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Sample records for nf nf nf

  1. NF_Eder_2013

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    24 October 2013 Online at stacks.iop.orgNF53113037 Abstract Modelling and mitigation of damage are crucial for safe and economical operation of high-power laser facilities. ...

  2. NF Energy Saving Corp | Open Energy Information

    Open Energy Info (EERE)

    NF Energy Saving Corp Jump to: navigation, search Name: NF Energy Saving Corp Place: Shenyang, Liaoning Province, China Sector: Services Product: China-based company provides...

  3. ARM - VAP Product - aerich2nf1turn

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Productsaerinfaerich2nf1turn Documentation Data Management Facility Plots (Quick Looks) Citation DOI: 10.54391027273 What is this? Generate Citation ARM Data Discovery Browse...

  4. ARM - VAP Product - aerich1nf1turn

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Productsaerinfaerich1nf1turn Documentation Data Management Facility Plots (Quick Looks) Citation DOI: 10.54391027272 What is this? Generate Citation ARM Data Discovery Browse...

  5. CMRR-NF Supplemental EIS Scoping Comments | National Nuclear Security

    National Nuclear Security Administration (NNSA)

    Administration | (NNSA) CMRR-NF Supplemental EIS Scoping Comments CMRR-NF Supplemental EIS Scoping Comments Additional CMRR Scoping Comments - 47A Additional CMRR Scoping Comments - 48A Additional CMRR Scoping Comments - 62 Additional CMRR Scoping Comments - 63 Additional CMRR Scoping Comments - 64 Additional CMRR Scoping Comments - 66A Additional CMRR Scoping Comments - 66B Additional CMRR Scoping Comments - 66C Additional CMRR Scoping Comments - 76 Additional CMRR Scoping Comments - 77

  6. IDS-NF Impact of Neutrino Cross Section Impact of Neutrino Cross Section

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    IDS-NF Impact of Neutrino Cross Section Impact of Neutrino Cross Section Knowledge on Oscillation Knowledge on Oscillation Measurements Measurements M. Sorel, IFIC (CSIC and U. of Valencia) IDS-NF, RAL, Jan 16-17 2008 M. Sorel - IFIC (Valencia U. & CSIC) 2 IDS-NF Neutrino Cross Sections: At What Energies Needed? Superbeams: Solid: T2K Dashed: NovA M. Sorel - IFIC (Valencia U. & CSIC) 3 IDS-NF Neutrino Cross Sections: At What Energies Needed? Superbeams: Solid: T2K Dashed: NovA Beta

  7. Smoothing single-crystalline SiC surfaces by reactive ion etching using pure NF{sub 3} and NF{sub 3}/Ar mixture gas plasmas

    SciTech Connect (OSTI)

    Tasaka, Akimasa; Kotaka, Yuki; Oda, Atsushi; Saito, Morihiro; Tojo, Tetsuro; Inaba, Minoru

    2014-09-01

    In pure NF{sub 3} plasma, the etching rates of four kinds of single-crystalline SiC wafer etched at NF{sub 3} pressure of 2 Pa were the highest and it decreased with an increase in NF{sub 3} pressure. On the other hand, they increased with an increase in radio frequency (RF) power and were the highest at RF power of 200 W. A smooth surface was obtained on the single-crystalline 4H-SiC after reactive ion etching at NF{sub 3}/Ar gas pressure of 2 Pa and addition of Ar to NF{sub 3} plasma increased the smoothness of SiC surface. Scanning electron microscopy observation revealed that the number of pillars decreased with an increase in the Ar-concentration in the NF{sub 3}/Ar mixture gas. The roughness factor (R{sub a}) values were decreased from 51.5 nm to 25.5 nm for the As-cut SiC, from 0.25 nm to 0.20 nm for the Epi-SiC, from 5.0 nm to 0.7 nm for the Si-face mirror-polished SiC, and from 0.20 nm to 0.16 nm for the C-face mirror-polished SiC by adding 60% Ar to the NF{sub 3} gas. Both the R{sub a} values of the Epi- and the C-face mirror-polished wafer surfaces etched using the NF{sub 3}/Ar (40:60) plasma were similar to that treated with mirror polishing, so-called the Catalyst-Referred Etching (CARE) method, with which the lowest roughness of surface was obtained among the chemical mirror polishing methods. Etching duration for smoothing the single-crystalline SiC surface using its treatment was one third of that with the CARE method.

  8. Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NF{kappa}B

    SciTech Connect (OSTI)

    Eliseev, Roman A. . E-mail: Roman_Eliseev@urmc.rochester.edu; Schwarz, Edward M.; Zuscik, Michael J.; O'Keefe, Regis J.; Drissi, Hicham; Rosier, Randy N.

    2006-01-01

    The transcription factor NF{kappa}B is constitutively activated in various tumor cells where it promotes proliferation and represses apoptosis. The bone morphogenetic proteins (BMPs) delay cell proliferation and promote differentiation and apoptosis of bone cells through activation of Smad downstream effectors and via Smad-independent mechanisms. Thus, NF{kappa}B and BMP pathways play opposing roles in regulating osteoblastic cell fate. Here, we show that in osteosarcoma Saos2 osteoblasts, NF{kappa}B regulates the activity of the BMP/Smad signaling. Inhibition of NF{kappa}B by overexpression of mI{kappa}B leads to the induction of osteoblast differentiation. Saos2 cells overexpressing mI{kappa}B (Saos2-mI{kappa}B) exhibit higher expression of osteoblast phenotypic genes such as alkaline phosphatase, Runx2 and osteocalcin and are more responsive to BMP2 in comparison to wild-type cells (Saos2-wt) or empty vector infected controls (Saos2-EV). Furthermore, BMP-2 signaling and Smad phosphorylation are significantly increased in Saos2-mI{kappa}B cells in comparison to Saos2-EV cells. Inhibition of NF{kappa}B signaling in Saos2-mI{kappa}B cells is associated with decreased expression of the BMP signaling inhibitor Smad7. While gain of Smad7 function in Saos2-mI{kappa}B cells results in inhibition of BMP signaling, anti-sense knockdown of Smad7 in Saos2-EV cells leads to upregulation of BMP signaling. We therefore conclude that in osteosarcoma Saos2 cells, NF{kappa}B represses BMP/Smad signaling and BMP2-induced differentiation through Smad7.

  9. Regulation Of Nf=kb And Mnsod In Low Dose Radiation Induced Adaptive Protection Of Mouse And Human Skin Cells

    SciTech Connect (OSTI)

    Jian Li

    2012-11-07

    A sampling of publications resulting from this grant is provided. One is on the subject of NF-κB-Mediated HER2 Overexpression in Radiation-Adaptive Resistance. Another is on NF-κB-mediated adaptive resistance to ionizing radiation.

  10. Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling

    SciTech Connect (OSTI)

    Jackson, Shawn S.; Oberley, Christopher; Hooper, Christopher P.; Grindle, Kreg; Wuerzberger-Davis, Shelly; Wolff, Jared; and others

    2015-02-01

    The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced by TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO–IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF-induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMO{sup Y308S} mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo. - Highlights: • Withaferin A, a NF-κB inhibitor, disrupts signaling induced NEMO localization, a novel point of inhibition. • NEMO can be localized to distinct signaling foci after treatment with TNF. • ABC-type DLCBL cells can be sensitized to apoptosis after treatment with Withaferin A.

  11. Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

    SciTech Connect (OSTI)

    Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao; and others

    2015-07-10

    Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

  12. Coal dust contiguity-induced changes in the concentration of TNF- and NF- B p65 on the ocular surface

    SciTech Connect (OSTI)

    Sun, Z.Y.; Hong, J.; Liu, Z.Y.; Jin, X.D.; Gu, C.H.

    2009-07-01

    To observe the influence of coal dust on ocular surface of coal miners and rabbits with coal dust contiguity on expression TNF- and NF- Bp65 and dry eye occurrence. Expression TNF- and NF- Bp65 in ocular surface were determined. Results showed tear production, BUT and lysozyme decreased for coal miners and rabbits with coal dust contiguity. Coal dust exposure was linked to development of xerophthalmia, and induced a higher expression of NF- B p65 and TNF- perhaps as a mechanism to resist coal dust ocular surface injury.

  13. BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

    SciTech Connect (OSTI)

    Zhang, Zhi-Xin; Liu, Zhi-Qiang; Jiang, Biao; Lu, Xin-Yang; Ning, Xiao-Fei; Yuan, Chuan-Tao; Wang, Ai-Liang

    2015-09-18

    Background and objective: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. Methods: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. Results: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. Conclusion: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis. - Highlights: • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823. • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis. • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression. • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth. • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth.

  14. XEDAR activates the non-canonical NF-κB pathway

    SciTech Connect (OSTI)

    Verhelst, Kelly; Gardam, Sandra; Borghi, Alice; Kreike, Marja; Carpentier, Isabelle; Beyaert, Rudi

    2015-09-18

    Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.

  15. Agreement Execution Process Study: CRADAs and NF-WFO Agreements and the Speed of Business

    SciTech Connect (OSTI)

    Harrer, Bruce J.; Cejka, Cheryl L.; Macklin, Richard; Miksovic, Ann

    2011-02-01

    This report summarizes the findings of a study on the execution of Cooperative Research and Development Agreements (CRADAs) and Non-Federal Work for Others (NF-WFO) agreements across the U.S. Department of Energy (DOE) laboratory complex. The study provides quantitiative estimates of times required to negotiate and execute these agreements across the DOE complex. It identifies factors impacting on cycle times and describes best practicies used at various laboratories and site offices that reduce cycle times.

  16. Characterization of the Kinetics of NF3-Fluorination of NpO2

    SciTech Connect (OSTI)

    Casella, Andrew M.; Scheele, Randall D.; McNamara, Bruce K.

    2015-12-23

    The exploitation of selected actinide and fission product fluoride volatilities has long been considered as a potentially attractive compact method for recycling used nuclear fuels to avoid generating the large volumes of radioactive waste arising from aqueous reprocessing [1-7]. The most developed process uses the aggressive and hazardous fluorinating agents hydrogen fluoride (HF) and/or molecular fluorine (F2) at high temperatures to volatilize the greatest fraction of the used nuclear fuel into a single gas stream. The volatilized fluorides are subsequently separated using a series of fractionation and condensation columns to recover the valuable fuel constituents and fission products. In pursuit of a safer and less complicated approach, we investigated an alternative fluoride volatility-based process using the less hazardous fluorinating agent nitrogen trifluoride (NF3) and leveraging its less aggressive nature to selectively evolve fission product and actinide fluorides from the solid phase based on their reaction temperatures into a single recycle stream [8-15]. In this approach, successive isothermal treatments using NF3 will first evolve the more thermally susceptible used nuclear fuel constituents leaving the other constituents in the residual solids until subsequent isothermal temperature treatments cause these others to volatilize. During investigation of this process, individual neat used fuel components were treated with isothermal NF3 in an attempt to characterize the kinetics of each fluorination reaction to provide input into the design of a new volatile fluoride separations approach. In these directed investigations, complex behavior was observed between NF3 and certain solid reactants such as the actinide oxides of uranium, plutonium, and neptunium. Given the similar thermal reaction susceptibilities of neptunium oxide (NpO2) and uranium dioxide (UO2) and the importance of Np and U, we initially focused our efforts on determining the reaction

  17. Nickel differentially regulates NFAT and NF-{kappa}B activation in T cell signaling

    SciTech Connect (OSTI)

    Saito, Rumiko; Hirakawa, Satoshi; Ohara, Hiroshi; Yasuda, Makoto; Yamazaki, Tomomi; Nishii, Shigeaki; Aiba, Setsuya

    2011-08-01

    Nickel is a potent hapten that induces contact hypersensitivity in human skin. While nickel induces the maturation of dendritic cells via NF-{kappa}B and p38 MAPK activation, it also exerts immunosuppressive effects on T cells through an unknown mechanism. To elucidate the molecular mechanisms of its effects on T cells, we examined the effects of NiCl{sub 2} on mRNA expression in human CD3+ T cells stimulated with CD3 and CD28 antibodies. Using a DNA microarray and Gene Ontology, we identified 70 up-regulated (including IL-1{beta}, IL-6 and IL-8) and 61 down-regulated (including IL-2, IL-4, IL-10 and IFN-{gamma}) immune responsive genes in NiCl{sub 2}-treated T cells. The DNA microarray results were verified using real-time PCR and a Bio-Plex{sup TM} suspension protein array. Suppression of IL-2 and IFN-{gamma} gene transcription by NiCl{sub 2} was also confirmed using Jurkat T cells transfected with IL-2 or IFN-{gamma} luciferase reporter genes. To explore the NiCl{sub 2}-regulated signaling pathway, we examined the binding activity of nuclear proteins to NFAT, AP-1, and NF-{kappa}B consensus sequences. NiCl{sub 2} significantly and dose-dependently suppressed NFAT- and AP-1-binding activity, but augmented NF-{kappa}B-binding activity. Moreover, NiCl{sub 2} decreased nuclear NFAT expression in stimulated T cells. Using Jurkat T cells stimulated with PMA/ionomycin, we demonstrated that NiCl{sub 2} significantly suppressed stimulation-evoked cytosolic Ca{sup 2+} increases, suggesting that NiCl{sub 2} regulates NFAT signals by acting as a blocker of Ca{sup 2+} release-activated Ca{sup 2+} (CRAC) channels. These data showed that NiCl{sub 2} decreases NFAT and increases NF-{kappa}B signaling in T cells. These results shed light on the effects of nickel on the molecular regulation of T cell signaling. - Graphical Abstract: Nickel suppresses stimulation-evoked cytosolic Ca{sup 2+} increase, which results in the suppression of NFAT signals. On the other hand, Ni rather

  18. Constitutive NF-?B activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production

    SciTech Connect (OSTI)

    Chung, Jin Sil; Lee, Sora; Yoo, Young Do

    2014-08-08

    Highlights: Romo1 expression is required for constitutive nuclear DNA-binding activity of NF-?B. Romo1 depletion suppresses tumor growth in vivo. Romo1 presents a potential therapeutic target for diseases. - Abstract: Deregulation of nuclear factor-?B (NF-?B) and related pathways contribute to tumor cell proliferation and invasion. Mechanisms for constitutive NF-?B activation are not fully explained; however, the underlying defects appear to generate and maintain pro-oxidative conditions. In hepatocellular carcinoma (HCC) tissues, up-regulation of reactive oxygen species modulator 1 (Romo1) correlates positively with tumor size. In the present study, we showed that Romo1 expression is required to maintain constitutive nuclear DNA-binding activity of NF-?B and transcriptional activity through constitutive I?B? phosphorylation. Overexpression of Romo1 promoted p65 nuclear translocation and DNA-binding activity. We also show that Romo1 depletion suppressed anchorage-independent colony formation by HCC cells and suppressed tumor growth in vivo. Based on these findings, Romo1 may be a principal regulatory factor in the maintenance of constitutive NF-?B activation in tumor cells. In the interest of anti-proliferative treatments for cancer, Romo1 may also present a productive target for drug development.

  19. XIAP Induces NF-kB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization

    SciTech Connect (OSTI)

    Lu,M.; Lin, S.; Huang, Y.; Kang, Y.; Rich, R.; Lo, Y.; Myszka, D.; Han, J.; Wu, H.

    2007-01-01

    In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP) induces NF-{kappa}B and MAP kinase activation during TGF-b and BMP receptor signaling and upon overexpression. Here we show that the BIR1 domain of XIAP, which has no previously ascribed function, directly interacts with TAB1 to induce NF-{kappa}B activation. TAB1 is an upstream adaptor for the activation of the kinase TAK1, which in turn couples to the NF-{kappa}B pathway. We report the crystal structures of BIR1, TAB1, and the BIR1/TAB1 complex. The BIR1/TAB1 structure reveals a striking butterfly-shaped dimer and the detailed interaction between BIR1 and TAB1. Structure-based mutagenesis and knockdown of TAB1 show unambiguously that the BIR1/TAB1 interaction is crucial for XIAP-induced TAK1 and NF-{kappa}B activation. We show that although not interacting with BIR1, Smac, the antagonist for caspase inhibition by XIAP, also inhibits the XIAP/TAB1 interaction. Disruption of BIR1 dimerization abolishes XIAP-mediated NF-{kappa}B activation, implicating a proximity-induced mechanism for TAK1 activation.

  20. FY13 Summary Report on the Augmentation of the Spent Fuel Composition Dataset for Nuclear Forensics: SFCOMPO/NF

    SciTech Connect (OSTI)

    Brady Raap, Michaele C.; Lyons, Jennifer A.; Collins, Brian A.; Livingston, James V.

    2014-03-31

    This report documents the FY13 efforts to enhance a dataset of spent nuclear fuel isotopic composition data for use in developing intrinsic signatures for nuclear forensics. A review and collection of data from the open literature was performed in FY10. In FY11, the Spent Fuel COMPOsition (SFCOMPO) excel-based dataset for nuclear forensics (NF), SFCOMPO/NF was established and measured data for graphite production reactors, Boiling Water Reactors (BWRs) and Pressurized Water Reactors (PWRs) were added to the dataset and expanded to include a consistent set of data simulated by calculations. A test was performed to determine whether the SFCOMPO/NF dataset will be useful for the analysis and identification of reactor types from isotopic ratios observed in interdicted samples.

  1. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    SciTech Connect (OSTI)

    Park, Sung-Dong; Cheon, So Yeong; Park, Tae-Yoon; Shin, Bo-Young; Oh, Hyunju; Ghosh, Sankar; Koo, Bon-Nyeo; Lee, Sang-Kyou

    2015-08-28

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model.

  2. 3D calculation of Tucson-Melbourne 3NF effect in triton binding energy

    SciTech Connect (OSTI)

    Hadizadeh, M. R.; Tomio, L.; Bayegan, S.

    2010-08-04

    As an application of the new realistic three-dimensional (3D) formalism reported recently for three-nucleon (3N) bound states, an attempt is made to study the effect of three-nucleon forces (3NFs) in triton binding energy in a non partial wave (PW) approach. The spin-isospin dependent 3N Faddeev integral equations with the inclusion of 3NFs, which are formulated as function of vector Jacobi momenta, specifically the magnitudes of the momenta and the angle between them, are solved with Bonn-B and Tucson-Melbourne NN and 3N forces in operator forms which can be incorporated in our 3D formalism. The comparison with numerical results in both, novel 3D and standard PW schemes, shows that non PW calculations avoid the very involved angular momentum algebra occurring for the permutations and transformations and it is more efficient and less cumbersome for considering the 3NF.

  3. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERKNF-?B signaling pathway

    SciTech Connect (OSTI)

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun; Gu, Wei; Wan, Xiao-Ping

    2014-03-28

    Highlights: IL-6 could promote endometrial cancer cells proliferation. IL-6 promotes its own production through an autocrine feedback loop. ERK and NF-?B pathway inhibitors inhibit IL-6 production and tumor growth. IL-6 secretion relies on the activation of ERKNF-?B pathway axis. An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-?B) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-?B pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERKNF-?B pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.

  4. 27-Oxygenated cholesterol induces expression of CXCL8 in macrophages via NF-κB and CD88

    SciTech Connect (OSTI)

    Kim, Sun-Mi; Lee, Chung Won; Kim, Bo-Young; Jung, Young-Suk; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

    2015-08-07

    We attempted to determine the effects of a milieu rich in cholesterol molecules on expression of chemokine CXCL8. A high-cholesterol diet led to an increased transcription of the IL-8 gene in the arteries and elevated levels of CXCL8 in sera of ApoE{sup −/−} mice, compared with those of wild-type C57BL/6 mice. Treatment of THP-1 monocyte/macrophage cells with 27-hydroxycholesterol (27OHChol) resulted in transcription of the IL-8 gene and increased secretion of its corresponding gene product whereas cholesterol did not induce expression of CXCL8 in THP-1 cells. 27OHChol-induced transcription of the IL-8 gene was blocked by cycloheximide, but not by polymyxin B. Treatment of THP-1 cells with 27OHChol caused translocation of p65 NF-κB subunit into the nucleus and up-regulation of CD88. Inhibition of NF-κB and CD88 using SN50 and W-54011, respectively, resulted in reduced transcription of the IL-8 gene and attenuated secretion of CXCL8 induced by 27OHChol. We propose that oxidatively modified cholesterol like 27OHChol, rather than cholesterol, is responsible for sustained expression of CXCL8 in monocytes/macrophages in atherosclerotic arteries. - Highlights: • Consumption of a high-cholesterol diet leads to increased CXCL8 expression in ApoE{sup −/−} mice. • 27OHChol, but not cholesterol, up-regulates expression of CXCL8 in macrophages. • 27OHChol enhances nuclear translocation of NF-κB and expression of CD88 in macrophages. • Inhibition of NF-κB or CD88 results in decreased CXCL8 expression induced by 27OHChol. • 27OHChol up-regulates CXCL8 expression via NF-κB and CD88 in macrophages.

  5. miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

    SciTech Connect (OSTI)

    Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

    2014-09-26

    Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

  6. PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling

    SciTech Connect (OSTI)

    Zheng, Peihao; Guo, Honggang; Li, Guangchao; Han, Siqi; Luo, Fei; Liu, Yi

    2015-03-06

    Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies. - Highlights: • First reported upregulation of PSMB4 in MM plasma and cell lines. • PSMB4 promoted MM cell growth and colony forming ability. • Further found miR-21 was up-regulated by PSMB4 in MM plasma and cell lines. • PSMB4-induced miR-21 expression was modulated by NF-κB. • PSMB4-NF-κB-miR-21 axis may be potential therapeutic targets of MM.

