, delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of orange fruit (Citrus sinensis L. Osbeck).

    PubMed

    Rapisarda, Paolo; Camin, Federica; Fabroni, Simona; Perini, Matteo; Torrisi, Biagio; Intrigliolo, Francesco

    2010-03-24

    To investigate the influence of different types of fertilizers on quality parameters, N-containing compounds, and the delta(15)N, delta(13)C, delta(2)H, delta (34)S, and delta(18)O values of citrus fruit, a study was performed on the orange fruit cv. 'Valencia late' (Citrus sinensis L. Osbeck), which was harvested in four plots (three organic and one conventional) located on the same farm. The results demonstrated that different types of organic fertilizers containing the same amount of nitrogen did not effect important changes in orange fruit quality parameters. The levels of total N and N-containing compounds such as synephrine in fruit juice were not statistically different among the different treatments. The delta(15)N values of orange fruit grown under fertilizer derived from animal origin as well as from vegetable compost were statistically higher than those grown with mineral fertilizer. Therefore, delta(15)N values can be used as an indicator of citrus fertilization management (organic or conventional), because even when applied organic fertilizers are of different origins, the natural abundance of (15)N in organic citrus fruit remains higher than in conventional ones. These treatments also did not effect differences in the delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of fruit.

  20. A Carcinogenicity Bioassay of Isobutyl 2-Cyanoacrylate (IBC) in Fischer- 344 Rats -- One-Year Interim Sacrifice Report. Volume 2. Part 2

    DTIC Science & Technology

    1988-03-01

    Hepatocellular degeneration and loss may accompany this change. Minimnal to severe 3 foci- minimal. BILE DUCT HYPERPLASIA Aging F344 rats frequently have foci...may or may not ensue. Score .Scoring Bile Duct Hyperplasia ".’-’."Score 1 1 to 3 portal areas have hyperplastic bile (trace) ducts. 2 4 to 9 portal...sclerosis are present. 4 Pericholangiolar fibrosis is from moderate to (marked) severe, with from mild to severe sclerosis in addition to hyperplasia

  1. Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.

    PubMed

    Behrendt, Patrick; Buchenauer, Tobias; Horn, Rüdiger; Brabant, Georg; Jacobs, Roland; Bode, Felix; Stephan, Michael; Nave, Heike

    2010-08-01

    The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin. Immune cell distribution in blood (by FACS analysis) and tissues (NK cells in spleen and liver, immunohistologically) as well as pro-inflammatory cytokines (IL-6, TNF-α; by flow cytometry) were investigated in 28 normal weight and 28 dio rats (n = 4-6/group). Pro-inflammatory cytokines were increased 3-fold for IL-6 and 7-fold for TNF-α in obese animals. Higher numbers of blood monocytes and NK cells were found in obese as compared to normal weight animals. In dio rats challenged with leptin and MADB106 tumor cells, monocyte numbers were decreased as compared to the obese control animals. Immunohistochemistry revealed an altered NK cell distribution in a compartment-, treatment-, and bodyweight-specific manner. In conclusion, our data reveal a distinct distribution pattern of monocytes and NK cells in dio rats as compared to normal weight littermates and an additional modulatory effect of a leptin- and MADB106 tumor cell challenge.

  2. [CSF enzyme activities in patients with head injury--especially on GOT, GPT, LDH, and CPK (AUTHOR'S TRANSL)].

    PubMed

    Nakamura, H; Mizuno, T; Kawamura, K; Kamino, T

    1976-08-01

    In our studies on patients with head injury, it was noted that there are some correlations between their clinical courses and the urinary excretion of creatine (cr), creatinine (Crn), 17-ketosteroid and 17-hydroxycorticosteroid. We observed the high urinary excretion of Cr in patients with severe head injury while almost negative in a mild case. We reported those facts in 1974. Also noted in patients with head injury is the relationship between the enzyme-activities (GOT, GPT, LDH and CPK) in the cerebrospinal fluid and their clinical courses. In this paper, we reported 34 cases of head injured patients (simple type: 2, concussion: 9, contusion: 8, acute intracranial hematoma: 7 and chronic intra-cranial hematoma: 8). The control values of CSF enzyme-activities were determined in these 14 cases (simple head injury, whip-lash injury and osteoma of the skull) as GOT less that 15, GPT less than 7, LDH less than 12 and CPK less than 8 units. In the moderate cases, a slight increase in activities of 4 enzymes in CSF were observed, while in severe or comatose cases, the enzyme-activities (especially LDH and CPK) were greater than in the controls. In the dead cases these values were five times as high as the normal case. In the patients recovering from a serious stage, these activities decreased to normal. High CSF enzyme-levels tend to indicate a poor prognosis and low levels a favorable progrosis. In the patients with a significant elevation of CSF enzymes, a high urinary excretion of Cr [normal range: 0-150 (ca. 50)mg/day] was often observed. There was no apparent correlation between the enzyme level in CSF and that in serum and the increase or decrease of these 4 enzymes are not always proprotionate with each other. As reported by Green (1958) and Lending (1961), cerebral cell necrosis and increased permeability of BLB, BBB or cerebral cell membrane can be related to the increase of enzymeactivities. With these observations, it can be considered that severe head

  3. Growth laws for sub-delta crevasses in the Mississippi River Delta

    NASA Astrophysics Data System (ADS)

    Yocum, T. A.; Georgiou, I. Y.; Straub, K. M.

    2017-12-01

    River deltas are threatened by environmental change, including subsidence, global sea level rise, reduced sediment inputs and other local factors. In the Mississippi River Delta (MRD) these impacts are exemplified, and have led to proposed solutions to build land that include sediment diversions to reinitiate the delta cycle. Deltas were studied extensively using numerical models, theoretical and conceptual frameworks, empirical scaling relationships, laboratory models and field observations. But predicting the future of deltas relies on field observations where for most deltas data are still lacking. Moreover, empirical and theoretical scaling laws may be influenced by the data used to develop them, while laboratory deltas may be influenced by scaling issues. Anthropogenic crevasses in the MRD are large enough to overcome limitations of laboratory deltas, and small enough to allow for rapid channel and wetland development, providing an ideal setting to investigate delta development mechanics. Here we assessed growth laws of sub-delta crevasses (SDC) in the MRD, in two experimental laboratory deltas (LD - weakly and strongly cohesive) and compared them to river dominated deltas worldwide. Channel and delta geometry metrics for each system were obtained using geospatial tools, bathymetric datasets, sediment size, and hydrodynamic observations. Results show that SDC follow growth laws similar to large river dominated deltas, with the exception of some that exhibit anomalous behavior with respect to the frequency and distance to a bifurcation and the fraction of wetted delta shoreline (allometry metrics). Most SDC exhibit a systematic decrease of non-dimensional channel geometries with increased bifurcation order, indicating that channels are adjusting to decreased flow after bifurcations occur, and exhibit linear trends for land allometry and width-depth ratio, although geometries decrease more rapidly per bifurcation order. Measured distance to bifurcations in SDC

  4. Developing a Truly Global Delta Database to Assess Delta Morphology and Morphodynamics

    NASA Astrophysics Data System (ADS)

    Caldwell, R. L.; Edmonds, D. A.; Baumgardner, S. E.; Whaling, A.

    2015-12-01

    Delta morphology reflects the interplay of various environmental parameters, though these relationships have only been tested on small datasets with 30-50 deltas. These datasets are biased toward the largest deltas, which typically have compound morphologies, form on passive margins, and may not be representative of the full breadth in delta morphology. With the goal of building more robust predictions of delta morphology to enhance hazard mitigation and resiliency planning, we have developed a truly global delta database including every delta on the world's marine coastlines. Using Google Earth imagery, we first identified all fluvial river mouths (≥ 50 m wide) connected to an upstream catchment. Deltas are defined geomorphically as river mouths that split into two or more active or relict distributary channels, end in a depositional protrusion from the shoreline, or do both. In our database we identified 5,801 river mouths, and 1,426 of those coastal rivers (~25%) have a geomorphic delta. ~75% of deltas exhibit an active or relict distributary network, while the remaining ~25% are single channel deltas with a basinward protrusion. Preliminary morphometric analysis (ratio of shore-parallel width, W, to shore-perpendicular length, L) on a subset of 159 deltas suggests W:L values range from 0.52 (elongate) to 23.6 (broad/cuspate). The median W:L value is 2.68, suggesting the majority of deltas are roughly semi-circular (W:L = 2), and the distribution is heavily skewed to the broad/cuspate deltas (~28% are >4 times wider than they are long). Preliminary comparison to downstream significant wave height data shows that the 'wider' deltas relate to higher wave heights (R2 = 0.42), though the data are scattered. Ultimately, the database will include additional measured morphometrics, including number of channel mouths and delta area, and morphodynamic data derived from serial Landsat imagery.

  5. 31 CFR 344.8 - What other provisions apply to subscriptions for Demand Deposit securities?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false What other provisions apply to subscriptions for Demand Deposit securities? 344.8 Section 344.8 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC...

  6. 31 CFR 344.8 - What other provisions apply to subscriptions for Demand Deposit securities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What other provisions apply to subscriptions for Demand Deposit securities? 344.8 Section 344.8 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC...

  7. 31 CFR 344.8 - What other provisions apply to subscriptions for Demand Deposit securities?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false What other provisions apply to subscriptions for Demand Deposit securities? 344.8 Section 344.8 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE FISCAL...

  8. 31 CFR 344.8 - What other provisions apply to subscriptions for Demand Deposit securities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What other provisions apply to subscriptions for Demand Deposit securities? 344.8 Section 344.8 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC...

  9. Brain Region-Specific Expression of Genes Mapped within Quantitative Trait Loci for Behavioral Responsiveness to Acute Stress in Fisher 344 and Wistar Kyoto Male Rats (Postprint)

    DTIC Science & Technology

    2018-03-12

    Integrative Genomics Viewer (Broad Institute, Cambridge, Massachusetts), we iden- tified the coding sequence variations between the F344 and WKY... abnormalities and disturbances in brain metabolism resem- bling those in depressive states [74]. Ifna2 is also known to induce memory, concentration, and...Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over Six Years. Clinical psychological science

  10. NTP Toxicology and Carcinogenesis Studies of Cobalt Sulfate Heptahydrate (CAS No. 10026-24-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    PubMed

    1998-08-01

    Cobalt sulfate is used in the electroplating and electro chemical industries. It is also used as a coloring agent for ceramics and as a drying agent in inks, paints, varnishes, and linoleum. Cobalt sulfate may be added to animal feed as a mineral supplement and has been used as a top dressing on pasture lands. Cobalt sulfate was nominated by the National Cancer Institute for study based on a lack of information on the toxicity of soluble salts. Male and female F344/N rats and B6C3F1 mice were exposed to cobalt sulfate heptahydrate (approximately 99% pure) by inhalation for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium. The results of prechronic inhalation toxicity studies were reported previously (Bucher et al., 1990; NTP, 1991). 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate heptahydrate 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights Survival of exposed males and females was similar to that of the chamber controls. Mean body weights of exposed male and female rats were similar to those of the chamber controls throughout the study. Pathology Findings The incidences and severities of proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were markedly greater in all exposed groups of male and female rats than in the chamber controls. The incidences of alveolar epithelial hyperplasia in all groups of exposed males and in females exposed to 3.0 mg/m3 were significantly greater than those in the chamber control groups, as were the incidences of squamous metaplasia in 1.0 mg/m3 females and atypical alveolar epithelial hyperplasia in 3.0 mg/m3 females. In 3.0 mg/m3 males, the combined incidence of alveolar/ bronchiolar neoplasms (adenoma and/or carcinoma) was significantly greater than in the chamber controls. In female rats exposed to 1.0 or 3.0 mg/m3, the incidences of

  11. Pulmonary and pleural responses in Fischer 344 rats following short-term inhalation of a synthetic vitreous fiber. II. Pathobiologic responses.

    PubMed

    Gelzleichter, T R; Bermudez, E; Mangum, J B; Wong, B A; Moss, O R; Everitt, J I

    1996-03-01

    The pleura is a target site for toxic effects induced by a variety of fibrous particulates, including both natural mineral and man-made vitreous fibers. We examined selected cytological and biochemical indicators of inflammation in both the pleural compartment and pulmonary parenchyma in F344 rats following inhalation of RCF-1, a kaolin-based ceramic fiber. Male F344 rats were exposed by inhalation to 89 mg/m3 (2645 WHO fibers/cc) RCF-1 6 hr/day for 5 consecutive days. In lung parenchyma, cytological and biochemical inflammatory responses occurred rapidly following exposure. In contrast, pleural responses were delayed in onset and of a much smaller magnitude than those observed in lung. At both Day 1 and Day 28 postexposure, increased quantities of lactate dehydrogenase, N-acetyl glucosaminidase, alkaline phosphatase, albumin, and neutrophils were present in bronchoalveolar lavage fluid. These responses were attenuated at the latter time point. No significant responses were detected in pleural lavage fluid until 28 days following exposure, at which time elevated numbers of macrophages and eosinophils, but not neutrophils, were observed. Increased albumin and fibronectin were also observed in PLF at this latter time point. These findings demonstrate that the onset of pleural and pulmonary responses following inhalation of RCF-1 are temporally separated and that pleural injury may increase in severity with time following exposure. The increase in severity of pleural inflammation found in the postexposure period cannot be readily explained by fiber translocation.

  12. Quark-hadron duality and parity violating asymmetry of electroweak reactions in the {delta} region

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

    Matsui, K.; Sato, T.; Lee, T.-S.H.

    2005-08-01

    A dynamical model [T. Sato and T.-S. H. Lee, Phys. Rev. C 54, 2660 (1996); 63, 055201 (2001); T. Sato, D. Uno, and T.-S. H. Lee, ibid. 67, 065201 (2003)] of electroweak pion production reactions in the {delta}(1232) region has been extended to include the neutral current contributions for examining the local quark-hadron duality in neutrino-induced reactions and for investigating how the axial N-{delta} form factor can be determined by the parity violating asymmetry of N(e{sup {yields}},e{sup '}) reactions. We first show that the recent data of (e,e{sup '}) structure functions F{sub 1} and F{sub 2}, which exhibit the quark-hadronmore » duality, are in good agreement with our predictions. For possible future experimental tests, we then predict that the structure functions F{sub 1},F{sub 2}, and F{sub 3} for ({nu},e) and ({nu},{nu}{sup '}) processes also show the similar quark-hadron duality. The spin-dependent structure functions g{sub 1} and g{sub 2} of (e,e{sup '}) have also been calculated from our model. It is found that the local quark-hadron duality is not seen in the calculated g{sub 1} and g{sub 2}, while our results for g{sub 1} and some polarization observables associated with the exclusive p(e{sup {yields}},e{sup '}{pi}) and p{sup {yields}}(e{sup {yields}},e{sup '}{pi}) reactions are in reasonably good agreement with the recent data. In the study of parity violating asymmetry A of N(e{sup {yields}},e{sup '}) reactions, the relative importance between the nonresonant mechanisms and the {delta} excitation is investigated by taking into account the unitarity condition. Predictions are made for using the data of A to test the axial N-{delta} form factors determined previously in the studies of N({nu}{sub {mu}},{mu}{sup -}{pi}) reactions. The predicted asymmetry A are also compared with the parton model predictions for future experimental investigations of quark-hadron duality.« less

  13. NTP Toxicology and Carcinogenesis Studies of 1,4-Dichlorobenzene (CAS No. 106-46-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1987-01-01

    1,4-Dichlorobenzene is commonly used as a space deodorant in toilets and for moth control. Because of its extensive production and use and the absence of carcinogenicity data, carcinogenesis studies were conducted by administering 1,4-dichlorobenzene (greater than 99% pure) in corn oil by gavage (5 days per week) to male F344/N rats at doses of 0, 150, or 300 mg/kg and to female F344/N rats and male and female B6C3F1 mice at doses of 0, 300, or 600 mg/kg per day for 2 years (50 animals per group). Fourteen-day and 13-week studies were performed to characterize the toxicity, identify affected sites, and set doses for the 2-year studies. Clinical chemistry and hematologic studies were performed during the 13-week studies to assess the effects of 1,4-dichlorobenzene on the liver, kidney, and hematopoietic system and to assess whether the compound produced hepatic porphyria. Two 13-week studies were performed in rats. In the first study, rats were dosed with 300-1,500 mg/kg 1,4-dichlorobenzene. Because histologic changes were observed in the kidney of male rats at all doses, a second 13-week study was performed at doses of 38-600 mg/kg. In the 13-week studies, survival was decreased in groups of male rats given 1,200 or 1,500 mg/kg and in female rats given 1,500 mg/kg. Weight gain was decreased in male rats receiving doses of 300 mg/kg or more and in female rats given doses of 1,200 or 1,500 mg/kg. Doses of 1,200 or 1,500 mg/kg produced degeneration and necrosis of hepatocytes, hypoplasia of the bone marrow, lymphoid depletion of the spleen and thymus, and epithelial necrosis of the nasal turbinates in male and female rats. Renal tubular cell degeneration was observed in male rats receiving 300 mg/kg or more in the first study, but only slight changes were seen at 300 mg/kg in the second study. Liver weight to brain weight ratios were increased at 900 mg/kg or more for both male and female rats. The kidney weight to brain weight ratio was increased in male rats

  14. 14-Week toxicity and cell proliferation of methyleugenol administered by gavage to F344 rats and B6C3F1 mice.

    PubMed

    Abdo, K M; Cunningham, M L; Snell, M L; Herbert, R A; Travlos, G S; Eldridge, S R; Bucher, J R

    2001-04-01

    Methyleugenol, a food flavor and fragrance agent, was tested for toxicity in male and female F344/N rats and B6C3F1 mice. Groups of 10 males and 10 females per sex per species were administered 0, 10, 30, 100, 300 or 1000 mg methyleugenol/kg body weight in 0.5% aqueous methylcellulose by gavage, 5 days per week for 14 weeks. Additional groups of rats and mice of each sex were dosed similarly and used for hematology and clinical chemistry studies. Groups of 10 male and 10 female rats and mice received the vehicle by gavage on the same dosing schedule and served as vehicle controls. For serum gastrin, gastric pH and cell proliferation studies groups of 10 female rats were given 0, 37, 75 or 150 mg/kg, once daily 5 days per week for 30 or 90 days or 300 or 1000 mg/kg for 30 days; male mice were given 0, 9, 18.5, 37, 75, 150 or 300 mg/kg for 30 or 90 days. For the gastrin, pH and cell proliferation studies, groups of 10 female rats and 10 male mice were given the vehicle for 30 or 90 days and served as controls. Methyleugenol administration to rats induced erythrocyte microcytosis and thrombocytosis in male and female rats. It also caused an increase in serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentration, suggesting hepatocellular injury, cholestasis or altered hepatic function. Additionally, methyleugenol induced hypoproteinemia and hypoalbuminemia, evidenced by decreased total protein and albumin concentrations in both male and female rats, suggesting in inefficiency of dietary protein utilization due to methyleugenol-induced toxic effects on the liver and glandular stomach of rats and mice. The increase in gastrin and gastric pH of rats and mice given methyleugenol suggests that gastrin feedback was impaired and resulted in conditions not conducive to protein digestion. In rats, methyleugenol caused an increase in the incidences of hepatocyte cytologic alteration, cytomegaly, Kupffer cell pigmentation, mixed foci of

  15. Holocene evolution of a wave-dominated fan-delta: Godavari delta, India

    NASA Astrophysics Data System (ADS)

    Saito, Y.; Nageswara Rao, K.; Nagakumar, K.; Demudu, G.; Rajawat, A.; Kubo, S.; Li, Z.

    2013-12-01

    The Godavari delta is one of the world's largest wave-dominated deltas. The Godavari River arises in the Western Ghats near the west coast of India and drains an area of about 3.1x10^5 km^2, flowing about 1465 km southeast across the Indian peninsula to the Bay of Bengal. The Godavari delta consists of a gentle seaward slope from its apex (12 m elevation) at Rajahmundry and a coastal beach-ridge plain over a distance of about 75 km and covers ~5200 km^2 as a delta plain. The river splits into two major distributary channels, the Gautami and the Vasishta, at a barrage constructed in the mid-1800s. The coastal environment of the deltaic coast is microtidal (~1 m mean tidal range) and wave-dominated (~1.5 m mean wave height in the June-September SW monsoon season, ~0.8 m in the NE monsoon season). Models of the Holocene evolution of the Godavari delta have changed from a zonal progradation model (e.g. Nageswara Rao & Sadakata, 1993) to a truncated cuspate delta model (Nageswara Rao et al., 2005, 2012). Twelve borehole cores (340 m total length), taken in the coastal delta plain during 2010-2013, yielded more than 100 C-14 dates. Sediment facies and C-14 dates from these and previous cores and remote-sensing data support a new delta evolution model. The Holocene coastal delta plain is divided into two parts by a set of linear beach ridges 12-14 km landward from the present shoreline in the central part of the delta. The location of the main depocenter (lobe) has shifted during the Holocene from 1) the center to 2) the west, 3) east, 4) center, 5) west, and 6) east. The linear beach ridges separate the first three from the last three stages. These lobe shifts are controlled by river channel shifts near the apex. Just as the current linear shoreline of the central part of the delta and the concave-up nearshore topography are the result of coastal erosion of a cuspate delta, the linear beach ridges indicate a former eroded shoreline. An unconformity within the deltaic

  16. Evolution of oil-generative window (OGW) in Niger delta basin

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

    Ejedawe, J.E.; Coker, S.J.L.; Lambert-Aikhionbare, D.O.

    1983-03-01

    Assuming a simple model of delta development involving progradation and uniform subsidence to present depths (rate, 500 m/m.y.; 1640 ft/m.y.), oil-genesis nomographs derived from the TTI method were constructed for various geothermal gradients of the Niger delta (2.2., 2.5., 2.9, 3.6, 4.0, 4.4, and 4.7/sup 0/C/100 m) and utilized in mapping the positions (depth, temperature) of the top of the oil-generative window (OGW) at arbitrarily selected times (40 m.y.B.P., 30 m.y.B.P., 15 m.y.B.P., and the present). About 200 data points were evaluated. During the active subsidence phase, oil generation within any megastructure was initiated at a temperature of 140 tomore » 146/sup 0/C (284 to 294/sup 0/F) and depth of 3000 to 5200 m (9842 to 17,060 ft) within 7 to 11 m.y. after deposition of the potential source rocks. After cessation of subsidence, upward movement of the OGW by 800 to 1600 m (2624 to 5249 ft) was accompanied by a temperature lowering of 23 to 54/sup 0/C (73 to 129/sup 0/F). Lower temperatures produced correspondingly heavier crudes. In some parts of the delta oil generation and expulsion from the lower part of the Agbada Formation predates the cessation of subsidence and structural deformation, while in others it postdates those events. In most parts of the Niger delta, the upper and normally compacted part of the Akata Formation appears to constitute the major source rock.« less

  17. The mitochondrion in bloodstream forms of Trypanosoma brucei is energized by the electrogenic pumping of protons catalysed by the F1F0-ATPase.

    PubMed

    Nolan, D P; Voorheis, H P

    1992-10-01

    Bloodstream forms of Trypanosoma brucei were found to maintain a significant membrane potential across their mitochondrial inner membrane (delta psi m) in addition to a plasma membrane potential (delta psi p). Significantly, the delta psi m was selectively abolished by low concentrations of specific inhibitors of the F1F0-ATPase, such as oligomycin, whereas inhibition of mitochondrial respiration with salicylhydroxamic acid was without effect. Thus, the mitochondrial membrane potential is generated and maintained exclusively by the electrogenic translocation of H+, catalysed by the mitochondrial F1F0-ATPase at the expense of ATP rather than by the mitochondrial electron-transport chain present in T. brucei. Consequently, bloodstream forms of T. brucei cannot engage in oxidative phosphorylation. The mitochondrial membrane potential generated by the mitochondrial F1F0-ATPase in intact trypanosomes was calculated after solving the two-compartment problem for the uptake of the lipophilic cation, methyltriphenylphosphonium (MePh3P+) and was shown to have a value of approximately 150 mV. When the value for the delta psi m is combined with that for the mitochondrial pH gradient (Nolan and Voorheis, 1990), the mitochondrial proton-motive force was calculated to be greater than 190 mV. It seems likely that this mitochondrial proton-motive force serves a role in the directional transport of ions and metabolites across the promitochondrial inner membrane during the bloodstream stage of the life cycle, as well as promoting the import of nuclear-encoded protein into the promitochondrion during the transformation of bloodstream forms into the next stage of the life cycle of T. brucei.

  18. A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.

    PubMed

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Mizuta, Yasuko; Yoshida, Midori; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-04-01

    3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10(-4) mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.

  19. Anaerobic Transformation of Furfural by Methanococcus deltae (Delta)LH

    PubMed Central

    Belay, N.; Boopathy, R.; Voskuilen, G.

    1997-01-01

    Methanococcus deltae (Delta)LH was grown on H(inf2)-CO(inf2) in the presence of various concentrations of furfural. Furfural at higher concentrations, namely, 20 and 25 mM, inhibited growth of this organism. At concentration of 5 and 10 mM, no inhibition of growth was observed. The other methanogens in this study were not inhibited by 10 mM furfural. Among the methanogens tested, M. deltae was capable of transforming furfural, whereas Methanobacterium thermoautotrophicum Marburg, Methanosarcina barkeri 227, Methanococcus thermolithotrophicus, and Methanobrevibacter ruminantium lacked this capability. One hundred percent removal of furfural was observed within 48 h of incubation in M. deltae cultures. The end product observed during furfural metabolism was furfuryl alcohol. An almost stoichiometric amount of furfuryl alcohol was produced by M. deltae. This transformation is likely to be of value in the detoxification of furfural and in its ultimate conversion to methane and CO(inf2) by anaerobic digestion. PMID:16535618

  20. NTP Toxicology and Carcinogenesis Studies of Xylenes (Mixed) (60% m-Xylene, 14% p-Xylene, 9% o-Xylene, and 17% Ethylbenzene) (CAS No. 1330-20-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1986-12-01

    The technical grade of xylenes (mixed) (hereafter termed xylenes) contains the three isomeric forms and ethylbenzene (percentage composition shown above). The annual production for 1985 was approximately 7.4 x 108 gallons. Xylenes is used as a solvent and a cleaning agent and as a degreaser and is a constituent of aviation and automobile fuels. Xylenes is also used in the production of benzoic acid, phthalate anhydride, and isophthalic and terephthalic acids as well as their dimethyl esters. Toxicology and carcinogenesis studies of xylenes were conducted in laboratory animals because a large number of workers are exposed and because the long- term effects of exposure to xylenes were not known. Exposure for the present studies was by gavage in corn oil. In single-administration studies, groups of five F344/N rats and B6C3F1 mice of each sex received 500, 1,000, 2,000, 4,000, or 6,000 mg/kg. Administration of xylenes caused deaths at 6,000 mg/kg in rats and mice of each sex and at 4,000 mg/kg in male rats. In rats, clinical signs observed within 24 hours of dosing at 4,000 mg/kg included prostration, muscular incoordination, and loss of hind limb movement; these effects continued through the second week of observation. Tremors, prone position, and slowed breathing were recorded for mice on day 3, but all mice appeared normal by the end of the 2- week observation period. In 14- day studies, groups of five rats of each sex were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg, and groups of five mice of each sex received 0, 250, 500, 1,000, 2,000, or 4,000 mg/kg. Chemical- related mortality occurred only at 2,000 mg/kg in rats and at 4,000 mg/kg in mice. Rats and mice exhibited shallow breathing and prostration within 48 hours following dosing at 2,000 mg/kg. These signs persisted until day 12 for rats, but no clinical signs were noted during the second week for mice. In 13- week studies, groups of 10 rats of each sex received 0, 62.5, 125, 250, 500, or 1,000 mg

  1. Toxicology and carcinogenesis studies of sodium dichromate dihydrate (Cas No. 7789-12-0) in F344/N rats and B6C3F1 mice (drinking water studies).

    PubMed

    2008-07-01

    Sodium dichromate dihydrate is one of a number of inorganic compounds containing hexavalent chromium (Cr VI) found in drinking water source supplies as a contaminant resulting from various industrial processes including electroplating operations, leather tanning, and textile manufacturing. Because of the lack of adequate experimental data on the toxicity and carcinogenicity of hexavalent chromium ingested orally and because hexavalent chromium has been found in drinking water source supplies, the California Congressional Delegation, the California Environmental Protection Agency, and the California Department of Health Services nominated hexavalent chromium to the National Toxicology Program for study. Results of 3 month toxicity studies in F344/N rats and B6C3F1, BALB/c, and am3-C57BL/6 mice were reported earlier in NTP Toxicity Report 72. In the current study, male and female F344/N rats and B6C3F1 mice were exposed to sodium dichromate dihydrate (greater than 99.7% pure) in drinking water for 2 years. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to drinking water containing 0, 14.3, 57.3, 172, or 516 mg/L sodium dichromate dihydrate (equivalent to 0, 5, 20, 60, or 180 mg/L chromium) for 2 years (equivalent to average daily doses of approximately 0.6, 2.2, 6, or 17 mg sodium dichromate dihydrate/kg body weight for males and 0.7, 2.7, 7, or 20 mg/kg for females). Survival of exposed groups was similar to that of the control groups. Mean body weights of 516 mg/L males and females were less than those of the controls throughout the study. The lower body weights were partly attributed to poor palatability of the dosed water and consequent reductions in water consumption. Water consumption by 172 and 516 mg/L rats was less than that by the controls throughout the study. Exposure to sodium dichromate dihydrate caused a microcytic hypochromic anemia in rats that ameliorated with time. Exposure to sodium dichromate dihydrate resulted in the

  2. Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats

    PubMed Central

    Kwon, Yong Hwan; Kim, Nayoung; Nam, Ryoung Hee; Park, Ji Hyun; Lee, Sun Min; Kim, Sung Kook; Lee, Hye Seung; Kim, Yong Sung; Lee, Dong Ho

    2017-01-01

    The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age. PMID:28045993

  3. NTP Toxicology and Carcinogenesis Studies of Chloroprene (CAS No. 126-99-8) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    PubMed

    1998-09-01

    Chloroprene is used almost exclusively in the manufacture of neoprene (polychloroprene). Chloroprene was chosen for study because it is a high-volume production chemical with limited information on its carcinogenic potential and because it is the 2-chloro analogue of 1,3-butadiene, a potent, multi-species, multi-organ carcinogen. Male and female F344/N rats and B6C3F1 mice were exposed to chloroprene (greater than 96% pure) by inhalation for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, and B6C3F1 mice (bone marrow cells and peripheral blood erythrocytes). 16-Day Study in Rats: Groups of 10 male and 10 female F344/N rats were exposed to 0, 32, 80, 200, or 500 ppm chloroprene by inhalation, 6 hours per day, 5 days per week, for 16 days. Three 500 ppm males died on day 2 or 3 of the study. Mean body weight gains of 200 ppm males and females and 500 ppm females were significantly less than those of the chamber control groups. On the first day of exposure, rats exposed to 500 ppm were hypoactive and unsteady and had rapid shallow breathing. These effects were also observed to some degree in animals exposed to 200 ppm. After the second day of exposure, the effects in these groups worsened, and hemorrhage from the nose was observed. A normocytic, normochromic, responsive anemia; thrombocytopenia; and increases in serum activities of alanine aminotransferase, glutamate dehydrogenase, and sorbitol dehydrogenase occurred on day 4 in 200 ppm females and 500 ppm males. Kidney weights of 80 and 500 ppm females were significantly greater than those of the chamber control group, as were the liver weights of 200 and 500 ppm females. The incidences of minimal to mild olfactory epithelial degeneration of the nose in all exposed groups of males and females were significantly greater than those in the chamber control groups. The incidence of squamous metaplasia of the respiratory epithelium was

  4. Growth laws for delta crevasses in the Mississippi River Delta: observations and modeling

    NASA Astrophysics Data System (ADS)

    Yocum, T. A.; Georgiou, I. Y.

    2016-02-01

    River deltas are accumulations of sedimentary deposits delivered by rivers via a network of distributary channels. Worldwide they are threatened by environmental changes, including subsidence, global sea level rise and a suite of other local factors. In the Mississippi River Delta (MRD) these impacts are exemplified, and have led to proposed solutions to build land that include sediment diversions, thereby reinitiating the delta cycle. While economically efficient, there are too few analogs of small deltas aside from laboratory studies, numerical modeling studies, theoretical approaches, and limited field driven observations. Anthropogenic crevasses in the modern delta are large enough to overcome limitations of laboratory deltas, and small enough to allow for "rapid" channel and wetland development, providing an ideal setting to investigate delta development mechanics. Crevasse metrics were obtained using a combination of geospatial tools, extracting key parameters (bifurcation length and width, channel order and depth) that were non-dimensionalized and compared to river-dominated delta networks previously studied. Analysis showed that most crevasses in the MRD appear to obey delta growth laws and delta allometry relationships, suggesting that crevasses do exhibit similar planform metrics to larger Deltas; the distance to mouth bar versus bifurcation order demonstrated to be a very reasonable first order estimate of delta-top footprint. However, some crevasses exhibited different growth metrics. To better understand the hydrodynamic and geomorphic controls governing crevasse evolution in the MRD, we assess delta dynamics via a suite of field observations and numerical modeling in both well-established and newly constructed crevasses. Our analysis suggests that delta development is affected by the relative influence of external (upstream and downstream) and internal controls on the hydrodynamic and sediment transport patterns in these systems.

  5. DEVELOPMENTAL TOXICITY OF ATRAZINE METABOLITES IN FISCHER 344 RATS

    EPA Science Inventory

    Previously we have shown that atrazine, a commonly used herbicide, causes full-litter resorption (FLR) in Fischer 344 rats at 50 mg/kg. In this study, we tested four atrazine metabolites for their potential to cause FLR and developmental toxicity. Desethylatrazine (DEA), desis...

  6. 42 CFR 486.344 - Condition: Evaluation and management of potential donors and organ placement and recovery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... donors and organ placement and recovery. 486.344 Section 486.344 Public Health CENTERS FOR MEDICARE... Designation and Conditions for Coverage: Organ Procurement Organizations Organ Procurement Organization... placement and recovery. The OPO must have written protocols for donor evaluation and management and organ...

  7. 42 CFR 486.344 - Condition: Evaluation and management of potential donors and organ placement and recovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... donors and organ placement and recovery. 486.344 Section 486.344 Public Health CENTERS FOR MEDICARE... Designation and Conditions for Coverage: Organ Procurement Organizations Organ Procurement Organization... placement and recovery. The OPO must have written protocols for donor evaluation and management and organ...

  8. Photoemission Spectroscopy of Delta- Plutonium: Experimental Review

    NASA Astrophysics Data System (ADS)

    Tobin, J. G.

    2002-03-01

    The electronic structure of Plutonium, particularly delta- Plutonium, remains ill defined and without direct experimental verification. Recently, we have embarked upon a program of study of alpha- and delta- Plutonium, using synchrotron radiation from the Advanced Light Source in Berkeley, CA, USA [1]. This work is set within the context of Plutonium Aging [2] and the complexities of Plutonium Science [3]. The resonant photoemission of delta-plutonium is in partial agreement with an atomic, localized model of resonant photoemission, which would be consistent with a correlated electronic structure. The results of our synchrotron- based studies will be compared with those of recent laboratory- based works [4,5,6]. The talk will conclude with a brief discussion of our plans for the future, such as the performance of spin-resolving and dichroic photoemission measurements of Plutonium [7] and the development of single crystal ultrathin films of Plutonium. This work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48. 1. J. Terry, R.K. Schulze, J.D. Farr, T. Zocco, K. Heinzelman, E. Rotenberg, D.K. Shuh, G. van der Laan, D.A. Arena, and J.G. Tobin, “5f Resonant Photoemission from Plutonium”, UCRL-JC-140782, Surf. Sci. Lett., accepted October 2001. 2. B.D. Wirth, A.J. Schwartz, M.J. Fluss, M.J. Caturla, M.A. Wall, and W.G. Wolfer, MRS Bulletin 26, 679 (2001). 3. S.S. Hecker, MRS Bulletin 26, 667 (2001). 4. T. Gouder, L. Havela, F. Wastin, and J. Rebizant, Europhys. Lett. 55, 705 (2001); MRS Bulletin 26, 684 (2001); Phys. Rev. Lett. 84, 3378 (2000). 5. A.J. Arko, J.J. Joyce, L. Morales, J. Wills, J. Lashley, F. Wastin, and J. Rebizant, Phys. Rev. B 62, 1773 (2000). 6. L.E. Cox, O. Eriksson, and B.R. Cooper, Phys. Rev. B 46, 13571 (1992). 7. J. Tobin, D.A. Arena, B. Chung, P. Roussel, J. Terry, R.K. Schulze, J.D. Farr, T. Zocco, K. Heinzelman, E

  9. 31 CFR 344.11 - How do I redeem a Special Zero Interest Security before maturity?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false How do I redeem a Special Zero... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.11 How do I redeem a Special Zero Interest Security before maturity? Follow the provisions of § 344.6(a...

  10. 31 CFR 344.11 - How do I redeem a Special Zero Interest Security before maturity?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false How do I redeem a Special Zero... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.11 How do I redeem a Special Zero Interest Security before maturity? Follow the provisions of § 344.6(a...

  11. 31 CFR 344.11 - How do I redeem a Special Zero Interest Security before maturity?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false How do I redeem a Special Zero... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.11 How do I redeem a Special Zero Interest Security before maturity? Follow the provisions of § 344.6(a...

  12. 31 CFR 344.11 - How do I redeem a Special Zero Interest Security before maturity?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false How do I redeem a Special Zero... U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.11 How do I redeem a Special Zero Interest Security before maturity? Follow the provisions of § 344.6(a...

  13. 31 CFR 344.11 - How do I redeem a Special Zero Interest Security before maturity?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false How do I redeem a Special Zero... SERVICE U.S. TREASURY SECURITIES-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.11 How do I redeem a Special Zero Interest Security before maturity? Follow the provisions of § 344.6...

  14. NTP 3-month toxicity studies of estragole (CAS No. 140-67-0) administered by gavage to F344/N rats and B6C3F1 mice.

    PubMed

    Bristol, D W

    2011-01-01

    Estragole is a natural organic compound that is used as an additive, flavoring agent, or fragrance in a variety of food, cleaning, and cosmetic products; as an herbal medicine; as an antimicrobial agent against acid-tolerant food microflora; and to produce synthetic anise oil. Estragole was nominated for toxicity testing by the National Institute of Environmental Health Sciences to characterize its toxicity when administered by gavage to F344/N rats and B6C3F1 mice and to determine how similar its effects might be to those of the structurally related compound, methyleugenol. Male and female F344/N rats and B6C3F1 mice were given estragole (greater than 99% pure) in corn oil by gavage for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. Core and special study (rats only) groups of 10 male and 10 female rats and mice were administered 37.5, 75, 150, 300, or 600 mg estragole/kg body weight in corn oil by gavage, 5 days per week. The core study groups were given estragole for 3 months and the special study groups for 30 days. All core study rats survived the 3-month exposure period. Mean body weights of the 300 and 600 mg/kg groups were 73% to 92%, respectively, of those of the vehicle control groups. A staining pattern on the ventral surface anterior to the genitalia beginning at week 9 in the 300 and 600 mg/kg groups was attributed to residue of estragole or metabolites in the urine. Alterations in the erythron related to estragole administration occurred in male and female rats; male rats demonstrated a stronger response. The changes in the erythron were characterized as a microcytic, normochromic, nonresponsive anemia. There were decreases in serum iron concentration in the 300 mg/kg females and 600 mg/kg males and females. The average percent saturation of total iron binding capacity was decreased in the 600 mg/kg males and females. Dose-related increases in platelet counts occurred in most of

  15. Classification of Martian deltas

    NASA Technical Reports Server (NTRS)

    Dehon, R. A.

    1993-01-01

    Water-borne sediments in streams are deposited, upon eventual cessation of flow, either as deltas or as alluvial fans or plains. Deltas and alluvial fans share a common characteristic; both may be described as deposition Al plains at the mouth of a river or stream. A delta is formed where a stream or river deposits its sedimentary load into a standing body of water such as an ocean or lake. An alluvial fan is produced where a stream loses capacity by a greatly decreased gradient. A delta has subaerial and subaqueous components, but an alluvial fan is entirely subaerial. In terrestrial conditions, deltas and alluvial fans are reasonably distinct landforms. The juxtaposition of concomitant features composition and internal structure are sufficiently explicit as to avoid any confusion regarding their proper identification on Mars, the recognition of deltas and their distinction from alluvial fans is made difficult by low resolution imaging. Further, although it may be demonstrated that standing bodies of water existed on the surface of Mars, many of these bodies may have existed for extremely short periods of time (a few days to months); hence, distinctive shoreline features were not developed. Thus, in an attempt to derive a Martian classification of deltas, the inclusion of wholly subaerial deposits may be unavoidable. A simple, broad, morphological classification of Martian deltas, primarily on planimetric shape, includes digitate deltas, fan-shaped deltas, and re-entrant deltas. A fourth, somewhat problematical class includes featureless plains at the end of many valley systems.

  16. Delta Scuti Variables

    NASA Astrophysics Data System (ADS)

    Handler, Gerald

    2009-09-01

    We review recent research on Delta Scuti stars from an observer's viewpoint. First, some signposts helping to find the way through the Delta Scuti jungle are placed. Then, some problems in studying individual pulsators in the framework of asteroseismology are given before a view on how the study of these variables has benefited (or not) from past and present high-precision asteroseismic space missions is presented. Some possible pitfalls in the analysis of data with a large dynamical range in pulsational amplitudes are pointed out, and a strategy to optimize the outcome of asteroseismic studies of Delta Scuti stars is suggested. We continue with some views on ``hybrid'' pulsators and interesting individual High Amplitude Delta Scuti stars, and then take a look on Delta Scuti stars in stellar systems of several different kinds. Recent results on pre-main sequence Delta Scuti stars are discussed as are questions related to the instability strip of these variables. Finally, some remarkable new theoretical results are highlighted before, instead of a set of classical conclusions, questions to be solved in the future, are raised.

  17. Increase of heat-shock protein and induction of gamma/delta T cells in peritoneal exudate of mice after injection of live Fusobacterium nucleatum.

    PubMed Central

    Saito, K; Katsuragi, H; Mikami, M; Kato, C; Miyamaru, M; Nagaso, K

    1997-01-01

    Fusobacterium nucleatum and Actinobacillus actinomycetemcomitans are Gram-negative rod periodontal pathogens. The peritoneal cavity of Institute of Cancer Research (ICR) mice was used as the local infection model. In vivo production of heat-shock proteins (hsp) was studied by injection of 1/10 minimum lethal dose (MLD) of each live bacteria into mice. Heat-shock proteins 70 and 60 were examined in the extract of peritoneal exudate cells (PEC) from mice injected intraperitoneally with either F. nucleatum or A. actinomycetemcomitans by using sodium dodecylsulphate-polyacrylamide gel electrophoresis and immunoblotting analysis. Although hsp are present in PEC without injection of the bacteria, both hsp increased and reached a peak on day 3 after F. nucleatum injection but not after A. actinomycetemcomitans. Kinetic study of gamma/delta cells in PEC after injection of bacteria showed that the increase of gamma/delta T cells was observed only in the PEC from mice injected with F. nucleatum but not A. actinomycetemcomitans. The gamma/delta T cells in PEC were either CD3+ and CD4+ or CD3+ and CD8+. The differential cell count of PEC suggested that gamma/delta T-cell induction is related to the expansion of the macrophage population. The phagocytic and chemiluminescence responses of macrophages against the same bacteria were compared after intensive immunization with live F. nucleatum and A. actinomycetemcomitans. Elevations of chemiluminescence response and phagocytic function by immunization were observed in the macrophages of mice immunized with F. nucleatum. These results suggest the sequential appearance of hsp, gamma/delta T cells and macrophage activation after fusobacterial infection. Images Figure 2 PMID:9135551

  18. Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition.

    PubMed

    Inuzuka, Tatsutoshi; Suzuki, Hironori; Kawasaki, Masato; Shibata, Hideki; Wakatsuki, Soichi; Maki, Masatoshi

    2010-08-06

    ALG-2 (a gene product of PDCD6) belongs to the penta-EF-hand (PEF) protein family and Ca2+-dependently interacts with various intracellular proteins including mammalian Alix, an adaptor protein in the ESCRT system. Our previous X-ray crystal structural analyses revealed that binding of Ca2+ to EF3 enables the side chain of R125 to move enough to make a primary hydrophobic pocket (Pocket 1) accessible to a short fragment of Alix. The side chain of F122, facing a secondary hydrophobic pocket (Pocket 2), interacts with the Alix peptide. An alternatively spliced shorter isoform, designated ALG-2DeltaGF122, lacks Gly121Phe122 and does not bind Alix, but the structural basis of the incompetence has remained to be elucidated. We solved the X-ray crystal structure of the PEF domain of ALG-2DeltaGF122 in the Ca2+-bound form and compared it with that of ALG-2. Deletion of the two residues shortened alpha-helix 5 (alpha5) and changed the configuration of the R125 side chain so that it partially blocked Pocket 1. A wall created by the main chain of 121-GFG-123 and facing the two pockets was destroyed. Surprisingly, however, substitution of F122 with Ala or Gly, but not with Trp, increased the Alix-binding capacity in binding assays. The F122 substitutions exhibited different effects on binding of ALG-2 to other known interacting proteins, including TSG101 (Tumor susceptibility gene 101) and annexin A11. The X-ray crystal structure of the F122A mutant revealed that removal of the bulky F122 side chain not only created an additional open space in Pocket 2 but also abolished inter-helix interactions with W95 and V98 (present in alpha4) and that alpha5 inclined away from alpha4 to expand Pocket 2, suggesting acquirement of more appropriate positioning of the interacting residues to accept Alix. We found that the inability of the two-residue shorter ALG-2 isoform to bind Alix is not due to the absence of bulky side chain of F122 but due to deformation of a main-chain wall facing

  19. Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats.

    PubMed

    Hasumura, Mai; Imai, Toshio; Cho, Young-Man; Ueda, Makoto; Hirose, Masao; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2011-01-01

    Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, was investigated with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats. For comparison, treatment with 0.0425% of AITC was similarly performed. Body weight gain was reduced in the 0.05% HRE and AITC males as compared to the 0% controls, and the cause was considered at least partly related to decreased water consumption due to the acrid smell of the test substance and decreased food consumption. Serum biochemistry demonstrated increased urea nitrogen in 0.025 and 0.05% HRE and AITC males and 0.0125-0.05% HRE and AITC females, along with decreased total cholesterol in 0.0125-0.05% HRE females. On histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder.

  20. Connectivity in river deltas

    NASA Astrophysics Data System (ADS)

    Passalacqua, P.; Hiatt, M. R.; Sendrowski, A.

    2016-12-01

    Deltas host approximately half a billion people and are rich in ecosystem diversity and economic resources. However, human-induced activities and climatic shifts are significantly impacting deltas around the world; anthropogenic disturbance, natural subsidence, and eustatic sea-level rise are major causes of threat to deltas and in many cases have compromised their safety and sustainability, putting at risk the people that live on them. In this presentation, I will introduce a framework called Delta Connectome for studying connectivity in river deltas based on different representations of a delta as a network. Here connectivity indicates both physical connectivity (how different portions of the system interact with each other) as well as conceptual (pathways of process coupling). I will explore several network representations and show how quantifying connectivity can advance our understanding of system functioning and can be used to inform coastal management and restoration. From connectivity considerations, the delta emerges as a leaky network that evolves over time and is characterized by continuous exchanges of fluxes of matter, energy, and information. I will discuss the implications of connectivity on delta functioning, land growth, and potential for nutrient removal.

  1. Man made deltas?

    NASA Astrophysics Data System (ADS)

    Maselli, V.; Trincardi, F.