  7. High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells

    SciTech Connect (OSTI)

    Huang, Wei; Department of Endocrinology, The People’s Hospital of Xindu, Xindu, Sichuang, 610500 ; Xu, Ling; Zhou, Xueqin; Department of Endocrinology, The People’s Hospital of Leshan, Sichuang ; Gao, Chenlin; Yang, Maojun; Chen, Guo; Zhu, Jianhua; Jiang, Lan; Gan, Huakui; Gou, Fang; Feng, Hong; Peng, Juan; Xu, Yong

    2013-08-30

    Highlights: •The expression of SUMO1, SUMO2/3 under high glucose was obviously enhanced. •High glucose induced degradation of IκBα and activation of NF-κB pathway. •Sumoylation of IκBα in high glucose were significantly decreased. •The proteasome inhibitor MG132 could partially revert the degradation of IκBα. -- Abstract: The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p < 0.05). However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which

  8. Thermal Reactions of Uranium Metal, UO2, U3O8, UF4, and UO2F2 with NF3 to Produce UF6

    SciTech Connect (OSTI)

    McNamara, Bruce K.; Scheele, Randall D.; Kozelisky, Anne E.; Edwards, Matthew K.

    2009-11-01

    he objective of this paper is to demonstrate that NF3 fluorinates uranium metal, UO2, UF4, UO3, U3O8, and UO2F22H2O to produce the volatile UF6 at temperatures between 100 and 500?C. Thermogravimetric reaction profiles are described that reflect changes in the uranium oxidation state and discrete chemical speciation. Differences in the onset temperatures for each system indicate that NF3-substrate interactions are important for the temperature at which NF3 reacts: U metal > UO3 > UO2 > UO2F2 > UF4 and in fact may indicate different fluorination mechanisms for these various substrates. These studies demonstrate that NF3 is a potential replacement fluorinating agent in the existing nuclear fuel cycle and in oft-proposed actinide volatility reprocessing.

  9. Microstructural evolution of NF709 (20Cr–25Ni–1.5MoNbTiN) under neutron irradiation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Kim, Byoungkoo; Tan, Lizhen; Xu, C.; Yang, Yong; Zhang, Xuan; Li, Meimei

    2015-12-30

    In this study, because of its superior creep and corrosion resistance as compared with general austenitic stainless steels, NF709 has emerged as a candidate structural material for advanced nuclear reactors. To obtain fundamental information about the radiation resistance of this material, this study examined the microstructural evolution of NF709 subjected to neutron irradiation to 3 displacements per atom at 500 °C. Transmission electron microscopy, scanning electron microscopy, and high-energy x-ray diffraction were employed to characterize radiation-induced segregation, Frank loops, voids, as well as the formation and reduction of precipitates. Radiation hardening of ~76% was estimated by nanoindentation, approximately consistent withmore » the calculation according to the dispersed barrier-hardening model, suggesting Frank loops as the primary hardening source.« less

  10. Microstructural evolution of NF709 (20Cr–25Ni–1.5MoNbTiN) under neutron irradiation

    SciTech Connect (OSTI)

    Kim, Byoungkoo; Tan, Lizhen; Xu, C.; Yang, Yong; Zhang, Xuan; Li, Meimei

    2015-12-30

    In this study, because of its superior creep and corrosion resistance as compared with general austenitic stainless steels, NF709 has emerged as a candidate structural material for advanced nuclear reactors. To obtain fundamental information about the radiation resistance of this material, this study examined the microstructural evolution of NF709 subjected to neutron irradiation to 3 displacements per atom at 500 °C. Transmission electron microscopy, scanning electron microscopy, and high-energy x-ray diffraction were employed to characterize radiation-induced segregation, Frank loops, voids, as well as the formation and reduction of precipitates. Radiation hardening of ~76% was estimated by nanoindentation, approximately consistent with the calculation according to the dispersed barrier-hardening model, suggesting Frank loops as the primary hardening source.

  11. Subneurotoxic copper(II)-induced NF-κB-dependent microglial activation is associated with mitochondrial ROS

    SciTech Connect (OSTI)

    Hu, Zhuqin; Yu, Fengxiang; Gong, Ping; Qiu, Yu; Zhou, Wei; Cui, Yongyao; Li, Juan Chen, Hongzhuan

    2014-04-15

    Microglia-mediated neuroinflammation and the associated neuronal damage play critical roles in the pathogenesis of neurodegenerative disorders. Evidence shows an elevated concentration of extracellular copper(II) in the brains of these disorders, which may contribute to neuronal death through direct neurotoxicity. Here we explored whether extracellular copper(II) triggers microglial activation. Primary rat microglia and murine microglial cell line BV-2 cells were cultured and treated with copper(II). The content of tumor necrosis factor-α (TNF-α) and nitric oxide in the medium was determined. Extracellular hydrogen peroxide was quantified by a fluorometric assay with Amplex Red. Mitochondrial superoxide was measured by MitoSOX oxidation. At subneurotoxic concentrations, copper(II) treatment induced a dose- and time-dependent release of TNF-α and nitric oxide from microglial cells, and caused an indirect, microglia-mediated neurotoxicity that was blocked by inhibition of TNF-α and nitric oxide production. Copper(II)-initiated microglial activation was accompanied with reduced IkB-α expression as well as phosphorylation and translocation of nuclear factor-κB (NF-κB) p65 and was blocked by NF-κB inhibitors (BAY11-7082 and SC-514). Moreover, copper(II) treatment evoked a rapid release of hydrogen peroxide from microglial cells, an effect that was not affected by NADPH oxidase inhibitors. N-acetyl-cysteine, a scavenger of reactive oxygen species (ROS), abrogated copper(II)-elicited microglial release of TNF-α and nitric oxide and subsequent neurotoxicity. Importantly, mitochondrial production of superoxide, paralleled to extracellular release of hydrogen peroxide, was induced after copper(II) stimulation. Our findings suggest that extracellular copper(II) at subneurotoxic concentrations could trigger NF-κB-dependent microglial activation and subsequent neurotoxicity. NADPH oxidase-independent, mitochondria-derived ROS may be involved in this activation

  12. SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling

    SciTech Connect (OSTI)

    Xu, Jun; Sun, Hui-Yan; Xiao, Feng-Jun; Wang, Hua; Yang, Yang; Wang, Lu; Gao, Chun-Ji; Guo, Zi-Kuan; Wu, Chu-Tse; Wang, Li-Sheng

    2015-05-01

    SUMO/sentrin specific protease 1 (Senp1) is an important regulation protease in the protein sumoylation, which affects the cell cycle, proliferation and differentiation. The role of Senp1 mediated protein desumoylation in pathophysiological progression of multiple myeloma is unknown. In this study, we demonstrated that Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. Lentivirus-mediated Senp1 knockdown triggers apoptosis and reduces viability, proliferation and colony forming ability of MM cells. The NF-κB family members including P65 and inhibitor protein IkBα play important roles in regulation of MM cell survival and proliferation. We further demonstrated that Senp1 inhibition decreased IL-6-induced P65 and IkBα phosphorylation, leading to inactivation of NF-kB signaling in MM cells. These results delineate a key role for Senp1in IL-6 induced proliferation and survival of MM cells, suggesting it may be a potential new therapeutic target in MM. - Highlights: • Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. • Senp1 knockdown triggers apoptosis and reduces proliferation of MM cells. • Senp1 inhibition decreased IL-6-induced P65 and IkBα phosphorylation.

  13. Oxaliplatin antagonizes HIV-1 latency by activating NF-κB without causing global T cell activation

    SciTech Connect (OSTI)

    Zhu, Xiaoli; Liu, Sijie; Wang, Pengfei; Qu, Xiying; Wang, Xiaohui; Zeng, Hanxian; Chen, Huabiao; Zhu, Huanzhang

    2014-07-18

    Highlights: • The chemotherapeutic drug oxaliplatin reactivates latent HIV-1 in this cell line model of HIV-1 latency. • Reactivation is synergized when oxaliplatin is used in combination with valproic acid. • Oxaliplatin reactivates latent HIV-1 through activation of NF-kB and does not induce T cell activation. - Abstract: Reactivation of latent HIV-1 is a promising strategy for the clearance of the viral reservoirs. Because of the limitations of current agents, identification of new latency activators is urgently required. Using an established model of HIV-1 latency, we examined the effect of Oxaliplatin on latent HIV-1 reactivation. We showed that Oxaliplatin, alone or in combination with valproic acid (VPA), was able to reactivate HIV-1 without inducing global T cell activation. We also provided evidence that Oxaliplatin reactivated HIV-1 expression by inducing nuclear factor kappa B (NF-κB) nuclear translocation. Our results indicated that Oxaliplatin could be a potential drug candidate for anti-latency therapies.

  14. Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-κB pathway in THP-1 macrophages

    SciTech Connect (OSTI)

    Wang, Yan; Wu, Jian-Feng; Tang, Yan-Yan; Zhang, Min; Li, Yuan; Chen, Kong; Zeng, Meng-Ya; Yao, Feng; Xie, Wei; Zheng, Xi-Long; Zeng, Gao-Feng; Tang, Chao-Ke

    2014-10-03

    Highlights: • U II reduces cholesterol efflux in THP-1 macrophages. • U II decreases the expression of ABCA1. • Inhibition of the ERK/NF-κB pathway reduces U II effects on ABCA1 expression and cholesterol efflux. - Abstract: Objective: Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages. Methods and results: Cultured THP-1 macrophages were treated with U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively. Conclusion: Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.

  15. Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

    SciTech Connect (OSTI)

    Verhaak, Roel GW; Hoadley, Katherine A; Purdom, Elizabeth; Wang, Victoria; Qi, Yuan; Wilkerson, Matthew D; Miller, C Ryan; Ding, Li; Golub, Todd; Mesirov, Jill P; Alexe, Gabriele; Lawrence, Michael; O'Kelly, Michael; Tamayo, Pablo; Weir, Barbara A; Gabriel, Stacey; Winckler, Wendy; Gupta, Supriya; Jakkula, Lakshmi; Feiler, Heidi S; Hodgson, J Graeme; James, C David; Sarkaria, Jann N; Brennan, Cameron; Kahn, Ari; Spellman, Paul T; Wilson, Richard K; Speed, Terence P; Gray, Joe W; Meyerson, Matthew; Getz, Gad; Perou, Charles M; Hayes, D Neil; Network, The Cancer Genome Atlas Research

    2009-09-03

    The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

  16. Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/AKT, MAPK, the NF-{kappa}B pathway, and MMP-9 expression

    SciTech Connect (OSTI)

    Kang, Myoung Hee; Oh, Sang Cheul; Kang, Han Na; Kim, Jung Lim; Kim, Jun Suk

    2011-07-15

    Bone morphogenetic proteins (BMPs) have been implicated in tumorigenesis and metastatic progression in various types of cancer cells, but the role and cellular mechanism in the invasive phenotype of gastric cancer cells is not known. Herein, we determined the roles of phosphoinositide 3-kinase (PI3K)/AKT, extracellular signal-regulated protein kinase (ERK), nuclear factor (NF)-{kappa}B, and matrix metalloproteinase (MMP) expression in BMP-2-mediated metastatic function in gastric cancer. We found that stimulation of BMP-2 in gastric cancer cells enhanced the phosphorylation of AKT and ERK. Accompanying activation of AKT and ERK kinase, BMP-2 also enhanced phosphorylation/degradation of I{kappa}B{alpha} and the nuclear translocation/activation of NF-{kappa}B. Interestingly, blockade of PI3K/AKT and ERK signaling using LY294002 and PD98059, respectively, significantly inhibited BMP-2-induced motility and invasiveness in association with the activation of NF-{kappa}B. Furthermore, BMP-2-induced MMP-9 expression and enzymatic activity was also significantly blocked by treatment with PI3K/AKT, ERK, or NF-{kappa}B inhibitors. Immunohistochemistry staining of 178 gastric tumor biopsies indicated that expression of BMP-2 and MMP-9 had a significant positive correlation with lymph node metastasis and a poor prognosis. These results indicate that the BMP-2 signaling pathway enhances tumor metastasis in gastric cancer by sequential activation of the PI3K/AKT or MAPK pathway followed by the induction of NF-{kappa}B and MMP-9 activity, indicating that BMP-2 has the potential to be a therapeutic molecular target to decrease metastasis.

  17. Nuclear NF-?B Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

    SciTech Connect (OSTI)

    Balermpas, Panagiotis [Department of Radiation Therapy and Oncology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany)] [Department of Radiation Therapy and Oncology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany); Michel, Yvonne [Senckenberg Institute of Pathology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany)] [Senckenberg Institute of Pathology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany); Wagenblast, Jens [Department of Otorhinolaryngology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany)] [Department of Otorhinolaryngology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany); Seitz, Oliver [Department of Maxillofacial Surgery, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany)] [Department of Maxillofacial Surgery, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany); Sipek, Florian; Rdel, Franz; Rdel, Claus [Department of Radiation Therapy and Oncology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany)] [Department of Radiation Therapy and Oncology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany); Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany)] [Department of Radiation Therapy and Oncology, J. W. Goethe University Frankfurt am Main, Frankfurt (Germany)

    2013-07-15

    Background: To examine whether nuclear NF-?B expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-?B p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-?B and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-?B/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-?B/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

  18. Coactivation of the PI3K/Akt and ERK signaling pathways in PCB153-induced NF-κB activation and caspase inhibition

    SciTech Connect (OSTI)

    Liu, Changjiang; Yang, Jixin; Fu, Wenjuan; Qi, Suqin; Wang, Chenmin; Quan, Chao; Yang, Kedi

    2014-06-15

    Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxicity, endocrine disruption and reproductive abnormalities. In order to verify the hypothesis that the PI3K/Akt and MAPK pathways play important roles in hepatotoxicity induced by PCBs, Sprague–Dawley (SD) rats were dosed with PCB153 intraperitoneally at 0, 4, 16 and 32 mg/kg for five consecutive days; BRL cells (rat liver cell line) were treated with PCB153 (0, 1, 5, and 10 μM) for 24 h. Results indicated that the PI3K/Akt and ERK pathways were activated in vivo and in vitro after exposure to PCB153, and protein levels of phospho-Akt and phospho-ERK were significantly increased. Nuclear factor-κB (NF-κB) activation and caspase-3, -8 and -9 inhibition caused by PCB153 were also observed. Inhibiting the ERK pathway significantly attenuated PCB153-induced NF-κB activation, whereas inhibiting the PI3K/Akt pathway hardly influenced phospho-NF-κB level. However, inhibiting the PI3K/Akt pathway significantly elevated caspase-3, -8 and -9 activities, while the ERK pathway only synergistically regulated caspase-9. Proliferating cell nuclear antigen (PCNA), a reliable indicator of cell proliferation, was also induced. Moreover, PCB153 led to hepatocellular hypertrophy and elevated liver weight. Taken together, PCB153 leads to aberrant proliferation and apoptosis of hepatocytes through NF-κB activation and caspase inhibition, and coactivated PI3K/Akt and ERK pathways play critical roles in PCB153-induced hepatotoxicity. - Highlights: • PCB153 led to hepatotoxicity through NF-κB activation and caspase inhibition. • The PI3K/Akt and ERK pathways were coactivated in vivo and in vitro by PCB153. • The ERK pathway regulated levels of phospho-NF-κB and caspase-9. • The PI3K/Akt pathway regulated levels of caspase-3, -8 and -9.

  19. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-?B signaling activation in CD4 + T cells

    SciTech Connect (OSTI)

    Shu, Guangwen; Yang, Tianming; Wang, Chaoyuan; Su, Hanwen; Xiang, Meixian

    2013-06-15

    Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor ?B (NF-?B) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-?B p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-?B-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: Gastrodin stimulates anticancer immune response. Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. Gastrodin activates NF-?B activity in CD4 + T cells.

  20. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

    SciTech Connect (OSTI)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang; Li, Junying

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

  1. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

    SciTech Connect (OSTI)

    Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong; Ma, Qinyun

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.

  2. ROS and NF-{kappa}B are involved in upregulation of IL-8 in A549 cells exposed to multi-walled carbon nanotubes

    SciTech Connect (OSTI)

    Ye Shefang Wu Yihui; Hou Zhenqing; Zhang Qiqing

    2009-02-06

    Carbon nanotubes (CNTs) have potential applications in biosensors, tissue engineering, and biomedical devices because of their unique physico-chemical, electronic and mechanical properties. However, there is limited literature data available concerning the biological properties and toxicity of CNTs. This study aimed to assess the toxicity exhibited by multi-walled CNTs (MWCNTs) and to elucidate possible molecular mechanisms underlying the biological effects of MWCNTs in A549 cells. Exposing A549 cells to MWCNTs led to cell death, changes in cell size and complexity, reactive oxygen species (ROS) production, interleukin-8 (IL-8) gene expression and nuclear factor (NF)-{kappa}B activation. Treatment of A549 cells with antioxidants prior to adding MWCNTs decreased ROS production and abrogated expression of IL-8 mRNA. Pretreatment of A549 cells with NF-{kappa}B inhibitors suppressed MWCNTs-induced IL-8 mRNA expression. These results indicate that MWCNTs are able to induce expression of IL-8 in A549 cells, at least in part, mediated by oxidative stress and NF-{kappa}B activation.

  3. Neutron and proton electric dipole moments from Nf=2+1 domain-wall fermion lattice QCD

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Shintani, Eigo; Blum, Thomas; Izubuchi, Taku; Soni, Amarjit

    2016-05-05

    We present a lattice calculation of the neutron and proton electric dipole moments (EDM’s) with Nf = 2 + 1 flavors of domain-wall fermions. The neutron and proton EDM form factors are extracted from three-point functions at the next-to-leading order in the θ vacuum of QCD. In this computation, we use pion masses 330 and 420 MeV and 2.7 fm3 lattices with Iwasaki gauge action and a 170 MeV pion and 4.6 fm3 lattice with I-DSDR gauge action, all generated by the RBC and UKQCD collaborations. The all-mode-averaging technique enables an efficient, high statistics calculation; however the statistical errors onmore » our results are still relatively large, so we investigate a new direction to reduce them, reweighting with the local topological charge density which appears promising. Furthermore, we discuss the chiral behavior and finite size effects of the EDM’s in the context of baryon chiral perturbation theory.« less

  4. Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: A mechanistic approach

    SciTech Connect (OSTI)

    Abhilash, P.A.; Harikrishnan, R.; Indira, M.

    2014-01-15

    Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signaling plays a major role in alcoholic liver fibrosis. We evaluated the effect of ascorbic acid (AA), silymarin and alcohol abstention on the alcohol induced endotoxemia and NF-κB activation cascade pathway in guinea pigs (Cavia porcellus). Guinea pigs were administered ethanol at a daily dose of 4 g/kg b.wt for 90 days. After 90 days, ethanol administration was stopped. The ethanol treated animals were divided into abstention, silymarin (250 mg/kg b.wt) and AA (250 mg/kg b.wt) supplemented groups and maintained for 30 days. The SIBO, intestinal permeability and endotoxin were significantly increased in the ethanol group. The mRNA expressions of intestinal proteins claudin, occludin and zona occludens-1 were significantly decreased in ethanol group. The mRNA levels of inflammatory receptors, activity of IKKβ and the protein expressions of phospho-IκBα, NF-κB, TNF-α, TGF-β{sub 1} and IL-6 were also altered in ethanol group. The expressions of fibrosis markers α-SMA, α{sub 1} (I) collagen and sirius red staining in the liver revealed the induction of fibrosis. But the supplementation of AA could induce greater reduction of ethanol induced SIBO, intestinal barrier defects, NF-κB activation and liver fibrosis than silymarin. The possible mechanism may be the inhibitory effect of AA on SIBO, intestinal barrier defect and IKKβ, which decreased the activation of NF-κB and synthesis of cytokines. This might have led to suppression of HSCs activation and liver fibrosis. - Highlights: • Alcohol increases intestinal bacterial overgrowth and permeability of endotoxin. • Endotoxin mediated inflammation plays a major role in alcoholic liver fibrosis. • Ascorbic acid reduces endotoxemia, NF-κB activation and proinflammatory cytokines. • AA's action is by inhibition of SIBO, IKKβ and alteration of

  5. Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice

    SciTech Connect (OSTI)

    Kim, Young Nam; Kim, Dae Won; Jo, Hyo Sang; Shin, Min Jea; Ahn, Eun Hee; Ryu, Eun Ji; Yong, Ji In; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Youn, Jong Kyu; Hwang, Jae Hyeok; Jeong, Ji-Heon; Kim, Duk-Soo; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-07-15

    Human carbonyl reductase 1 (CBR1) plays a crucial role in cell survival and protects against oxidative stress response. However, its anti-inflammatory effects are not yet clearly understood. In this study, we examined whether CBR1 protects against inflammatory responses in macrophages and mice using a Tat-CBR1 protein which is able to penetrate into cells. The results revealed that purified Tat-CBR1 protein efficiently transduced into Raw 264.7 cells and inhibited lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2), nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) expression levels. In addition, Tat-CBR1 protein leads to decreased pro-inflammatory cytokine expression through suppression of nuclear transcription factor-kappaB (NF-κB) and mitogen activated protein kinase (MAPK) activation. Furthermore, Tat-CBR1 protein inhibited inflammatory responses in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation when applied topically. These findings indicate that Tat-CBR1 protein has anti-inflammatory properties in vitro and in vivo through inhibition of NF-κB and MAPK activation, suggesting that Tat-CBR1 protein may have potential as a therapeutic agent against inflammatory diseases. - Highlights: • Transduced Tat-CBR1 reduces LPS-induced inflammatory mediators and cytokines. • Tat-CBR1 inhibits MAPK and NF-κB activation. • Tat-CBR1 ameliorates inflammation response in vitro and in vivo. • Tat-CBR1 may be useful as potential therapeutic agent for inflammation.