    2014-12-01

    During the last few millennia, southern European fluvio-deltaic systems have evolved in response to changes in the hydrological cycle, mostly driven by high-frequency climate oscillations and increasing anthropic pressure on natural landscapes. The review of geochronological and historical data documents that the bulk of the four largest northern Mediterranean and Black Sea deltas (Ebro, Rhone, Po and Danube) formed during two short and synchronous intervals during which anthropogenic land cover change was the main driver for enhanced sediment production. These two major growth phases occurred under contrasting climatic regimes and were both followed by generalized delta retreat, supporting the hypothesis of human-driven delta progradation. Delta retreat, in particular, was the consequence of reduced soil erosion for renewed afforestation after the fall of the Roman Empire, and of river dams construction that overkilled the still increasing sediment production in catchment basins since the Industrial Era. In this second case, in particular, the effect of a reduced sediment flux to the coasts is amplified by the sinking of modern deltas, due to land subsidence and sea level rise, that hampers delta outbuilding and increases the vulnerability of coastal zone to marine erosion and flooding.

  2. 31 CFR 344.0 - What does this part cover?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... GOVERNMENT SERIES General Information § 344.0 What does this part cover? (a) What is the purpose of the SLGS... Local Government Series (SLGS) securities to provide issuers of tax-exempt securities with investments... governed by this part? This part governs the following SLGS securities: (1) Time Deposit securities—may be...

  3. 31 CFR 344.0 - What does this part cover?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... GOVERNMENT SERIES General Information § 344.0 What does this part cover? (a) What is the purpose of the SLGS... Local Government Series (SLGS) securities to provide issuers of tax-exempt securities with investments... governed by this part? This part governs the following SLGS securities: (1) Time Deposit securities—may be...

  4. 31 CFR 344.0 - What does this part cover?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... GOVERNMENT SERIES General Information § 344.0 What does this part cover? (a) What is the purpose of the SLGS... Local Government Series (SLGS) securities to provide issuers of tax-exempt securities with investments... governed by this part? This part governs the following SLGS securities: (1) Time Deposit securities—may be...

  5. 31 CFR 344.0 - What does this part cover?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... GOVERNMENT SERIES General Information § 344.0 What does this part cover? (a) What is the purpose of the SLGS... Local Government Series (SLGS) securities to provide issuers of tax-exempt securities with investments... governed by this part? This part governs the following SLGS securities: (1) Time Deposit securities—may be...

  6. 31 CFR 344.1 - What special terms do I need to know to understand this part?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What special terms do I need to know to understand this part? 344.1 Section 344.1 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT U.S...

  7. Depositional environment, foraminifer content and ESR ages of Quaternary Gediz Delta Sediments (Eastern Aegean Sea, İzmir-Western Turkey)

    NASA Astrophysics Data System (ADS)

    Gökçe Benli, Ekin; Aydın, Hülya; İşintek, İsmail; Engin, Birol; Şengöçmen, Berna

    2016-04-01

    Sediments and fossil content of Gediz Delta (Eastern Aegean Sea - İzmir) were examined based on the drilling core samples of the YSK-C and SK-246 drilling. W-SW part of the Delta is represented by continental delta sediments up to 6 meters and shallow marine detritic sediments up to 35 meters in the YSK-C drilling. Continental part consists of an soiled, graveled, muddy and sandy sediment in terms of rich organic substance. As for marine part, it consists of bioclast, muddy, fine graveled sand and by repetition of pebble, sand and bioclast bearing mud layers. Bioclasts comprise of bivalvia, echinoid, ostracod, gastropod, foramifer and bryozoa fragments. Benthic foraminiferal fauna determinated in the marine levels are represented by 55 bethic, 2 planktonic species. These foraminifers and bioclasts reflect that the W-SW part of the delta, has been occured in marine conditions between 8-31m deep. E-NE part of the delta is generally represented by continental sediments up to 43.5m in SK-246 drilling. In addition, it includes marine levels in 18-19 m, 23-24 m and 36-37,5 m intervals. Continental sediments of E-NE part is generally represented by calcareous and sandy mud rocks which mostly includes ash, tuff, and pebble derived from Neogene volcanic rocks. As for marine levels, it is composed of calcareous mud stones and calcareous clay stones including very thin gastropod, bivalvia and ostracod in 18- 19 and 36-37.5 meters whereas it is represented by sandy mud stones including a great deal of bentic foraminifer, bivalvia, bryozoa, echinoid, gastropod in 23-24 metres. Thus show that E-NE part of the delta is usually in continental condition but it is occasionally covered by sea. In aging studies of YSK-C core done by ESR method, age of 8-9 m interval is determined to be 11. 376 ± 0,067 Ka; however ages of 10-11m and 24-25 m intervals are revealed to be 16.466 ± 0,016 Ka and 15.344 ± 0,021 Ka respectively; finally age of 25-26 m interval is found to be 19.995 ± 0

  8. Age-related changes in HSP25 expression in basal ganglia and cortex of F344/BN rats

    PubMed Central

    Gupte, Anisha A.; Morris, Jill K.; Zhang, Hongyu; Bomhoff, Gregory L.; Geiger, Paige C.; Stanford, John A.

    2010-01-01

    Normal aging is associated with chronic oxidative stress. In the basal ganglia, oxidative stress may contribute to the increased risk of Parkinson's disease in the elderly. Neurons are thought to actively utilize compensatory defense mechanisms, such as heat shock proteins (HSPs), to protect from persisting stress. Despite their protective role, little is known about HSP expression in the aging basal ganglia. The purpose of this study was to examine HSP expression in striatum, substantia nigra, globus pallidus and cortex in 6-, 18- and 30-month-old Fischer 344/Brown Norway rats. We found robust age-related increases in phosphorylated and total HSP25 in each brain region studied. Conversely, HSP72 (the inducible form of HSP70) was reduced with age, but only in the striatum. p38 MAPK, a protein implicated in activating HSP25, did not change with age, nor did HSC70 (the constitutive form of HSP70), or HSP60. These results suggest that HSP25 is especially responsive to age-related stress in the basal ganglia. PMID:20144690

  9. Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid.

    PubMed

    Cahoon, E B; Ripp, K G; Hall, S E; Kinney, A J

    2001-01-26

    Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

  10. Alanine and glycine conjugates of (2S,4R)-4-[18F]fluoroglutamine for tumor imaging.

    PubMed

    Zha, Zhihao; Ploessl, Karl; Lieberman, Brian P; Wang, Limin; Kung, Hank F

    2018-05-01

    Glutamine is an essential source of energy, metabolic substrates, and building block for supporting tumor proliferation. Previously, (2S,4R)-4-[ 18 F]fluoroglutamine (4F-Gln) was reported as a glutamine-related metabolic imaging agent. To improve the in vivo kinetics of this radiotracer, two new dipeptides, [ 18 F]Gly-(2S,4R)4-fluoroglutamine (Gly-4F-Gln) and [ 18 F]Ala-(2S,4R)4-fluoroglutamine (Ala-4F-Gln) were investigated. Radiolabeling was performed via 2-steps 18 F-fluorination. Cell uptake studies of Gly-4F-Gln and Ala-4F-Gln were investigated in 9 L cell lines. In vitro and in vivo metabolism studies were carried out in Fisher 344 rats. Biodistribution and microPET imaging studies were performed in 9 L tumor-bearing rats. In vitro incubation of these [ 18 F]dipeptides in rat and human blood showed a rapid conversion to (2S,4R)-4-[ 18 F]fluoroglutamine (t 1/2  = 2.3 and 0.2 min for [ 18 F]Gly-4F-Gln and [ 18 F]Ala-4F-Gln, respectively for human blood). Biodistribution and PET imaging in Fisher 344 rats bearing 9 L tumor xenografts showed that these dipeptides rapidly localized in the tumors, comparable to that of (2S,4R)-4-[ 18 F]fluoroglutamine (4F-Gln). The results support that these dipeptides, [ 18 F]Gly-4F-Gln and [ 18 F]Ala-4F-Gln, are prodrugs, which hydrolyze in the blood after an iv injection. They appear to be selectively taken up and trapped by tumor tissue in vivo. The dipeptide, [ 18 F]Ala-4F-Gln, may be suitable as a PET tracer for imaging glutaminolysis in tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Martian deltas: Morphology and distribution

    NASA Technical Reports Server (NTRS)

    Rice, J. W., Jr.; Scott, D. H.

    1993-01-01

    Recent detailed mapping has revealed numerous examples of Martian deltas. The location and morphology of these deltas are described. Factors that contribute to delta morphology are river regime, coastal processes, structural stability, and climate. The largest delta systems on Mars are located near the mouths of Maja, Maumee, Vedra, Ma'adim, Kasei, and Brazos Valles. There are also several smaller-scale deltas emplaced near channel mouths situated in Ismenius Lacus, Memnonia, and Arabia. Delta morphology was used to reconstruct type, quantity, and sediment load size transported by the debouching channel systems. Methods initially developed for terrestrial systems were used to gain information on the relationships between Martian delta morphology, river regime, and coastal processes.

  12. 40 CFR 63.344 - Performance test requirements and test methods.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... blanket type fume suppressants are used to control chromium emissions from a hard chromium electroplating... National Emission Standards for Chromium Emissions From Hard and Decorative Chromium Electroplating and Chromium Anodizing Tanks § 63.344 Performance test requirements and test methods. (a) Performance test...

  13. 40 CFR 63.344 - Performance test requirements and test methods.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... blanket type fume suppressants are used to control chromium emissions from a hard chromium electroplating... National Emission Standards for Chromium Emissions From Hard and Decorative Chromium Electroplating and Chromium Anodizing Tanks § 63.344 Performance test requirements and test methods. (a) Performance test...

  14. 40 CFR 63.344 - Performance test requirements and test methods.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... blanket type fume suppressants are used to control chromium emissions from a hard chromium electroplating... National Emission Standards for Chromium Emissions From Hard and Decorative Chromium Electroplating and Chromium Anodizing Tanks § 63.344 Performance test requirements and test methods. (a) Performance test...

  15. 40 CFR 415.344 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Pretreatment standards for existing... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS INORGANIC CHEMICALS MANUFACTURING POINT SOURCE CATEGORY Chrome Pigments Production Subcategory § 415.344 Pretreatment standards for existing sources (PSES). (a) Existing...

  16. The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

    PubMed

    Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

    2017-02-01

    The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. The Delta Connectome: A network-based framework for studying connectivity in river deltas

    NASA Astrophysics Data System (ADS)

    Passalacqua, Paola

    2017-01-01

    Many deltas, including the Mississippi River Delta, have been losing land at fast rates compromising the safety and sustainability of their ecosystems. Knowledge of delta vulnerability has raised global concern and stimulated active interdisciplinary research as deltas are densely populated landscapes, rich in agriculture, fisheries, oil and gas, and important means for navigation. There are many ways of looking at this problem which all contribute to a deeper understanding of the functioning of coastal systems. One aspect that has been overlooked thus far, yet fundamental for advancing delta science is connectivity, both physical (how different portions of the system interact with each other) as well as conceptual (pathways of process coupling). In this paper, I propose a framework called Delta Connectome for studying connectivity in river deltas based on different representations of a delta as a network. After analyzing the classic network representation as a set of nodes (e.g., bifurcations and junctions or regions with distinct physical or statistical behavior) and links (e.g., channels), I show that from connectivity considerations the delta emerges as a leaky network that continuously exchanges fluxes of matter, energy, and information with its surroundings and evolves over time. I explore each network representation and show through several examples how quantifying connectivity can bring to light aspects of deltaic systems so far unexplored and yet fundamental to understanding system functioning and informing coastal management and restoration. This paper serves both as an introduction to the Delta Connectome framework as well as a review of recent applications of the concepts of network and connectivity to deltaic systems within the Connectome framework.

  18. Zambezi River Delta

    NASA Image and Video Library

    2013-08-29

    It drains a watershed that spans eight countries and nearly 1.6 million square kilometers 600,000 square miles. The Zambezi also Zambeze is the fourth largest river in Africa, and the largest east-flowing waterway. The Operational Land Imager on the Landsat 8 satellite acquired this natural-color image of the Zambezi Delta on August 29, 2013. Sandbars and barrier spits stretch across the mouths of the delta, and suspended sediment extends tens of kilometers out into the sea. The sandy outflow turns the coastal waters to a milky blue-green compared to the deep blue of open water in the Indian Ocean. The Zambezi Delta includes 230 kilometers of coastline fronting 18,000 square kilometers (7,00 square miles) of swamps, floodplains, and even savannahs (inland). The area has long been prized by subsistence fishermen and farmers, who find fertile ground for crops like sugar and fertile waters for prawns and fish. Two species of endangered cranes and one of the largest concentration of buffalo in Africa -- among many other species of wildlife -- have found a haven in this internationally recognized wetland. However, the past six decades have brought great changes to the Zambezi Delta, which used to pour more water and sediment off of the continent. Hydropower dams upstream-most prominently, the Kariba and the Cahora Bassa-greatly reduce river flows during the wet season; they also trap sediments that would otherwise flow downstream. The result has been less water reaching the delta and the floodplains, which rely on pulses of nutrients and sediments from annual (and mostly benign) natural flooding. The change in the flow of the river affects freshwater availability and quality in the delta. Strong flows push fresh water further out into the sea and naturally keep most of a delta full of fresh (or mostly fresh) water. When that fresh flow eases, the wetlands become drier and more prone to fire. Salt water from the Indian Ocean also can penetrate further into the marsh

  19. Toxicology and Carcinogenesis Studies of Furfuryl Alcohol (CAS No. 98-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    PubMed

    1999-02-01

    Furfuryl alcohol-based resins are used as binding agents in foundry sand and as corrosion inhibitors in mortar, grout, and cement. Because of their heat resistance, furan resins are used in the manufacture of fiberglass-reinforced plastic equipment. Furfuryl alcohol was selected for evaluation because of the absence of data on its carcinogenic potential and its large production volume, widespread use in manufacturing, and ubiquitous presence in consumer goods. Male and female F344/N rats and B6C3F1 mice were exposed to furfuryl alcohol (greater than 98% pure) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female rats exposed to 250 ppm died by day 2 of the study, and one male rat exposed to 125 ppm died on day 5. Final mean body weights of male and female rats exposed to 125 ppm were significantly less than those of the chamber control groups. Male rats exposed to 31, 63, or 125 ppm and female rats exposed to 125 ppm gained less weight than the chamber control groups. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge in males and females exposed to 63, 125, or 250 ppm. All exposed animals developed lesions in the nasal respiratory epithelium and olfactory epithelium, and the severities of these lesions generally increased with increasing exposure concentration. 16-DAY STUDY IN MICE: Groups of five male and five female mice were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female mice exposed to 250 ppm died by day 4 of the study, and one female mouse exposed to 125 ppm died on day

  20. 31 CFR 344.10 - What are Special Zero Interest securities?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.10 What are Special Zero.... The provisions of subpart B of this part (Time Deposit securities) apply except as specified in... zero interest securities available after October 28, 1996, are zero interest Time Deposit securities...

  1. 31 CFR 344.10 - What are Special Zero Interest securities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.10 What are Special Zero.... The provisions of subpart B of this part (Time Deposit securities) apply except as specified in... zero interest securities available after October 28, 1996, are zero interest Time Deposit securities...

  2. 31 CFR 344.10 - What are Special Zero Interest securities?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.10 What are Special Zero.... The provisions of subpart B of this part (Time Deposit securities) apply except as specified in... zero interest securities available after October 28, 1996, are zero interest Time Deposit securities...

  3. Glucose pump test can be used to measure blood flow rate of native arteriovenous fistula in chronic hemodialysis.

    PubMed

    Yavuz, Y C; Selcuk, N Y; Altıntepe, L; Güney, I; Yavuz, S

    2018-01-01

    In chronic hemodialysis patients, the low flow of vascular access may leads to inadequate dialysis, increased rate of hospitalization, morbidity, and mortality. It was found that surveillance should be performed for native arteriovenous (AV) should not be performed for AV graft in various studies. However, surveillance was done in graft AV fistulas in most studies. Doppler ultrasonography (US) was suggested for surveillance of AV fistulas by the last vascular access guideline of National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI). The aim of study is to determine whether glucose pump test (GPT) is used for surveillance of native AV fistulas by using Doppler US as reference. In 93 chronic hemodialysis patients with native AV fistula, blood flow rates were measured by Doppler US and GPT. For GPT, glucose was infused to 16 mL/min by pump and was measured at basal before the infusion and 11 s after the start of the infusion by glucometer. Doppler US was done by an expert radiologist. Used statistical tests were Mann-Whitney U test, Friedman test, regression analysis, and multiple regression analysis. Median values of blood flow rates measured by GPT (707 mL/min) and by Doppler US (700 mL/min) were not different (Z = 0.414, P = 0.678). Results of GPT and Doppler US measurements were positive correlate by regression analysis. The mean GPT value of diabetic patients (n = 39; 908 mL/min) was similar to that of nondiabetic patients (n = 54; 751 mL/min; Z = 1.31, P = 0.188). GPT values measured at three different dialysis session did not differ from each other that by Friedman test (F = 0.92, P = 0.39). This showed that GPT was stable and reliable. Glucose pump test can be used to measure blood flow rate of native AV fistula. GPT is an accurate and reliable test.

  4. Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: 18F-Fallypride Positron Emission Tomography Study

    PubMed Central

    Kuepper, Rebecca; Ceccarini, Jenny; Lataster, Johan; van Os, Jim; van Kroonenburgh, Marinus; van Gerven, Joop M. A.; Marcelis, Machteld; Van Laere, Koen; Henquet, Cécile

    2013-01-01

    Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and 18F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ9-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ9-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in 18F-fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ9-THC administration, reflecting dopamine release. While Δ9-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ9-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ9-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis. PMID:23936196

  5. Rise and Fall of one of World's largest deltas; the Mekong delta in Vietnam

    NASA Astrophysics Data System (ADS)

    Minderhoud, P. S. J.; Eslami Arab, S.; Pham, H. V.; Erkens, G.; van der Vegt, M.; Oude Essink, G.; Stouthamer, E.; Hoekstra, P.

    2017-12-01

    The Mekong delta is the third's largest delta in the world. It is home to almost 20 million people and an important region for the food security in South East Asia. As most deltas, the Mekong delta is the dynamic result of a balance of sediment supply, sea level rise and subsidence, hosting a system of fresh and salt water dynamics. Ongoing urbanization, industrialization and intensification of agricultural practices in the delta, during the past decades, resulted in growing domestic, agricultural and industrial demands, and have led to a dramatic increase of fresh water use. Since the year 2000, the amount of fresh groundwater extracted from the subsurface increased by 500%. This accelerated delta subsidence as the groundwater system compacts, with current sinking rates exceeding global sea level rise up to an order of magnitude. These high sinking rates have greatly altered the sediment budget of the delta and, with over 50% of the Mekong delta surface elevated less than 1 meter above sea level, greatly increase vulnerability to flooding and storm surges and ultimately, permanent inundation. Furthermore, as the increasingly larger extractions rapidly reduce the fresh groundwater reserves, groundwater salinization subsequently increases. On top of that, dry season low-flows by the Mekong river cause record salt water intrusion in the delta's estuarine system, creating major problems for rice irrigation. We present the work of three years research by the Dutch-Vietnamese `Rise and Fall' project on land subsidence and salinization in both groundwater and surface water in the Vietnamese Mekong delta.

  6. Delta Niobium or Delta VICE?

    NASA Astrophysics Data System (ADS)

    Hofmann, A. W.

    2006-12-01

    Delta Niobium or Delta VICE? Niobium is one of a few chemical elements that can be used to discriminate between melts derived from upwelling mantle, represented by MORBs and OIBs, and those derived from subduction and continental crust environments. The Nb/U ratio was introduced because these two elements appear to partition nearly identically in upwelling environments, but very differently (from one another) in subduction and continental environments (Hofmann et al., 1986). Fitton et al. (1997, 2003) have taken a radically different approach, using log(Nb/Y)-log(Zr/Y) correlations that appear to discriminate between MORB and OIB (or plume) environments. MORB correlations are parallel to, and at lower Nb/Y ratios than, Iceland basalt correlations. This is expressed by a discrimination parameter defined as Delta Nb = 1.74 + log(Nb/Y) - 1.92 log(Zr/Y). N-MORB have negative Delta-Nb values, whereas Iceland and other OIBs have positive values. Fitton et al. interpret this in terms of a niobium deficiency in MORB that is balanced by a Nb excess in OIBs. This interpretation conflicts with evidence based on Nb/U ratios (Hofmann et al., 1986), that MORB and OIB are parts of a common reservoir, which is different from, and complementary to, the continental crust. Both parts of this MORB-OIB reservoir are characterized by higher-than-primitive Nb/U and Nb/Th ratios, whereas continental crust has dramatically lower Nb/U and Nb/Th ratios. The use of VICE/MICE (very-incompatible- element to moderately-incompatible-element) ratios, such as Nb/Y, obscures this. The significance of the VICE/MICE plot becomes clear if one replaces Nb by other VICEs in the log(Nb/Y)-log(Zr/Y) plot. This shows that any of these VICEs yield similar topologies as Nb/Y. Thus for a given Zr/Y ratio, depleted MORB have consistently lower Ba/Y, Th/Y, and La/Y ratios than do Iceland basalts, even the most incompatible-element- depleted Iceland picrites. This is caused by a less extreme depletion of

  7. Losing ground in mega-deltas: basin-scale response to existential threats to the Mekong Delta

    NASA Astrophysics Data System (ADS)

    Arias, M. E.; Kondolf, G. M.; Schmitt, R. J. P.; Carling, P. A.; Darby, S. E.; Bizzi, S.; Castelletti, A.; Cochrane, T. A.; Gibson, S.; Kummu, M.; Oeurng, C.; Rubin, Z.; Wild, T. B.

    2017-12-01

    The Mekong Delta is, in terms of the number of livelihoods it supports, its economic importance, and in its vulnerability to climate change and sinking lands, one of the world's critically threatened mega-deltas. Livelihoods depend on the mere existence of the delta, but also on ecosystem services provided by the delta's drainage basin spanning 795,000 km2 in six abutting countries. These ecosystem services include delivery of sand required to build delta land in the face of rising sea-levels and sediment bound nutrients, provision of spawning habitat for fish that are ultimately harvested in the delta, and hydrologic regulation driving the delta's unique flood-pulse regime. However, while the delta is mainly located in Vietnam, the basin of the Mekong River is shared among China, Myanmar, Laos, Thailand, Cambodia, and Vietnam. In the context of the region's dynamic growth, individual countries are pushing their own development agendas, which include extensive dam building, in-channel sand mining, construction of dykes and canals, and groundwater pumping, all of which contribute to subsidence and erosion of the Delta. Our synthesis of recent research indicates that most of the Mekong's delta land will likely fall below sea-level by 2100 as result of these drivers, exacerbating the impacts of global climatic changes. In this context, local infrastructural projects and changes in land- and water-management may temporarily mitigate some negative effects, but do not address the existential threat to the delta as a whole. To prevent, or at least substantially postpone, the drowning of the Mekong Delta requires identification of the key drivers and immediate concerted management actions on the basin-scale to change the trajectory of subsidence and sediment deficit. A specific challenge is to find the institutional arrangements in this transnational context that could support the needed management changes and equitably distribute costs and impacts. The Mekong Delta is

  8. Genotoxicity of doxorubicin in F344 rats by combining the comet assay, flow-cytometric peripheral blood micronucleus test, and pathway-focused gene expression profiling.