  6. The plant limonoid 7-oxo-deacetoxygedunin inhibits RANKL-induced osteoclastogenesis by suppressing activation of the NF-{kappa}B and MAPK pathways

    SciTech Connect (OSTI)

    Wisutsitthiwong, Chonnaree; Buranaruk, Chayanit; Pudhom, Khanitha; Palaga, Tanapat

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer A gedunin type limonoid from seeds of mangroves, 7-oxo-7-deacetoxygedunin, exhibits strong anti-osteoclastogenic activity. Black-Right-Pointing-Pointer Treatment with this limonoid results in significant decrease in expression of NFATc1 and osteoclast-related genes. Black-Right-Pointing-Pointer The mode of action of this limonoid is by inhibiting activation of the NF-{kappa}B and MAPK pathways which are activated by RANKL. -- Abstract: Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. Aberrations in osteoclast differentiation and activity contribute to osteopenic disease. Osteoclasts differentiate from monocyte/macrophage progenitors, a process that is initiated by the interaction between receptor activator of NF-{kappa}B (RANK) and its ligand, RANKL. In this study, we identified 7-oxo-7-deacetoxygedunin (7-OG), a gedunin type limonoid from seeds of the mangrove Xylocarpus moluccensis, as a potent inhibitor of osteoclastogenesis. Additionally, 7-OG showed strong anti-osteoclastogenic activity with low cytotoxicity against the monocyte/macrophage progenitor cell line, RAW264.7. The IC50 for anti-osteoclastogenic activity was 4.14 {mu}M. Treatment with 7-OG completely abolished the appearance of multinucleated giant cells with tartrate-resistant acid phosphatase activity in RAW264.7 cells stimulated with RANKL. When the expression of genes related to osteoclastogenesis was investigated, a complete downregulation of NFATc1 and cathepsin K and a delayed downregulation of irf8 were observed upon 7-OG treatment in the presence of RANKL. Furthermore, treatment with this limonoid suppressed RANKL-induced activation of p38, MAPK and Erk and nuclear localization of NF-{kappa}B p65. Taken together, we present evidence indicating a plant limonoid as a novel osteoclastogenic inhibitor that could be used for osteoporosis and related conditions.

  7. Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2NF?B pathways

    SciTech Connect (OSTI)

    Das, Joydeep; Ghosh, Jyotirmoy; Roy, Anandita; Sil, Parames C.

    2012-04-01

    Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantly increased the nuclear translocation of NF?B and elevated iNOS protein expression. The same exposure also elevated TNF-?, IFN-?, IL-1?, IL-6, IL-12, IL-18 and decreased IL-10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GST?. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NF?B inhibition. Highlights: ?Galactosamine induces hepatocytes death via oxidative and nitrosative stress. ?Mangiferin exerts hepatoprotective effect/antioxidant defense via Nrf2 pathway. ?Mangiferin exerts anti-inflammatory responses by inhibiting NF-?B. ?Mangiferin suppresses galactosamine-induced repression of IL-10 mRNA.

  8. HSF1 and NF-κB p65 participate in the process of exercise preconditioning attenuating pressure overload-induced pathological cardiac hypertrophy

    SciTech Connect (OSTI)

    Xu, Tongyi; Zhang, Ben; Yang, Fan; Cai, Chengliang; Wang, Guokun; Han, Qingqi; Zou, Liangjian

    2015-05-08

    Pathological cardiac hypertrophy, often accompanied by hypertension, aortic stenosis and valvular defects, is typically associated with myocyte remodeling and cardiac dysfunction. Exercise preconditioning (EP) has been proven to enhance the tolerance of the myocardium to cardiac ischemia-reperfusion injury. However, the effects of EP in pathological cardiac hypertrophy are rarely reported. 10-wk-old male Sprague–Dawley rats (n = 80) were randomly divided into four groups: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and the EP + TAC and TAC groups were followed by TAC operations. The sham and EP + sham groups underwent the same operation without aortic constriction. Eight weeks after the surgery, we evaluated the effects of EP by echocardiography, morphology, and histology and observed the expressions of the associated proteins. Compared with the respective control groups, hypertrophy-related indicators were significantly increased in the TAC and EP + TAC groups (p < 0.05). However, between the TAC and EP + TAC groups, all of these changes were effectively inhibited by EP treatment (p < 0.05). Furthermore, EP treatment upregulated the expression of HSF1 and HSP70, increased the HSF1 levels in the nuclear fraction, inhibited the expression of the NF-κB p65 subunit, decreased the NF-κB p65 subunit levels in the nuclear fraction, and reduced the IL2 levels in the myocardia of rats. EP could effectively reduce the cardiac hypertrophic responses induced by TAC and may play a protective role by upregulating the expressions of HSF1 and HSP70, activating HSF1 and then inhibiting the expression of NF-κB p65 and nuclear translocation. - Highlights: • EP could effectively reduce the cardiac hypertrophic responses induced by TAC. • EP may play a protective role by upregulating the expressions of HSF1 and HSP70 and then activating HSF1. • EP may play a protective role by inhibiting the expression

  9. OSU-A9 inhibits angiogenesis in human umbilical vein endothelial cells via disrupting AktNF-?B and MAPK signaling pathways

    SciTech Connect (OSTI)

    Omar, Hany A.; Arafa, El-Shaimaa A.; Salama, Samir A.; Arab, Hany H.; Wu, Chieh-Hsi; Weng, Jing-Ru

    2013-11-01

    Since the introduction of angiogenesis as a useful target for cancer therapy, few agents have been approved for clinical use due to the rapid development of resistance. This problem can be minimized by simultaneous targeting of multiple angiogenesis signaling pathways, a potential strategy in cancer management known as polypharmacology. The current study aimed at exploring the anti-angiogenic activity of OSU-A9, an indole-3-carbinol-derived pleotropic agent that targets mainly Aktnuclear factor-kappa B (NF-?B) signaling which regulates many key players of angiogenesis such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Human umbilical vein endothelial cells (HUVECs) were used to study the in vitro anti-angiogenic effect of OSU-A9 on several key steps of angiogenesis. Results showed that OSU-A9 effectively inhibited cell proliferation and induced apoptosis and cell cycle arrest in HUVECs. Besides, OSU-A9 inhibited angiogenesis as evidenced by abrogation of migration/invasion and Matrigel tube formation in HUVECs and attenuation of the in vivo neovascularization in the chicken chorioallantoic membrane assay. Mechanistically, Western blot, RT-PCR and ELISA analyses showed the ability of OSU-A9 to inhibit MMP-2 production and VEGF expression induced by hypoxia or phorbol-12-myristyl-13-acetate. Furthermore, dual inhibition of AktNF-?B and mitogen-activated protein kinase (MAPK) signaling, the key regulators of angiogenesis, was observed. Together, the current study highlights evidences for the promising anti-angiogenic activity of OSU-A9, at least in part through the inhibition of AktNF-?B and MAPK signaling and their consequent inhibition of VEGF and MMP-2. These findings support OSU-A9's clinical promise as a component of anticancer therapy. - Highlights: The antiangiogenic activity of OSU-A9 in HUVECs was explored. OSU-A9 inhibited HUVECs proliferation, migration, invasion and tube formation. OSU-A9 targeted signaling

  10. TGF-{beta}1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-{kappa}B/IL-6/MMP-2

    SciTech Connect (OSTI)

    Binker, Marcelo G.; CBRHC Research Center, Buenos Aires ; Binker-Cosen, Andres A.; Gaisano, Herbert Y.; Cosen, Rodica H. de; Cosen-Binker, Laura I.

    2011-02-04

    Research highlights: {yields} Rac1 mediates TGF-{beta}1-induced SW1990 invasion through MMP-2 secretion and activation. {yields} NADPH-generated ROS act downstream of Rac1 in TGF-{beta}1-challenged SW1990 cells. {yields} TGF-{beta}1-stimulated ROS activate NF-{kappa}B in SW1990 cells. {yields} NF{kappa}B-induced IL-6 release is required for secretion and activation of MMP-2 in SW1990 cells. -- Abstract: Human pancreatic cancer invasion and metastasis have been found to correlate with increased levels of active matrix metalloproteinase 2 (MMP-2). The multifunctional cytokine transforming growth factor beta 1 (TGF-{beta}1) has been shown to increase both secretion of MMP-2 and invasion by several pancreatic cancer cell types. In the present study, we investigated the signaling pathway involved in TGF-{beta}1-promoted MMP-2 secretion and invasion by human pancreatic cancer cells SW1990. Using specific inhibitors, we found that stimulation of these tumor cells with TGF-{beta}1 induced secretion and activation of the collagenase MMP-2, which was required for TGF-{beta}1-stimulated invasion. Our results also indicate that signaling events involved in TGF-{beta}1-enhanced SW1990 invasiveness comprehend activation of Rac1 followed by generation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate-oxidase, activation of nuclear factor-kappa beta, release of interleukin-6, and secretion and activation of MMP-2.

  11. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

    SciTech Connect (OSTI)

    Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja; Joseph, Binoy; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Yin, Yuanqin; Roy, Ram Vinod; Lu, Jian; Zhang, Zhuo; Wang, Yitao; and others

    2014-10-01

    Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE{sub 2} and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. - Highlights: • C3G inhibited UVB-induced oxidative damage and inflammation. • C3G inhibited UVB-induced COX-2, iNOS and PGE{sub 2} production. • C3G

  12. The (3He,tf) as a surrogate reaction to determine (n,f) cross sections in the 10 to 20 MeV energy range

    SciTech Connect (OSTI)

    Basunia, M. S.; Clark, R. M.; Goldblum, B. L.; Bernstein, L. A.; Phair, L.; Burke, J. T.; Beausang, C. W.; Bleuel, D. L.; Darakchieva, B.; Dietrich, F. S.; Evtimova, M.; Fallon, P.; Gibelin, J.; Hatarik, R.; Jewett, C. C.; Lesher, S. R.; McMahan, M. A.; Rodriguez-Vieitez, E.; Wiedeking, M.

    2009-02-25

    The surrogate reaction 238U(3He,tf) is used to determine the 237Np(n,f) cross section indirectly over an equivalent neutron energy range from 10 to 20 MeV. A self-supporting ~;;761 mu g/cm2 metallic 238U foil was bombarded with a 42 MeV 3He2+ beam from the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory (LBNL). Outgoing charged particles and fission fragments were identified using the Silicon Telescope Array for Reaction Studies (STARS), consists of two 140 mu m and one 1000 mu m Micron S2 type silicon detectors. The 237Np(n,f) cross sections, determined indirectly, were compared with the 237Np(n,f) cross section data from direct measurements, the Evaluated Nuclear Data File (ENDF/B-VII.0), and the Japanese Evaluated Nuclear Data Library (JENDL 3.3) and found to closely follow those datasets. Use of the (3He,tf) reaction as a surrogate to extract (n,f) cross section in the 10 to 20 MeV equivalent neutron energy is found to be suitable.

  13. Dietary turmeric modulates DMBA-induced p21{sup ras}, MAP kinases and AP-1/NF-{kappa}B pathway to alter cellular responses during hamster buccal pouch carcinogenesis

    SciTech Connect (OSTI)

    Garg, Rachana; Ingle, Arvind; Maru, Girish

    2008-11-01

    The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12 weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished the DMBA-induced mRNA expression of proto-oncogenes (c-jun, c-fos) and NF-{kappa}B, leading to decreased protein levels and in further attenuation of DMBA-induced AP-1/NF-{kappa}B DNA-binding in the buccal pouch nuclear extracts. Besides, buccal pouch of hamsters receiving turmeric diet showed significant alterations in DMBA-induced effects: (a) decrease in cell proliferation (diminished PCNA and Bcl2 expression), (b) enhanced apoptosis (increased expression of Bax, caspase-3 and apoptotic index), (c) decrease in inflammation (levels of Cox-2, the downstream target of AP-1/NF-{kappa}B, and PGE2) and (d) aberrant expression of differentiation markers, the cytokeratins (1, 5, 8, and 18). Together, the protective effects of dietary turmeric converge on augmenting apoptosis of the initiated cells and decreasing cell proliferation in DMBA-treated animals, which in turn, is reflected in decreased tumor burden, multiplicity and enhanced latency period. Some of these biomarkers are likely to be helpful in monitoring clinical trials and evaluating drug effect measurements.

  14. The REMOTE SENSlNf

    Office of Legacy Management (LM)

    ... Nuclear Safety 20:736-47. Beck, H. L.; De Campo, J.; and Gogolak, C. 1972. In Situ Ge (Li) and N@ fT) Gamma Ray Spectrometry. HASL-258. (United States Atomic Energy CornmIssIon, ...

  15. Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis of H1299 cells via ROS-dependent and p53-independent NF-κB activation

    SciTech Connect (OSTI)

    Yun, Hong Shik; Baek, Jeong-Hwa; Yim, Ji-Hye; Lee, Su-Jae; Lee, Chang-Woo; Song, Jie-Young; Um, Hong-Duck; Park, Jong Kuk; Park, In-Chul; Hwang, Sang-Gu

    2014-07-11

    Highlights: • HRP-3 is a radiation- and anticancer drug-responsive protein in H1299 cells. • Depletion of HRP-3 induces apoptosis of radio- and chemoresistant H1299 cells. • Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. • ROS generation enhances NF-κB activity, which acts as an upstream signal in the c-Myc/Noxa apoptotic pathway. - Abstract: We previously identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistant biomarker in p53 wild-type A549 cells and found that p53-dependent induction of the PUMA pathway was a critical event in regulating the radioresistant phenotype. Here, we found that HRP-3 knockdown regulates the radioresistance of p53-null H1299 cells through a distinctly different molecular mechanism. HRP-3 depletion was sufficient to cause apoptosis of H1299 cells by generating substantial levels of reactive oxygen species (ROS) through inhibition of the Nrf2/HO-1 antioxidant pathway. Subsequent, ROS-dependent and p53-independent NF-κB activation stimulated expression of c-Myc and Noxa proteins, thereby inducing the apoptotic machinery. Our results thus extend the range of targets for the development of new drugs to treat both p53 wild-type or p53-null radioresistant lung cancer cells.

  16. Materials Data on TiH12(NF2)4 (SG:56) by Materials Project

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  17. Results of radiological measurements taken in the Niagara Falls, New York, area (NF002)

    SciTech Connect (OSTI)

    Williams, J.K.; Berven, B.A.

    1986-11-01

    The results of a radiological survey of 100 elevated gamma radiation anomalies in the Niagara Falls, New York, area are presented. These radiation anomalies were identified by a mobile gamma scanning survey during the period October 3-16, 1984, and were recommended for an onsite survey to determine if the elevated levels of radiation may be related to the transportation of radioactive waste material to the Lake Ontario Ordnance Works for storage. In this survey, radiological measurements included outdoor gamma exposure rates at 1 m above the surface; outdoor gamma exposure rates at the surface, range of gamma exposure rates during scan; and uranium, radium, and thorium concentrations in biased surface soil samples. The results show 38 anomalies (35 located along Pletcher Road and 3 associated with other unreleated locations) were found to exceed Formerly Utilized Sites Remedial Action Program (FUSRAP) remedial action guidelines and were recommended for formal characterization surveys. (Since the time of this survey, remedial actions have been conducted on the 38 anomalies identified as exceeding FUSRAP guidelines, and the radioactive material above guidelines has been removed.) The remaining 62 anomalies are associated with asphalt driveways and parking lots, which used a phosphate slag material (previously identified as cyclowollastonite, synthetic CaSiO/sub 3/). This rocky-slag waste material was used for bedding under asphalt surfaces and in general gravel applications. Most of the contaminated soil and rock samples collected at the latter anomalies had approximately equal concentrations of /sup 226/Ra and /sup 238/U and, therefore, are not related to materials connected with the Niagara Falls Storage Site (NFSS), including material that was transported to the NFSS. 13 refs., 7 figs., 14 tabs.

  18. Materials Data on Ca2NF (SG:141) by Materials Project

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  19. Materials Data on Pr3NF6 (SG:1) by Materials Project

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  20. Materials Data on H5NF2 (SG:53) by Materials Project

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  1. Suppression of NF-κB signaling and NLRP3 inflammasome activation...

    Office of Scientific and Technical Information (OSTI)

    ... Resource Type: Journal Article Resource Relation: Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 281; Journal Issue: 1; Other Information: Copyright (c) 2014 ...

  2. Nucleon, $$\\Delta$$ and $$\\Omega$$ excited states in $N_f=2+1$ lattice QCD

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    John Bulava; Edwards, Robert G.; Engelson, Eric; Joo, Balint; Lin, Huey -Wen; Morningstar, Colin; Richards, David G.; Wallace, Stephen J.

    2010-07-22

    The energies of the excited states of the Nucleon,more » $$\\Delta$$ and $$\\Omega$$ are computed in lattice QCD, using two light quarks and one strange quark on anisotropic lattices. The calculation is performed at three values of the light quark mass, corresponding to pion masses $$m_{\\pi}$$ = 392(4), 438(3) and 521(3) MeV. We employ the variational method with a large basis of interpolating operators enabling six energies in each irreducible representation of the lattice to be distinguished clearly. We compare our calculation with the low-lying experimental spectrum, with which we find reasonable agreement in the pattern of states. In addition, the need to include operators that couple to the expected multi-hadron states in the spectrum is clearly identified.« less

  3. Property:SurfaceManager | Open Energy Information

    Open Energy Info (EERE)

    + COCONINO NF + AZA-009169 + COCONINO NF + AZA-009170 + COCONINO NF + AZA-009171 + FOREST SERVICE + AZA-009172 + FOREST SERVICE + AZA-009173 + FOREST SERVICE + AZA-009174 +...

  4. Pioglitazone inhibits angiotensin II-induced atrial fibroblasts proliferation via NF-?B/TGF-?1/TRIF/TRAF6 pathway

    SciTech Connect (OSTI)

    Chen, Xiao-qing; Liu, Xu; Wang, Quan-xing; Zhang, Ming-jian; Guo, Meng; Liu, Fang; Jiang, Wei-feng; Zhou, Li

    2015-01-01

    The exact mechanisms underlying inhibitory effects of pioglitazone (Pio) on Angiotensin II (AngII)-induced atrial fibrosis are complex and remain largely unknown. In the present study, we examined the effect of Pio on AngII-induced mice atrial fibrosis in vivo and atrial fibroblasts proliferation in vitro. In vivo study showed that AngII infusion induced atrial fibrosis and increased expressions of Toll/IL-1 receptor domain-containing adaptor inducing IFN-? (TRIF) and tumor necrosis factor receptor associated factor 6 (TRAF6) in mice models. However, those effects could be attenuated by Pio (P<0.01). As for in vitro experiment, Pio suppressed AngII-induced atrial fibroblasts proliferation via nuclear factor-?B/transforming growth factor-?1/TRIF/TRAF6 signaling pathway in primary cultured mice atrial fibroblasts (P<0.01). In conclusion, suppression of Pio on AngII-induced atrial fibrosis might be related to its inhibitory effects on above signaling pathway. - Highlights: Angiotensin II increased atrial fibrosis and related gene expressions in mice. Angiotensin II induced atrial fibroblasts proliferation by activating signaling pathway. Pioglitazone reversed both aforementioned changes.

  5. 1992 CBECS C & E

    U.S. Energy Information Administration (EIA) Indexed Site

    of District Heat by End Use, 1989 District Heat Consumption (trillion Btu) Space Water a Total Heating Heating Other RSE Building Row Characteristics Factor 1.0 NF NF NF RSE...

  6. 1992 CBECS C & E

    U.S. Energy Information Administration (EIA) Indexed Site

    0. Consumption of Fuel Oil by End Use, 1989 Fuel Oil Consumption (trillion Btu) Space Water a Total Heating Heating Other RSE Building Row Characteristics Factor 1.0 NF NF NF RSE...

  7. S:\VM3\RX97\TBL_LIST.WPD

    U.S. Energy Information Administration (EIA) Indexed Site

    Million U.S. Households, 1997 Housing Unit Characteristics RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.4 1.1 1.1 1.2 1.7 Total .............................................................. 101.5 6.8 11.5 7.0 5.9 NF Census Region and Division Northeast ..................................................... 19.7 6.8 -- -- -- NF New England ............................................. 5.3 Q -- -- -- NF Middle Atlantic

  8. Evolutionary analyses of non-family genes in plants

    SciTech Connect (OSTI)

    Ye, Chuyu; Li, Ting; Yin, Hengfu; Weston, David; Tuskan, Gerald A; Tschaplinski, Timothy J; Yang, Xiaohan

    2013-03-01

    There are a large number of non-family (NF) genes that do not cluster into families with three or more members per genome. While gene families have been extensively studied, a systematic analysis of NF genes has not been reported. We performed comparative studies on NF genes in 14 plant species. Based on the clustering of protein sequences, we identified ~94,000 NF genes across these species that were divided into five evolutionary groups: Viridiplantae-wide, angiosperm-specific, monocot-specific, dicot-specific, and those that were species-specific. Our analysis revealed that the NF genes resulted largely from less frequent gene duplications and/or a higher rate of gene loss after segmental duplication relative to genes in both low-copy-number families (LF; 3 10 copies per genome) and high-copy-number families (HF; >10 copies). Furthermore, we identified functions enriched in the NF gene set as compared with the HF genes. We found that NF genes were involved in essential biological processes shared by all plant lineages (e.g., photosynthesis and translation), as well as gene regulation and stress responses associated with phylogenetic diversification. In particular, our analysis of an Arabidopsis protein-protein interaction network revealed that hub proteins with the top 10% most connections were over-represented in the NF set relative to the HF set. This research highlights the roles that NF genes may play in evolutionary and functional genomics research.

  9. Evolutionary analyses of non-family genes in plants

    SciTech Connect (OSTI)

    Ye, Chuyu; Li, Ting; Yin, Hengfu; Weston, David; Tuskan, Gerald A; Tschaplinski, Timothy J; Yang, Xiaohan

    2013-01-01

    There are a large number of non-family (NF) genes that do not cluster into families with three or more members per genome. While gene families have been extensively studied, a systematic analysis of NF genes has not been reported. We performed comparative studies on NF genes in 14 plant species. Based on the clustering of protein sequences, we identified ~94 000 NF genes across these species that were divided into five evolutionary groups: Viridiplantae wide, angiosperm specific, monocot specific, dicot specific, and those that were species specific. Our analysis revealed that the NF genes resulted largely from less frequent gene duplications and/or a higher rate of gene loss after segmental duplication relative to genes in both lowcopy- number families (LF; 3 10 copies per genome) and high-copy-number families (HF; >10 copies). Furthermore, we identified functions enriched in the NF gene set as compared with the HF genes. We found that NF genes were involved in essential biological processes shared by all plant lineages (e.g. photosynthesis and translation), as well as gene regulation and stress responses associated with phylogenetic diversification. In particular, our analysis of an Arabidopsis protein protein interaction network revealed that hub proteins with the top 10% most connections were over-represented in the NF set relative to the HF set. This research highlights the roles that NF genes may play in evolutionary and functional genomics research.

  10. NVN-079292 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1980.23 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  11. UTU-085605 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSECOMPPOST2005 Total Acreage 2441.53 Bid PriceAcre Managing Field Office none provided Surface Manager FISHLAKE NF Lessee 1 ENEL...

  12. EIS-0350-S1: Mitigation Action Plan | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Los Alamos, NM This Mitigation Action Plan (MAP) describes mitigation and monitoring commitments for constructing and operating the Modified CMRR-NF. The commitments made in this ...

  13. USFS Humboldt-Toiyabe National Forest | Open Energy Information

    Open Energy Info (EERE)

    USFS Humboldt-Toiyabe National Forest Jump to: navigation, search Name: USFS Humboldt-Toiyabe National Forest Abbreviation: Humbolt-Toiyabe NF Address: 1200 Franklin Way Place:...

  14. NVN-074253 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1280 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  15. NVN-074250 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1199 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  16. NVN-077646 | Open Energy Information

    Open Energy Info (EERE)

    Acres) Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 80 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  17. NVN-079352 | Open Energy Information

    Open Energy Info (EERE)

    Acres) Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1160 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  18. NVN-074254 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 2280 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  19. NVN-079310 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 655 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  20. NVN-079667 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1920 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  1. NVN-079664 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1280 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  2. NVN-079276 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 640 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  3. Carbon Free Developments | Open Energy Information

    Open Energy Info (EERE)

    Free Developments Jump to: navigation, search Name: Carbon Free Developments Place: United Kingdom Zip: W11 3NF Sector: Wind energy Product: UK-based onshore wind project...

  4. Lattice QCD gauge ensemble: USQCD/MILC/asqtad/2064f21b678m010m050b

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Aubin, Christopher Alan [Fordham U.; Bernard, Claude W. [Washington U. St. Louis; Burch, Tommy [U. Regensburg; Datta, Saumen [Tata Institute; DeGrand, Thomas Alan [Colorado U., Boulder; DeTar, Carleton E. [Utah U.; Gottlieb, Steven A. [Indiana U., Bloomington; Gregory, Eric Brittain [Wuppertal U.; Heller, Urs M. [American Physical Society; Hetrick, James Edward [U. Pacific, Stockton; Orginos, Kostas Nikolaou [William-Mary Coll.; Osborn, James C. [Argonne National Laboratory, ALCF; Toussaint, W. Doug [Arizona U.; Sugar, Robert L. [U. C., Santa Barbara

    2015-01-01

    MILC asqtad QCD SU(3) gauge ensemble; series=b; a=0.11fm minus 0.0022fm; Ls=2.16fm; Nf=2+1; u0.m0=(0.010,0.050)

  5. Lattice QCD gauge ensemble: USQCD/MILC/asqtad/2064f21b678m010m050

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Aubin, Christopher Alan [Fordham U.; Bernard, Claude W. [Washington U. St. Louis; Burch, Tommy [U. Regensburg; Datta, Saumen [Tata Institute; DeGrand, Thomas Alan [Colorado U., Boulder; DeTar, Carleton E. [Utah U.; Gottlieb, Steven A. [Indiana U., Bloomington; Gregory, Eric Brittain [Wuppertal U.; Heller, Urs M. [American Physical Society; Hetrick, James Edward [U. Pacific, Stockton; Orginos, Kostas Nikolaou [William-Mary Coll.; Osborn, James C. [Argonne National Laboratory, ALCF; Toussaint, W. Doug [Arizona U.; Sugar, Robert L. [U. C., Santa Barbara

    2015-01-01

    MILC asqtad QCD SU(3) gauge ensemble; series=a; a=0.11fm minus 0.0022fm ; Ls=2.16fm; Nf=2+1; u0.m0=(0.010,0.050)

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Lam, Amy Y. (1) Lamothe, Betty (1) Lin, Su-Chang (1) Lo, Yu-Chih (1) Min, Tongpil (1) ... of the NF-B Inhibitor A20 Lin, Su-Chang ; Chung, Jee Y. ; Lamothe, Betty ; ...

  7. NVN-080159 | Open Energy Information

    Open Energy Info (EERE)

    PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 NGP BLUE MOUNTAIN I LLC Lessee 2 none provided Effective Date 7312016 Expire Date Held By...

  8. CACA-014407 | Open Energy Information

    Open Energy Info (EERE)

    Acres) Case Status Authorized Case Type GEOLSECOMPPRE2005 Total Acreage 2561.25 Bid PriceAcre Managing Field Office none provided Surface Manager INYO NF Lessee 1 ORNI 51 LLC...

  9. NVN-079105 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 2356.36 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 ORNI 16...

  10. Lattice QCD gauge ensemble: USQCD/MILC/asqtad/2064f21b678m010m050

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Aubin, Christopher Alan [Fordham U.; Bernard, Claude W. [Washington U. St. Louis; Burch, Tommy [U. Regensburg; Datta, Saumen [Tata Institute; DeGrand, Thomas Alan [Colorado U., Boulder; DeTar, Carleton E. [Utah U.; Gottlieb, Steven A. [Indiana U., Bloomington; Gregory, Eric Brittain [Wuppertal U.; Heller, Urs M. [American Physical Society; Hetrick, James Edward [U. Pacific, Stockton; Orginos, Kostas Nikolaou [William-Mary Coll.; Osborn, James C. [Argonne National Laboratory, ALCF; Toussaint, W. Doug [Arizona U.; Sugar, Robert L. [U. C., Santa Barbara

    MILC asqtad QCD SU(3) gauge ensemble; series=a; a=0.11fm minus 0.0022fm ; Ls=2.16fm; Nf=2+1; u0.m0=(0.010,0.050)

  11. Lattice QCD gauge ensemble: USQCD/MILC/asqtad/2064f21b678m010m050b

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Aubin, Christopher Alan [Fordham U.; Bernard, Claude W. [Washington U. St. Louis; Burch, Tommy [U. Regensburg; Datta, Saumen [Tata Institute; DeGrand, Thomas Alan [Colorado U., Boulder; DeTar, Carleton E. [Utah U.; Gottlieb, Steven A. [Indiana U., Bloomington; Gregory, Eric Brittain [Wuppertal U.; Heller, Urs M. [American Physical Society; Hetrick, James Edward [U. Pacific, Stockton; Orginos, Kostas Nikolaou [William-Mary Coll.; Osborn, James C. [Argonne National Laboratory, ALCF; Toussaint, W. Doug [Arizona U.; Sugar, Robert L. [U. C., Santa Barbara

    MILC asqtad QCD SU(3) gauge ensemble; series=b; a=0.11fm minus 0.0022fm; Ls=2.16fm; Nf=2+1; u0.m0=(0.010,0.050)

  12. AZA-009191 | Open Energy Information

    Open Energy Info (EERE)

    PriceAcre Managing Field Office none provided Surface Manager COCONINO NF Lessee 1 HUNT OIL USA INC Lessee 2 none provided Effective Date Expire Date Held By Production (HBP) HBP...

  13. AZA-009190 | Open Energy Information

    Open Energy Info (EERE)

    PriceAcre Managing Field Office none provided Surface Manager COCONINO NF Lessee 1 HUNT OIL USA INC Lessee 2 none provided Effective Date Expire Date Held By Production (HBP) HBP...

  14. AZA-009186 | Open Energy Information

    Open Energy Info (EERE)

    PriceAcre Managing Field Office none provided Surface Manager COCONINO NF Lessee 1 HUNT OIL USA INC Lessee 2 none provided Effective Date Expire Date Held By Production (HBP) HBP...

  15. Subject:

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    rotation reversals, poloidal impurity asymmetries and "non-local" heat transport Gao thesis 2015, Rice NF 2013). We are not yet certain if our RF L-mode target plasmas will...

  16. 1992 CBECS C & E

    U.S. Energy Information Administration (EIA) Indexed Site

    of Natural Gas by End Use, 1989 Natural Gas Consumption (trillion Btu) Space Water a Total Heating Heating Cooking Other RSE Building Row Characteristics Factor 1.0 NF...

  17. Systems and methods for treating material

    DOE Patents [OSTI]

    Scheele, Randall D; McNamara, Bruce K

    2014-10-21

    Systems for treating material are provided that can include a vessel defining a volume, at least one conduit coupled to the vessel and in fluid communication with the vessel, material within the vessel, and NF.sub.3 material within the conduit. Methods for fluorinating material are provided that can include exposing the material to NF.sub.3 to fluorinate at least a portion of the material. Methods for separating components of material are also provided that can include exposing the material to NF.sub.3 to at least partially fluorinate a portion of the material, and separating at least one fluorinated component of the fluorinated portion from the material. The materials exposed to the NF.sub.3 material can include but are not limited to one or more of U, Ru, Rh, Mo, Tc, Np, Pu, Sb, Ag, Am, Sn, Zr, Cs, Th, and/or Rb.

  18. CACA-011667 | Open Energy Information

    Open Energy Info (EERE)

    Surface Manager INYO NF Lessee 1 MAMMOTH-PACIFIC LP Lessee 2 none provided Effective Date 311982 Expire Date Held By Production (HBP) HELD BY PROD-Actual HBP Date 12221990...

  19. NVN-079291 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 612006 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  20. NVN-079666 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 712005 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  1. NVN-078688 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 REESE RIVER GEO POWER LLC Lessee 2 none provided Effective Date 1012004 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  2. NVN-079665 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 712005 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  3. NVN-079307 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 712006 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  4. NVN-079106 | Open Energy Information

    Open Energy Info (EERE)

    Surface Manager TOIYABE NF Lessee 1 ORNI 16 LLC Lessee 2 none provided Effective Date 912006 Expire Date Held By Production (HBP) HBP Date RoyaltyRate 10% - 5% - 5% Most...

  5. NVN-077647 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 612006 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  6. NVN-079662 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 6302015 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  7. NVN-074249 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 912007 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  8. NVN-079663 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 712005 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  9. CACA-011672 | Open Energy Information

    Open Energy Info (EERE)

    provided Surface Manager INYO NF Lessee 1 ORNI 10 LLC Lessee 2 none provided Effective Date 111982 Expire Date Held By Production (HBP) HELD BY PROD-Actual HBP Date 12311998...

  10. NVN-078687 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 REESE RIVER GEO POWER LLC Lessee 2 none provided Effective Date 1012004 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  11. NVN-079668 | Open Energy Information

    Open Energy Info (EERE)

    Manager TOIYABE NF Lessee 1 GRADIENT RESOURCES INC Lessee 2 none provided Effective Date 712005 Expire Date Held By Production (HBP) HBP Date RoyaltyRate Most Recent Action...

  12. CACA-014408 | Open Energy Information

    Open Energy Info (EERE)

    Surface Manager INYO NF Lessee 1 MAMMOTH-PACIFIC LP Lessee 2 none provided Effective Date 7191983 Expire Date Held By Production (HBP) HELD BY PROD-Actual HBP Date 782006...

  13. YEAR

    National Nuclear Security Administration (NNSA)

    300 YEAR 2011 Males 109 Females 191 YEAR 2011 SES 9 EJEK 1 NN (Engineering) 2 NQ (ProfTechAdmin) 203 NU (TechAdmin Support) 38 NF (Future Ldrs) 47 YEAR 2011 American Indian...

  14. YEAR

    National Nuclear Security Administration (NNSA)

    86 YEAR 2012 Males 103 Females 183 YEAR 2012 SES 7 EJEK 1 NN (Engineering) 1 NQ (ProfTechAdmin) 202 NU (TechAdmin Support) 30 NF (Future Ldrs) 45 YEAR 2012 American Indian Male...

  15. Bioremediation of contaminated groundwater

    DOE Patents [OSTI]

    Hazen, T.C.; Fliermans, C.B.

    1994-01-01

    Disclosed is an apparatus and method for in situ remediation of contaminated subsurface soil or groundwater contaminated by chlorinated hydrocarbons. A nutrient fluid (NF) is selected to simulated the growth and reproduction of indigenous subsurface microorganisms capable of degrading the contaminants; an oxygenated fluid (OF) is selected to create an aerobic environment with anaerobic pockets. NF is injected periodically while OF is injected continuously and both are extracted so that both are drawn across the plume. NF stimulates microbial colony growth; withholding it periodically forces the larger, healthy colony of microbes to degrade the contaminants. Treatment is continued until the subsurface concentration of contaminants is acceptable. NF can be methane and OF be air, for stimulating production of methanotrophs to break down chlorohydrocarbons, especially TCE and tetrachloroethylene.

  16. Nucleophilic fluorination of aromatic compounds

    DOE Patents [OSTI]

    Satyamurthy, Nagichettiar; Barrio, Jorge R

    2014-03-18

    Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO.sub.2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me.sub.4NF, Et.sub.4NF, n-Bu.sub.4NF, (PhCH.sub.2).sub.4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

  17. AZA-009169 | Open Energy Information

    Open Energy Info (EERE)

    (40 Acres) Case Status Closed Case Type GEOLSENONCOMPPRE2005 Total Acreage 2560 Bid PriceAcre Managing Field Office none provided Surface Manager COCONINO NF Lessee 1 HUNT W H...

  18. AZA-009170 | Open Energy Information

    Open Energy Info (EERE)

    (40 Acres) Case Status Closed Case Type GEOLSENONCOMPPRE2005 Total Acreage 1920 Bid PriceAcre Managing Field Office none provided Surface Manager COCONINO NF Lessee 1 HUNT W H...

  19. NVN-077739 | Open Energy Information

    Open Energy Info (EERE)

    Lot Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1271.82 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 PATUA...

  20. AZA-009168 | Open Energy Information

    Open Energy Info (EERE)

    (40 Acres) Case Status Closed Case Type GEOLSENONCOMPPRE2005 Total Acreage 2005 Bid PriceAcre Managing Field Office none provided Surface Manager COCONINO NF Lessee 1 HUNT W H...

  1. AZA-009175 | Open Energy Information

    Open Energy Info (EERE)

    (40 Acres) Case Status Closed Case Type GEOLSENONCOMPPRE2005 Total Acreage 2190 Bid PriceAcre Managing Field Office none provided Surface Manager COCONINO NF Lessee 1 HUNT W H...

  2. NVN-079305 | Open Energy Information

    Open Energy Info (EERE)

    1 Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 1811.109 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  3. NVN-079104 | Open Energy Information

    Open Energy Info (EERE)

    Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 2480.99 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 ORNI 16...

  4. NVN-080086 | Open Energy Information

    Open Energy Info (EERE)

    Acres) Case Status Authorized Case Type GEOLEASENONCOMPETITI Total Acreage 650.32 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 NGP BLUE...

  5. NVN-079306 | Open Energy Information

    Open Energy Info (EERE)

    B Case Status Authorized Case Type GEOLSENONCOMPPRE2005 Total Acreage 2140.53 Bid PriceAcre Managing Field Office none provided Surface Manager TOIYABE NF Lessee 1 GRADIENT...

  6. Structural studies of magnesium nitride fluorides by powder neutron diffraction

    SciTech Connect (OSTI)

    Brogan, Michael A.; Hughes, Robert W.; Smith, Ronald I.; Gregory, Duncan H.

    2012-01-15

    Samples of ternary nitride fluorides, Mg{sub 3}NF{sub 3} and Mg{sub 2}NF have been prepared by solid state reaction of Mg{sub 3}N{sub 2} and MgF{sub 2} at 1323-1423 K and investigated by powder X-ray and powder neutron diffraction techniques. Mg{sub 3}NF{sub 3} is cubic (space group: Pm3m) and has a structure related to rock-salt MgO, but with one cation site vacant. Mg{sub 2}NF is tetragonal (space group: I4{sub 1}/amd) and has an anti-LiFeO{sub 2} related structure. Both compounds are essentially ionic and form structures in which nitride and fluoride anions are crystallographically ordered. The nitride fluorides show temperature independent paramagnetic behaviour between 5 and 300 K. - Graphical abstract: Definitive structures of the ternary magnesium nitride fluorides Mg{sub 3}NF{sub 3} and the lower temperature polymorph of Mg{sub 2}NF have been determined from powder neutron diffraction data. The nitride halides are essentially ionic and exhibit weak temperature independent paramagnetic behaviour. Highlights: Black-Right-Pointing-Pointer Definitive structures of Mg{sub 3}NF{sub 3} and Mg{sub 2}NF were determined by neutron diffraction. Black-Right-Pointing-Pointer Nitride and fluoride anions are crystallographically ordered in both structures. Black-Right-Pointing-Pointer Both compounds exhibit weak, temperature independent paramagnetic behaviour. Black-Right-Pointing-Pointer The compounds are essentially ionic with ionicity increasing with F{sup -} content.

  7. Comparative evaluations of the weldability of modified 800H and other advanced austenitic stainless steels

    SciTech Connect (OSTI)

    Lundin, C.D.; Qiao, C.Y.P.

    1993-07-01

    The weldability of modified 800H was evaluated in terms of HAZ hot cracking susceptibility and HAZ softening tendency. Four other types of austenitic alloys, modified 316, 310Ta, HR3C and NF709, were employed to carry out a comparative study. It was found that modified 800H exhibits good weldability in terms of operability as contrasted to NF709. However, a higher HAZ hot cracking susceptibility for the modified 800H tubing heats was revealed as compared to the commercial tubing heats of HR3C and NF709. The hot cracking test results for the small laboratory prepared modified 800H heats showed an equivalent or better HAZ hot cracking resistance as compared to HR3C and NF709. Thus, it is anticipated that modified 800H tubing can show a hot cracking resistance equivalent to NF709 and HR3C if the base metal grain size is properly controlled and an optimum thermal mechanical treatment has been performed. The preliminary assessment on HAZ softening behavior for modified 800H, modified 316, 310Ta, HR3C and NF709 alloys is discussed.

  8. Life Cycle Nitrogen Trifluoride Emissions from Photovoltaics

    SciTech Connect (OSTI)

    Fthenakis, V.

    2010-10-25

    Amorphous- and nanocrystalline-silicon thin-film photovoltaic modules are made in high-throughput manufacturing lines that necessitate quickly cleaning the reactor. Using NF{sub 3}, a potent greenhouse gas, as the cleaning agent triggered concerns as recent reports reveal that the atmospheric concentrations of this gas have increased significantly. We quantified the life-cycle emissions of NF{sub 3} in photovoltaic (PV) manufacturing, on the basis of actual measurements at the facilities of a major producer of NF{sub 3} and of a manufacturer of PV end-use equipment. From these, we defined the best practices and technologies that are the most likely to keep worldwide atmospheric concentrations of NF{sub 3} at very low radiative forcing levels. For the average U.S. insolation and electricity-grid conditions, the greenhouse gas (GHG) emissions from manufacturing and using NF{sub 3} in current PV a-Si and tandem a-Si/nc-Si facilities add 2 and 7 g CO{sub 2eq}/kWh, which can be displaced within the first 1-4 months of the PV system life.

  9. Anomalous magnetic behavior in nanocomposite materials of reduced graphene oxide-Ni/NiFe{sub 2}O{sub 4}

    SciTech Connect (OSTI)

    Kollu, Pratap E-mail: anirmalagrace@vit.ac.in; Prathapani, Sateesh; Varaprasadarao, Eswara K.; Mallick, Sudhanshu; Bahadur, D. E-mail: anirmalagrace@vit.ac.in; Santosh, Chella; Grace, Andrews Nirmala E-mail: anirmalagrace@vit.ac.in

    2014-08-04

    Magnetic Reduced Graphene Oxide-Nickel/NiFe{sub 2}O{sub 4} (RGO-Ni/NF) nanocomposite has been synthesized by one pot solvothermal method. Respective phase formations and their purities in the composite are confirmed by High Resolution Transmission Electron Microscope and X Ray Diffraction, respectively. For the RGO-Ni/NF composite material finite-size effects lead to the anomalous magnetic behavior, which is corroborated in temperature and field dependent magnetization curves. Here, we are reporting the behavior of higher magnetization values for Zero Field Cooled condition to that of Field Cooled for the RGO-Ni/NF nanocomposite. Also, the observed negative and positive moments in Hysteresis loops at relatively smaller applied fields (100?Oe and 200?Oe) are explained on the basis of surface spin disorder.