    PubMed

    Manjanatha, Mugimane G; Bishop, Michelle E; Pearce, Mason G; Kulkarni, Rohan; Lyn-Cook, Lascelles E; Ding, Wei

    2014-01-01

    Doxorubicin (DOX) is an antineoplastic drug effective against many human malignancies. DOX's clinical efficacy is greatly limited because of severe cardiotoxicity. To evaluate if DOX is genotoxic in the heart, ~7-week-old, male F344 rats were administered intravenously 1, 2, and 3 mg/kg bw DOX at 0, 24, 48, and 69 hr and the Comet assays in heart, liver, kidney, and testis and micronucleus (MN) assay in the peripheral blood (PB) erythrocytes using flow cytometry were conducted. Rats were euthanized at 72 hr and PB was removed for the MN assay and single cells were isolated from multiple tissues for the Comet assays. None of the doses of DOX induced a significant DNA damage in any of the tissues examined by the alkaline Comet assay. Contrastingly, the glycosylase enzymes-modified Comet assay showed a significant dose dependent increase in the oxidative DNA damage in the cardiac tissue (P ≤ 0.05). In the liver, only the top dose induced significant increase in the oxidative DNA damage (P ≤ 0.05). The histopathology showed no severe cardiotoxicity but non-neoplastic lesions were present in both untreated and treated samples. A severe toxicity likely occurred in the bone marrow because no viable reticulocytes could be screened for the MN assay. Gene expression profiling of the heart tissues showed a significant alteration in the expression of 11 DNA damage and repair genes. These results suggest that DOX is genotoxic in the heart and the DNA damage may be induced primarily via the production of reactive oxygen species. Copyright © 2013 Wiley Periodicals, Inc.

  9. Delta(13)C, delta(15)N and delta(2)H isotope ratio mass spectrometry of ephedrine and pseudoephedrine: application to methylamphetamine profiling.

    PubMed

    Collins, Michael; Cawley, Adam T; Heagney, Aaron C; Kissane, Luke; Robertson, James; Salouros, Helen

    2009-07-01

    Conventional chemical profiling of methylamphetamine has been used for many years to determine the synthetic route employed and where possible to identify the precursor chemicals used. In this study stable isotope ratio analysis was investigated as a means of determining the origin of the methylamphetamine precursors, ephedrine and pseudoephedrine. Ephedrine and pseudoephedrine may be prepared industrially by several routes. Results are presented for the stable isotope ratios of carbon (delta(13)C), nitrogen (delta(15)N) and hydrogen (delta(2)H) measured in methylamphetamine samples synthesized from ephedrine and pseudoephedrine of known provenance. It is clear from the results that measurement of the delta(13)C, delta(15)N and delta(2)H stable isotope ratios by elemental analyzer/thermal conversion isotope ratio mass spectrometry (EA/TC-IRMS) in high-purity methylamphetamine samples will allow determination of the synthetic source of the ephedrine or pseudoephedrine precursor as being either of a natural, semi-synthetic, or fully synthetic origin. Copyright (c) 2009 Commonwealth of Australia.

  10. Tumor promotion by dietary fat in azoxymethane-induced colon carcinogenesis in female F344 rats: influence of amount and source of dietary fat.

    PubMed

    Reddy, B S; Maeura, Y

    1984-03-01

    The promoting effect of dietary corn oil (CO), safflower oil (SO), olive oil (OO), coconut oil (CC), and medium-chain triglycerides (MCT) on azoxymethane (AOM)-induced colon tumors was studied in female F344 rats. The animals were fed low-fat diets containing 5% CO, 5% SO, or 5% OO 2 weeks before, during, and 1 week after sc injection of 20 mg AOM/kg body weight. One week after the AOM treatment, groups of animals were transferred to high-fat diets containing 23.52% CO, 23.52% SO, 23.52% OO, and 23.52% CC, or 5.88% CO + 17.64% MCT; the remaining animals were continued on 5% fat diets. All animals were fed these diets until the termination of the experiment. Body weights and intakes of calories, protein, and micronutrients were comparable among the various dietary groups. The incidence of colon tumors was increased in rats fed diets containing high-CO and high-SO compared to those fed low-CO and low-SO diets, whereas the diets containing high OO, CC, or MCT had no promoting effect on colon tumor incidence. There was a significant increase in the excretion of fecal deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid in animals fed the high-CO and high-SO diets and no difference in these secondary bile acids excretion in animals fed the high-OO and high-CC diets compared to those animals fed their respective 5% fat diets. This study thus indicates that not only the amount of dietary fat but also the fatty acid composition (type) of fat are important factors in the determination of the promoting effect in colon carcinogenesis.

  11. SU-F-T-238: Analyzing the Performance of MapCHECK2 and Delta4 Quality Assurance Phantoms in IMRT and VMAT Plans

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

    Lu, SH; Tsai, YC; Lan, HT

    2016-06-15

    Purpose: Intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) have been widely investigated for use in radiotherapy and found to have a highly conformal dose distribution. Delta{sup 4} is a novel cylindrical phantom consisting of 1069 p-type diodes with true treatments measured in the 3D target volume. The goal of this study was to compare the performance of a Delta{sup 4} diode array for IMRT and VMAT planning with ion chamber and MapCHECK2. Methods: Fifty-four IMRT (n=9) and VMAT (n=45) plans were imported to Philips Pinnacle Planning System 9.2 for recalculation with a solid water phantom, MapCHECK2, and themore » Delta4 phantom. To evaluate the difference between the measured and calculated dose, we used MapCHECK2 and Delta{sup 4} for a dose-map comparison and an ion chamber (PTW 31010 Semiflex 0.125 cc) for a point-dose comparison. Results: All 54 plans met the criteria of <3% difference for the point dose (at least two points) by ion chamber. The mean difference was 0.784% with a standard deviation of 1.962%. With a criteria of 3 mm/3% in a gamma analysis, the average passing rates were 96.86%±2.19% and 98.42%±1.97% for MapCHECK2 and Delta{sup 4}, respectively. The student t-test of MapCHECK2/Delta{sup 4}, ion chamber/Delta{sup 4}, and ion chamber/MapCHECK2 were 0.0008, 0.2944, and 0.0002, respectively. There was no significant difference in passing rates between MapCHECK2 and Delta{sup 4} for the IMRT plan (p = 0.25). However, a higher pass rate was observed in Delta{sup 4} (98.36%) as compared to MapCHECK2 (96.64%, p < 0.0001) for the VMAT plan. Conclusion: The Pinnacle planning system can accurately calculate doses for VMAT and IMRT plans. The Delta{sup 4} shows a similar result when compared to ion chamber and MapCHECK2, and is an efficient tool for patient-specific quality assurance, especially for rotation therapy.« less

  12. Measuring delta volumetric change and composition using a streakline-based method on the Wax Lake Delta

    NASA Astrophysics Data System (ADS)

    Hurlbut, K.; Estep, J. D.; Shaw, J.; Edmonds, D. A.

    2016-12-01

    Estimating river delta growth is essential for determining coastal sustainability. We use a new method to quantify the recent accretion and composition of the Wax Lake Delta, a rapidly prograding delta in Louisiana. The method identifies the area of significant (subaqueous) delta aggradation from delta flow patterns, which are visible in aerial imagery through biogenic streaklines that naturally occur on the water surface. Comparison of bathymetric maps and streaklines shows that channel tips and the associated seaward extent of significant delta deposition occur where the divergence of flow direction equals 0 (+/- 400 m). Delta volumes calculated using this method, the 1974 pre-delta shoreline, and a measured average delta thickness of 1.6 m provide an estimate of the delta volume which we found to increase by 2.0*106 m3/yr between 1992 and 2014. We then compared this rate to the total volume of silt and sand discharged to the WLD using USGS measurements. Over the same period, the WLD received 1.4*106 m3/yr of sand and 9.0*106 m3/yr of silt and clay. Assuming all sand supplied to the delta is sequestered, volume comparisons show that the sand fraction of the WLD is between 18-38%, lower than previous estimates. Further, between 44-69% of the total suspended silt and clay bypasses the delta. These composition estimates can be used to predict land growth from engineered diversions, and the method can be used to monitor the resulting delta growth.

  13. Hepatitis delta genotypes in chronic delta infection in the northeast of Spain (Catalonia).

    PubMed

    Cotrina, M; Buti, M; Jardi, R; Quer, J; Rodriguez, F; Pascual, C; Esteban, R; Guardia, J

    1998-06-01

    Based on genetic analysis of variants obtained around the world, three genotypes of the hepatitis delta virus have been defined. Hepatitis delta virus variants have been associated with different disease patterns and geographic distributions. To determine the prevalence of hepatitis delta virus genotypes in the northeast of Spain (Catalonia) and the correlation with transmission routes and clinical disease, we studied the nucleotide divergence of the consensus sequence of HDV RNA obtained from 33 patients with chronic delta hepatitis (24 were intravenous drug users and nine had no risk factors), and four patients with acute self-limited delta infection. Serum HDV RNA was amplified by the polymerase chain reaction technique and a fragment of 350 nucleotides (nt 910 to 1259) was directly sequenced. Genetic analysis of the nucleotide consensus sequence obtained showed a high degree of conservation among sequences (93% of mean). Comparison of these sequences with those derived from different geographic areas and pertaining to genotypes I, II and III, showed a mean sequence identity of 92% with genotype I, 73% with genotype II and 61% with genotype III. At the amino acid level (aa 115 to 214), the mean identity was 87% with genotype I, 63% with genotype II and 56% with genotype III. Conserved regions included the RNA editing domain, the carboxyl terminal 19 amino acids of the hepatitis delta antigen and the polyadenylation signal of the viral mRNA. Hepatitis delta virus isolates in the northeast of Spain are exclusively genotype I, independently of the transmission route and the type of infection. No hepatitis delta virus subgenotypes were found, suggesting that the origin of hepatitis delta virus infection in our geographical area is homogeneous.

  14. 31 CFR 344.10 - What are Special Zero Interest securities?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false What are Special Zero Interest...-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.10 What are Special Zero Interest securities? Special zero interest securities were issued as certificates of indebtedness and notes...

  15. 31 CFR 344.10 - What are Special Zero Interest securities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What are Special Zero Interest...-STATE AND LOCAL GOVERNMENT SERIES Special Zero Interest Securities § 344.10 What are Special Zero Interest securities? Special zero interest securities were issued as certificates of indebtedness and notes...

  16. Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI.

    PubMed

    Lin, Ai-Ling; Fox, Peter T; Yang, Yihong; Lu, Hanzhang; Tan, Li-Hai; Gao, Jia-Hong

    2009-01-01

    The aim of this study was to investigate the relationship between relative cerebral blood flow (delta CBF) and relative cerebral metabolic rate of oxygen (delta CMRO(2)) during continuous visual stimulation (21 min at 8 Hz) with fMRI biophysical models by simultaneously measuring of BOLD, CBF and CBV fMRI signals. The delta CMRO(2) was determined by both a newly calibrated single-compartment model (SCM) and a multi-compartment model (MCM) and was in agreement between these two models (P>0.5). The duration-varying delta CBF and delta CMRO(2) showed a negative correlation with time (r=-0.97, P<0.001); i.e., delta CBF declines while delta CMRO(2) increases during continuous stimulation. This study also illustrated that without properly calibrating the critical parameters employed in the SCM, an incorrect and even an opposite appearance of the flow-metabolism relationship during prolonged visual stimulation (positively linear coupling) can result. The time-dependent negative correlation between flow and metabolism demonstrated in this fMRI study is consistent with a previous PET observation and further supports the view that the increase in CBF is driven by factors other than oxygen demand and the energy demands will eventually require increased aerobic metabolism as stimulation continues.

  17. The wave-tide-river delta classification revisited: Introducing the effects of Humans on delta equilibriu

    NASA Astrophysics Data System (ADS)

    Besset, M.; Anthony, E.; Sabatier, F.

    2016-12-01

    The influence of physical processes on river deltas has long been identified, mainly on the basis of delta morphology. A cuspate delta is considered as wave-dominated, a delta with finger-like extensions is characterized as river-dominated, and a delta with estuarine re-entrants is considered tide-dominated (Galloway, 1975). The need for a more quantitative classification is increasingly recognized, and is achievable through quantified combinations, a good example being Syvitski and Saito (2007) wherein the joint influence of marine power - wave and tides - is compared to that of river influence. This need is further justified as deltas become more and more vulnerable. Going forward from the Syvitski and Saito (2007) approach, we confront, from a large database on 60 river deltas, the maximum potential power of waves and the tidal range (both representing marine power), and the specific stream power and river sediment supply reflecting an increasingly human-impacted river influence. The results show that 45 deltas (75%) have levels of marine power that are significantly higher than those of specific stream power. Five deltas have sufficient stream power to counterbalance marine power but a present sediment supply inadequate for them to be statistically considered as river-dominated. Six others have a sufficient sediment supply but a specific stream power that is not high enough for them to be statistically river-dominated. A major manifestation of the interplay of these parameters is accelerated delta erosion worldwide, shifting the balance towards marine power domination. Deltas currently eroding are mainly influenced by marine power (93%), and small deltas (< 300 km2 of deltaic protuberance) are the most vulnerable (82%). These high levels of erosion domination, compounded by accelerated subsidence, are related to human-induced sediment supply depletion and changes in water discharge in the face of the sediment-dispersive capacity of waves and currents.

  18. MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway

    PubMed Central

    Xu, Hong; Wu, Yuting; Li, Li; Yuan, Weifeng; Zhang, Deming; Yan, Qitao; Guo, Zhenhui; Huang, Wenjie

    2017-01-01

    Objectives COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA). MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders. Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD. Materials and methods miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats. The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay. Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene. Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells. Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed. Results COPD rat model was successfully induced by smoke inhalation. Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene. In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2. In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition. Conclusion Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients. PMID:28243080

  19. Controls on delta formation, area, and topset slope: New predictive relationships developed using a global delta dataset

    NASA Astrophysics Data System (ADS)

    Caldwell, R. L.; Edmonds, D. A.; Baumgardner, S. E.; Paola, C.; Roy, S.; Nienhuis, J.

    2017-12-01

    River deltas are irreplaceable natural and societal resources, though they are at risk of drowning due to sea-level rise and decreased sediment delivery. To enhance hazard mitigation efforts in the face of global environmental change, we must understand the controls on delta growth. Previous empirical studies of delta growth are based on small datasets and often biased towards large, river-dominated deltas. We are currently lacking relationships that predict delta formation, area, or topset slope across the full breadth of global deltas. To this end, we developed a global dataset of 5,229 rivers (with and without deltas) paired with nine upstream (e.g., sediment discharge) and four downstream (e.g., wave height) environmental variables. Using Google Earth imagery, we identify all coastal river mouths (≥ 50 m wide) connected to an upstream catchment, and define deltas as river mouths that split into two or more distributary channels, end in a depositional protrusion from the shoreline, or do both. Delta area is defined as the area of the polygon connecting the delta node, two lateral shoreline extent points, and the basinward-most extent of the delta. Topset slope is calculated as the average, linear slope from the delta node elevation (extracted from SRTM data) to the main channel mouth, and shoreline and basinward extent points. Of the 5,229 rivers in our dataset, 1,816 (35%) have a delta. Using 495 rivers (those with data available for all variables), we build an empirically-derived relationship that predicts delta formation with 76% success. Delta formation is controlled predominantly by upstream water and sediment discharge, with secondary control by downstream waves and tides that suppress delta formation. For those rivers that do form deltas, we show that delta area is best predicted by sediment discharge, bathymetric slope, and drainage basin area (R2 = 0.95, n = 170), and exhibits a negative power-law relationship with topset slope (R2 = 0.85, n = 1

  20. Welcome to CALFED Bay-Delta Program

    Science.gov Websites

    Skip to: Content | Footer | Accessibility Search: Search CALFED Search CA.GOV | CALFED Bay-Delta California Delta Delta Home About the Delta CALFED Science About the Program Independent Science Board , CALFED Director photo of blue heron Bay-Delta Public Advisory Committee CALFED Agencies Calendar

  1. Tides Stabilize Deltas until Humans Interfere

    NASA Astrophysics Data System (ADS)

    Hoitink, T.; Zheng Bing, W.; Vermeulen, B.; Huismans, Y.; Kastner, K.

    2017-12-01

    Despite global concerns about river delta degradation caused by extraction of natural resources, sediment retention by reservoirs and sea-level rise, human activity in the world's largest deltas intensifies. In this review, we argue that tides tend to stabilize deltas until humans interfere. Under natural circumstances, delta channels subject to tides are more stable than their fluvial-dominated counterparts. The oscillatory tidal flow counteracts the processes responsible for bank erosion, which explains why unprotected tidal channels migrate only slowly. Peak river discharges attenuate the tides, which creates storage space to accommodate the extra river discharge during extreme events and as a consequence, reduce flood risk. With stronger tides, the river discharge is being distributed more evenly over the various branches in a delta, preventing silting up of smaller channels. Human interference in deltas is massive. Storm surge barriers are constructed, new land is being reclaimed and large-scale sand excavation takes place, to collect building material. Evidence from deltas around the globe shows that in human-controlled deltas the tidal motion often plays a destabilizing role. In channels of the Rhine-Meuse Delta, some 100 scour holes are identified, which relates to the altered tidal motion after completion of a storm surge barrier. Sand mining has led to widespread river bank failures in the tidally-influenced Mekong Delta. The catastrophic flood event in the Gauges-Brahmaputra Delta by Cyclone Aila, which caused the inundation of an embanked polder area for over two years, was preceded by river bank erosion at the mouths of formal tidal channels that were blocked by the embankment. Efforts to predict the developments of degrading deltas are few. Existing delta models are capable of reproducing expanding deltas, which is essentially a matter of simulating the transport of sediment from source in a catchment to the sink in a delta. Processes of soil

  2. Nile Delta, Egypt

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The Nile Delta of Egypt (30.0N, 31.0E) irrigated by the Nile River and its many distributaries, is some of the richest farm land in the world and home to some 45 million people, over half of Egypt's population of 57 million. The capital city of Cairo is at the apex of the delta in the middle of the scene. Across the river from Cairo can be seen the three big pyramids and sphinx at Giza and the Suez Canal is just to the right of the delta.

  3. Understanding pesticides in California's Delta

    USGS Publications Warehouse

    Kuivila, Kathryn; Orlando, James L.

    2012-01-01

    The Sacramento-San Joaquin River Delta (Delta) is the hub of California’s water system and also an important habitat for imperiled fish and wildlife. Aquatic organisms are exposed to mixtures of pesticides that flow through the maze of Delta water channels from sources including agricultural, landscape, and urban pest-control applications. While we do not know all of the effects pesticides have on the ecosystem, there is evidence that they cause some damage to organisms in the Delta. Decades of USGS research have provided a good understanding of when, where, and how pesticides enter the Delta. However, pesticide use is continually changing. New field studies and methods are needed so that scientists can analyze which pesticides are present in the Delta, and at what concentrations, enabling them to estimate exposure and ultimate effects on organisms. Continuing research will provide resource managers and stakeholders with crucial information to manage the Delta wisely.

  4. Renal histopathology in toxicity and carcinogenicity studies with tert-butyl alcohol administered in drinking water to F344 rats: a pathology working group review and re-evaluation.

    PubMed

    Hard, Gordon C; Bruner, Richard H; Cohen, Samuel M; Pletcher, John M; Regan, Karen S

    2011-04-01

    An independent Pathology Working Group (PWG) re-evaluated the kidney changes in National Toxicology Program (NTP) toxicology/carcinogenicity studies of tert-butyl alcohol (TBA) in F344/N rats to determine possible mode(s) of action underlying renal tubule tumors in male rats at 2-years. In the 13-week study, the PWG confirmed that the normal pattern of round hyaline droplets in proximal convoluted tubules was replaced by angular droplet accumulation, and identified precursors of granular casts in the outer medulla, changes typical of alpha(2u)-globulin (α(2u)-g) nephropathy. In the 2-year study, the PWG confirmed the NTP observation of increased renal tubule tumors in treated male groups. Linear papillary mineralization, another hallmark of the α(2u)-g pathway was present only in treated male rats. Chronic progressive nephropathy (CPN) was exacerbated in high-dose males and females, with a relationship between advanced grades of CPN and renal tumor occurrence. Hyperplasia of the papilla lining was a component of CPN in both sexes, but there was no pelvic urothelial hyperplasia. High-dose females showed no TBA-related nephrotoxicity. The PWG concluded that both α(2u)-g nephropathy and exacerbated CPN modes of action were operative in TBA renal tumorigenicity in male rats, neither of which has relevance for human cancer risk. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. 38 CFR 21.344 - Facility offering training or rehabilitation services.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and Employment Under 38 U.S.C. Chapter 31 Leaves of Absence § 21.344 Facility offering training or rehabilitation services. (a) Approval of leaves of absence required. Leaves of absence normally must be approved... facility. (c) Conditions permitting approval of leaves of absence. (1) The case manager may approve leaves...

  6. 38 CFR 21.344 - Facility offering training or rehabilitation services.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and Employment Under 38 U.S.C. Chapter 31 Leaves of Absence § 21.344 Facility offering training or rehabilitation services. (a) Approval of leaves of absence required. Leaves of absence normally must be approved... facility. (c) Conditions permitting approval of leaves of absence. (1) The case manager may approve leaves...

  7. 38 CFR 21.344 - Facility offering training or rehabilitation services.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and Employment Under 38 U.S.C. Chapter 31 Leaves of Absence § 21.344 Facility offering training or rehabilitation services. (a) Approval of leaves of absence required. Leaves of absence normally must be approved... facility. (c) Conditions permitting approval of leaves of absence. (1) The case manager may approve leaves...

  8. 38 CFR 21.344 - Facility offering training or rehabilitation services.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and Employment Under 38 U.S.C. Chapter 31 Leaves of Absence § 21.344 Facility offering training or rehabilitation services. (a) Approval of leaves of absence required. Leaves of absence normally must be approved... facility. (c) Conditions permitting approval of leaves of absence. (1) The case manager may approve leaves...

  9. 38 CFR 21.344 - Facility offering training or rehabilitation services.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and Employment Under 38 U.S.C. Chapter 31 Leaves of Absence § 21.344 Facility offering training or rehabilitation services. (a) Approval of leaves of absence required. Leaves of absence normally must be approved... facility. (c) Conditions permitting approval of leaves of absence. (1) The case manager may approve leaves...

  10. Extending the performance of KrF laser for microlithography by using novel F2 control technology

    NASA Astrophysics Data System (ADS)

    Zambon, Paolo; Gong, Mengxiong; Carlesi, Jason; Padmabandu, Gunasiri G.; Binder, Mike; Swanson, Ken; Das, Palash P.

    2000-07-01

    Exposure tools for 248nm lithography have reached a level of maturity comparable to those based on i-line. With this increase in maturity, there is a concomitant requirement for greater flexibility from the laser by the process engineers. Usually, these requirements pertain to energy, spectral width and repetition rate. By utilizing a combination of laser parameters, the process engineers are often able to optimize throughput, reduce cost-of-operation or achieve greater process margin. Hitherto, such flexibility of laser operation was possible only via significant changes to various laser modules. During our investigation, we found that the key measure of the laser that impacts the aforementioned parameters is its F2 concentration. By monitoring and controlling its slope efficiency, the laser's F2 concentration may be precisely controlled. Thus a laser may tune to operate under specifications as diverse as 7mJ, (Delta) (lambda) FWHM < 0.3 pm and 10mJ, (Delta) (lambda) FWHM < 0.6pm and still meet the host of requirements necessary for lithography. We discus this new F2 control technique and highlight some laser performance parameters.

  11. Major carcinogenic pathways identified by gene expression analysis of peritoneal mesotheliomas following chemical treatment in F344 rats

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

    Kim, Yongbaek; Thai-Vu Ton; De Angelo, Anthony B.