  10. Worksheet

    U.S. Energy Information Administration (EIA) Indexed Site

    4,"Ames City of",6,1,"Omaha Public Power District","NF",127,0,0,6037,6037 554,"Ames City of",6,2,"MidAmerican Energy Co.","NF",52,0,0,3171,3171 554,"Ames City of",6,3,"Iowa State University","NF",62,0,0,2661,2661 590,"Anaheim City of",6,1,"American Electric Power",,7592,,,343620,343620 590,"Anaheim City of",6,2,"Arizona Public Service C0.",,41600,,,583600,583600

  11. Propionic acid production by extractive fermentation. 1. Solvent considerations

    SciTech Connect (OSTI)

    Gu, Z.; Glatz, B.A.; Glatz, C.E.

    1998-02-20

    Solvent selection for extractive fermentation for propionic acid was conducted with three systems: Alamine{reg_sign} 304-1 (trilaurylamine) in 2-octanol, 1-dodecanol, and Witcohol{reg_sign} 85 NF (oleyl alcohol). Among them, the solvent containing 2-octanol exhibited the highest partition coefficient in acid extraction, but it was also toxic to propionibacteria. The most solvent-resistant strain among five strains of the microorganism was selected. Solvent toxicity was eliminated via two strategies: entrapment of dissolved toxic solvent in the culture growth medium with vegetable oils such as corn, olive, or soybean oils; or replacement of the toxic 2-octanol with nontoxic Witcohol 85 NF. The complete recovery of acids from the Alamine 304-1/Witcohol 85 NF was also realized with vacuum distillation.

  12. Consider nanofiltration for membrane separations

    SciTech Connect (OSTI)

    Raman, L.P. ); Cheryna, M.; Rajagopalan, N. )

    1994-03-01

    The best known liquid-phase membrane processes are reverse osmosis (RO), ultrafiltration (UF), microfiltration (MF), dialysis, and electrodialysis (ED). However, over the past few years, a new membrane process called nanofiltration (NF) has emerged that promises to significantly widen the application of membranes in liquid-phase separations. This paper discusses the following: NF operating range, membrane properties, and the following applications: demineralizing water, cleaning up contaminated groundwater, ultrapure water, effluents containing heavy metals, offshore oil platforms, yeast production, pulp and paper mills, textile production, electroless copper plating, and cheese whey production.

  13. Report on thermal aging effects on tensile properties of ferritic-martensitic steels.

    SciTech Connect (OSTI)

    Li, M.; Soppet, W.K.; Rink, D.L.; Listwan, J.T.; Natesan, K.

    2012-05-10

    This report provides an update on the evaluation of thermal-aging induced degradation of tensile properties of advanced ferritic-martensitic steels. The report is the first deliverable (level 3) in FY11 (M3A11AN04030103), under the Work Package A-11AN040301, 'Advanced Alloy Testing' performed by Argonne National Laboratory, as part of Advanced Structural Materials Program for the Advanced Reactor Concepts. This work package supports the advanced structural materials development by providing tensile data on aged alloys and a mechanistic model, validated by experiments, with a predictive capability on long-term performance. The scope of work is to evaluate the effect of thermal aging on the tensile properties of advanced alloys such as ferritic-martensitic steels, mod.9Cr-1Mo, NF616, and advanced austenitic stainless steel, HT-UPS. The aging experiments have been conducted over a temperature of 550-750 C for various time periods to simulate the microstructural changes in the alloys as a function of time at temperature. In addition, a mechanistic model based on thermodynamics and kinetics has been used to address the changes in microstructure of the alloys as a function of time and temperature, which is developed in the companion work package at ANL. The focus of this project is advanced alloy testing and understanding the effects of long-term thermal aging on the tensile properties. Advanced materials examined in this project include ferritic-martensitic steels mod.9Cr-1Mo and NF616, and austenitic steel, HT-UPS. The report summarizes the tensile testing results of thermally-aged mod.9Cr-1Mo, NF616 H1 and NF616 H2 ferritic-martensitic steels. NF616 H1 and NF616 H2 experienced different thermal-mechanical treatments before thermal aging experiments. NF616 H1 was normalized and tempered, and NF616 H2 was normalized and tempered and cold-rolled. By examining these two heats, we evaluated the effects of thermal-mechanical treatments on material microstructures and

  14. http://www.ornl.gov/Procurement.PDF

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    8/93 1. All Grade 5 and Grade 8 fasteners of foreign origin which do not bear any manufacturer's headmarks: Grade 5 Grade 8 2. Grade 5 fasteners with the following manufacturers' headmarks: J Jinn Her (TW) KS Kosaka Kogyo (JP) J KS 3. Grade 8 fasteners with the following manufacturers' headmarks: A Asahi Mfg (JP) KS Kosaka Kogyo (JP) A KS NF RT NF Nippon Fasteners (JP) RT Takai Ltd (JP) H Hinomoto Metal (JP) FM Fastener Co (of JP) H FM J M MS KY M Minamida Sieybo (JP) KY Kyoei (JP) MS Minato

  15. Nuclear factor-?B is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

    SciTech Connect (OSTI)

    Hinoi, Eiichi; Iezaki, Takashi; Ozaki, Kakeru; Yoneda, Yukio

    2014-10-03

    Highlights: GDF5 expression is up-regulated by IL-1?, TNF-? and palmitate in brown pre-adipocytes. NF-?B stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. Recruitment of NF-?B to the GDF5 promoter is facilitated in BAT from ob/ob mice. An NF-?B inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-?B (NF-?B) binding site in the 5?-flanking region of mouse GDF5, whereas introduction of NF-?B subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-?B to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-?B inhibitor in cultured brown pre-adipocytes exposed to IL-1?, TNF-? and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a mechanism relevant to activation of the

  16. Use of nanofiltration to reduce cooling tower water consumption.

    SciTech Connect (OSTI)

    Altman, Susan Jeanne; Ciferno, Jared

    2010-10-01

    Nanofiltration (NF) can effectively treat cooling-tower water to reduce water consumption and maximize water usage efficiency of thermoelectric power plants. A pilot is being run to verify theoretical calculations. A side stream of water from a 900 gpm cooling tower is being treated by NF with the permeate returning to the cooling tower and the concentrate being discharged. The membrane efficiency is as high as over 50%. Salt rejection ranges from 77-97% with higher rejection for divalent ions. The pilot has demonstrated a reduction of makeup water of almost 20% and a reduction of discharge of over 50%.

  17. Use of nanofiltration to reduce cooling tower water usage.

    SciTech Connect (OSTI)

    Sanchez, Andres L.; Everett, Randy L.; Jensen, Richard Pearson; Cappelle, Malynda A.; Altman, Susan Jeanne

    2010-09-01

    Nanofiltration (NF) can effectively treat cooling-tower water to reduce water consumption and maximize water usage efficiency of thermoelectric power plants. A pilot is being run to verify theoretical calculations. A side stream of water from a 900 gpm cooling tower is being treated by NF with the permeate returning to the cooling tower and the concentrate being discharged. The membrane efficiency is as high as over 50%. Salt rejection ranges from 77-97% with higher rejection for divalent ions. The pilot has demonstrated a reduction of makeup water of almost 20% and a reduction of discharge of over 50%.

  18. Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

    SciTech Connect (OSTI)

    Xiao, Xiao; Gang, Yi; Wang, Honghong; Wang, Jiayin; Zhao, Lina; Xu, Li; Liu, Zhiguo

    2015-02-06

    Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity.

  19. ASN Aircraft accident Beechcraft 1900C N27RA Tonopah-Test Range...

    National Nuclear Security Administration (NNSA)

    Accident description languages: Share 0 Statd,LB:5E)(WEWkNF75WLEW)w(Ni7wkE.(wnNa75WLEW)w(... According to the Air Force Materiel Command Accident Investigation Board report, the pilot ...

  20. Microsoft PowerPoint - 2009_DEMO_Career_Paths_DCB_Salaries.ppt...

    National Nuclear Security Administration (NNSA)

    Band 02 60,989 to 79,280 Band 03 73,100 to 95,026 Band 04 86,927 to 113,007 Future Leader (NF) Band 01 33,269 - 59,333 Band 02 50,408 - 79,280 Band 03 73,100 - 113,007...

  1. Microsoft PowerPoint - 2009_DEMO_Career_Paths_RUS_Salaries.ppt...

    National Nuclear Security Administration (NNSA)

    Band 02 56,411 to 73,329 Band 03 67,613 to 87,893 Band 04 80,402 to 104,525 Future Leader (NF) Band 01 30,772 - 54,879 Band 02 46,625 - 73,329 Band 03 67,613 - 104,52...

  2. Microsoft PowerPoint - 2009_DEMO_Career_Paths_OAK_Salaries.ppt...

    National Nuclear Security Administration (NNSA)

    Band 02 66,562 to 86,525 Band 03 79,781 to 103,710 Band 04 94,871 to 123,335 Future Leader (NF) Band 01 36,309 - 64,755 Band 02 55,015 - 86,525 Band 03 79,781 - 123,33...

  3. Ni(OH){sub 2} nanoflakes electrodeposited on Ni foam-supported vertically oriented graphene nanosheets for application in asymmetric supercapacitors

    SciTech Connect (OSTI)

    Wang, Xin; Liu, Jiyue; Wang, Yayu; Zhao, Cuimei; Zheng, Weitao

    2014-04-01

    Highlights: Ni(OH){sub 2}/vertically oriented graphene nanosheets (V-GNs) was prepared. Ni(OH){sub 2}/V-GNs had enhanced specific capacitance, cycling reversibility and stability. Performance of Ni(OH){sub 2}/GNs/NF-AC asymmetric supercapacitor was studied. - Abstract: Binderless Ni(OH){sub 2} nanoflakes grown on Ni foam (NF)-supported vertically oriented graphene nanosheets (V-GNs) has been fabricated as a positive electrode material for asymmetric supercapacitor (ASC), coupled with activated carbon (AC) as a counter electrode material. The introduction of V-GNs leads to dense growth of nanocrystalline ?-Ni(OH){sub 2} that is confirmed by X-ray diffraction, transmission electron microscopic and scanning electron microscopic analyses. The electrochemical performances of the Ni(OH){sub 2}/GNs/NF electrode are characterized by cyclic voltammetry and chargedischarge tests, which exhibit high specific capacitance of 2215 F g{sup ?1} at a scan current density of 2.3 A g{sup ?1}, enhanced cycling stability and high rate capability. The Ni(OH){sub 2}/GNs/NF-AC-based ASC can achieve a cell voltage of 1.4 V and a specific energy density of 11.11 Wh kg{sup ?1} at 0.5 mA cm{sup ?2} with a nearly 100% coulombic efficiency at room temperature.

  4. Radiation-induced gene responses

    SciTech Connect (OSTI)

    Woloschak, G.E.; Paunesku, T.; Shearin-Jones, P.; Oryhon, J.

    1996-12-31

    In the process of identifying genes that are differentially regulated in cells exposed to ultraviolet radiation (UV), we identified a transcript that was repressed following the exposure of cells to a combination of UV and salicylate, a known inhibitor of NF-kappaB. Sequencing this band determined that it has identify to lactate dehydrogenase, and Northern blots confirmed the initial expression pattern. Analysis of the sequence of the LDH 5` region established the presence of NF-kappaB, Sp1, and two Ap-2 elements; two partial AP- 1; one partial RE, and two halves of E-UV elements were also found. Electromobility shift assays were then performed for the AP-1, NF- kappaB, and E-UV elements. These experiments revealed that binding to NF-kappaB was induced by UV but repressed with salicylic acid; UV did not affect AP-1 binding, but salicylic acid inhibited it alone or following UV exposure; and E-UV binding was repressed by UV, and salicylic acid had little effect. Since the binding of no single element correlated with the expression pattern of LDH, it is likely that multiple elements govern UV/salicylate-mediated expression.

  5. SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells

    SciTech Connect (OSTI)

    Takeda-Watanabe, Ai; Kitada, Munehiro; Kanasaki, Keizo; Koya, Daisuke

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer SIRT1 inactivation decreases autophagy in THP-1 cell. Black-Right-Pointing-Pointer Inhibition of autophagy induces inflammation. Black-Right-Pointing-Pointer SIRT1 inactivation induces inflammation through NF-{kappa}B activation. Black-Right-Pointing-Pointer The p62/Sqstm1 accumulation by impairment of autophagy is related to NF-{kappa}B activation. Black-Right-Pointing-Pointer SIRT1 inactivation is involved in the activation of mTOR and decreased AMPK activation. -- Abstract: Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are some of the cells involved in the inflammatory process in atherogenesis. Autophagy exerts a protective effect against cellular stresses like inflammation, and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway includes SIRT1, a NAD{sup +}-dependent histone deacetylase, which is implicated in the regulation of a variety of cellular processes including inflammation and autophagy. The mechanism through which the dysfunction of SIRT1 contributes to the regulation of inflammation in relation to autophagy in monocytes/macrophages is unclear. In the present study, we demonstrate that treatment with 2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a chemical inhibitor of SIRT1, induces the overexpression of inflammation-related genes such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 through nuclear factor (NF)-{kappa}B signaling activation, which is associated with autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3-methyladenine, also induces inflammation-related NF-{kappa}B activation. In p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-{kappa}B activation is blocked. In addition, inhibition of SIRT1 is involved in the activation of the mammalian target of rapamycin (mTOR) pathway and

  6. Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells

    SciTech Connect (OSTI)

    Hossain, Ekhtear; Ota, Akinobu; Karnan, Sivasundaram; Damdindorj, Lkhagvasuren; Takahashi, Miyuki; Konishi, Yuko; Konishi, Hiroyuki; Hosokawa, Yoshitaka

    2013-12-15

    Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis. - Highlights: • Sodium arsenite (SA) increases LOX-1 expression in mouse aortic endothelial cells. • SA enhances cellular uptake of oxidized LDL in dose-dependent manner. • SA-induced ROS generation enhances phosphorylation of NF-κB. • SA upregulates LOX-1 expression through ROS-activated NF-κB signaling pathway.

  7. Daily treatment with {alpha}-naphthoflavone enhances follicular growth and ovulation rate in the rat

    SciTech Connect (OSTI)

    Barreiro, Karina A.; Di Yorio, Maria P.; Artillo-Guida, Romina D.; Paz, Dante A.; Faletti, Alicia G.

    2011-04-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and the first protein involved in a variety of physiological and toxicological processes, including those of xenobiotic metabolizing enzymes. AhR has been found in the ovary of many species and seems to mediate the ovarian toxicity of many environmental contaminants, which are AhR ligands. However, the role of AhR in the ovarian function is unknown. Therefore, the aim of this work was to study the action of {alpha}-naphthoflavone ({alpha}NF), known to be an AhR antagonist, on both follicular growth and ovulation. Immature Sprague-Dawley rats were daily injected intraperitoneally with {alpha}NF (0.1-80 mg/kg) or vehicle for 12 days, and primed with gonadotrophins (eCG/hCG) to induce follicular growth and ovulation. Ovaries were obtained 20 h after hCG administration. By means of immunohistochemistry, we found that the numbers of primordial, primary and antral follicles were increased in rats treated with 80 mg/kg {alpha}NF and that there were no differences with other doses. Likewise, the ovarian weight and the ovulation rate, measured by both number of oocytes within oviducts and corpora lutea in ovarian sections, were increased when the rats received either 1 or 10 mg/kg daily. Although further studies are necessary to know the mechanism of action of {alpha}NF, it is possible that the different ovarian processes can be differentially responsive to the presence of different levels of {alpha}NF, and that the same or different endogenous AhR ligands can be involved in these ovarian processes in a cell type-dependent manner.

  8. Spontaneous supersymmetry breaking in two dimensional lattice super QCD

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Catterall, Simon; Veernala, Aarti

    2015-10-02

    We report on a non-perturbative study of two dimensional N=(2,2) super QCD. Our lattice formulation retains a single exact supersymmetry at non-zero lattice spacing, and contains Nf fermions in the fundamental representation of a U(Nc) gauge group. The lattice action we employ contains an additional Fayet-Iliopoulos term which is also invariant under the exact lattice supersymmetry. This work constitutes the first numerical study of this theory which serves as a toy model for understanding some of the issues that are expected to arise in four dimensional super QCD. As a result, we present evidence that the exact supersymmetry breaks spontaneouslymore » when Nf < Nc in agreement with theoretical expectations.« less

  9. Measurement of the EMC effect in the deuteron

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Griffioen, Keith A.; Arrington, John R.; Christy, M. Eric; Ent, Rolf; Kalantarians, Narbe; Keppel, Cynthia E.; Kuhn, Sebastian E.; Melnitchouk, Wally; Niculescu, Gabriel; Niculescu, Ioana; et al

    2015-07-01

    We have determined the structure function ratiomore » $$R^d_{\\rm EMC}=F_2^d/(F_2^n+F_2^p)$$ from recently published $F_2^n/F_2^d$ data taken by the BONuS experiment using CLAS at Jefferson Lab. This ratio deviates from unity, with a slope $$dR_{\\rm EMC}^{d}/dx= -0.10\\pm 0.05$$ in the range of Bjorken $x$ from 0.35 to 0.7, for invariant mass $W>1.4$ GeV and $Q^2>1$ GeV$^2$. The observed EMC effect for these kinematics is consistent with conventional nuclear physics models that include off-shell corrections, as well as with empirical analyses that find the EMC effect proportional to the probability of short-range nucleon-nucleon correlations.« less

  10. Pancreatic cancer: Pathogenesis, prevention and treatment

    SciTech Connect (OSTI)

    Sarkar, Fazlul H. Banerjee, Sanjeev; Li, Yiwei

    2007-11-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-{kappa}B pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-{kappa}B, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer.

  11. Possible mechanisms for arsenic-induced proliferative diseases

    SciTech Connect (OSTI)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A.

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  12. Sulfur mustard primes human neutrophils for increased degranulation and stimulates cytokine release via TRPM2/p38 MAPK signaling

    SciTech Connect (OSTI)

    Ham, Hwa-Yong; Hong, Chang-Won; Lee, Si-Nae; Kwon, Min-Soo; Kim, Yeon-Ja; Song, Dong-Keun

    2012-01-01

    Sulfur mustard (2,2′-bis-chloroethyl-sulfide; SM) has been a military threat since the World War I. The emerging threat of bioterrorism makes SM a major threat not only to military but also to civilian world. SM injury elicits an inflammatory response characterized by infiltration of neutrophils. Although SM was reported to prime neutrophils, the mechanism has not been identified yet. In the present study, we investigated the mechanism of SM-induced priming in human neutrophils. SM increased [Ca{sup 2+}]{sub i} in human neutrophils in a concentration-dependent fashion. Transient receptor potential melastatin (TRPM) 2 inhibitors (clotrimazole, econazole and flufenamic acid) and silencing of TRPM2 by shRNA attenuated SM-induced [Ca{sup 2+}]{sub i} increase. SM primed degranulation of azurophil and specific granules in response to activation by fMLP as previously reported. SB203580, an inhibitor of p38 MAPK, inhibited SM-induced priming. Neither PD98057, an ERK inhibitor, nor SP600215, a JNK inhibitor, inhibited SM-induced priming. In addition, SM enhanced phosphorylation of NF-kB p65 and release of TNF-α, interleukin (IL)-6 and IL-8. SB203580 inhibited SM-induced NF-kB phosphorylation and cytokine release. These results suggest the involvement of TRPM2/p38 MAPK pathway in SM-induced priming and cytokines release in neutrophils. -- Highlights: ► SM increased [Ca{sup 2+}]{sub i} in human neutrophils through TPRM2-mediated calcium influx. ► SM primed degranulation of azurophil and specific granules. ► SM enhanced p38 MAPK and NF-κB p65 phosphorylation in human neutrophils. ► SM enhanced release of TNF-α, interleukin (IL)-6 and IL-8 from human neutrophils. ► SB203580 inhibited SM-induced priming, NF-κB p65 phosphorylation and cytokine release.

  13. Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

    SciTech Connect (OSTI)

    He, Yi; Zhang, Qing; Shen, Yi; Chen, Xia; Zhou, Feng; Peng, Dan

    2014-07-04

    Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.

  14. Assessment of energetic costs of AhR activation by β-naphthoflavone in rainbow trout (Oncorhynchus mykiss) hepatocytes using metabolic flux analysis

    SciTech Connect (OSTI)

    Nault, Rance; Abdul-Fattah, Hiba; Mironov, Gleb G.; Berezovski, Maxim V.; Moon, Thomas W.

    2013-08-15

    Exposure to environmental contaminants such as activators of the aryl hydrocarbon receptor (AhR) leads to the induction of defense and detoxification mechanisms. While these mechanisms allow organisms to metabolize and excrete at least some of these environmental contaminants, it has been proposed that these mechanisms lead to significant energetic challenges. This study tests the hypothesis that activation of the AhR by the model agonist β-naphthoflavone (βNF) results in increased energetic costs in rainbow trout (Oncorhynchus mykiss) hepatocytes. To address this hypothesis, we employed traditional biochemical approaches to examine energy allocation and metabolism including the adenylate energy charge (AEC), protein synthesis rates, Na{sup +}/K{sup +}-ATPase activity, and enzyme activities. Moreover, we have used for the first time in a fish cell preparation, metabolic flux analysis (MFA) an in silico approach for the estimation of intracellular metabolic fluxes. Exposure of trout hepatocytes to 1 μM βNF for 48 h did not alter hepatocyte AEC, protein synthesis, or Na{sup +}/K{sup +}-ATPase activity but did lead to sparing of glycogen reserves and changes in activities of alanine aminotransferase and citrate synthase suggesting altered metabolism. Conversely, MFA did not identify altered metabolic fluxes, although we do show that the dynamic metabolism of isolated trout hepatocytes poses a significant challenge for this type of approach which should be considered in future studies. - Highlights: • Energetic costs of AhR activation by βNF was examined in rainbow trout hepatocytes. • Metabolic flux analysis was performed on a fish cell preparation for the first time. • Exposure to βNF led to sparing of glycogen reserves and altered enzyme activities. • Adenylate energy charge was maintained despite temporal changes in metabolism.

  15. TITLE

    Office of Legacy Management (LM)

    CULTURAL RESOURCES STUDY BACKQROUND RESEARCH REPORT Off-NfS Cukural Rasowcmr Studks: Background Research for Project Shot11 Prepared by Maureen King Alvin R. McLane and William Gray Johnson MAY 1993 DESERT RESEARCH INSTITUTE CULTURAL RESOURCES STUDY BACKGROUND RESEARCH REPORT Off-NTS Cultural Resources Studies: Background Research for Project Shoal Prepared by Maureen King Alvin R. McLane and William Gray Johnson Prepared for the U.S. Department of Energy Nevada Field Office Las Vegas, Nevada

  16. HASL-258 IN SITU Ge(Li) AND Nal(T1) GAMMA-RAY SPECTROMETRY

    Office of Scientific and Technical Information (OSTI)

    ... 5.57 0.67 5.48 18.1 - 60 - TABLE 1 9 PEAK AREA PER U N I T EXPOSURE RATE (NfI)* FOR 60 ... 5 3 6 4 4 2 8 60 1 537 4 8 7 1 5 9 7 4 9 7 512 6 2 2 6 6 2 7 2 4 7 57 7 6 6 8 3 5 5 9 6 5 ...

  17. ER85357_Phase2_Eltron | netl.doe.gov

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Unconventional High Temperature Nanofiltration for Produced Water Treatment Last Reviewed 6/25/2013 DE-10ER85357 Goal The project goal is to further develop a proprietary, high-temperature nanofiltration (NF) technology (DurafluxTM) to remove salt and other dissolved solids from produced water originating from domestic oil and gas production. Treated water can be re-used in the extraction process without cooling/re-heating costs or can be recycled as an acceptable supply of source water. Project

  18. PCR-based polymorphisms in neurofibromatosis type 1 (NFI)

    SciTech Connect (OSTI)

    Lai, P.S.; Chee, S.; Low, P.S.

    1994-09-01

    Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders in humans with an incidence of 1 in 3,000. The NF1 gene is located on chromosome 17q 11.2 and encodes an ubiquitously expressed transcript of about 13kb. Direct mutation detection is difficult in this disorder due to the large gene size, high mutation rate and variety of mutations. We have studied the allele frequencies of seven PCR-based polymorphisms. Six of the probes used flank the NF1 gene, namely p11.3C4.2/Msp I (proximal), pEW206/Msp I (distal), p2.f9.8/Rsa I (distal), pEW207/Bgl II (distal), pEW207/Hind III (distal) and pHHH202/Rsa I (proximal). An intragenic RFLP, pEvi 2B-B/Eco R1 polymorphism in intron 27, was also analyzed by PCR. Allele frequencies for 48 normal unrelated individuals were obtained as follows: A1 = 0.40, A2 = 0.6 (p11.3C4.2/Msp I), A1 = 0.44, A2 = 0.56 (pEW206/Msp I), A1 = 0.17, A2 = 0.83 (p2.F9.8/Rsa I), A1 = 0.64, A2 = 0.36 (pEW207/Bgl I), A1 = 0.45, A2 = 0.55 (pEvi 2B-B/Eco RI). Heterozygosity rates of the alleles ranged from 20.8% to 51.7%. Using a combination of these markers, seven local families with NF1 were studied. Normal Mendelian segregation of alleles was observed in these families and no recombination was detected so far. These PCR-based markers were found to be useful for linkage analysis in our families.

  19. Section 27

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    NF o N e ' f (N,$,Zb,h,8,u,<) Session Papers 117 (1) (2) A Test of the Validity of Cumulus Cloud Parameterizations for Longwave Radiation Calculations D. Han and R.G. Ellingson Department of Meteorology University of Maryland College Park, Maryland Introduction Longwave radiative transfer under broken cloud conditions is often treated as a problem in cloud bulk geometry, especially for cumulus clouds, because individual clouds are nearly black. However, climate models ignore cloud geometry

  20. DOE - NNSA/NFO -- Photo Library General

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    General NNSA/NFO Language Options U.S. DOE/NNSA - Nevada Field Office Photo Library - General Photos related to the Nevada Field Office which do not fall under the other photo categories are located here. Instructions: Click the photograph THUMBNAIL to view the photograph details Click the Category, Number, or Date table header links to sort the information. Thumbnail Category Number Date http://www.nv.doe.gov/library/photos/thumbs/nf1648.jpg General

  1. EIS-0350-S1: Supplemental Environmental Impact Statement for the Nuclear Facility Portion of the Chemistry and Metallurgy Research Building Replacement Project at Los Alamos National Laboratory, New Mexico

    Office of Energy Efficiency and Renewable Energy (EERE)

    This Supplemental EIS evaluates the completion of the Chemistry and Metallurgy Research Building Replacement (CMRR) Project, which consists of constructing the nuclear facility portion (CMRR-NF) at Los Alamos National Laboratory (LANL). The CMRR Project provides the analytical chemistry and materials characterization capabilities currently or previously performed in the existing Chemistry and Metallurgy Research (CMR) Building. Because of recent detailed site geotechnical investigations, certain aspects of the CMRR-NR project have changed resulting in change to the environmental impacts.

  2. Microsoft Word - DOE-ID-14-064 Illinois EC B3-6.doc

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 SECTION A. Project Title: Fundamental Studies of Irradiation-Induced Modification in Microstructural Evolution and Mechanical Properties of Advanced Alloys - University of Illinois SECTION B. Project Description The University of Illinois will conduct research that will: (1) establish ion-to-neutron irradiation correlations between available neutron-irradiated reference alloys (Grade 91, Grade 92 and NF709) and the ion irradiations on these materials, and (2) to use these correlations to

  3. Microsoft Word - DOE-ID-15-035 Colorado SofM EC B3-6.doc

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    5 SECTION A. Project Title: Assessment of Aging Degradation Mechanisms of Alloy 709 for Sodium Fast Reactors - Colorado School of Mines SECTION B. Project Description The Colorado School of Mines proposes to develop sufficient understanding of the mechanisms responsible for behavior of NF 709 under accelerated testing conditions to confidently predict long-term creep and creep-fatigue behavior at the times (500,000 hours) and temperatures (550 o C) of interest for fast reactor structural

  4. S:\VM3\RX97\TBL_LIST.WPD

    U.S. Energy Information Administration (EIA) Indexed Site

    b. Housing Unit Characteristics by Four Most Populated States, Percent of U.S. Households, 1997 Housing Unit Characteristics RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.4 1.1 1.1 1.2 1.7 Total .............................................................. 100.0 100.0 100.0 100.0 100.0 0.0 Census Region and Division Northeast ..................................................... 19.4 100.0 -- -- -- NF New England

  5. This publication is available from the Superintendent of Documents, U.S. Governm

    Gasoline and Diesel Fuel Update (EIA)

    0a. Housing Unit Characteristics by Midwest Census Region, Million U.S. Households, 2001 Housing Unit Characteristics RSE Column Factor: Total U.S. Midwest Census Region RSE Row Factors Total Census Division East North Central West North Central 0.5 1.0 1.2 1.8 Total .............................................................. 107.0 24.5 17.1 7.4 NE Census Region and Division Northeast ..................................................... 20.3 -- -- -- NF New England

  6. Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism

    SciTech Connect (OSTI)

    Jeon, Byung-Joon; Yang, Yoolhee; Kyung Shim, Su; Yang, Heung-Mo; Cho, Daeho; Ik Bang, Sa

    2013-10-15

    Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin ?4 (T?4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. T?4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between T?4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous T?4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous T?4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased T?4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of T?4-enhanced proliferation. Moreover, T?4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-?B. These observation provide that T?4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-?B pathways. Therefore, T?4 could be used as a tool for MSC expansion in cell therapeutics. - Highlights: This is fundamental information required to correlate T?4 with MSC expansion. MSC expansion by T?4 is involved in enhancement of IL-8 and ERK/NF-?B pathway. T?4 could be used as a tool for MSC expansion in cell therapeutics.

  7. Correlation ECE diagnostic in Alcator C-Mod

    SciTech Connect (OSTI)

    Sung, C.; White, A. E.; Howard, N. T.; Mikkelsen, D.; Irby, J.; Leccacorvi, R.; Vieira, R.; Oi, C.; Rice, J.; Reinke, M.; Gao, C.; Ennever, P.; Porkolab, M.; Churchill, R.; Theiler, C.; Walk, J.; Hughes, J.; Hubbard, A.; Greenwald, M.

    2015-03-12

    Correlation ECE (CECE) is a diagnostic technique that allows measurement of small amplitude electron temperature, Te, fluctuations through standard cross-correlation analysis methods. In Alcator C-Mod, a new CECE diagnostic has been installed[Sung RSI 2012], and interesting phenomena have been observed in various plasma conditions. We find that local Te fluctuations near the edge (ρ ~ 0:8) decrease across the linearto- saturated ohmic confinement transition, with fluctuations decreasing with increasing plasma density[Sung NF 2013], which occurs simultaneously with rotation reversals[Rice NF 2011]. Te fluctuations are also reduced across core rotation reversals with an increase of plasma density in RF heated L-mode plasmas, which implies that the same physics related to the reduction of Te fluctuations may be applied to both ohmic and RF heated L-mode plasmas. In I-mode plasmas, we observe the reduction of core Te fluctuations, which indicates changes of turbulence occur not only in the pedestal region but also in the core across the L/I transition[White NF 2014]. The present CECE diagnostic system in C-Mod and these experimental results are described in this paper.

  8. Correlation ECE diagnostic in Alcator C-Mod

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Sung, C.; White, A. E.; Howard, N. T.; Mikkelsen, D.; Irby, J.; Leccacorvi, R.; Vieira, R.; Oi, C.; Rice, J.; Reinke, M.; et al

    2015-03-12

    Correlation ECE (CECE) is a diagnostic technique that allows measurement of small amplitude electron temperature, Te, fluctuations through standard cross-correlation analysis methods. In Alcator C-Mod, a new CECE diagnostic has been installed[Sung RSI 2012], and interesting phenomena have been observed in various plasma conditions. We find that local Te fluctuations near the edge (ρ ~ 0:8) decrease across the linearto- saturated ohmic confinement transition, with fluctuations decreasing with increasing plasma density[Sung NF 2013], which occurs simultaneously with rotation reversals[Rice NF 2011]. Te fluctuations are also reduced across core rotation reversals with an increase of plasma density in RF heated L-modemore » plasmas, which implies that the same physics related to the reduction of Te fluctuations may be applied to both ohmic and RF heated L-mode plasmas. In I-mode plasmas, we observe the reduction of core Te fluctuations, which indicates changes of turbulence occur not only in the pedestal region but also in the core across the L/I transition[White NF 2014]. The present CECE diagnostic system in C-Mod and these experimental results are described in this paper.« less

  9. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    SciTech Connect (OSTI)

    Li, Weifeng Huang, Huimin; Niu, Xiaofeng Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

  10. Achieving very low mercury levels in refinery wastewater by membrane filtration.

    SciTech Connect (OSTI)

    Urgun Demirtas, M.; Benda, P.; Gillenwater, P. S.; Negri, M. C.; Xiong, H.; Snyder, S. W.

    2012-05-15

    Microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) membranes were evaluated for their ability to achieve the world's most stringent Hg discharge criterion (<1.3 ng/L) in an oil refinery's wastewater. The membrane processes were operated at three different pressures to demonstrate the potential for each membrane technology to achieve the targeted effluent mercury concentrations. The presence of mercury in the particulate form in the refinery wastewater makes the use of MF and UF membrane technologies more attractive in achieving very low mercury levels in the treated wastewater. Both NF and RO were also able to meet the target mercury concentration at lower operating pressures (20.7 bar). However, higher operating pressures ({ge}34.5 bar) had a significant effect on NF and RO flux and fouling rates, as well as on permeate quality. SEM images of the membranes showed that pore blockage and narrowing were the dominant fouling mechanisms for the MF membrane while surface coverage was the dominant fouling mechanism for the other membranes. The correlation between mercury concentration and particle size distribution was also investigated to understand mercury removal mechanisms by membrane filtration. The mean particle diameter decreased with filtration from 1.1 {+-} 0.0 {micro}m to 0.74 {+-} 0.2 {micro}m after UF.

  11. Solvothermal synthesis of NiAl double hydroxide microspheres on a nickel foam-graphene as an electrode material for pseudo-capacitors

    SciTech Connect (OSTI)

    Momodu, Damilola; Bello, Abdulhakeem; Dangbegnon, Julien; Barzeger, Farshad; Taghizadeh, Fatimeh; Fabiane, Mopeli; Manyala, Ncholu; Johnson, A. T. Charlie

    2014-09-15

    In this paper, we demonstrate excellent pseudo-capacitance behavior of nickel-aluminum double hydroxide microspheres (NiAl DHM) synthesized by a facile solvothermal technique using tertbutanol as a structure-directing agent on nickel foam-graphene (NF-G) current collector as compared to use of nickel foam current collector alone. The structure and surface morphology were studied by X-ray diffraction analysis, Raman spectroscopy and scanning and transmission electron microscopies respectively. NF-G current collector was fabricated by chemical vapor deposition followed by an ex situ coating method of NiAl DHM active material which forms a composite electrode. The pseudocapacitive performance of the composite electrode was investigated by cyclic voltammetry, constant chargedischarge and electrochemical impedance spectroscopy measurements. The composite electrode with the NF-G current collector exhibits an enhanced electrochemical performance due to the presence of the conductive graphene layer on the nickel foam and gives a specific capacitance of 1252 F g{sup ?1} at a current density of 1 A g{sup ?1} and a capacitive retention of about 97% after 1000 chargedischarge cycles. This shows that these composites are promising electrode materials for energy storage devices.

  12. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    SciTech Connect (OSTI)

    Sabatino, Mara Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto; Mascanfroni, Ivn Daro; Pellizas, Claudia Gabriela; Gutirrez, Silvina; Torres, Alicia Ins; De Paul, Ana Luca

    2013-11-15

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-?B activation in this effect. In addition, the role of 17?-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-?B after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-?B co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17?-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  13. Molecular mapping of chromosomes 17 and X

    SciTech Connect (OSTI)

    Barker, D.F.

    1989-01-01

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  14. Molecular mapping of chromosomes 17 and X. Progress report

    SciTech Connect (OSTI)

    Barker, D.F.

    1989-12-31

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  15. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    SciTech Connect (OSTI)

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  16. Inhibition of IRAK-4 activity for rescuing endotoxin LPS-induced septic mortality in mice by lonicerae flos extract

    SciTech Connect (OSTI)

    Park, Sun Hong; Roh, Eunmiri; Kim, Hyun Soo; Baek, Seung-Il; Choi, Nam Song; Kim, Narae; Hwang, Bang Yeon; Han, Sang-Bae; Kim, Youngsoo

    2013-12-13

    Highlights: •Lonicerae flos extract (HS-23) is a clinical candidate, Phase I for sepsis treatment. •Here, HS-23 or its major constituents rescued LPS-induced septic mortality in mice. •As a mechanism, they directly inhibited IRAK-4-catalyzed kinase activity. •Thus, they suppressed LPS-induced expression of NF-κB/AP-1-target inflammatory genes. -- Abstract: Lonicerae flos extract (HS-23) is a clinical candidate currently undergoing Phase I trial in lipopolysaccharide (LPS)-injected healthy human volunteers, but its molecular basis remains to be defined. Here, we investigated protective effects of HS-23 or its major constituents on Escherichia coli LPS-induced septic mortality in mice. Intravenous treatment with HS-23 rescued LPS-intoxicated C57BL/6J mice under septic conditions, and decreased the levels of cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and high-mobility group box-1 (HMGB-1) in the blood. Chlorogenic acid (CGA) and its isomers were assigned as major constituents of HS-23 in the protection against endotoxemia. As a molecular mechanism, HS-23 or CGA isomers inhibited endotoxin LPS-induced autophosphorylation of the IL-1 receptor-associated kinase 4 (IRAK-4) in mouse peritoneal macrophages as well as the kinase activity of IRAK-4 in cell-free reactions. HS-23 consequently suppressed downstream pathways critical for LPS-induced activation of nuclear factor (NF)-κB or activating protein 1 (AP-1) in the peritoneal macrophages. HS-23 also inhibited various toll-like receptor agonists-induced nitric oxide (NO) production, and down-regulated LPS-induced expression of NF-κB/AP-1-target inflammatory genes in the cells. Taken together, HS-23 or CGA isomers exhibited anti-inflammatory therapy against LPS-induced septic mortality in mice, at least in part, mediated through the inhibition of IRAK-4.

  17. Role of endoplasmic reticulum stress in acrolein-induced endothelial activation

    SciTech Connect (OSTI)

    Haberzettl, Petra; Vladykovskaya, Elena; Srivastava, Sanjay [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States); Bhatnagar, Aruni [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)], E-mail: aruni@louisville.edu

    2009-01-01

    Acrolein is a ubiquitous environmental pollutant and an endogenous product of lipid peroxidation. It is also generated during the metabolism of several drugs and amino acids. In this study, we examined the effects of acrolein on endothelial cells. Treatment of human umbilical vein endothelial cells (HUVECs) with 2 to 10 {mu}M acrolein led to an increase in the phosphorylation of eIF-2{alpha} within 10 to 30 min of exposure. This was followed by alternate splicing of XBP-1 mRNA and an increase in the expression of the endoplasmic reticulum (ER) chaperone genes Grp78 and Herp. Within 2-4 h of treatment, acrolein also increased the abundance and the nuclear transport of the transcription factors ATF3, AFT4, and CHOP. Acrolein-induced increase in ATF3 was prevented by treating the cells with the chemical chaperone - phenylbutyric acid (PBA). Treatment with acrolein increased phosphorylation of ERK1/2, p38, and JNK. The increase in JNK phosphorylation was prevented by PBA. Acrolein treatment led to activation and nuclear translocation of the transcription factor NF-{kappa}B and an increase in TNF-{alpha}, IL-6 and IL-8, but not MCP-1, mRNA. Increased expression of cytokine genes and NF-{kappa}B activation were not observed in cells treated with PBA. These findings suggest that exposure to acrolein induces ER stress and triggers the unfolded protein response and that NF-{kappa}B activation and stimulation of cytokine production by acrolein could be attributed, in part, to ER stress. Chemical chaperones of protein-folding may be useful in treating toxicological and pathological states associated with excessive acrolein exposure or production.

  18. Insights antifibrotic mechanism of methyl palmitate: Impact on nuclear factor kappa B and proinflammatory cytokines

    SciTech Connect (OSTI)

    Mantawy, Eman M.; Tadros, Mariane G.; Awad, Azza S.; Hassan, Dina A.A.; El-Demerdash, Ebtehal

    2012-01-01

    Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment is evident. The present study was designed to assess the potential antifibrotic effect of MP and whether MP can attenuate the severity of oxidative stress and inflammatory response in chronic liver injury. Male albino rats were treated with either CCl{sub 4} (1 ml/kg, twice a week) and/or MP (300 mg/kg, three times a week) for six weeks. CCl{sub 4}-intoxication significantly increased liver weight, serum aminotransferases, total cholesterol and triglycerides while decreased albumin level and these effects were prevented by co-treatment with MP. As indicators of oxidative stress, CCl{sub 4}-intoxication caused significant glutathione depletion and lipid peroxidation while MP co-treatment preserved them within normal values. As markers of fibrosis, hydroxyproline content and ?-SMA expression increased markedly in the CCl{sub 4} group and MP prevented these alterations. Histopathological examination by both light and electron microscope further confirmed the protective efficacy of MP. To elucidate the antifibrotic mechanisms of MP, the expression of NF-?B, iNOS and COX-2 and the tissue levels of TNF-? and nitric oxide were assessed; CCl{sub 4} increased the expression of NF-?B and all downstream inflammatory cascade while MP co-treatment inhibited them. Collectively these findings indicate that MP possesses a potent antifibrotic effect which may be partly a consequence of its antioxidant and anti-inflammatory properties. -- Highlights: ? Methyl palmitate is free fatty acid methyl ester. ? It possesses a strong antifibrotic effect. ? It inhibits NF-?B and the consequent proinflammatory and oxidative stress response.