    2006-07-15

    This study was performed to characterize the gene expression profile and to identify the major carcinogenic pathways involved in rat peritoneal mesothelioma (RPM) formation following treatment of Fischer 344 rats with o-nitrotoluene (o-NT) or bromochloracetic acid (BCA). Oligo arrays, with over 20,000 target genes, were used to evaluate o-NT- and BCA-induced RPMs, when compared to a non-transformed mesothelial cell line (Fred-PE). Analysis using Ingenuity Pathway Analysis software revealed 169 cancer-related genes that were categorized into binding activity, growth and proliferation, cell cycle progression, apoptosis, and invasion and metastasis. The microarray data were validated by positive correlation with quantitative real-time RT-PCRmore » on 16 selected genes including igf1, tgfb3 and nov. Important carcinogenic pathways involved in RPM formation included insulin-like growth factor 1 (IGF-1), p38 MAPkinase, Wnt/{beta}-catenin and integrin signaling pathways. This study demonstrated that mesotheliomas in rats exposed to o-NT- and BCA were similar to mesotheliomas in humans, at least at the cellular and molecular level.« less

  12. Man made deltas

    PubMed Central

    Maselli, Vittorio; Trincardi, Fabio

    2013-01-01

    The review of geochronological and historical data documents that the largest southern European deltas formed almost synchronously during two short intervals of enhanced anthropic pressure on landscapes, respectively during the Roman Empire and the Little Ice Age. These growth phases, that occurred under contrasting climatic regimes, were both followed by generalized delta retreat, driven by two markedly different reasons: after the Romans, the fall of the population and new afforestation let soil erosion in river catchments return to natural background levels; since the industrial revolution, instead, flow regulation through river dams overkill a still increasing sediment production in catchment basins. In this second case, furthermore, the effect of a reduced sediment flux to the coasts is amplified by the sinking of modern deltas, due to land subsidence and sea level rise, that hampers delta outbuilding and increases the vulnerability of coastal zone to marine erosion and flooding. PMID:23722597

  13. Toxicology and carcinogenesis studies of sodium nitrite (CAS NO. 7632-00-0) in F344/N rats and B6C3F1 mice (drinking water studies).

    PubMed

    2001-05-01

    Sodium nitrite is used as a color fixative and preservative in meats and fish. It is also used in manufacturing diazo dyes, nitroso compounds, and other organic compounds; in dyeing and printing textile fabrics and bleaching fibers; in photography; as a laboratory reagent and a corrosion inhibitor; in metal coatings for phosphatizing and detinning; and in the manufacture of rubber chemicals. Sodium nitrite also has been used in human and veterinary medicine as a vasodilator, a bronchial dilator, an intestinal relaxant, and an antidote for cyanide poisoning. Sodium nitrite was nominated by the FDA for toxicity and carcinogenesis studies based on its widespread use in foods. Male and female F344/N rats and B6C3F1 mice were exposed to sodium nitrite (99% pure) in drinking water for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow, and mouse peripheral blood. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to 0, 375, 750, 1500, 3,000, or 5000 ppm sodium nitrite (equivalent to average daily doses of approximately 30, 55, 115, 200, or 310 mg sodium nitrite/kg body weight to males and 40, 80, 130, 225, or 345 mg/kg to females) in drinking water for 14 weeks. Clinical pathology study groups of 15 male and 15 female rats were exposed to the same concentrations for 70 or 71 days. One female exposed to 3000 ppm died before the end of the study. Body weights of males exposed to 3000 or 5000 ppm and females exposed to 5000 ppm were significantly less than those of the controls. Water consumption by 5000 ppm males and 3000 and 5000 ppm females was less than that by the controls at weeks 2 and 14. Clinical findings related to sodium nitrite exposure included brown discoloration in the eyes and cyanosis of the mouth, tongue, ears, and feet of males exposed to 3000 or 5000 ppm and of females exposed to 1500 ppm or greater. Reticulocyte counts were increased in males and females exposed to

  14. Migration in Deltas: An Integrated Analysis

    NASA Astrophysics Data System (ADS)

    Nicholls, Robert J.; Hutton, Craig W.; Lazar, Attila; Adger, W. Neil; Allan, Andrew; Arto, Inaki; Vincent, Katharine; Rahman, Munsur; Salehin, Mashfiqus; Sugata, Hazra; Ghosh, Tuhin; Codjoe, Sam; Appeaning-Addo, Kwasi

    2017-04-01

    Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise, with the potential for mass displacement of exposed populations. The assumption of mass displacement of populations in deltas requires a comprehensive reassessment in the light of present and future migration in deltas, including the potential role of adaptation to influence these decisions. At present, deltas are subject to multiple drivers of environmental change and often have high population densities as they are accessible and productive ecosystems. Climate change, catchment management, subsidence and land cover change drive environmental change across all deltas. Populations in deltas are also highly mobile, with significant urbanization trends and the growth of large cities and mega-cities within or adjacent to deltas across Asia and Africa. Such migration is driven primarily by economic opportunity, yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on the role of migration within regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to discern specific issues pertinent to delta regions. It develops a new integrated methodology to assess present and future migration in deltas using the Volta delta in Ghana, Mahanadi delta in India and Ganges-Brahmaputra-Meghna delta across India and Bangladesh. The integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and enable adaptation. The analysis is facilitated by a range of

  15. Mississippi River Delta

    NASA Image and Video Library

    2002-06-11

    As the Mississippi River enters the Gulf of Mexico, it loses energy and dumps its load of sediment that it has carried on its journey through the mid continent. This pile of sediment, or mud, accumulates over the years building up the delta front. As one part of the delta becomes clogged with sediment, the delta front will migrate in search of new areas to grow. The area shown on this image is the currently active delta front of the Mississippi. The migratory nature of the delta forms natural traps for oil. Most of the land in the image consists of mud flats and marsh lands. There is little human settlement in this area due to the instability of the sediments. The main shipping channel of the Mississippi River is the broad stripe running northwest to southeast. This image was acquired on May 24, 2001 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER will image Earth for the next 6 years to map and monitor the changing surface of our planet. http://photojournal.jpl.nasa.gov/catalog/PIA03497

  16. Delta FosB regulates wheel running.

    PubMed

    Werme, Martin; Messer, Chad; Olson, Lars; Gilden, Lauren; Thorén, Peter; Nestler, Eric J; Brené, Stefan

    2002-09-15

    DeltaFosB is a transcription factor that accumulates in a region-specific manner in the brain after chronic perturbations. For example, repeated administration of drugs of abuse increases levels of DeltaFosB in the striatum. In the present study, we analyzed the effect of spontaneous wheel running, as a model for a natural rewarding behavior, on levels of DeltaFosB in striatal regions. Moreover, mice that inducibly overexpress DeltaFosB in specific subpopulations of striatal neurons were used to study the possible role of DeltaFosB on running behavior. Lewis rats given ad libitum access to running wheels for 30 d covered what would correspond to approximately 10 km/d and showed increased levels of DeltaFosB in the nucleus accumbens compared with rats exposed to locked running wheels. Mice that overexpress DeltaFosB selectively in striatal dynorphin-containing neurons increased their daily running compared with control littermates, whereas mice that overexpress DeltaFosB predominantly in striatal enkephalin-containing neurons ran considerably less than controls. Data from the present study demonstrate that like drugs of abuse, voluntary running increases levels of DeltaFosB in brain reward pathways. Furthermore, overexpression of DeltaFosB in a distinct striatal output neuronal population increases running behavior. Because previous work has shown that DeltaFosB overexpression within this same neuronal population increases the rewarding properties of drugs of abuse, results of the present study suggest that DeltaFosB may play a key role in controlling both natural and drug-induced reward.

  17. NTP Toxicology and Carcinogenesis Studies of Primidone (CAS No. 125-33-7) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    PubMed

    2000-09-01

    Primidone is used alone or with other anticonvulsants in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy. Primidone was nominated by the National Cancer Institute for 2-year toxicology and carcinogenicity studies due to its human use as an anticonvulsant. Male and female F344/N rats and B6C3F1 mice received primidone (greater than 99% pure) in feed for 14 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 14-DAY STUDY IN RATS: Five male and five female rats were exposed to 0, 1,250, 2,500, 5,000, 10,000 or 20,000 ppm primidone (equivalent to average daily doses of approximately 120, 240, 500, 970, or 1,100 mg primidone/kg body weight to males and 120, 240, 500, or 900 mg/kg to females) in feed for 14 days. All 20,000 ppm females died before the end of the study as did one 10,000 ppm male and two 20,000 ppm males. The mean body weights of 10,000 ppm males and females and 20,000 ppm males were significantly less than those of the controls. Feed consumption by all exposed rats was generally similar to that by the controls. Males and females in the 10,000 and 20,000 ppm groups were observed to have eye discharge, ataxia, and abnormal posture and were thin and lethargic. 14-DAY STUDY IN MICE: Five male and five female mice were exposed to 0, 625, 1,250, 2,500, 5,000 or 10,000 ppm primidone (equivalent to average daily doses of approximately 100, 200, 400, or 800 mg/kg body weight to males and 100, 250, 500, or 900 mg/kg to females) in feed for 14 days. All mice in the 10,000 ppm groups and one male and one female mouse in the 5,000 ppm groups died on day 3 of the study. The mean body weights of mice in the 625, 1,250, 2,500, and 5,000 ppm groups were similar to those of the controls. Feed consumption by all exposed mice was generally similar to that by the

  18. Flow patterns and bathymetric signatures on the delta front of a prograding river delta

    NASA Astrophysics Data System (ADS)

    Shaw, J.; Mohrig, D. C.; Wagner, R. W.

    2016-02-01

    The transition of water between laterally confined channels and the unchannelized delta front controls the growth pattern of river deltas, but is difficult to measure on field-scale deltas. We quantify flow patterns, bathymetry and bathymetric evolution for the subaqueous delta front on the Wax Lake Delta (WLD), a rapidly prograding delta in coastal Louisiana. The flow direction field, mapped using streaklines composed of biogenic slicks on the water surface, shows that a significant portion of flow ( 59%) departs subaqueous channels laterally over the subaqueous margins of the channel seaward of the shoreline. Synoptic datasets of bathymetry and flow direction allow spatial changes in flow velocity to be quantified. Most lateral flow divergence and deceleration occurs within 3-8 channel widths outboard of subaqueous channel margins, rather than downstream of channel tips. In interdistributary bays, deposit elevation decreases with a basinward slope of 2.4 x 10-4 with distance from a channel margin along any flow path. Flow patterns and this slope produce constructional features called interdistributary troughs - topographic lows in the center of interdistributary bays. These data show that flow patterns and bathymetry on the delta front are coupled both at the transition from channelized to unchannelized flow and in the depositional regions outside the distributary network.

  19. Evolution of oil-generative window and oil and gas occurrence in Tertiary Niger delta basin/sup 1/

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

    Ejedawe, J.E.; Adoh, F.O.; Alofe, K.B.

    1984-11-01

    Assuming a simple model of delta development involving progradation and uniform burial at 500 m/m.y. (1,640 ft/m.y.) to present depths, oil-genesis nomographs derived from the time-temperature index (TTI) method were constructed for geothermal gradients ranging from 2.2/sup 0/ to 5.1/sup 0/ C/100 m (1.2/sup 0/-2.8/sup 0/ F/100 ft) of the Niger delta and used in mapping the positions (depth, temperature) of the top of the oil-generative window (OGW) at various times between 40 m.y.B.P. and the present. During the active subsidence phase, oil generation within any megasedimentary unit was initiated at a temperature of 140/sup 0/-146/sup 0/C (284/sup 0/-294.8/sup 0/F)more » and depth of 3,000-5,200 m (9,843-17,060 ft) within 7-11 m.y. after deposition of the potential source rocks. After cessation of subsidence, vertical upward movement of the OGW by 800-1,600 m (2,625-5,249 ft) was accompanied by a temperature lowering of 23/sup 0/-54/sup 0/C (41/sup 0/-97/sup 0/F), producing correspondingly heavier crudes. In a central belt of the delta, hydrocarbon generation and expulsion from the lower part of the Agbada Formation predate the cessation of subsidence and structural deformation, whereas, in other areas, it postdates the cessation of subsidence and structural deformation. In this central belt, the Agbada is the major oil source, with the Akata serving as a gas source. In the other areas, both the Agbada and Akata constitute oil sources, which implies that the thermal conditions rather than the kerogen type influence the oil/gas mix in the Niger delta basin.« less

  20. Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies).

    PubMed

    2011-05-01

    Milk thistle extracts have been used as medicinal herbs in the treatment of liver cirrhosis, chronic hepatitis (liver inflammation), and gallbladder disorders. Treatment claims also include lowering cholesterol levels; reducing insulin resistance; reducing the growth of cancer cells in breast, cervical, and prostate gland cancers; and antiviral activity. Other reported uses of milk thistle in folk medicine include as a treatment for malarial fever, bronchitis, gallstones, jaundice, peritonitis, uterine congestion, varicose veins, and as a milk production stimulant for nursing mothers. The roots soaked in water overnight are used in food, and the despined leaves are added to salads. Roasted milk thistle fruit has been used as a coffee substitute. Milk thistle extract was nominated for study by the National Institute of Environmental Health Sciences because it is one of the most widely used herbs in the United States. Male and female F344/N rats and B6C3F1 mice were exposed to an ethanol/water extract of milk thistle fruit (milk thistle extract) containing approximately 65% silymarin in feed for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli and mouse peripheral blood erythrocytes. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were fed diets containing 0, 3,125, 6,250, 12,500, 25,000, or 50,000 ppm milk thistle extract (equivalent to average daily doses of approximately 260, 525, 1,050, 2,180, or 4,500 mg milk thistle extract/kilogram body weight to males and 260, 510, 1,050, 2,150, or 4,550 mg/kg to females) for 14 weeks. All rats survived to the end of the study. Mean body weights of exposed groups were within 10% of those of the controls. Feed consumption by exposed and control groups was similar. The sperm motility in 12,500, 25,000, and 50,000 ppm males was decreased by 5%, 11%, and 9%, respectively, relative to that of the controls; the total number of spermatid heads per testis

  1. Environmental modulation of autoimmune arthritis involves the spontaneous microbial induction of T cell responses to regulatory determinants within heat shock protein 65.

    PubMed

    Moudgil, K D; Kim, E; Yun, O J; Chi, H H; Brahn, E; Sercarz, E E

    2001-03-15

    Both genetic and environmental factors are believed to be involved in the induction of autoimmune diseases. Adjuvant arthritis (AA) is inducible in susceptible rat strains by injection of Mycobacterium tuberculosis, and arthritic rats raise T cell responses to the 65-kDa mycobacterial heat-shock protein (Bhsp65). We observed that Fischer 344 (F344) rats raised in a barrier facility (BF-F344) are susceptible to AA, whereas F344 rats maintained in a conventional facility (CV-F344) show significantly reduced incidence and severity of AA, despite responding well to the arthritogenic determinant within Bhsp65. The acquisition of protection from AA can be circumvented if rats are maintained on neomycin/acidified water. Strikingly, naive unimmunized CV-F344 rats but not BF-F344 rats raised T cell responses to Bhsp65 C-terminal determinants (BCTD) (we have previously shown that BCTD are involved in regulation of acute AA in the Lewis rat); however, T cells of naive CV-F344 and BF-F344 gave a comparable level of proliferative response to a mitogen, but no response at all to an irrelevant Ag. Furthermore, adoptive transfer into naive BF-F344 rats of splenic cells of naive CV-F344 rats (restimulated with BCTD in vitro) before induction of AA resulted in a considerably reduced severity of AA. These results suggest that spontaneous (inadvertent) priming of BCTD-reactive T cells, owing to determinant mimicry between Bhsp65 and its homologues in microbial agents in the conventional environment, is involved in modulating the severity of AA in CV-F344 rats. These results have important implications in broadening understanding of the host-microbe interaction in human autoimmune diseases.

  2. Large old trees influence patterns of delta13C and delta15N in forests.

    PubMed

    Weber, Pascale; Bol, Roland; Dixon, Liz; Bardgett, Richard D

    2008-06-01

    Large old trees are the dominant primary producers of native pine forest, but their influence on spatial patterns of soil properties and potential feedback to tree regeneration in their neighbourhood is poorly understood. We measured stable isotopes of carbon (delta(13)C) and nitrogen (delta(15)N) in soil and litter taken from three zones of influence (inner, middle and outer zone) around the trunk of freestanding old Scots pine (Pinus sylvestris L.) trees, to determine the trees' influence on below-ground properties. We also measured delta(15)N and delta(13)C in wood cores extracted from the old trees and from regenerating trees growing within their three zones of influence. We found a significant and positive gradient in soil delta(15)N from the inner zone, nearest to the tree centre, to the outer zone beyond the tree crown. This was probably caused by the higher input of (15)N-depleted litter below the tree crown. In contrast, the soil delta(13)C did not change along the gradient of tree influence. Distance-related trends, although weak, were visible in the wood delta(15)N and delta(13)C of regenerating trees. Moreover, the wood delta(15)N of small trees showed a weak negative relationship with soil N content in the relevant zone of influence. Our results indicate that large old trees control below-ground conditions in their immediate surroundings, and that stable isotopes might act as markers for the spatial and temporal extent of these below-ground effects. John Wiley & Sons, Ltd

  3. Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray.

    PubMed

    Higashiyama, Hiroyuki; Billin, Andrew N; Okamoto, Yuji; Kinoshita, Mine; Asano, Satoshi

    2007-05-01

    Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR-delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner.

  4. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

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

    Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov; Johnson, Jerry D.; Hong, S. Peter

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males followingmore » administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. •

  5. Catalyzing action towards the sustainability of deltas: deltas as integrated socio-ecological systems and sentinels of regional and global change

    NASA Astrophysics Data System (ADS)

    Foufoula-Georgiou, E.; Tessler, Z. D.; Brondizio, E.; Overeem, I.; Renaud, F.; Sebesvari, Z.; Nicholls, R. J.; Anthony, E.

    2016-12-01

    Deltas are highly dynamic and productive environments: they are food baskets of the world, home to biodiverse and rich ecosystems, and they play a central role in food and water security. However, they are becoming increasingly vulnerable to risks arising from human activities, land subsidence, regional water management, global sea-level rise, and climate extremes. Our Belmont Forum DELTAS project (BF-DELTAS: Catalyzing actions towards delta sustainability) encompasses an international network of interdisciplinary research collaborators with focal areas in the Mekong, Ganges Brahmaputra, and the Amazon deltas. The project is organized around five main modules: (1) developing an analytical framework for assessing delta vulnerability and scenarios of change (Delta-SRES), (2) developing an open-acess, science-based integrative modeling framework for risk assessment and decision support (Delta-RADS), (3) developing tools to support quantitative mapping of the bio-physical and socio-economic environments of deltas and consolidate bio-physical and social data within shared data repositories (Delta-DAT), (4) developing Global Delta Vulnerability Indices (Delta-GDVI) that capture current and projected scenarios for major deltas around the world , and (5) collaborating with regional stakeholders to put the science, modeling, and data into action (Delta-ACT). In this talk, a research summary will be presented on three research domains around which significant collaborative work was developed: advancing biophysical classification of deltas, understanding deltas as coupled socio-ecological systems, and analyzing and informing social and environmental vulnerabilities in delta regions.

  6. Measuring and predicting Delta(vap)H298 values of ionic liquids.

    PubMed

    Deyko, Alexey; Lovelock, Kevin R J; Corfield, Jo-Anne; Taylor, Alasdair W; Gooden, Peter N; Villar-Garcia, Ignacio J; Licence, Peter; Jones, Robert G; Krasovskiy, Vladimir G; Chernikova, Elena A; Kustov, Leonid M

    2009-10-14

    We report the enthalpies of vaporisation (measured using temperature programmed desorption by mass spectrometry) of twelve ionic liquids (ILs), covering four imidazolium, [C(m)C(n)Im]+, five pyrrolidinium, [C(n)C(m)Pyrr]+, two pyridinium, [C(n)Py]+, and a dication, [C3(C1Im)2]2+ based IL. These cations were paired with a range of anions: [BF4]-, [FeCl4]-, [N(CN)2]-, [PF3(C2F5)3]- ([FAP]-), [(CF3SO2)2N]- ([Tf2N]-) and [SCN]-. Using these results, plus those for a further eight imidazolium based ILs published earlier (which include the anions [CF3SO3]- ([TfO]-), [PF6]- and [EtSO4]-), we show that the enthalpies of vaporisation can be decomposed into three components. The first component is the Coulombic interaction between the ions, DeltaU(Cou,R), which is a function of the IL molar volume, V(m), and a parameter R(r) which quantifies the relative change in anion-cation distance on evaporation from the liquid phase to the ion pair in the gas phase. The second and third components are the van der Waals contributions from the anion, DeltaH(vdw,A), and the cation, DeltaH(vdw,C). We derive a universal value for R(r), and individual values of DeltaH(vdw,A) and DeltaH(vdw,C) for each of the anions and cations considered in this study. Given the molar volume, it is possible to estimate the enthalpies of vaporisation of ILs composed of any combination of the ions considered here; values for fourteen ILs which have not yet been studied experimentally are given.

  7. The Niger Delta petroleum system; Niger Delta Province, Nigeria, Cameroon, and equatorial Guinea, Africa

    USGS Publications Warehouse

    Tuttle, Michele L.W.; Charpentier, Ronald R.; Brownfield, Michael E.

    1999-01-01

    In the Niger Delta province, we have identified one petroleum system--the Tertiary Niger Delta (Akata-Agbada) petroleum system. The delta formed at the site of a rift triple junction related to the opening of the southern Atlantic starting in the Late Jurassic and continuing into the Cretaceous. The delta proper began developing in the Eocene, accumulating sediments that now are over 10 kilometers thick. The primary source rock is the upper Akata Formation, the marine-shale facies of the delta, with possibly contribution from interbedded marine shale of the lowermost Agbada Formation. Oil is produced from sandstone facies within the Agbada Formation, however, turbidite sand in the upper Akata Formation is a potential target in deep water offshore and possibly beneath currently producing intervals onshore. Known oil and gas resources of the Niger Delta rank the province as the twelfth largest in the world. To date, 34.5 billion barrels of recoverable oil and 93.8 trillion cubic feet of recoverable gas have been discovered. In 1997, Nigeria was the fifth largest crude oil supplier to the United States, supplying 689,000 barrels/day of crude.

  8. Delta Morphodynamics Matters! Ecosystem Services, Poverty and Morphodynamic Change in the Ganges-Brahmaputra Mega-Delta

    NASA Astrophysics Data System (ADS)

    Nicholls, R. J.; Adger, N.; Allan, A.; Darby, S. E.; Hutton, C.; Matthews, Z.; Rahman, M.; Whitehead, P. G.; Wolf, J.

    2013-12-01

    The world's deltas are probably the most vulnerable type of coastal environment, and they face multiple stresses in the coming decades. These stresses include, amongst others, local drivers due to land subsidence, population growth and urbanisation within the deltas, regional drivers due to changes in catchment management (e.g. upstream land use and dam construction), as well as global climate change impacts such as sea-level rise. At the same time, the ecosystem services of river deltas support high population densities, with around 14% of the global population inhabiting deltas. A large proportion of these people experience extremes of poverty and they are therefore severely exposed to vulnerability from environmental and ecological stress and degradation. In areas close to or below the poverty boundary, both subsistence and cash elements of the economy tend to rely disproportionately heavily on ecosystem services which underpin livelihoods. Therefore, to sustainably manage delta environments they must be viewed as complex social-environmental systems where change is only partially driven by physical drivers such as sea level rise and climate change, and human-induced development activities are also critical. Here we outline a new conceptual framework for the development of methods to understand and characterise the key drivers of change in ecosystem services that affect the environment and economic status of populous deltas, focusing specifically on the Ganges-Brahmaputra-Meghna (GBM) mega-delta. The GBM delta is characterised by densely populated coastal lowlands with significant poverty, with livelihoods supported to a large extent by natural ecosystems such as the Sunderbahns (the largest mangrove forest in the world). However, the GBM delta is under severe development pressure due to many growing cities. At present the importance of ecosystems services to poverty and livelihoods is poorly understood. This is due to due to the complexity of interactions

  9. Bringing Culture to Life through Children's Literature: The Mississippi Delta in the 1930's

    ERIC Educational Resources Information Center

    Hopper, Peggy F.