  19. Isotropic plasma etching of Ge Si and SiNx films

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Henry, Michael David; Douglas, Erica Ann

    2016-05-01

    This study reports on selective isotropic dry etching of chemically vapor deposited (CVD) Ge thin film, release layers using a Shibaura chemical downstream etcher (CDE) with NF3 and Ar based plasma chemistry. Relative etch rates between Ge, Si and SiNx are described with etch rate reductions achieved by adjusting plasma chemistry with O2. Formation of oxides reducing etch rates were measured for both Ge and Si, but nitrides or oxy-nitrides created using direct injection of NO into the process chamber were measured to increase Si and SiNx etch rates while retarding Ge etching.

  20. Microsoft PowerPoint - Managing Uncertainty and Demonstrating Compliance

    Office of Environmental Management (EM)

    Low Dose DOE's Low Dose R di ti R h R di ti R h Radiation Research Radiation Research Program Program g g NF Metting, Sc.D., Program Manager Nuclear Energy Advisory Committee Meeting Nuclear Energy Advisory Committee Meeting L'Enfant Plaza Hotel L'Enfant Plaza Hotel 6 December 2012 Office of Science Office of Biological and Environmental Research DOE's Low Dose Program: DOE s Low Dose Program: Is unique within the U.S. government in focusing on low dose biological research aimed at informing

  1. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    SciTech Connect (OSTI)

    Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana; Borkar, Roshan M.; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Srinivas, R.; Shyam Sunder, R.; Sistla, Ramakrishna

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  2. Inhibition of HIV-1 entry by the tricyclic coumarin GUT-70 through the modification of membrane fluidity

    SciTech Connect (OSTI)

    Matsuda, Kouki; Hattori, Shinichiro; Kariya, Ryusho; Komizu, Yuji; Kudo, Eriko; Goto, Hiroki; Taura, Manabu; Ueoka, Ryuichi; Kimura, Shinya; Okada, Seiji

    2015-02-13

    Membrane fusion between host cells and HIV-1 is the initial step in HIV-1 infection, and plasma membrane fluidity strongly influences infectivity. In the present study, we demonstrated that GUT-70, a natural product derived from Calophyllum brasiliense, stabilized plasma membrane fluidity, inhibited HIV-1 entry, and down-regulated the expression of CD4, CCR5, and CXCR4. Since GUT-70 also had an inhibitory effect on viral replication through the inhibition of NF-κB, it is expected to be used as a dual functional and viral mutation resistant reagent. Thus, these unique properties of GUT-70 enable the development of novel therapeutic agents against HIV-1 infection.

  3. A Non-scaling Fixed Field Alternating Gradient Accelerator for the Final Acceleration Stage of the International Design Study of the Neutrino Factory.

    SciTech Connect (OSTI)

    Berg, J.S.; Aslaninejad, M.; Pasternak, J.; Witte, H.; Bliss, N. Cordwell M.; Jones, T.; Muir, A., Kelliher, D.; Machida, S.

    2011-09-04

    The International Design Study of the Neutrino Factory (IDS-NF) has recently completed its Interim Design Report (IDR), which presents our current baseline design of the neutrino factory. To increase the efficiency and reduce the cost of acceleration, the IDR design uses a linear non-scaling fixed field alternating gradient accelerator (FFAG) for its final acceleration stage. We present the current lattice design of that FFAG, including the main ring plus its injection and extraction systems. We describe parameters for the main ring magnets, kickers, and septa, as well as the power supplies for the kickers. We present a first pass at an engineering layout for the ring and its subsystems.

  4. Microsoft PowerPoint - Low Dose Update Metting 6 Dec 2012

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Low Dose DOE's Low Dose R di ti R h R di ti R h Radiation Research Radiation Research Program Program g g NF Metting, Sc.D., Program Manager Nuclear Energy Advisory Committee Meeting Nuclear Energy Advisory Committee Meeting L'Enfant Plaza Hotel L'Enfant Plaza Hotel 6 December 2012 Office of Science Office of Biological and Environmental Research DOE's Low Dose Program: DOE s Low Dose Program: Is unique within the U.S. government in focusing on low dose biological research aimed at informing

  5. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    SciTech Connect (OSTI)

    Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2?-, 3?-cyclic-nucleotide-3?-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. The attenuation in myelin and axon is synergistic. The optic nerve and brain demonstrate reduced glutamine synthetase. The retina

  6. S:\VM3\RX97\TBL_LIST.WPD

    U.S. Energy Information Administration (EIA) Indexed Site

    1997 Household Characteristics RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.4 1.1 1.2 1.4 1.4 Total .............................................................. 101.5 6.8 11.5 7.0 5.9 NF 1997 Household Income Category Less than $5,000 ......................................... 3.8 0.3 0.3 0.3 0.1 16.2 $5,000 to $9,999 ......................................... 9.6 0.9 1.1 0.6 0.7 14.2 $10,000 to $14,999

  7. S:\VM3\RX97\TBL_LIST.WPD

    U.S. Energy Information Administration (EIA) Indexed Site

    1997 Space Heating Characteristics RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.5 1.2 0.9 1.3 1.5 Total .............................................................. 101.5 6.8 11.5 7.0 5.9 NF Main Heating Fuel and Equipment Natural Gas ................................................. 53.5 3.4 7.8 3.8 0.7 8.6 Central Warm-Air Furnace ........................ 38.4 1.8 4.7 2.3 0.6 12.2 For One Housing Unit ..............................

  8. S:\VM3\RX97\TBL_LIST.WPD [PFP#201331587]

    U.S. Energy Information Administration (EIA) Indexed Site

    1997 Appliance Types and Characteristics RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.4 1.3 1.2 1.2 1.4 Total .............................................................. 101.5 6.8 11.5 7.0 5.9 NF Households With Electric Air-Conditioning Equipment ...................... 73.6 4.3 4.8 6.4 5.7 3.5 Central Equipment Not Used ....................... 0.3 Q 0.1 (*) 0.1 29.3 Room Air Conditioners Not Used ................ 0.7 Q Q Q 0.1 36.9

  9. S:\VM3\RX97\TBL_LIST.WPD [PFP#201331587]

    U.S. Energy Information Administration (EIA) Indexed Site

    1997 Home Office Equipment RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.4 1.1 1.1 1.5 1.3 Total .............................................................. 101.5 6.8 11.5 7.0 5.9 NF Households Using Office Equipment ......................................... 80.5 5.4 8.9 5.2 4.7 1.9 Personal Computers ................................... 35.6 2.2 4.6 2.6 2.0 5.9 Number of PCs 1

  10. S:\VM3\RX97\TBL_LIST.WPD [PFP#201331587]

    U.S. Energy Information Administration (EIA) Indexed Site

    Million U.S. Households, 1997 Usage Indicators RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.4 1.2 1.1 1.3 1.5 Total .............................................................. 101.5 6.8 11.5 7.0 5.9 NF Weekday Home Activities Home Used for Business Yes ............................................................ 7.4 0.5 0.9 0.4 0.4 13.5 No .............................................................. 94.1 6.3 10.6 6.5 5.6 2.2

  11. ABORATOtiY

    Office of Legacy Management (LM)

    ABORATOtiY ., . . . .' _ RESULTS OF THE RADIOLOGICAi SURVEY AT SUMITOMO MACHINERY CORPORATION OF AMERICA, 7 MALCOLM AVENUE, TETERBORO;NEW JERSEY (TJoo~) R. D. Foley L. M. Floyd Printed in the United States of America. Available from National Technical ' Information Serwce U.S. Department of Commerce 5265 Port Royal Road, Springfield, Virginia 22161 NTIS price codes-Printed Copy:A03 Microfiche A01 This report was prepared as an aCCo"nf of Work sponsored by an agency 01 Ihe

  12. E. 1. DU PONT DE NEMOURS & COMPANY

    Office of Legacy Management (LM)

    E. 1. DU PONT DE NEMOURS & COMPANY ,*Eo~UI~ WILMINGTON 99, DELAWARE IQ?. R. L. Kilburn, Director (2) Technical and Production Division Savannah River Operations Office U. S. Atomic Energy Commission -:; ;:~~~~!,~:c';~,~"s-,fi,:-~~~i:~!~~,,,,~~, ,';;'nf;;G;h=;cr;lina :J "'- I Dear IfI. Kilburn: RESEARCH PROGRAMS IN SUPPORT OF SAVANNAH RIVER In a letter to you dated April 19, 1956, ~~14-56-218, we recommended that the Savannah River Operations Office set aside funds to cover certain

  13. I"

    Office of Legacy Management (LM)

    .., ..6'"w' I, . v -+"+.~ f, :. 6 ~,i.//bJc-iC ' ; 1-i -5' ; i - *> i-i> I ii I-t t n,.,4 ( .I , f ' .I f x c . : ' . ,"", ' C.--c rn ' 2. I _ i ' L :_ ;) --lr>[-0-t. ' I" c j-j! : , :- ) L (, 3 uTALL.URCICAL PROJECT FOmc W-73 The University of Chicago Chicago, Illinois s docurrient consists of--.TL,y. es and ._______ C? . _ - _ _ ._.__ d..nf ______ &?copiesl fig ____________________-----. 2 Series_.. re%~~IC~ 0~ T~WINATI~N OF SUBCONTRACT _ _____ Contract

  14. SNOiioaroad A9U3N3

    Gasoline and Diesel Fuel Update (EIA)

    1997 Household Characteristics RSE Column Factor: Total Four Most Populated States RSE Row Factors New York California Texas Florida 0.4 1.1 1.2 1.4 1.4 Total .............................................................. 101.5 6.8 11.5 7.0 5.9 NF 1997 Household Income Category Less than $5,000 ......................................... 3.8 0.3 0.3 0.3 0.1 16.2 $5,000 to $9,999 ......................................... 9.6 0.9 1.1 0.6 0.7 14.2 $10,000 to $14,999

  15. INSTITUTE OF PHYSICS PUBLISHING

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 (2004) 162-171 PII: S0029-5515(04)72612-5 Equilibrium reconstruction in the Madison Symmetric Torus reversed field pinch J.K. Anderson, C.B. Forest, T.M. Biewer a , J.S. Sarff and J.C. Wright b Department of Physics, University of Wisconsin, Madison, WI 53706, USA Received 21 December 2002, accepted for publication 18 November 2003 Published 17 December 2003 Online at stacks.iop.org/NF/44/162 (DOI: 10.1088/0029-5515/44/1/018) Abstract A non-linear Grad-Shafranov toroidal equilibrium

  16. INSTITUTE OF PHYSICS PUBLISHING

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 (2006) 521-531 doi:10.1088/0029-5515/46/5/004 Coupling to the electron Bernstein wave using a phased array of waveguides in MST reversed field pinch M. Cengher, J.K. Anderson, V. Svidzinski and C.B. Forest 1 Department of Physics, University of Wisconsin, 1150 University Ave, Madison, WI 53706, USA E-mail: cbforest@wisc.edu Received 31 August 2005, accepted for publication 20 February 2006 Published 23 March 2006 Online at stacks.iop.org/NF/46/521 Abstract Coupling to the electron Bernstein

  17. ISABELA-QA: query-driven analytics with ISABELA-compressed extreme-scale

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    scientific data | Argonne Leadership Computing Facility ISABELA-QA: query-driven analytics with ISABELA-compressed extreme-scale scientific data Authors: Lakshminarasimhan,S., Jenkins, J., Latham,R., Samatova, N.F., Arkatkar, I., Gong, Z., Kolla, H., Chen, J., Ku, S.H. Chang, C.S., Ethier, S., Klasky, S. Efficient analytics of scientific data from extreme-scale simulations is quickly becoming a top-notch priority. The increasing simulation output data sizes demand for a paradigm shift in how

  18. The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells

    SciTech Connect (OSTI)

    Zhang, Yingyi; Zhao, Yu; Li, Leilei; Shen, Yu; Cai, Xiaoli; Zhang, Xiaodong; Ye, Lihong

    2013-05-03

    Highlights: HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. HBXIP serves as a coactivator of activating transcription factor Sp1. HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-?B (NF-?B) in breast cancer cells. As an oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays crucial roles in carcinogenesis. In the present study, we found that both HBXIP and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP was able to increase transcriptional activity of NF-?B through PDGFB, suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was able to upregulate PDGFB at the levels of mRNA, protein and promoter in the cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through activating transcription factor Sp1. In function, HBXIP enhanced the proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote proliferation of breast cancer cells.

  19. Id1 expression promotes peripheral CD4{sup +} T cell proliferation and survival upon TCR activation without co-stimulation

    SciTech Connect (OSTI)

    Liu, Chen; Jin, Rong; Wang, Hong-Cheng; Tang, Hui; Liu, Yuan-Feng; Qian, Xiao-Ping; Sun, Xiu-Yuan; Ge, Qing; Sun, Xiao-Hong; Zhang, Yu

    2013-06-21

    Highlights: •Id1 expression enables naïve T cell proliferation without anti-CD28 co-stimulation. •Id1 expression facilitates T cells survival when stimulated with anti-CD3. •Elevation of IL-2 production by Id1 contributes increased proliferation and survival. •Id1 potentiates NF-κB activation by anti-CD3 stimulation. -- Abstract: Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïve CD4{sup +} cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.

  20. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    SciTech Connect (OSTI)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T.; Wani, Mohan R.

    2010-09-03

    Research highlights: {yields} IL-3 inhibits receptor activator of NF-{kappa}B ligand (RANKL)-induced osteoclastogenesis. {yields} IL-3 inhibits RANKL-induced JNK activation. {yields} IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. {yields} IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. {yields} IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-{kappa}B (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  1. Lipocalin-2 inhibits osteoclast formation by suppressing the proliferation and differentiation of osteoclast lineage cells

    SciTech Connect (OSTI)

    Kim, Hyun-Ju; Yoon, Hye-Jin; Yoon, Kyung-Ae; Gwon, Mi-Ri; Jin Seong, Sook; Suk, Kyoungho; Kim, Shin-Yoon; Yoon, Young-Ran

    2015-06-10

    Lipocalin-2 (LCN2) is a member of the lipocalin superfamily and plays a critical role in the regulation of various physiological processes, such as inflammation and obesity. In this study, we report that LCN2 negatively modulates the proliferation and differentiation of osteoclast precursors, resulting in impaired osteoclast formation. The overexpression of LCN2 in bone marrow-derived macrophages or the addition of recombinant LCN2 protein inhibits the formation of multinuclear osteoclasts. LCN2 suppresses macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursor cells without affecting their apoptotic cell death. Interestingly, LCN2 decreases the expression of the M-CSF receptor, c-Fms, and subsequently blocks its downstream signaling cascades. In addition, LCN2 inhibits RANKL-induced osteoclast differentiation and attenuates the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important modulators in osteoclastogenesis. Mechanistically, LCN2 inhibits NF-κB signaling pathways, as demonstrated by the suppression of IκBα phosphorylation, nuclear translocation of p65, and NF-κB transcriptional activity. Thus, LCN2 is an anti-osteoclastogenic molecule that exerts its effects by retarding the proliferation and differentiation of osteoclast lineage cells. - Highlights: • LCN2 expression is regulated during osteoclast development. • LCN2 suppresses M-CSF-mediated osteoclast precursor proliferation. • LCN2 inhibits RANKL-induced osteoclast differentiation.

  2. Salmon trypsin stimulates the expression of interleukin-8 via protease-activated receptor-2

    SciTech Connect (OSTI)

    Larsen, Anett K.; Seternes, Ole-Morten; Larsen, Merethe; Aasmoe, Lisbeth; Bang, Berit

    2008-08-01

    In this study, we focus on salmon trypsin as an activator of inflammatory responses in airway cells in vitro. The rationale behind the investigation is that salmon industry workers are exposed to aerosols containing enzymes, which are generated during industrial processing of the fish. Knowing that serine proteases such as trypsin are highly active mediators with diverse biological activities, the stimulation of nuclear factor-kappa B (NF-{kappa}B) and interleukin (IL)-8 and the role of protease-activated receptors (PAR) in inflammatory signal mediation were investigated. Protease-activated receptors are considered important under pathological situations in the human airways, and a thorough understanding of PAR-induced cellular events and their consequences in airway inflammation is necessary. Human airway epithelial cells (A549) were exposed to trypsin isolated from fish (Salmo salar), and we observed that purified salmon trypsin could generate secretion of IL-8 in a concentration-dependent manner. Furthermore, we demonstrate that PAR-2 activation by salmon trypsin is coupled to an induction of NF-{kappa}B-mediated transcription using a PAR-2 transfected HeLa cell model. Finally, we show that the release of IL-8 from A549 following stimulation with purified salmon trypsin is mediated through activation of PAR-2 using specific small interfering RNAs (siRNAs). The results presented suggest that salmon trypsin, via activation of PAR-2, might influence inflammation processes in the airways if inhaled in sufficient amounts.

  3. Fenofibrate, a peroxisome proliferator-activated receptor ? ligand, prevents abnormal liver function induced by a fastingrefeeding process

    SciTech Connect (OSTI)

    Lee, Joon No; Dutta, Raghbendra Kumar; Kim, Seul-Gi; Lim, Jae-Young; Kim, Se-Jin; Choe, Seong-Kyu; Yoo, Kyeong-Won; Immune-network Pioneer Research Center, Department of Biochemistry, College of Medicine, Dong-A University, Busan ; Song, Seung Ryel; Park, Do-Sim; Department of Laboratory of Medicine, School of Medicine, Wonkwang University, Iksan ; So, Hong-Seob; Park, Raekil

    2013-12-06

    Highlights: A fastingrefeeding high fat diet (HDF) model mimics irregular eating habit. A fastingrefeeding HFD induces liver ballooning injury. A fastingrefeeding HDF process elicits hepatic triglyceride accumulation. Fenofibrate, PPAR? ligand, prevents liver damage induced by refeeding HFD. -- Abstract: Fenofibrate, a peroxisome proliferator-activated receptor ? (PPAR?) agonist, is an anti-hyperlipidemic agent that has been widely used in the treatment of dyslipidemia. In this study, we examined the effect of fenofibrate on liver damage caused by refeeding a high-fat diet (HFD) in mice after 24 h fasting. Here, we showed that refeeding HFD after fasting causes liver damage in mice determined by liver morphology and liver cell death. A detailed analysis revealed that hepatic lipid droplet formation is enhanced and triglyceride levels in liver are increased by refeeding HFD after starvation for 24 h. Also, NF-?B is activated and consequently induces the expression of TNF-?, IL1-?, COX-2, and NOS2. However, treating with fenofibrate attenuates the liver damage and triglyceride accumulation caused by the fastingrefeeding HFD process. Fenofibrate reduces the expression of NF-?B target genes but induces genes for peroxisomal fatty acid oxidation, peroxisome biogenesis and mitochondrial fatty acid oxidation. These results strongly suggest that the treatment of fenofibrate ameliorates the liver damage induced by fastingrefeeding HFD, possibly through the activation of fatty acid oxidation.

  4. Bar code application to nuclear material accountancy

    SciTech Connect (OSTI)

    Usui, S.; Sano, H. )

    1991-01-01

    For the purpose of efficient implementation of IAEA safeguards inspection, operators ought to prepare the information which is related to the strata for flow verification in a timely manner, such as physical inventory listing and summary of the fuel bundles. Today the use of bar code technique in tracing of products related data or counting number of items has been more and more applied to many facets of industry. From these points of view, the Japan Nuclear Fuel Company (NF) has been developing JNF Total Bar Code System. Now JNF has established an on-line input system of the fuel bundle accountability data by use of the bar code system to quickly prepare the information necessary for the inspection. As the first step, JNF implemented this bar code system at the flow verification to prepare physical inventory summary and location map of the fuel bundles in the storage. This paper reports that as a result of this, NF confirmed that this bar code system made it possible to input easily and quickly nuclear material accountancy information, and therefore this system is utilized as an effective and efficient measure of timely preparation for the inspection.

  5. Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages

    SciTech Connect (OSTI)

    Fernandes, Claudia A.; Fievez, Laurence; Neyrinck, Audrey M.; Delzenne, Nathalie M.; Bureau, Fabrice; Vanbever, Rita

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer Lipopolysaccharide-stimulated macrophages were treated with cambinol and sirtinol. Black-Right-Pointing-Pointer Cambinol and sirtinol decreased lipopolysaccharide-induced cytokines. Black-Right-Pointing-Pointer Cambinol decreased NF-{kappa}B activity but had no impact on p38 MAPK activation. Black-Right-Pointing-Pointer Sirtuins are an interesting target for the treatment of inflammatory diseases. -- Abstract: In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-{alpha}) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-{kappa}B) activity and inhibitor kappa B alpha (I{kappa}B{alpha}) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.

  6. A multichannel magnetic probe system for analysing magnetic fluctuations in helical axis plasmas

    SciTech Connect (OSTI)

    Haskey, S. R.; Blackwell, B. D.; Seiwald, B.; Hole, M. J.; Pretty, D. G.; Howard, J.; Wach, J. [Plasma Research Laboratory, Research School of Physical Sciences and Engineering, The Australian National University, Canberra, ACT 0200 (Australia)] [Plasma Research Laboratory, Research School of Physical Sciences and Engineering, The Australian National University, Canberra, ACT 0200 (Australia)

    2013-09-15

    The need to understand the structure of magnetic fluctuations in H-1NF heliac [S. Hamberger et al., Fusion Technol. 17, 123 (1990)] plasmas has motivated the installation of a sixteen former, tri-axis helical magnetic probe Mirnov array (HMA). The new array complements two existing poloidal Mirnov arrays by providing polarisation information, higher frequency response, and improved toroidal resolution. The helical placement is ideal for helical axis plasmas because it positions the array as close as possible to the plasma in regions of varying degrees of favourable curvature in the magnetohydrodynamic sense, but almost constant magnetic angle. This makes phase variation with probe position near linear, greatly simplifying the analysis of the data. Several of the issues involved in the design, installation, data analysis, and calibration of this unique array are presented including probe coil design, frequency response measurements, mode number identification, orientation calculations, and mapping probe coil positions to magnetic coordinates. Details of specially designed digitally programmable pre-amplifiers, which allow gains and filters to be changed as part of the data acquisition initialisation sequence and stored with the probe signals, are also presented. The low shear heliac geometry [R. Jimnez-Gmez et al., Nucl. Fusion 51, 033001 (2011)], flexibility of the H-1NF heliac, and wealth of information provided by the HMA create a unique opportunity for detailed study of Alfvn eigenmodes, which could be a serious issue for future fusion reactors.