    2011-01-01

    After hearing reminisces from her parents about childhood adventures that took place in the 1930's Mississippi Delta, the author, Peggy F. Hopper, decided to document these stores in two children's books, "Peggy Sue and the Pepper Patch" and "The Adventures of Theodore Roosevelt Hollumway Jones and John Hart: Chasing Bandits."…

  10. Ab initio investigation of the ground and low-lying states of the diatomic fluorides TiF, VF, CrF, and MnF.

    PubMed

    Koukounas, Constantine; Kardahakis, Stavros; Mavridis, Aristides

    2004-06-22

    The electronic structure of the ground and low-lying states of the diatomic fluorides TiF, VF, CrF, and MnF was examined by multireference and coupled cluster methods in conjunction with extended basis sets. For a total of 34 states we report binding energies, spectroscopic constants, dipole moments, separation energies, and charge distributions. In addition, for all states we have constructed full potential curves. The suggested ground state binding energies of TiF(X (4)Phi), VF(X (5)Pi), CrF(X (6)Sigma(+)), and MnF(X (7)Sigma(+)) are 135, 130, 110, and 108 kcal/mol, respectively, with first excited states A (4)Sigma(-), A (5)Delta, A (6)Pi, and a (5)Sigma(+) about 2, 3, 23, and 19 kcal/mol higher. In essence all our numerical findings are in harmony with experimental results. For all molecules and states studied it is clear that the in situ metal atom (M) shows highly ionic character, therefore the binding is described realistically by M(+)F(-). (c) 2004 American Institute of Physics.

  11. Delta-Beta Thalassaemia in a Pathan Family.

    PubMed

    Ahmad, Saqib Qayyum; Zafar, Saerah Iffat; Malik, Hamid Saeed; Ahmed, Suhaib

    2017-11-01

    Delta-beta-thalassaemia (δβ-thalassaemia) is a rare type of thalassaemia which mostly results from deletion of δ and β genes with preservation of γ genes. δβ-thalassaemia is classified into (δβ)+ and (δβ)0 types. The (δβ)0-thalassemia is further divided into GγAγ(δβ)0-thalassaemia and Gγ(Aγδβ)0-thalassaemia. In heterozygous state, (δβ)0mutations give rise to phenotype resembling β-thalassaemia trait but with raised Hb-F, ranging from 5 to 20%, without a rise in Hb-A2. In homozygotes, the clinical picture is usually that of thalassaemia intermedia and the patients have 100% Hb-F. Workup of a 1-year child suffering from pallor, chronic ill health, and splenomegaly referred to our laboratory with the suspicion of β-thalassaemia, ultimately resulted in a diagnosis on polymerase chain reaction as having homozygous inversion/deletion Gγ(Aγδβ)0-thalassaemia. Her family members were also investigated.

  12. 20 CFR 404.344 - Your relationship by marriage to the insured.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Your relationship by marriage to the insured...; Period of Disability Benefits for Spouses and Divorced Spouses § 404.344 Your relationship by marriage to..., widow, or widower is based upon a deemed valid marriage as described in § 404.346. ...

  13. Pion-nucleon scattering in covariant baryon chiral perturbation theory with explicit Delta resonances

    NASA Astrophysics Data System (ADS)

    Yao, De-Liang; Siemens, D.; Bernard, V.; Epelbaum, E.; Gasparyan, A. M.; Gegelia, J.; Krebs, H.; Meißner, Ulf-G.

    2016-05-01

    We present the results of a third order calculation of the pion-nucleon scattering amplitude in a chiral effective field theory with pions, nucleons and delta resonances as explicit degrees of freedom. We work in a manifestly Lorentz invariant formulation of baryon chiral perturbation theory using dimensional regularization and the extended on-mass-shell renormalization scheme. In the delta resonance sector, the on mass-shell renormalization is realized as a complex-mass scheme. By fitting the low-energy constants of the effective Lagrangian to the S- and P -partial waves a satisfactory description of the phase shifts from the analysis of the Roy-Steiner equations is obtained. We predict the phase shifts for the D and F waves and compare them with the results of the analysis of the George Washington University group. The threshold parameters are calculated both in the delta-less and delta-full cases. Based on the determined low-energy constants, we discuss the pion-nucleon sigma term. Additionally, in order to determine the strangeness content of the nucleon, we calculate the octet baryon masses in the presence of decuplet resonances up to next-to-next-to-leading order in SU(3) baryon chiral perturbation theory. The octet baryon sigma terms are predicted as a byproduct of this calculation.

  14. Future Change to Tide-Influenced Deltas

    NASA Astrophysics Data System (ADS)

    Nienhuis, Jaap H.; Hoitink, A. J. F. (Ton); Törnqvist, Torbjörn E.

    2018-04-01

    Tides tend to widen deltaic channels and shape delta morphology. Here we present a predictive approach to assess a priori the effect of fluvial discharge and tides on deltaic channels. We show that downstream channel widening can be quantified by the ratio of the tide-driven discharge and the fluvial discharge, along with a second metric representing flow velocities. A test of our new theory on a selection of 72 deltas globally shows good correspondence to a wide range of environments, including wave-dominated deltas, river-dominated deltas, and alluvial estuaries. By quantitatively relating tides and fluvial discharge to delta morphology, we offer a first-order prediction of deltaic change that may be expected from altered delta hydrology. For example, we expect that reduced fluvial discharge in response to dam construction will lead to increased tidal intrusion followed by enhanced tide-driven sediment import into deltas, with implications for navigation and other human needs.

  15. Nile River Delta, Egypt

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The Nile River Delta of Egypt (30.0N, 31.0E) irrigated by the Nile River and its many distributaries, is some of the richest farm land in the world and home to some 45 million people, over half of Egypt's population. The capital city of Cairo is at the apex of the delta. Just across the river from Cairo can be seen the ancient three big pyramids and sphinx at Giza and the Suez Canal is just to the right of the delta.

  16. Nile River Delta, Egypt

    NASA Image and Video Library

    1984-10-13

    The Nile River Delta of Egypt (30.0N, 31.0E) irrigated by the Nile River and its many distributaries, is some of the richest farm land in the world and home to some 45 million people, over half of Egypt's population. The capital city of Cairo is at the apex of the delta. Just across the river from Cairo can be seen the ancient three big pyramids and sphinx at Giza and the Suez Canal is just to the right of the delta.

  17. The Devil's in the Delta

    ERIC Educational Resources Information Center

    Luyben, William L.

    2007-01-01

    Students frequently confuse and incorrectly apply the several "deltas" that are used in chemical engineering. The deltas come in three different flavors: "out minus in", "big minus little" and "now versus then." The first applies to a change in a stream property as the stream flows through a process. For example, the "[delta]H" in an energy…

  18. Inhalation exposure to JP-8 jet fuel alters pulmonary function and substance P levels in Fischer 344 rats.

    PubMed

    Pfaff, J; Parton, K; Lantz, R C; Chen, H; Hays, A M; Witten, M L

    1995-01-01

    In a simulated military flightline exposure protocol, Fischer 344 rats (F344) were used to investigate the pulmonary effects of JP-8 jet fuel inhalation. Exposures were nose only and for 1 h daily. Groups were exposed for 7 days (7D) or 28 days (28D). Each exposure group had a matched longitudinal control group (LC7 and LC28). Exposure concentrations of 520 mg m-3 caused an increase in dynamic compliance after 7 days of exposure, but compliance changes were not seen with continued exposure (28D, 495 mg m-3). Pulmonary resistance was increased in both 7- and 28-day JP-8-exposed groups. Changes in pulmonary function were accompanied by a decrease in substance P concentrations from the bronchoalveolar lavage fluid (BALF). No significant change was observed in BALF levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, which is a marker of endothelial cell function. The JP-8-exposed rats gained significantly less weight during the study period than the LC7 and LC28 groups, and the lungs of the 7D group were heavier by wet lung/body weight ratio (WtL/WtB). Alveolar clearance of technetium-labelled diethylenetriamine pentaacetate ([99mTc]DTPA) was increased in jet fuel-exposed groups. Light microscopy showed no pathological evidence of lung injury. Recovery from the early pulmonary effects of JP-8 inhalation occurred with continued exposure, as seen by recovery of pulmonary compliance and WtL/WtB.

  19. From Natural to Design River Deltas

    NASA Astrophysics Data System (ADS)

    Giosan, Liviu

    2016-04-01

    Productive and biologically diverse, deltaic lowlands attracted humans since prehistory and may have spurred the emergence of the first urban civilizations. Deltas continued to be an important nexus for economic development across the world and are currently home for over half a billion people. But recently, under the double whammy of sea level rise and inland sediment capture behind dams, they have become the most threatened coastal landscape. Here I will address several deceptively simple questions to sketch some unexpected answers using example deltas from across the world from the Arctic to the Tropics, from the Danube to the Indus, Mississippi to Godavari and Krishna, Mackenzie to Yukon. What is a river delta? What is natural and what is not in a river delta? Are the geological and human histories of a delta important for its current management? Is maintaining a delta the same to building a new one? Can we design better deltas than Nature? These answers help us see clearly that survival of deltas in the next century depends on human intervention and is neither assured nor simple to address or universally applicable. Empirical observations on the hydrology, geology, biology and biochemistry of deltas are significantly lagging behind modeling capabilities endangering the applicability of numerical-based reconstruction solutions and need to be ramped up significantly and rapidly across the world.

  20. Gamma delta lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes.

    PubMed Central

    Roura-Mir, I C; Alcalde, L; Vargas, F; Tolosa, E; Obiols, G; Foz, M; Jaraquemada, D; Pujol-Borrell, R

    1993-01-01

    Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes which use the gamma delta heterodimer as T cell receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine autoimmunity we have determined the proportion of gamma delta T cells in the peripheral blood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves' disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow cytometry on peripheral blood mononuclear cells using MoAbs UCHT1 (CD3), TCR delta 1 (gamma delta TCR), WT31 and beta F1 (alpha beta TCR) and both the percentage of T cells expressing gamma delta and the ratio gamma delta/alpha beta were calculated. In the diabetic patients gamma delta cells were not significantly different from the control group (7.7 +/- 54% versus 8.0 +/- 5.5% of T cells, P NS). There was no relation between the proportion of gamma delta lymphocytes and the presence of islet cell antibodies (ICA) in the sera. The Graves' patients showed a tendency towards a higher proportion of gamma delta T lymphocytes than the controls (gamma delta/alpha beta ratios: 0.095 +/- 0.047 versus 0.063 +/- 0.022, P = 0.03). In 14 Graves' patients the number of gamma delta were measured in paired samples of peripheral and intrathyroidal lymphocytes, demonstrating an expansion of gamma delta within the thyroid glands (0.21 +/- 0.3 versus 0.095 +/- 0.047, P = 0.032). Immunohistochemical studies showed that gamma delta cells were scattered among the predominant alpha beta lymphocytes infiltrating the thyroid gland and that they account for 10% of intraepithelial lymphocytes. No relation was found between the increase of gamma delta lymphocytes and any clinical features. PMID:8485915

  1. IMMUNOTOXICITY OF 2-METHOXYETHANOL FOLLOWING ORAL ADMINISTRATION IN FISCHER 344 RATS

    EPA Science Inventory

    The immunotoxicity of the glycol ether 2-methoxyethanol (ME) as evaluated in adult Fischer 344 rats using a variety of in vitro and in vivo immune function assays. n the first phase of this study, male rats are dosed by oral gavage with ME in water, at dosages ranging from 50 to ...

  2. 12 CFR 344.6 - Notification by agreement; alternative forms and times of notification.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ....5. The bank may charge a reasonable fee for providing the information described in § 344.5. (d) Cash management sweep accounts. A bank effecting a securities transaction for a cash management sweep account...

  3. Anti-cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting mitochondrial NADH: ubiquinone oxidoreductase (Complex I)

    PubMed Central

    Lim, Sze Chern; Carey, Kirstyn T; McKenzie, Matthew

    2015-01-01

    Isoflavonoids have been shown to inhibit tumor proliferation and metastasis by activating cell death pathways. As such, they have been widely studied as potential therapies for cancer prevention. The second generation synthetic isoflavan analogues ME-143 and ME-344 also exhibit anti-cancer effects, however their specific molecular targets have not been completely defined. To identify these targets, we examined the effects of ME-143 and ME-344 on cellular metabolism and found that they are potent inhibitors of mitochondrial oxidative phosphorylation (OXPHOS) complex I (NADH: ubiquinone oxidoreductase) activity. In isolated HEK293T mitochondria, ME-143 and ME-344 reduced complex I activity to 14.3% and 28.6% of control values respectively. In addition to the inhibition of complex I, ME-344 also significantly inhibited mitochondrial complex III (ubiquinol: ferricytochrome-c oxidoreductase) activity by 10.8%. This inhibition of complex I activity (and to a lesser extent complex III activity) was associated with a reduction in mitochondrial oxygen consumption. In permeabilized HEK293T cells, ME-143 and ME-344 significantly reduced the maximum ADP-stimulated respiration rate to 62.3% and 70.0% of control levels respectively in the presence of complex I-linked substrates. Conversely, complex II-linked respiration was unaffected by either drug. We also observed that the inhibition of complex I-linked respiration caused the dissipation of the mitochondrial membrane potential (ΔΨm). Blue native (BN-PAGE) analysis revealed that prolonged loss of ΔΨm results in the destabilization of the native OXPHOS complexes. In particular, treatment of 143B osteosarcoma, HeLa and HEK293T human embryonic kidney cells with ME-344 for 4 h resulted in reduced steady-state levels of mature complex I. Degradation of the complex I subunit NDUFA9, as well as the complex IV (ferrocytochrome c: oxygen oxidoreductase) subunit COXIV, was also evident. The identification of OXPHOS complex I as a

  4. Anti-cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting mitochondrial NADH: ubiquinone oxidoreductase (Complex I).

    PubMed

    Lim, Sze Chern; Carey, Kirstyn T; McKenzie, Matthew

    2015-01-01

    Isoflavonoids have been shown to inhibit tumor proliferation and metastasis by activating cell death pathways. As such, they have been widely studied as potential therapies for cancer prevention. The second generation synthetic isoflavan analogues ME-143 and ME-344 also exhibit anti-cancer effects, however their specific molecular targets have not been completely defined. To identify these targets, we examined the effects of ME-143 and ME-344 on cellular metabolism and found that they are potent inhibitors of mitochondrial oxidative phosphorylation (OXPHOS) complex I (NADH: ubiquinone oxidoreductase) activity. In isolated HEK293T mitochondria, ME-143 and ME-344 reduced complex I activity to 14.3% and 28.6% of control values respectively. In addition to the inhibition of complex I, ME-344 also significantly inhibited mitochondrial complex III (ubiquinol: ferricytochrome-c oxidoreductase) activity by 10.8%. This inhibition of complex I activity (and to a lesser extent complex III activity) was associated with a reduction in mitochondrial oxygen consumption. In permeabilized HEK293T cells, ME-143 and ME-344 significantly reduced the maximum ADP-stimulated respiration rate to 62.3% and 70.0% of control levels respectively in the presence of complex I-linked substrates. Conversely, complex II-linked respiration was unaffected by either drug. We also observed that the inhibition of complex I-linked respiration caused the dissipation of the mitochondrial membrane potential (ΔΨm). Blue native (BN-PAGE) analysis revealed that prolonged loss of ΔΨm results in the destabilization of the native OXPHOS complexes. In particular, treatment of 143B osteosarcoma, HeLa and HEK293T human embryonic kidney cells with ME-344 for 4 h resulted in reduced steady-state levels of mature complex I. Degradation of the complex I subunit NDUFA9, as well as the complex IV (ferrocytochrome c: oxygen oxidoreductase) subunit COXIV, was also evident. The identification of OXPHOS complex I as a

  5. [Reliability study on the infrared spectrometry for measuring the delta over baseline for breath 13C].

    PubMed

    Wang, Min; Wang, Zhiling; Gou, Lingyan; Zhang, Yuhui; Yang, Xiaoguang; Sha, Lei; Li, Min

    2013-03-01

    To assess the validity and reliability of the infrared spectrometry for measuring the delta over baseline for breath 13C. Twenty-four healthy adults were selected, including twelve males and twelve females. 13C-Leucine was used as tracer in stable isotope metabolic experiments. One baseline breath was collected before the tracer protocol began. Other breath samples were collected at 60, 120, 180, 195, 210, 225, 240, 255, 270 and 300 min post-tracer challenge. The delta over baseline for breath 13C was measured by the infrared spectrometry and Heliview 13C breath analyzer. No significant differences were found between the infrared spectrometry and Heliview 13C breath analyzer in measuring the delta over baseline for breath 13C. The F value and p value of two-way ANOVA were 0.29 and 0.5874 respectively. The t and p value of consistency test were 0.48 and 0.6346 respectively. The 13C infrared spectrometry can reliably measure the delta over baseline for breath 13C.

  6. Free-jet testing at Mach 3.44 in GASL's aero/thermo test facility

    NASA Technical Reports Server (NTRS)

    Cresci, D.; Koontz, S.; Tsai, C. Y.

    1993-01-01

    A supersonic blow-down tunnel has been used to conduct tests of a hydrogen burning ramjet engine at simulated Mach 3.44 conditions. A pebble-bed type storage heater, a free standing test cabin, and a 48 foot diameter vacuum sphere are used to simulate the flight conditions at nearly matched enthalpy and dynamic pressure. A two dimensional nozzle with a nominal 13.26 inch square exit provides a free-jet test environment. The facility used for these tests is described as are the results of a flow calibration performed on the M = 3.44 nozzle. Some facility/model interactions are discussed as are the eventual hardware modifications and operational procedures required to alleviate the interactions. Some engine test results are discussed briefly to document the success of the test program.

  7. Phytochemicals in Morinda citrifolia fruit selectively modulate age-associated immunity and antioxidant enzyme activities through ERK pathway in splenic lymphocytes of male F344 rats.

    PubMed

    Pratap, Uday P; Anand, Krithika; Yasmine, Fariya; Hima, Lalgi; Priyanka, Hannah P; Thyagarajan, Srinivasan

    2016-01-01

    The mechanisms of immunomodulatory effects of Morinda citrifolia (Noni) were examined through intracellular signaling pathways in the splenocytes and their modulation by phytochemicals using bioinformatics tools. Noni fruit juices without seeds (NSL) and with seeds (NWS) were co-incubated in vitro with splenocytes from young, middle-aged and old F344 male rats and proliferation of lymphocytes, cytokine production, antioxidant enzyme activities and intracellular signaling markers were measured. NSL decreased lymphoproliferation in early middle-aged rats, and IL-2 and IFN-γ production in old rats. In contrast, NWS enhanced lymphoproliferation in young and old rats, IL-2 and IFN-γ production in middle-aged and old rats. The activities of antioxidant enzymes were augmented by NWS and NSL in old rats. NWS reversed age-related increase in lipid peroxidation in all age-groups, while NSL increased lipid peroxidation in old rats. NSL increased p-ERK in old rats and decreased p-CREB in young and middle-aged rats. In contrast, NWS decreased p-ERK in all age groups and increased p-CREB in old rats. Both NSL and NWS increased p-Akt expression in middle-aged and old rats. Both NSL and NWS suppressed p-NF-κB expression in middle-aged and old rats. Docking studies demonstrated that Noni phytochemicals, damnacanthal, myricetin and ursolic acid, are potent inhibitors of ERK with binding sites in the catalytic and phosphorylation sites of the molecule. These results suggest that Noni fruit juices with or without seeds modulate cell-mediated immunity and antioxidant enzyme activities based on the phytochemicals that may differentially influence cell signaling and therefore, age-associated immunity.

  8. Exercise Is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats

    PubMed Central

    Mika, Agnieszka; Van Treuren, Will; González, Antonio; Herrera, Jonathan J.; Knight, Rob; Fleshner, Monika

    2015-01-01

    The mammalian intestine harbors a complex microbial ecosystem that influences many aspects of host physiology. Exposure to specific microbes early in development affects host metabolism, immune function, and behavior across the lifespan. Just as the physiology of the developing organism undergoes a period of plasticity, the developing microbial ecosystem is characterized by instability and may also be more sensitive to change. Early life thus presents a window of opportunity for manipulations that produce adaptive changes in microbial composition. Recent insights have revealed that increasing physical activity can increase the abundance of beneficial microbial species. We therefore investigated whether six weeks of wheel running initiated in the juvenile period (postnatal day 24) would produce more robust and stable changes in microbial communities versus exercise initiated in adulthood (postnatal day 70) in male F344 rats. 16S rRNA gene sequencing was used to characterize the microbial composition of juvenile versus adult runners and their sedentary counterparts across multiple time points during exercise and following exercise cessation. Alpha diversity measures revealed that the microbial communities of young runners were less even and diverse, a community structure that reflects volatility and malleability. Juvenile onset exercise altered several phyla and, notably, increased Bacteroidetes and decreased Firmicutes, a configuration associated with leanness. At the genus level of taxonomy, exercise altered more genera in juveniles than in the adults and produced patterns associated with adaptive metabolic consequences. Given the potential of these changes to contribute to a lean phenotype, we examined body composition in juvenile versus adult runners. Interestingly, exercise produced persistent increases in lean body mass in juvenile but not adult runners. Taken together, these results indicate that the impact of exercise on gut microbiota composition as well as

  9. SU-F-T-586: Pre-Treatment QA of InCise2 MLC Plans On a Cyberknife-M6 Using the Delta4 System in SBRT

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

    Schmidhalter, D; Henzen, D; Malthaner, M

    Purpose: Performing pre-treatment quality assurance (QA) with the Delta4 system (ScandiDos Inc., Madison, WI) is well established for linac-based radiotherapy. This is not true when using a Cyberknife (Accuray Inc., Sunnyvale, CA) where, typically film-based QA is applied. The goal of this work was to test the feasibility to use the Delta4 system for pre-treatment QA for stereotactic body radiation therapy (SBRT) using a Cyberknife-M6 equipped with the InCise2 multileaf collimator (MLC). Methods: In order to perform measurements without accelerator pulse signal, the Tomotherapy option within the Delta4 software was used. Absolute calibration of the Delta4 phantom was performed usingmore » a 10×10 cm{sup 2} field shaped by the InCise2 MLC of the Cyberknife-M6. Five fiducials were attached to the Delta4 phantom in order to be able to track the phantom before and during measurements. For eight SBRT treatment plans (two liver, two prostate, one lung, three bone metastases) additional verification plans were recalculated on the Delta4 phantom using MultiPlan. Dicom data was exported from MultiPlan and was adapted in order to be compatible with the Delta4 software. The measured and calculated dose distributions were compared using the gamma analysis of the Delta4 system. Results: All eight SBRT plans were successfully measured with the aid of the Delta4 system. In the mean, 98.0±1.9%, 95.8±4.1% and 88.40±11.4% of measured dose points passed the gamma analysis using a global dose deviation criterion of 3% (100% corresponds to the dose maximum) and a distance-to-agreement criterion of 3 mm, 2 mm and 1 mm, respectively, and a threshold of 20%. Conclusion: Pre-treatment QA of SBRT plans using the Delta4 system on a Cyberknife-M6 is feasible. Measured dose distributions of SBRT plans showed clinically acceptable agreement with the corresponding calculated dose distributions.« less

  10. Improved γ-linolenic acid production in Mucor circinelloides by homologous overexpressing of delta-12 and delta-6 desaturases.

    PubMed

    Zhang, Yao; Luan, Xiao; Zhang, Huaiyuan; Garre, Victoriano; Song, Yuanda; Ratledge, Colin

    2017-06-21

    γ-Linolenic acid (GLA) is important because of its nutritional value and medicinal applications. Although the biosynthetic pathways of some plant and microbial GLA have been deciphered, current understanding of the correlation between desaturases and GLA synthesis in oleaginous fungi is incomplete. In previous work, we found that a large amount of oleic acid (OA) had not been converted to linoleic acid (LA) or GLA in Mucor circinelloides CBS 277.49, which may be due to inadequate activities of the delta-12 or delta-6 desaturases, and thus leading to the accumulation of OA and LA. Thus, it is necessary to explore the main contributing factor during the process of GLA biosynthesis in M. circinelloides. To enhance GLA production in M. circinelloides, homologous overexpression of delta-12 and two delta-6 desaturases (named delta-6-1 and delta-6-2, respectively) were analyzed. When delta-6 desaturase were overexpressed in M. circinelloides, up to 43% GLA was produced in the total fatty acids, and the yield of GLA reached 180 mg/l, which were, respectively, 38 and 33% higher than the control strain. These findings revealed that delta-6 desaturase (especially for delta-6-1 desaturase) plays an important role in GLA synthesis by M. circinelloides. The strain overexpressing delta-6-1 desaturase may have potential application in microbial GLA production.

  11. Multiple opioid receptors in endotoxic shock: evidence for delta involvement and mu-delta interactions in vivo.

    PubMed Central

    D'Amato, R; Holaday, J W

    1984-01-01

    The use of selective delta and mu opioid antagonists has provided evidence that delta opioid receptors within the brain mediate the endogenous opioid component of endotoxic shock hypotension. The selectivity of these delta and mu antagonists was demonstrated by their differing effects upon morphine analgesia and endotoxic hypotension. The mu antagonist beta-funaltrexamine, at doses that antagonized morphine analgesia, failed to alter shock, whereas the delta antagonist M 154,129: [N,N-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH] (ICI) reversed shock at doses that failed to block morphine analgesia. Therefore, selective delta antagonists may have therapeutic value in reversing circulatory shock without altering the analgesic actions of endogenous or exogenous opioids. Additional data revealed that prior occupancy of mu binding sites by irreversible opioid antagonists may allosterically attenuate the actions of antagonists with selectivity for delta binding sites. For endogenous opioid systems, this observation provides an opportunity to link in vivo physiological responses with receptor-level biochemical interactions. PMID:6326151

  12. SUBCHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The subchronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 rats was evaluated by feeding a powdered certified laboratory diet containing 0, 66.7, 400 and 800 mg TNB/kg diet for 90 days. The calculated average TNB intake was 4.29, 24.70, and 49.28 mg/kg...

  13. Hair analysis for delta(9)-THC, delta(9)-THC-COOH, CBN and CBD, by GC/MS-EI. Comparison with GC/MS-NCI for delta(9)-THC-COOH.

    PubMed

    Baptista, Maria João; Monsanto, Paula Verâncio; Pinho Marques, Estela Gouveia; Bermejo, Ana; Avila, Sofia; Castanheira, Alice Martelo; Margalho, Cláudia; Barroso, Mário; Vieira, Duarte Nuno

    2002-08-14

    A sensitive analytical method was developed for quantitative analysis of delta(9)-tetrahydrocannabinol (delta(9)-THC), 11-nor-delta(9)-tetrahydrocannabinol-carboxylic acid (delta(9)-THC-COOH), cannabinol (CBN) and cannabidiol (CBD) in human hair. The identification of delta(9)-THC-COOH in hair would document Cannabis use more effectively than the detection of parent drug (delta(9)-THC) which might have come from environmental exposure. Ketamine was added to hair samples as internal standard for CBN and CBD. Ketoprofen was added to hair samples as internal standard for the other compounds. Samples were hydrolyzed with beta-glucuronidase/arylsulfatase for 2h at 40 degrees C. After cooling, samples were extracted with a liquid-liquid extraction procedure (with chloroform/isopropyl alcohol, after alkalinization, and n-hexane/ethyl acetate, after acidification), which was developed in our laboratory. The extracts were analysed before and after derivatization with pentafluoropropionic anhydride (PFPA) and pentafluoropropanol (PFPOH) using a Hewlett Packard gas chromatographer/mass spectrometer detector, in electron impact mode (GC/MS-EI). Derivatized delta(9)-THC-COOH was also analysed using a Hewlett Packard gas chromatographer/mass spectrometer detector, in negative ion chemical ionization mode (GC/MS-NCI) using methane as the reagent gas. Responses were linear ranging from 0.10 to 5.00 ng/mg hair for delta(9)-THC and CBN, 0.10-10.00 ng/mg hair for CBD, 0.01-5.00 ng/mg for delta(9)-THC-COOH (r(2)>0.99). The intra-assay precisions ranged from <0.01 to 12.40%. Extraction recoveries ranged from 80.9 to 104.0% for delta(9)-THC, 85.9-100.0% for delta(9)-THC-COOH, 76.7-95.8% for CBN and 71.0-94.0% for CBD. The analytical method was applied to 87 human hair samples, obtained from individuals who testified in court of having committed drug related crimes. Quantification of delta(9)-THC-COOH using GC/MS-NCI was found to be more convenient than GC/MS-EI. The latter may give rise

  14. Entropy and optimality in river deltas

    NASA Astrophysics Data System (ADS)

    Tejedor, Alejandro; Longjas, Anthony; Edmonds, Douglas A.; Zaliapin, Ilya; Georgiou, Tryphon T.; Rinaldo, Andrea; Foufoula-Georgiou, Efi

    2017-10-01

    The form and function of river deltas is intricately linked to the evolving structure of their channel networks, which controls how effectively deltas are nourished with sediments and nutrients. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. To date, however, a unified theory explaining how deltas self-organize to distribute water and sediment up to the shoreline remains elusive. Here, we provide evidence for an optimality principle underlying the self-organized partition of fluxes in delta channel networks. By introducing a suitable nonlocal entropy rate (nER) and by analyzing field and simulated deltas, we suggest that delta networks achieve configurations that maximize the diversity of water and sediment flux delivery to the shoreline. We thus suggest that prograding deltas attain dynamically accessible optima of flux distributions on their channel network topologies, thus effectively decoupling evolutionary time scales of geomorphology and hydrology. When interpreted in terms of delta resilience, high nER configurations reflect an increased ability to withstand perturbations. However, the distributive mechanism responsible for both diversifying flux delivery to the shoreline and dampening possible perturbations might lead to catastrophic events when those perturbations exceed certain intensity thresholds.

  15. Elevated plus-maze performance of Fischer-344 rats as a function of age and of exposure to 56Fe particles

    NASA Astrophysics Data System (ADS)

    Rabin, Bernard M.; Carrihill-Knoll, Kirsty L.; Carey, Amanda N.; Shukitt-Hale, Barbara; Joseph, James A.; Foster, Brian C.

    The aging process is characterized by a series of changes in neurochemical functioning and in motor and cognitive performance. In addition to changes in cognitive/behavioral performance, aged rats also show an increase in baseline anxiety measured using the elevated plus-maze. Exposure to 56Fe particles, a component of cosmic rays, produces neurochemical and behavioral changes in young animals which are characteristic of aged organisms. The present study was designed to determine the relationships between aging and exposure to 56Fe particles on anxiety. Fischer-344 (F-344), which were 2, 7, 12, and 16 months of age at the time of irradiation, were exposed to 56Fe particles (50 200 cGy). Concordant with previous results, the oldest rats spent less time exploring the open arms of the maze. Exposure to 56Fe particles also produced decreased exploration of the open arms of the plus-maze. The dose needed to produce increased levels of anxiety was a function of age at the time of irradiation. The dose of 56Fe particles needed to produce a decrease in open arm exploration was significantly lower in the rats that were irradiated at 7 and 12 months of age than in the rats irradiated at 2 months of age. These results suggest the possibility that exposing middle-aged astronauts to cosmic rays during exploratory class missions outside the magnetosphere, and the resultant effects on exploration-induced anxiety, may affect their ability to successfully complete mission requirements.

  16. Ganges River Delta

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The Ganges River forms an extensive delta where it empties into the Bay of Bengal. The delta is largely covered with a swamp forest known as the Sunderbans, which is home to the Royal Bengal Tiger. It is also home to most of Bangladesh, one of the world's most densely populated countries. Roughly 120 million people live on the Ganges Delta under threat of repeated catastrophic floods due to heavy runoff of meltwater from the Himalayas, and due to the intense rainfall during the monsoon season. This image was acquired by Landsat 7's Enhanced Thematic Mapper plus (ETM+) sensor on February 28, 2000. This is a false-color composite image made using green, infrared, and blue wavelengths. Image provided by the USGS EROS Data Center Satellite Systems Branch

  17. A TWO-YEAR DOSE-RESPONSE STUDY OF LESION SEQUENCES DURING HEPATOCELLULAR CARCINOGENESIS IN THE MALE B6C3F1 MOUSE GIVEN THE DRINKING WATER CHEMICAL DICHLOROACETIC ACID

    EPA Science Inventory

    ABSTRACT

    Dichloroacetic acid (DCA) is carcinogenic to the B6C3F 1 mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver, and the known concentrations of this compound in drinking water, reliable biologically-based models to reduce the uncertai...

  18. 31 CFR Appendix A to Part 344 - Early Redemption Market Charge Formulas and Examples for Subscriptions From December 28, 1976...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Early Redemption Market Charge Formulas and Examples for Subscriptions From December 28, 1976, Through October 27, 1996 A Appendix A to... GOVERNMENT SERIES Pt. 344, App. A Appendix A to Part 344—Early Redemption Market Charge Formulas and Examples...

  19. 31 CFR Appendix A to Part 344 - Early Redemption Market Charge Formulas and Examples for Subscriptions From December 28, 1976...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Early Redemption Market Charge Formulas and Examples for Subscriptions From December 28, 1976, Through October 27, 1996 A Appendix A to... GOVERNMENT SERIES Pt. 344, App. A Appendix A to Part 344—Early Redemption Market Charge Formulas and Examples...

  20. Offshore Deterioration in the Mekong Delta, Vietnam

    NASA Astrophysics Data System (ADS)

    Stattegger, K.; Unverricht, D.; Heinrich, C.

    2016-02-01

    The interplay of river, tide and wave forcing controls shape and sedimentation at the front of the Mekong Delta. Specific hydro- and morphodynamic conditions in the western subaqueous part of the asymmetric Mekong Delta generate a sand ridge - channel system (SRCS) which is unique in subaqueous delta formation. This large-scale morphological element extends 130 km along the delta front consisting of two sand ridges and two erosional channels. Three different zones within SRCS can be distinguished. The eastern initial zone stretches along delta slope and inner shelf platform southwest of the Bassac river mouth, the largest and westernmost distributary of the Mekong Delta. In the central zone SRCS covers the outer part of the subaqueous delta platform with a pronounced sand-ridge and erosional channel morphology. Cross-sections of the SRCS reveal an asymmetric shape including steeper ridge flanks facing into offshore direction. Channels incise down to 18.2 m water depth (wd) and 10.5 down the ridge top at the outer subaqueous delta platform, respectively. Towards the west the sand ridges pinch out while the two channels merge into one and form a giant erosional scour of up to 33 m wd within the subaqueous delta platform. In the western zone, the channel gets shallower and vanishes along the south-western edge of the subaqueous delta platform around Ca Mau Cape. Sediment transport from the Mekong River nourishes the sand ridges. In contrast, tide and wind-driven currents cut the erosional channels, which act also as fine-sediment conveyor from eroding headlands to the distal part of the delta front that is 200 km apart of the Bassac river mouth. SRCS in the subaqueous Mekong Delta is a relevant indicator of delta-front instability and erosion.

  1. MACROMOLECULAR ADDUCTION BY TRICHLOROACETONITRILE IN THE FISCHER 344 RAT FOLLOWING ORAL GAVAGE

    EPA Science Inventory

    Male Fischer 344 rats were administered 1- or 2-[14C]-trichloroacetonitrile (TCAN) by ral gavage. NA was isolated from the liver, kidneys and stomach and several protein fractions (globin, albumin and blobulins) were isolated from blood. CAN binds to both the DNA and the blood pr...

  2. Delta modulation

    NASA Technical Reports Server (NTRS)

    Schilling, D. L.

    1971-01-01

    The conclusions of the design research of the song adaptive delta modulator are presented for source encoding voice signals. The variation of output SNR vs input signal power/when 8, 9, and 10 bit internal arithmetic is employed. Voice intelligibility tapes to test the 10-bit system are used. An analysis of a delta modulator is also presented designed to minimize the in-band rms error. This is accomplished by frequency shaping the error signal in the modulator prior to hard limiting. The result is a significant increase in the output SNR measured after low pass filtering.

  3. Identifying hazards associated with lava deltas

    USGS Publications Warehouse

    Poland, Michael P.; Orr, Tim R.

    2014-01-01

    Lava deltas, formed where lava enters the ocean and builds a shelf of new land extending from the coastline, represent a significant local hazard, especially on populated ocean island volcanoes. Such structures are unstable and prone to collapse—events that are often accompanied by small explosions that can deposit boulders and cobbles hundreds of meters inland. Explosions that coincide with collapses of the East Lae ‘Apuki lava delta at Kīlauea Volcano, Hawai‘i, during 2005–2007 followed an evolutionary progression mirroring that of the delta itself. A collapse that occurred when the lava–ocean entry was active was associated with a blast of lithic blocks and dispersal of spatter and fine, glassy tephra. Shortly after delta growth ceased, a collapse exposed hot rock to cold ocean water, resulting in an explosion composed entirely of lithic blocks and lapilli. Further collapse of the delta after several months of inactivity, by which time it had cooled significantly, resulted in no recognizable explosion deposit. Seaward displacement and subsidence of the coastline immediately inland of the delta was measured by both satellite and ground-based sensors and occurred at rates of several centimeters per month even after the lava–ocean entry had ceased. The anomalous deformation ended only after complete collapse of the delta. Monitoring of ground deformation may therefore provide an indication of the potential for delta collapse, while the hazard associated with collapse can be inferred from the level of activity, or the time since the last activity, on the delta.

  4. NTP Toxicology and Carcinogenesis Studies of l-Epinephrine Hydrochloride (CAS No. 55-31-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    PubMed

    1990-03-01

    l-Epinephrine, an endogenous neurotransmitter hormone, is widely used for the treatment of allergic and respiratory disorders. NTP Toxicology and Carcinogenesis studies of epinephrine hydrochloride were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to an aerosol containing epinephrine hydrochloride for 14 days, 13 weeks, 15 months, or 2 years. During the 14-day and 13-week studies, control animals were exposed to dilute aerosols of hydrochloric acid (pH 2.8), whereas during the 15-month and 2-year studies, controls were exposed to aerosols of water. Genetic toxicology studies of epinephrine were conducted in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Fourteen-Day Studies: Rats and mice were exposed to 0 or 12.5-200 mg/m3 epinephrine hydrochloride. Deaths occurred in male rats exposed to 12.5 mg/m3 or more and in females exposed to 25 mg/m3 or more. Deaths of mice occurred at concentrations of 50 mg/m3 or higher. Compound-related clinical signs included an increased respiratory rate in all groups of epinephrine-exposed rats and mice. At higher concentrations (100 and 200 mg/m3), excessive lacrimation and dyspnea in rats and exaggerated visual and auditory reflexes in mice were observed. Thirteen-Week Studies: Rats and mice were exposed to 0 or 2.5-40 mg/m3 epinephrine hydrochloride. Deaths in rats and mice were not concentration related. Final mean body weights of chemically exposed and hydrochloric acid aerosol control rats and mice were generally similar. Increased respiratory rates were noted in rats and mice exposed to 40 mg/m3. Heart and adrenal gland weights of rats and mice and liver weights of mice exposed to 40 mg/m3 were greater than those of aerosol controls. Squamous metaplasia occurred in the respiratory epithelium of the nasal mucosa of rats and mice exposed to 40 mg/m3. Degenerative lesions of the laryngeal muscle were seen in male and female rats exposed to 20 or 40 mg/m3. Inflammation in the glandular

  5. 75 FR 45172 - Withdrawal of Regulatory Guides 3.44 and 3.49

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-02

    ... Format and Content for the Safety Analysis Report for an Independent Spent Fuel Storage Installation... on the format and content of the safety analysis report that is required as part of an application to...: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 3.44, ``Standard Format and Content...

  6. The DELTA MONSTER: An RPV designed to investigate the aerodynamics of a delta wing platform

    NASA Technical Reports Server (NTRS)

    Connolly, Kristen; Flynn, Mike; Gallagher, Randy; Greek, Chris; Kozlowski, Marc; Mcdonald, Brian; Mckenna, Matt; Sellar, Rich; Shearon, Andy

    1989-01-01

    The mission requirements for the performance of aerodynamic tests on a delta wind planform posed some problems, these include aerodynamic interference; structural support; data acquisition and transmission instrumentation; aircraft stability and control; and propulsion implementation. To eliminate the problems of wall interference, free stream turbulence, and the difficulty of achieving dynamic similarity between the test and actual flight aircraft that are associated with aerodynamic testing in wind tunnels, the concept of the remotely piloted vehicle which can perform a basic aerodynamic study on a delta wing was the main objective for the Green Mission - the Delta Monster. The basic aerodynamic studies were performed on a delta wing with a sweep angle greater than 45 degrees. These tests were performed at various angles of attack and Reynolds numbers. The delta wing was instrumented to determine the primary leading edge vortex formation and location, using pressure measurements and/or flow visualization. A data acquisition system was provided to collect all necessary data.

  7. Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model.

    PubMed

    Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

    2012-01-01

    The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of

  8. NTP toxicity studies of sodium dichromate dihydrate (CAS No. 7789-12-0) administered in drinking water to male and female F344/N rats and B6C3F1 mice and male BALB/c and am3-C57BL/6 mice.

    PubMed

    Bucher, John R

    2007-01-01

    Sodium dichromate dihydrate is one of a number of inorganic compounds containing hexavalent chromium (CR VI) found in drinking water supplies as a contaminant resulting from various industrial processes including electroplating operations, leather tanning, and textile manufacturing. Because of the lack of adequate experimental data on the toxicity and carcinogenicity of hexavalent chromium ingested orally, and because hexavalent chromium has been found in human drinking water supplies, the California Congressional delegation and the California Environmental Protection Agency nominated hexavalent chromium to the NTP for study. In study 1, male and female F344/N rats and B6C3F1 mice were exposed to sodium dichromate dihydrate (greater than 99% pure) in drinking water for 3 months. In study 2, sodium dichromate dihydrate was administered in drinking water to male B6C3F1, BALB/c, and am3-C57BL/6 mice for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. In study 1, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were given drinking water containing 0, 62.5, 125, 250, 500, or 1,000 mg sodium dichromate dihydrate/L for 3 months (equivalent to average daily doses of approximately 5, 10, 17, 32, or 60 mg sodium dichromate dihydrate/kg body weight to rats and 9, 15, 26, 45, or 80 mg/kg to mice). On a molecular weight basis, these doses are equivalent to approximately 1.7, 3.5, 5.9, 11.2, and 20.9 mg hexavalent chromium/kg body weight per day to rats and 3.1, 5.2, 9.1, 15.7, and 27.9 mg/kg per day to mice. Additional groups of 10 rats per sex were exposed to the same concentrations of sodium dichromate dihydrate for 4 weeks. All rats and mice survived to the end of the study. Reduced body weights occurred in 500 and 1,000 mg/L male rats, 1,000 mg/L female rats, and in male and female mice exposed to 125 mg/L or greater. Water consumption by male and female rats exposed to 250

  9. SU-F-T-294: The Analysis of Gamma Criteria for Delta4 Dosimetry Using Statistical Process Control

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

    Cho, S; Ahn, S; Kim, J

    Purpose: To evaluate the sensitivity of gamma criteria for patient-specific volumetric modulated arc therapy(VMAT) quality assurance of the Delta{sup 4} dosimetry program using the statistical process control(SPC) methodology. Methods: The authors selected 20 patient-specific VMAT QA cases which were undertaken MapCHECK and ArcCHECK with gamma pass rate better than 97%. The QAs data were collected Delta4 Phantom+ and Elekta Agility six megavolts without using an angle incrementer. The gamma index(GI) were calculated in 2D planes with normalizing deviation to local dose(local gamma). The sensitivity of the GI methodology using criterion of 3%/3mm, 3%/2mm and 2%/3mm was analyzed with using processmore » acceptability indices. We used local confidence(LC) level, the upper control limit(UCL) and lower control limit(LCL) of I-MR chart for process capability index(Cp) and a process acceptability index (Cpk). Results: The lower local confidence levels of 3%/3mm, 3%/2mm and 2%/3mm were 92.0%, 83.6% and 78.8% respectively. All of the calculated Cp and Cpk values that used LC level were under 1.0 in this study. The calculated LCLs of I-MR charts were 89.5%, 79.0% and 70.5% respectively. These values were higher than 1.0 which means good quality of QA. For the generally used lower limit of 90%, we acquired over 1.3 of Cp value for the gamma index of 3%/3mm and lower than 1.0 in the rest of GI. Conclusion: We applied SPC methodology to evaluate the sensitivity of gamma criteria and could see the lower control limits of VMAT QA for the Delta 4 dosimetry and could see that Delta 4 phantom+ dosimetry more affected by the position error and the I-MR chart derived values are more suitable for establishing lower limits. Acknowledgement: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (No. 2015R1D1A1A01060463)« less

  10. NTP Toxicology and Carcinogenesis Studies of 3,3'-Dimethoxybenzidine Dihydrochloride (CAS No. 20325-40-0) in F344/N Rats (Drinking Water Studies).

    PubMed

    1990-01-01

    3,3'-Dimethoxybenzidine dihydrochloride is an off-white powder with a melting point of 274 degrees C. 3,3'-Dimethoxybenzidine is used principally as an intermediate in the production of commercial bisazobiphenyl dyes for coloring textiles, paper, plastic, rubber, and leather. In the synthesis of the bisazobiphenyl dyes, the amine groups of 3,3'-dimethoxybenzidine are chemically linked with other aromatic amines. A small quantity of 3,3'-dimethoxybenzidine is also used as an intermediate in the production of o-dianisidine diisocyanate, which is used in isocyanate-based adhesive systems and as a component of polyurethane elastomers. 3,3'-Dimethoxybenzidine dihydrochloride was evaluated in toxicity and carcinogenicity studies as part of the National Toxicology Program's Benzidine Dye Initiative. This Initiative was designed to evaluate the representative benzidine congeners and benzidine congener-derived and benzidine-derived dyes. 3,3'-Dimethoxybenzidine dihydrochloride was nominated for study because of the potential for human exposure during production of bisazobiphenyl dyes and because benzidine, a structurally related chemical, is a known human carcinogen. NTP Toxicology and Carcinogenesis studies were conducted by administering 3,3'-dimethoxybenzidine dihydrochloride (greater than 97.5% pure) in drinking water to groups of F344/N rats of each sex for 14 days, 13 weeks, 9 months, or 21-months. The 21-month studies were intended to last 24 months but were terminated early because of rapidly declining survival due to neoplasia. Studies were performed only in rats because similar studies are being performed in mice at the National Center for Toxicology Research. Genetic toxicology studies were conducted with Salmonella typhimurium, Chinese hamster over (CHO) cells, and Drosophila melanogaster. Fourteen-Day Studies: All rats receiving drinking water concentrations up to 4,500 ppm lived to the end of the studies. Rats that received water containing 4,500 ppm 3

  11. Investigation of leading-edge flap performance on delta and double-delta wings at supersonic speeds

    NASA Technical Reports Server (NTRS)

    Covell, Peter F.; Wood, Richard M.; Miller, David S.

    1987-01-01

    An investigation of the aerodynamic performance of leading-edge flaps on three clipped delta and three clipped double-delta wing planforms with aspect ratios of 1.75, 2.11, and 2.50 was conducted in the Langley Unitary Plan Wind Tunnel at Mach numbers of 1.60, 1.90, and 2.16. A primary set of fullspan leading-edge flaps with similar root and tip chords were investigated on each wing, and several alternate flap planforms were investigated on the aspect-ratio-1.75 wings. All leading-edge flap geometries were effective in reducing the drag at lifting conditions over the range of wing aspect ratios and Mach numbers tested. Application of a primary flap resulted in better flap performance with the double-delta planform than with the delta planform. The primary flap geometry generally yielded better performance than the alternate flap geometries tested. Trim drag due to flap-induced pitching moments was found to reduce the leading-edge flap performance more for the delta planform than for the double-delta planform. Flow-visualization techniques showed that leading-edge flap deflection reduces crossflow shock-induced separation effects. Finally, it was found that modified linear theory consistently predicts only the effects of leading-edge flap deflection as related to pitching moment and lift trends.

  12. Morphologic and stratigraphic evolution of muddy ebb-tidal deltas along a subsiding coast: Barataria Bay, Mississippi River delta

    USGS Publications Warehouse

    FitzGerald, D.M.; Kulp, M.; Penland, S.; Flocks, J.; Kindinger, J.

    2004-01-01

    The Barataria barrier coast formed between two major distributaries of the Mississippi River delta: the Plaquemines deltaic headland to the east and the Lafourche deltaic headland to the west. Rapid relative sea-level rise (1??03 cm year-1) and other erosional processes within Barataria Bay have led to substantial increases in the area of open water (> 775 km2 since 1956) and the attendant bay tidal prism. Historically, the increase in tidal discharge at inlets has produced larger channel cross-sections and prograding ebb-tidal deltas. For example, the ebb delta at Barataria Pass has built seaward > 2??2 km since the 1880s. Shoreline erosion and an increasing bay tidal prism also facilitated the formation of new inlets. Four major lithofacies characterize the Barataria coast ebb-tidal deltas and associated sedimentary environments. These include a proximal delta facies composed of massive to laminated, fine grey-brown to pale yellow sand and a distal delta facies consisting of thinly laminated, grey to pale yellow sand and silty sand with mud layers. The higher energy proximal delta deposits contain a greater percentage of sand (75-100%) compared with the distal delta sediments (60-80%). Associated sedimentary units include a nearshore facies consisting of horizontally laminated, fine to very fine grey sand with mud layers and an offshore facies that is composed of grey to dark grey, laminated sandy silt to silty clay. All facies coarsen upwards except the offshore facies, which fines upwards. An evolutionary model is presented for the stratigraphic development of the ebb-tidal deltas in a regime of increasing tidal energy resulting from coastal land loss and tidal prism growth. Ebb-tidal delta facies prograde over nearshore sediments, which interfinger with offshore facies. The seaward decrease in tidal current velocity of the ebb discharge produces a gradational contact between proximal and distal tidal delta facies. As the tidal discharge increases and the inlet

  13. Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats.

    PubMed

    McCarty; Pacak; Goldstein; Eisenhofer

    1997-12-01

    Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.

  14. CCDS concept paper: Delta-DOR

    NASA Technical Reports Server (NTRS)

    Berry, David S.; Broder, James S.

    2005-01-01

    This Concept Paper proposes the development of Consultative Committee for Space Data Systemes (CCSDS) standards for the deep space navigation technique known as 'delta-DOR' (Delta Differential One-Way Ranging).

  15. CCSDS concept paper: Delta-DOR

    NASA Technical Reports Server (NTRS)

    Berry, David S.; Border, James S.

    2005-01-01

    This Concept Paper proposes the development of Consultative Committee for Space Data Systems (CCSDS) standards for the deep space navigation technique known as 'delta-DOR' (Delta Differential One-Way Ranging).

  16. A Single Bout of Fasting (24 h) Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats.

    PubMed

    Speaker, Kristin J; Paton, Madeline M; Cox, Stewart S; Fleshner, Monika

    2016-01-01

    Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease), duration (transient versus chronic), and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to ad libitum access to food or fasted for 24 h prior to 0 (control), 10, or 100, 1.5 mA-5 s intermittent, inescapable tail shocks (IS). Glucose, nonesterified free fatty acids (NEFAs), insulin, leptin, and corticosterone were measured in plasma and tumor necrosis factor- (TNF-) α , interleukin- (IL-) 1 β , IL-6, and IL-10 in plasma, and subcutaneous, intraperitoneal, and visceral compartments of white adipose tissue (WAT). In control rats, a 24 h fast reduced all measured basal cytokines in plasma and visceral WAT, IL-1 β and IL-6 in subcutaneous WAT, and IL-6 in intraperitoneal WAT. In stressed rats (IS), fasting reduced visceral WAT TNF- α , subcutaneous WAT IL-1 β , and plasma insulin and leptin. Short-term fasting may thus prove to be a useful dietary strategy for reducing peripheral inflammatory states associated with visceral obesity and chronic stress.

  17. Resting-state EEG delta power is associated with psychological pain in adults with a history of depression.

    PubMed

    Meerwijk, Esther L; Ford, Judith M; Weiss, Sandra J

    2015-02-01

    Psychological pain is a prominent symptom of clinical depression. We asked if frontal alpha asymmetry, frontal EEG power, and frontal fractal dimension asymmetry predicted psychological pain in adults with a history of depression. Resting-state frontal EEG (F3/F4) was recorded while participants (N=35) sat upright with their eyes closed. Frontal delta power predicted psychological pain while controlling for depressive symptoms, with participants who exhibited less power experiencing greater psychological pain. Frontal fractal dimension asymmetry, a nonlinear measure of complexity, also predicted psychological pain, such that greater left than right complexity was associated with greater psychological pain. Frontal alpha asymmetry did not contribute unique variance to any regression model of psychological pain. As resting-state delta power is associated with the brain's default mode network, results suggest that the default mode network was less activated during high psychological pain. Findings are consistent with a state of arousal associated with psychological pain. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Tidal controls on river delta morphology

    NASA Astrophysics Data System (ADS)

    Hoitink, A. J. F.; Wang, Z. B.; Vermeulen, B.; Huismans, Y.; Kästner, K.

    2017-09-01

    River delta degradation has been caused by extraction of natural resources, sediment retention by reservoirs, and sea-level rise. Despite global concerns about these issues, human activity in the world’s largest deltas intensifies. Harbour development, construction of flood defences, sand mining and land reclamation emerge as key contemporary factors that exert an impact on delta morphology. Tides interacting with river discharge can play a crucial role in the morphodynamic development of deltas under pressure. Emerging insights into tidal controls on river delta morphology suggest that--despite the active morphodynamics in tidal channels and mouth bar regions--tidal motion acts to stabilize delta morphology at the landscape scale under the condition that sediment import during low flows largely balances sediment export during high flows. Distributary channels subject to tides show lower migration rates and are less easily flooded by the river because of opposing non-linear interactions between river discharge and the tide. These interactions lead to flow changes within channels, and a more uniform distribution of discharge across channels. Sediment depletion and rigorous human interventions in deltas, including storm surge defence works, disrupt the dynamic morphological equilibrium and can lead to erosion and severe scour at the channel bed, even decades after an intervention.

  19. Potential exposure of larval and juvenile delta smelt to dissolved pesticides in the Sacramento-San Joaquin Delta, California

    USGS Publications Warehouse

    Kuivila, K.M.; Moon, G.E.

    2004-01-01

    The San Francisco Estuary is critical habitat for delta smelt Hypomesus transpacificus, a fish whose abundance has declined greatly since 1983 and is now listed as threatened. In addition, the estuary receives drainage from the Central Valley, an urban and agricultural region with intense and diverse pesticide usage. One possible factor of the delta smelt population decline is pesticide toxicity during vulnerable larval and juvenile stages, but pesticide concentrations are not well characterized in delta smelt spawning and nursery habitat. The objective of this study was to estimate the potential exposure of delta smelt during their early life stages to dissolved pesticides. For 3 years (1998-2000), water samples from the Sacramento-San Joaquin Delta were collected during April-June in coordination with the California Department of Fish and Game's delta smelt early life stage monitoring program. Samples were analyzed for pesticides using solid-phase extraction and gas chromatography/mass spectrometry. Water samples contained multiple pesticides, ranging from 2 to 14 pesticides in each sample. In both 1999 and 2000, elevated concentrations of pesticides overlapped in time and space with peak densities of larval and juvenile delta smelt. In contrast, high spring outflows in 1998 transported delta smelt away from the pesticide sampling sites so that exposure could not be estimated. During 2 years, larval and juvenile delta smelt were potentially exposed to a complex mixture of pesticides for a minimum of 2-3 weeks. Although the measured concentrations were well below short-term (96-h) LC50 values for individual pesticides, the combination of multiple pesticides and lengthy exposure duration could potentially have lethal or sublethal effects on delta smelt, especially during early larval development.

  20. 21 CFR 184.1318 - Glucono delta-lactone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glucono delta-lactone. 184.1318 Section 184.1318... Listing of Specific Substances Affirmed as GRAS § 184.1318 Glucono delta-lactone. (a) Glucono delta-lactone (C6H10O6, CAS Reg. No. 90-80-2), also called D-gluconic acid delta-lactone or D-glucono-1,5...

  1. 21 CFR 184.1318 - Glucono delta-lactone.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glucono delta-lactone. 184.1318 Section 184.1318... Listing of Specific Substances Affirmed as GRAS § 184.1318 Glucono delta-lactone. (a) Glucono delta-lactone (C6H10O6, CAS Reg. No. 90-80-2), also called D-gluconic acid delta-lactone or D-glucono-1,5...

  2. Dissipation of the Proton Electrochemical Potential in Intact Chloroplasts (II. The pH Gradient Monitored by Cytochrome f Reduction Kinetics).

    PubMed Central

    Nishio, J. N.; Whitmarsh, J.

    1993-01-01

    The potency of various uncouplers for collapsing the light-induced pH gradient across thylakoid membranes in intact chloroplasts was investigated by time-resolved optical spectroscopy. The thylakoid transmembrane pH gradient ([delta]pH) was monitored indirectly by measuring the rate of cytochrome (Cyt) f reduction following a light flash of sufficient duration to create a sizable [delta]pH. The results show that the rate of Cyt f reduction is controlled in part by the internal pH of the thylakoid inner aqueous space. At pH values from 6.5 to 8.0, the Cyt f reduction rate was maximal, whereas at lower pH values from 6.5 to 5.5 the reduction rate decreased to 25% of the maximal rate. The ability of three uncouplers, nigericin, carbonylcyanide m-chlorophenylhydrazone, and gramicidin, to accelerate the rate of Cyt f reduction was determined for intact chloroplasts isolated from spinach (Spinacia oleracea). The efficacy of the uncouplers for collapsing the [delta]pH was determined using the empirical relationship between the [delta]pH and the Cyt f reduction rate. For intact chloroplasts, nigericin was the most effective uncoupler, followed by carbonylcyanide m-chlorophenylhydrazone, which interacted strongly with bovine serum albumin. Gramicidin D, even at high gramicidin:chlorophyll ratios, did not completely collapse the pH gradient, probably because it partitions in the envelope membranes and does not enter the intact chloroplast. PMID:12231669

  3. 124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

    PubMed Central

    2010-01-01

    Background 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of 18F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized CH2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaCH2), radiolabeled with iodine-124 (124I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging. Methods HuCC49deltaCH2 was radiolabeled with 124I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of 124I-HuCC49deltaCH2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of 18F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection. Results At approximately 1 hour after i.v. injection, 124I-HuCC49deltaCH2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, 124I-HuCC49deltaCH2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, 124I-HuCC49deltaCH2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, 18F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands

  4. Optimality and self-organization in river deltas

    NASA Astrophysics Data System (ADS)

    Tejedor, A.; Longjas, A.; Edmonds, D. A.; Zaliapin, I. V.; Georgiou, T. T.; Rinaldo, A.; Foufoula-Georgiou, E.

    2017-12-01

    Deltas are nourished by channel networks, whose connectivity constrains, if not drives, the evolution, functionality and resilience of these systems. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. However, in contrast to tributary channel networks, to date, no theory has been proposed to explain how deltas self-organize to distribute water and sediment to the delta top and the shoreline. Here, we hypothesize the existence of an optimality principle underlying the self-organized partition of fluxes in delta channel networks. Specifically, we hypothesize that deltas distribute water and sediment fluxes on a given delta topology such as to maximize the diversity of flux delivery to the shoreline. By introducing the concept of nonlocal Entropy Rate (nER) and analyzing ten field deltas in diverse environments, we present evidence that supports our hypothesis, suggesting that delta networks achieve dynamically accessible maxima of their nER. Furthermore, by analyzing six simulated deltas using the Delf3D model and following their topologic and flux re-organization before and after major avulsions, we further study the evolution of nER and confirm our hypothesis. We discuss how optimal flux distributions in terms of nER, when interpreted in terms of resilience, are configurations that reflect an increased ability to withstand perturbations.

  5. Subsidence driving forces in large Delta Plain

    NASA Astrophysics Data System (ADS)

    Grall, C.; Steckler, M. S.

    2017-12-01

    Recent studies show large variability in subsidence rates among large delta plains that directly impact coastal management of these highly vulnerable environments. Observations show both significant spatial variation in subsidence across each delta, as well as large differences in magnitude between different deltas. This variability raises the question of what are the driving forces that control subsidence in large delta plains that this study aims to address. Subsidence and sediment compaction is studied in 4 end-member large Delta Plains: the Ganges-Brahmaputra, the Mekong, the Mississippi and the Nile. Those large delta plains drastically contrast in subsidence rates (from values to several mm/yr to several cm/yr), in the nature of the sediment (notably in clay and organic matter content), and in the volume of sediment supplied by the large rivers that feed those coastal environments. The volume of sediment deposited in each delta plain during the Holocene is estimated and the compaction of the underlying sedimentary column is computed by using a backstripping approach. Sediment compaction behaviors are defined accordingly to the observed clay, silt and organic contents, and the rate of subsidence associated with compaction is determined. Results suggest that about 2/3 of observed Holocene subsidence may be associated with the mechanical and chemical compaction of the underlying sedimentary column due to the load of sediment deposited. The compaction appears to be significantly higher in delta plains characterized by a high sediment input and a high organic matter and clay content. Thus, the observed subsidence rates in the (muddy) Mekong delta appear to be one order of magnitude higher than other delta plains. In contrast, subsidence rates are modest in the Ganges-Brahmaputra, the Mississippi and the Nile delta plains, except away from the major rivers where deposits are muddier.

  6. Transcriptome Sequence and Plasmid Copy Number Analysis of the Brewery Isolate Pediococcus claussenii ATCC BAA-344T during Growth in Beer

    PubMed Central

    Pittet, Vanessa; Phister, Trevor G.; Ziola, Barry

    2013-01-01

    Growth of specific lactic acid bacteria in beer leads to spoiled product and economic loss for the brewing industry. Microbial growth is typically inhibited by the combined stresses found in beer (e.g., ethanol, hops, low pH, minimal nutrients); however, certain bacteria have adapted to grow in this harsh environment. Considering little is known about the mechanisms used by bacteria to grow in and spoil beer, transcriptome sequencing was performed on a variant of the beer-spoilage organism Pediococcus claussenii ATCC BAA-344T (Pc344-358). Illumina sequencing was used to compare the transcript levels in Pc344-358 growing mid-exponentially in beer to those in nutrient-rich MRS broth. Various operons demonstrated high gene expression in beer, several of which are involved in nutrient acquisition and overcoming the inhibitory effects of hop compounds. As well, genes functioning in cell membrane modification and biosynthesis demonstrated significantly higher transcript levels in Pc344-358 growing in beer. Three plasmids had the majority of their genes showing increased transcript levels in beer, whereas the two cryptic plasmids showed slightly decreased gene expression. Follow-up analysis of plasmid copy number in both growth environments revealed similar trends, where more copies of the three non-cryptic plasmids were found in Pc344-358 growing in beer. Transcriptome sequencing also enabled the addition of several genes to the P . claussenii ATCC BAA-344T genome annotation, some of which are putatively transcribed as non-coding RNAs. The sequencing results not only provide the first transcriptome description of a beer-spoilage organism while growing in beer, but they also highlight several targets for future exploration, including genes that may have a role in the general stress response of lactic acid bacteria. PMID:24040005

  7. F-region neutral winds from ionosonde measurements of h/sub mF2/ at low-latitude magnetic conjugate regions

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

    Bittencourt, J.A.

    1977-08-01

    The behavior of the F2-peak height difference, delta h/sub F2/, between low-latitude magnetic conjugate points, is known to be governed by thermospheric winds blowing along the magnetic meridian. Ground-based ionosonde measurement of h/sub m F2/, at two pairs of magnetic conjugate stations, were analyzed in conjunction with the results of a realistic dynamic computer model of the tropical ionospheric F-region, to determine thermospheric wind velocities. The behavior of monthly average values of the sun, at conjugate points, of the thermospheric horizontal wind velocity component in the magnetic meridian, at low latitudes, is inferred for months of solstice and equinox, asmore » well as for periods of low and high solar activity.« less

  8. Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: Effect of anatomical site

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

    Moody, R.P.; Ritter, L.

    1989-01-01

    Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of themore » forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical.« less

  9. Observation of TiF+ by Velocity Modulation Laser Spectroscopy and Analysis of the

    PubMed

    Focsa; Pinchemel; Collet; Huet

    1998-06-01

    The molecular ion TiF+ has been observed for the first time using high-resolution spectroscopy. The ions were produced in the positive column of an AC glow discharge with a gas mixture of He/TiF4. A single-mode cw dye laser along with the velocity modulation detection technique was used to record an absorption spectrum in the spectral region 16 800-18 600 cm-1. The observed system was assigned to the 0-0 and 1-1 bands of the [17.6]3Delta-X3Phi transition of TiF+. The rotational analysis of the main subbands has been performed up to J values equal to 77 and 56 for the 0-0 and 1-1 bands, respectively. Despite a careful search, no intercombination band was observed. A set of effective molecular parameters has been determined, characterizing the v = 0, 1 levels of the [17.6]3Delta and X3Phi states. The spin-orbit constants Ae and the vibrational constants omegae, omegaexe have been estimated for both electronic states, as well as their equilibrium distances Re (1.7509 and 1.7800) Å for the [17.6]3Delta and X3Phi states, respectively). Copyright 1998 Academic Press.

  10. The Concentration Dependence of the (Delta)s Term in the Gibbs Free Energy Function: Application to Reversible Reactions in Biochemistry

    ERIC Educational Resources Information Center

    Gary, Ronald K.

    2004-01-01

    The concentration dependence of (delta)S term in the Gibbs free energy function is described in relation to its application to reversible reactions in biochemistry. An intuitive and non-mathematical argument for the concentration dependence of the (delta)S term in the Gibbs free energy equation is derived and the applicability of the equation to…

  11. 78 FR 21491 - DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-10

    ... SMALL BUSINESS ADMINISTRATION [License No. 02/02-0662, 02/02-0661] DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that DeltaPoint Capital IV, L.P. and DeltaPoint...

  12. The Synthetic α-Bromo-2′,3,4,4′-Tetramethoxychalcone (α-Br-TMC) Inhibits the JAK/STAT Signaling Pathway

    PubMed Central

    Brueggemann, Susanne; Besl, Elisabeth; Al-Rifai, Nafisah; Petkes, Hermina; Amslinger, Sabine; Rascle, Anne

    2014-01-01

    Signal transducer and activator of transcription STAT5 and its upstream activating kinase JAK2 are essential mediators of cytokine signaling. Their activity is normally tightly regulated and transient. However, constitutive activation of STAT5 is found in numerous cancers and a driving force for malignant transformation. We describe here the identification of the synthetic chalcone α-Br-2′,3,4,4′-tetramethoxychalcone (α-Br-TMC) as a novel JAK/STAT inhibitor. Using the non-transformed IL-3-dependent B cell line Ba/F3 and its oncogenic derivative Ba/F3-1*6 expressing constitutively activated STAT5, we show that α-Br-TMC targets the JAK/STAT pathway at multiple levels, inhibiting both JAK2 and STAT5 phosphorylation. Moreover, α-Br-TMC alters the mobility of STAT5A/B proteins in SDS-PAGE, indicating a change in their post-translational modification state. These alterations correlate with a decreased association of STAT5 and RNA polymerase II with STAT5 target genes in chromatin immunoprecipitation assays. Interestingly, expression of STAT5 target genes such as Cis and c-Myc was differentially regulated by α-Br-TMC in normal and cancer cells. While both genes were inhibited in IL-3-stimulated Ba/F3 cells, expression of the oncogene c-Myc was down-regulated and that of the tumor suppressor gene Cis was up-regulated in transformed Ba/F3-1*6 cells. The synthetic chalcone α-Br-TMC might therefore represent a promising novel anticancer agent for therapeutic intervention in STAT5-associated malignancies. PMID:24595334

  13. Cattle Grazing in Delta Forests

    Treesearch

    Robert L. Johnson

    1960-01-01

    What effects do grazing cattle have on the hardwood forests of the Mississippi Delta? What is the value of the forage to the cattle? To answer such questions, grazing studies were conducted in 1957 on the Delta Experimental Forest, near Stoneville.

  14. 31 CFR 344.9 - How do I redeem a Demand Deposit security?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false How do I redeem a Demand Deposit...-STATE AND LOCAL GOVERNMENT SERIES Demand Deposit Securities § 344.9 How do I redeem a Demand Deposit security? (a) When must I notify Fiscal Service to redeem a security? A Demand Deposit security can be...

  15. 31 CFR 344.9 - How do I redeem a Demand Deposit security?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false How do I redeem a Demand Deposit...-STATE AND LOCAL GOVERNMENT SERIES Demand Deposit Securities § 344.9 How do I redeem a Demand Deposit security? (a) When must I notify BPD to redeem a security? A Demand Deposit security can be redeemed at the...

  16. 31 CFR 344.9 - How do I redeem a Demand Deposit security?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false How do I redeem a Demand Deposit...-STATE AND LOCAL GOVERNMENT SERIES Demand Deposit Securities § 344.9 How do I redeem a Demand Deposit security? (a) When must I notify BPD to redeem a security? A Demand Deposit security can be redeemed at the...

  17. 31 CFR 344.9 - How do I redeem a Demand Deposit security?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false How do I redeem a Demand Deposit...-STATE AND LOCAL GOVERNMENT SERIES Demand Deposit Securities § 344.9 How do I redeem a Demand Deposit security? (a) When must I notify BPD to redeem a security? A Demand Deposit security can be redeemed at the...

  18. 31 CFR 344.9 - How do I redeem a Demand Deposit security?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false How do I redeem a Demand Deposit...-STATE AND LOCAL GOVERNMENT SERIES Demand Deposit Securities § 344.9 How do I redeem a Demand Deposit security? (a) When must I notify BPD to redeem a security? A Demand Deposit security can be redeemed at the...

  19. Delta Clipper vehicle design for supportability

    NASA Astrophysics Data System (ADS)

    Smiljanic, Ray R.; Klevatt, Paul L.; Steinmeyer, Donald A.

    1993-02-01

    The paper describes the Single Stage Rocket Technology (SSRT) Delta Clipper vehicle design. As a means of reducing vehicle processing and turnaround times, the SSRT Delta Clipper design, contrary to past practices, incorporates support ability engineering features into its initial set of design requirements. The engineering process used to 'design-in' supportability into the Delta Clipper vehicle is described in detail and is illustrated using diagrams.

  20. Changes in the areal extents of the Athabasca River, Birch River, and Cree Creek Deltas, 1950-2014, Peace-Athabasca Delta, Canada

    NASA Astrophysics Data System (ADS)

    Timoney, Kevin; Lee, Peter

    2016-04-01

    Deltas form where riverborne sediment accumulates at the interface of river mouths and their receiving water bodies. Their areal extent is determined by the net effect of processes that increase their extent, such as sediment accumulation, and processes that decrease their extent, such as erosion and subsidence. Through sequential mapping and construction of river discharge and sediment histories, this study examined changes in the subaerial extents of the Cree Creek and Athabasca River Deltas (both on the Athabasca River system) and the Birch River Delta in northern Canada over the period 1950-2014. The purpose of the study was to determine how, when, and why the deltas changed in areal extent. Temporal growth patterns were similar across the Athabasca and Birch River systems indicative of a climatic signal. Little or no areal growth occurred from 1950 to 1968; moderate growth occurred between 1968 and the early to mid-1980s; and rapid growth occurred between 1992 and 2012. Factors that affected delta progradation included dredging, sediment supply, isostatic drowning, delta front bathymetry, sediment capture efficiency, and storms. In relation to sediment delivered, areal growth rates were lowest in the Athabasca Delta, intermediate in the Birch Delta, and highest in the Cree Creek Delta. Annual sediment delivery is increasing in the Cree Creek Delta; there were no significant trends in annual sediment delivery in the Birch and Athabasca Deltas. There was a lag of up to several years between sediment delivery events and progradation. Periods of delta progradation were associated with low water levels of the receiving basins. Predicted climate-change driven declines in river discharge and lake levels may accelerate delta progradation in the region. In the changing ecosystems of northeastern Alberta, inadequate monitoring of vegetation, landforms, and sediment regimes hampers the elucidation of the nature, rate, and causality of ecosystem changes.