  7. Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models

    SciTech Connect (OSTI)

    Saeed, Noha M.; El-Demerdash, Ebtehal; Abdel-Rahman, Hanaa M.; Algandaby, Mardi M.; Al-Abbasi, Fahad A.; Abdel-Naim, Ashraf B.

    2012-10-01

    Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6). MP and EP decreased NF-?B expression in liver and lung tissues and ameliorated histopathological changes caused by LPS. Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ? Efficacy of MP and EP in combating inflammation was displayed in several models. ? MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ? MP and EP decreased TNF-? and IL-6 levels in experimental endotoxemia. ? MP and EP reduced NF-?B expression and histological changes in rat liver and lung. ? MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.

  8. Use of Treated Municipal Wastewater as Power Plant Cooling System Makeup Water: Tertiary Treatment versus Expanded Chemical Regimen for Recirculating Water Quality Management

    SciTech Connect (OSTI)

    David Dzombak; Radisav Vidic; Amy Landis

    2012-06-30

    Treated municipal wastewater is a common, widely available alternative source of cooling water for thermoelectric power plants across the U.S. However, the biodegradable organic matter, ammonia-nitrogen, carbonate and phosphates in the treated wastewater pose challenges with respect to enhanced biofouling, corrosion, and scaling, respectively. The overall objective of this study was to evaluate the benefits and life cycle costs of implementing tertiary treatment of secondary treated municipal wastewater prior to use in recirculating cooling systems. The study comprised bench- and pilot-scale experimental studies with three different tertiary treated municipal wastewaters, and life cycle costing and environmental analyses of various tertiary treatment schemes. Sustainability factors and metrics for reuse of treated wastewater in power plant cooling systems were also evaluated. The three tertiary treated wastewaters studied were: secondary treated municipal wastewater subjected to acid addition for pH control (MWW_pH); secondary treated municipal wastewater subjected to nitrification and sand filtration (MWW_NF); and secondary treated municipal wastewater subjected nitrification, sand filtration, and GAC adsorption (MWW_NFG). Tertiary treatment was determined to be essential to achieve appropriate corrosion, scaling, and biofouling control for use of secondary treated municipal wastewater in power plant cooling systems. The ability to control scaling, in particular, was found to be significantly enhanced with tertiary treated wastewater compared to secondary treated wastewater. MWW_pH treated water (adjustment to pH 7.8) was effective in reducing scale formation, but increased corrosion and the amount of biocide required to achieve appropriate biofouling control. Corrosion could be adequately controlled with tolytriazole addition (4-5 ppm TTA), however, which was the case for all of the tertiary treated waters. For MWW_NF treated water, the removal of ammonia by

  9. Crucial role of Toll-like receptors in the zinc/nickel-induced inflammatory response in vascular endothelial cells

    SciTech Connect (OSTI)

    Tsou, Tsui-Chun; Liou, Saou-Hsing; Yeh, Szu-Ching; Tsai, Feng-Yuan; Chao, How-Ran

    2013-12-15

    ICAM-1/IL‑8 expression in endothelial cells via TLRs. • Nickel induces the inflammatory responses via a TLR-4/NF-κB pathway. • Zinc causes the inflammatory responses via a broader TLRs/NF-κB signaling. • Nickel shows a significantly higher inflammatory effect than zinc. • NF-κB activation is the primary mechanism involved in the inflammatory responses.

  10. Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine

    SciTech Connect (OSTI)

    Chen, Jiann-Hwa; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

    2014-09-15

    Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30 mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. - Graphical abstract: Schematic presentation of the signaling pathways involved in magnolol inhibited transient global ischemia brain apoptosis and inflammation in rats. The effect of magnolol on the scavenger of ROS, which inhibits p38 MAPK and CHOP protein inactivation

  11. Ethanol increases matrix metalloproteinase-12 expression via NADPH oxidase-dependent ROS production in macrophages

    SciTech Connect (OSTI)

    Kim, Mi Jin; Nepal, Saroj; Lee, Eung-Seok; Jeong, Tae Cheon; Kim, Sang-Hyun; Park, Pil-Hoon

    2013-11-15

    Matrix metalloproteinase-12 (MMP-12), an enzyme responsible for degradation of extracellular matrix, plays an important role in the progression of various diseases, including inflammation and fibrosis. Although most of those are pathogenic conditions induced by ethanol ingestion, the effect of ethanol on MMP-12 has not been explored. In the present study, we investigated the effect of ethanol on MMP-12 expression and its potential mechanisms in macrophages. Here, we demonstrated that ethanol treatment increased MMP-12 expression in primary murine peritoneal macrophages and RAW 264.7 macrophages at both mRNA and protein levels. Ethanol treatment also significantly increased the activity of nicotinamide adenine dinucleotide (NADPH) oxidase and the expression of NADPH oxidase-2 (Nox2). Pretreatment with an anti-oxidant (N-acetyl cysteine) or a selective inhibitor of NADPH oxidase (diphenyleneiodonium chloride (DPI)) prevented ethanol-induced MMP-12 expression. Furthermore, knockdown of Nox2 by small interfering RNA (siRNA) prevented ethanol-induced ROS production and MMP-12 expression in RAW 264.7 macrophages, indicating a critical role for Nox2 in ethanol-induced intracellular ROS production and MMP-12 expression in macrophages. We also showed that ethanol-induced Nox2 expression was suppressed by transient transfection with dominant negative IκB-α plasmid or pretreatment with Bay 11-7082, a selective inhibitor of NF-κB, in RAW 264.7 macrophages. In addition, ethanol-induced Nox2 expression was also attenuated by treatment with a selective inhibitor of p38 MAPK, suggesting involvement of p38 MAPK/NF-κB pathway in ethanol-induced Nox2 expression. Taken together, these results demonstrate that ethanol treatment elicited increase in MMP-12 expression via increase in ROS production derived from Nox2 in macrophages. - Highlights: • Ethanol increases ROS production through up-regulation of Nox2 in macrophages. • Enhanced oxidative stress contributes to ethanol

  12. Lasing in the UV, IR and visible spectral ranges in a runaway-electron-preionised diffuse dischrage

    SciTech Connect (OSTI)

    Vil'tovskii, P O; Lomaev, Mikhail I; Panchenko, Aleksei N; Panchenko, N A; Rybka, D V; Tarasenko, Viktor F

    2013-07-31

    Lasers on the mixtures of inert gases, H{sub 2}, D{sub 2}, and nitrogen with NF{sub 3} and (or) SF{sub 6} are studied under pumping by the volume (diffusive) discharge formed in a nonuniform electric field due to runaway-electron preionisation. Generation in the IR, visible and UV spectral ranges is obtained on atomic transitions of neon ({lambda} = 585.3 nm), argon (750.3 nm) and fluorine (712.8 and 731.1 nm), and on molecular transitions of N2 (337.1 nm), XeF * (351 and 353 nm), HF (2.8 - 3.2 {mu}m) and DF (3.8 - 4.2 {mu}m). It is shown that in N{sub 2} - SF{sub 6}, H{sub 2} - SF{sub 6} and D{sub 2} - SF{sub 6} mixtures the generation efficiency approaches the limiting values. (lasers)

  13. SULFUR HEXAFLUORIDE TREATMENT OF USED NUCLEAR FUEL TO ENHANCE SEPARATIONS

    SciTech Connect (OSTI)

    Gray, J.; Torres, R.; Korinko, P.; Martinez-Rodriguez, M.; Becnel, J.; Garcia-Diaz, B.; Adams, T.

    2012-09-25

    Reactive Gas Recycling (RGR) technology development has been initiated at Savannah River National Laboratory (SRNL), with a stretch-goal to develop a fully dry recycling technology for Used Nuclear Fuel (UNF). This approach is attractive due to the potential of targeted gas-phase treatment steps to reduce footprint and secondary waste volumes associated with separations relying primarily on traditional technologies, so long as the fluorinators employed in the reaction are recycled for use in the reactors or are optimized for conversion of fluorinator reactant. The developed fluorination via SF{sub 6}, similar to the case for other fluorinators such as NF{sub 3}, can be used to address multiple fuel forms and downstream cycles including continued processing for LWR via fluorination or incorporation into a aqueous process (e.g. modified FLUOREX) or for subsequent pyro treatment to be used in advanced gas reactor designs such metal- or gas-cooled reactors. This report details the most recent experimental results on the reaction of SF{sub 6} with various fission product surrogate materials in the form of oxides and metals, including uranium oxides using a high-temperature DTA apparatus capable of temperatures in excess of 1000{deg}C . The experimental results indicate that the majority of the fission products form stable solid fluorides and sulfides, while a subset of the fission products form volatile fluorides such as molybdenum fluoride and niobium fluoride, as predicted thermodynamically. Additional kinetic analysis has been performed on additional fission products. A key result is the verification that SF{sub 6} requires high temperatures for direct fluorination and subsequent volatilization of uranium oxides to UF{sub 6}, and thus is well positioned as a head-end treatment for other separations technologies, such as the volatilization of uranium oxide by NF{sub 3} as reported by colleagues at PNNL, advanced pyrochemical separations or traditional full recycle

  14. Cascade morphology transition in bcc metals

    SciTech Connect (OSTI)

    Setyawan, Wahyu; Selby, A.; Juslin, Niklas; Stoller, Roger E.; Wirth, Brian D.; Kurtz, Richard J.

    2015-06-10

    Energetic atom collisions in solids induce shockwaves with complex morphologies. In this paper, we establish the existence of a morphological transition in such cascades. The order parameter of the morphology is defined as the exponent, $b$, in the defect production curve as a function of cascade energy ($N_F$$ \\sim$$E_{MD}^b$). Response of different bcc metals can be compared in a consistent energy domain when the energy is normalized by the transition energy, $\\mu$, between the high- and the low-energy regime. Using Cr, Fe, Mo and W data, an empirical formula of $\\mu$ as a function of displacement threshold energy, $E_d$, is presented for bcc metals.

  15. Analysis and Annotation of Nucleic Acid Sequence

    SciTech Connect (OSTI)

    States, David J.

    2004-07-28

    The aims of this project were to develop improved methods for computational genome annotation and to apply these methods to improve the annotation of genomic sequence data with a specific focus on human genome sequencing. The project resulted in a substantial body of published work. Notable contributions of this project were the identification of basecalling and lane tracking as error processes in genome sequencing and contributions to improved methods for these steps in genome sequencing. This technology improved the accuracy and throughput of genome sequence analysis. Probabilistic methods for physical map construction were developed. Improved methods for sequence alignment, alternative splicing analysis, promoter identification and NF kappa B response gene prediction were also developed.

  16. Analysis and Annotation of Nucleic Acid Sequence

    SciTech Connect (OSTI)

    David J. States

    1998-08-01

    The aims of this project were to develop improved methods for computational genome annotation and to apply these methods to improve the annotation of genomic sequence data with a specific focus on human genome sequencing. The project resulted in a substantial body of published work. Notable contributions of this project were the identification of basecalling and lane tracking as error processes in genome sequencing and contributions to improved methods for these steps in genome sequencing. This technology improved the accuracy and throughput of genome sequence analysis. Probabilistic methods for physical map construction were developed. Improved methods for sequence alignment, alternative splicing analysis, promoter identification and NF kappa B response gene prediction were also developed.

  17. P+

    Office of Legacy Management (LM)

    zt- n.2 - _ ,I ---. -y , _ _._. s ~ .. <; ,. -* a.a----- -_ .S$ P+ -i ,4+y+&: .: ( 4 -fhP ,. I. ,* P 0 ' 9". ' - cn pi: %f . . : =1 - z ; ; (n ;' = g 5 G ," : 5 ; b f . . 4 3 \ . . . I i 8 : i 5 8 > --I n ;: 2-c 3" 5; 2 ? l 14 ? - i? 8 s =! 5 : ID z c! - ,I: -0 ;$ . . . i i I# : ii PM! c sgq, I 2 m Q 4 & 4 iii : -4 al- 2: p n-F! z i?" pw- p 48 $5 h A z r 8 i; 4 0 8 3 m N :a[ IO II i: g! j * / "a---= g : -4 O-IV' @ 42 % if 9 5 ;: 8 z, ,$ z 2 9 ;! 1'0 12 u)

  18. Tri And Rot Effects In Ternary Fission: What Can Be Learned?

    SciTech Connect (OSTI)

    Goennenwein, F.; Gagarski, A.; Petrov, G.; Guseva, I.; Zavarukhina, T.; Mutterer, M.; Kalben, J. von; Kopatch, Yu.; Tiourine, G.; Trzaska, W.; Sillanpaea, M.; Soldner, T.; Nesvizhevsky, V.

    2010-04-30

    Inducing fission by polarized neutrons allows studying subtle effects of the dynamics of the process. In the present experiments ternary fission of {sup 235}U and {sup 239}Pu was investigated with cold neutrons in the (n,f) reaction at the Institut Laue-Langevin, Grenoble. Asymmetries in the emission of ternary particles were discovered by making use of the neutron spin flipping. It was found that two effects are interfering. There is first an asymmetry in the total yields of ternary particles having been called the TRI-effect. Second, it was observed that the angular distributions of ternary particles are shifted back and forth when flipping the neutron spin. This shift was named ROT effect. Guided by trajectory calculations of the three-body decay, the signs and sizes of the ROT effect are interpreted in terms of the K-numbers of the transition states at the saddle point of fission.

  19. Strongly interacting dynamics and the search for new physics at the LHC

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Appelquist, T.; Brower, R. C.; Fleming, G. T.; Hasenfratz, A.; Jin, X. Y.; Kiskis, J.; Neil, E. T.; Osborn, J. C.; Rebbi, C.; Rinaldi, E.; et al

    2016-06-21

    We present results for the spectrum of a strongly interacting SU(3) gauge theory with Nf = 8 light fermions in the fundamental representation. Carrying out nonperturbative lattice calculations at the lightest masses and largest volumes considered to date, we confirm the existence of a remarkably light singlet scalar particle. We explore the rich resonance spectrum of the 8-flavor theory in the context of the search for new physics beyond the standard model at the Large Hadron Collider (LHC). Lastly, connecting our results to models of dynamical electroweak symmetry breaking, we estimate the vector resonance mass to be about 2 TeVmore » with a width of roughly 450 GeV, and predict additional resonances with masses below ~3 TeV.« less

  20. Method for studying a sample of material using a heavy ion induced mass spectrometer source

    DOE Patents [OSTI]

    Fries, D.P.; Browning, J.F.

    1999-02-16

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu. 3 figs.

  1. Method for studying a sample of material using a heavy ion induced mass spectrometer source

    DOE Patents [OSTI]

    Fries, David P.; Browning, James F.

    1999-01-01

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu.

  2. System for studying a sample of material using a heavy ion induced mass spectrometer source

    DOE Patents [OSTI]

    Fries, D.P.; Browning, J.F.

    1998-07-21

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high (n,f) reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu. 3 figs.

  3. System for studying a sample of material using a heavy ion induced mass spectrometer source

    DOE Patents [OSTI]

    Fries, David P.; Browning, James F.

    1998-01-01

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu.

  4. RECENT PROGRESS TOWARD A MUON RECIRCULATING LINEAR ACCELERATOR

    SciTech Connect (OSTI)

    Slawomir Bogacz, Vasiliy Morozov, Yves Roblin, Kevin Beard

    2012-07-01

    Both Neutrino Factories (NF) and Muon Colliders (MC) require very rapid acceleration due to the short lifetime of muons. After a capture and bunching section, a linac raises the energy to about 900 MeV, and is followed by one or more Recirculating Linear Accelerators (RLA), possibly followed by a Rapid Cycling Synchnotron (RCS) or Fixed-Field Alternating Gradient (FFAG) ring. A RLA reuses the expensive RF linac section for a number of passes at the price of having to deal with different energies within the same linac. Various techniques including pulsed focusing quadruopoles, beta frequency beating, and multipass arcs have been investigated via simulations to improve the performance and reduce the cost of such RLAs.

  5. Recirculating Linac Accelerators For Future Muon Facilities

    SciTech Connect (OSTI)

    Yves Roblin, Alex Bogacz, Vasiliy Morozov, Kevin Beard

    2012-04-01

    Neutrino Factories (NF) and Muon Colliders (MC) require rapid acceleration of shortlived muons to multi-GeV and TeV energies. A Recirculating Linear Accelerator (RLA) that uses superconducting RF structures can provide exceptionally fast and economical acceleration to the extent that the focusing range of the RLA quadrupoles allows each muon to pass several times through each high-gradient cavity. A new concept of rapidly changing the strength of the RLA focusing quadrupoles as the muons gain energy is being developed to increase the number of passes that each muon will make in the RF cavities, leading to greater cost effectiveness. We discuss the optics and technical requirements for RLA designs, using RF cavities capable of simultaneous acceleration of both m+ and m- species. The design will include the optics for the multi-pass linac and droplet-shaped return arcs.

  6. Nano-structure multilayer technology fabrication of high energy density capacitors for the power electronic building book

    SciTech Connect (OSTI)

    Barbee, T.W.; Johnson, G.W.; Wagner, A.V.

    1997-10-21

    Commercially available capacitors do not meet the specifications of the Power Electronic Building Block (PEBB) concept. We have applied our propriety nanostructure multilayer materials technology to the fabrication of high density capacitors designed to remove this impediment to PEBB progress. Our nanostructure multilayer capacitors will also be enabling technology in many industrial and military applications. Examples include transient suppression (snubber capacitors), resonant circuits, and DC filtering in PEBB modules. Additionally, weapon applications require compact energy storage for detonators and pulsed-power systems. Commercial applications run the gamut from computers to lighting to communications. Steady progress over the last five years has brought us to the threshold of commercial manufacturability. We have demonstrated a working dielectric energy density of > 11 J/cm3 in 20 nF devices designed for 1 kV operation.

  7. Injection/Extraction Studies for the Muon FFAG

    SciTech Connect (OSTI)

    Pasternak, J.; Berg, J. Scott; Kelliher, D. J.; Machida, S.

    2010-03-30

    The non-scaling fixed field alternating gradient (NS-FFAG) ring is a candidate muon accelerator in the Neutrino Factory complex according to the present baseline, which is currently being addressed by the International Design Study (IDS-NF). In order to achieve small orbit excursion, motivated by magnet cost reduction, and small time of flight variation, dictated by the need to use high RF frequency, lattices with a very compact cell structure and short straight sections are required. The resulting geometry dictates very difficult constraints on the injection/extraction systems. Beam dynamics in the non-scaling FFAG is studied using codes capable of correctly tracking with large transverse amplitude and momentum spread. The feasibility of injection/extraction is studied and various implementations focusing on minimization of kicker/septum strength are presented. Finally the parameters of the resulting kicker magnets are estimated.

  8. An investigation of meson spectroscopy on isotropic clover lattices at the SU(3) flavor-symmetric point

    SciTech Connect (OSTI)

    Richards, David G.; Orginos, Konstantinos

    2014-06-23

    We present an investigation of the excited meson spectrum at the N_f= 3 point obtained on isotropic clover lattices with a plaquette Wilson gauge action, and a NP-improved clover fermion action, at a lattice spacing of a \\simeq 0.08 fm, and compare with corresponding calculations on an anisotropic lattice at fine temporal lattice spacing but a spatial lattice spacing of a_s \\simeq 0.125 fm. The methodology adopted follows that employed in the calculation of the spectrum on anisotropic lattices, and we test the efficacy of that approach for isotropic lattices. In particular, we explore the extent to which rotational symmetry for predominantly single-hadron states is realized. By comparison of the energy levels with that obtained using the anisotropic lattice, we obtain an indication of discretization uncertainties in the single-hadron spectrum.

  9. Sandia National Laboratories: Z Pulsed Power Facility: How Does the Z

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Machine Work? How Does the Z Machine Work? z-machine i Marx Bank Generator Marx Bank. Each Marx bank has sixty 2.6 μF capacitors (43 nF per Marx when erected) that are charged in parallel and discharged in series. When charged to 85 kV its output voltage is 5.1 MV, and stored energy is 20 MJ for all 36. (For a 90 kV charge it is 5.4 MV and 23 MJ.) When discharged, the peak current of each Marx is about 150 kA with a 1.5 μs time to peak. i Intermediate-Store Capacitor Intermediate-Store

  10. Fireside corrosion testing of candidate superheater tube alloys, coatings, and claddings -- Phase 2 field testing

    SciTech Connect (OSTI)

    Blough, J.L.

    1996-08-01

    In Phase 1 of this project, a variety of developmental and commercial tubing alloys and claddings was exposed to laboratory fireside corrosion testing simulating a superheater or reheater in a coal-fired boiler. Phase 2 (in situ testing) has exposed samples of 347, RA85H, HR3C, 253MA, Fe{sub 3}Al + 5Cr, 310 modified, NF 709, 690 clad, and 671 clad for over 10,000 hours to the actual operating conditions of a 250-MW coal-fired boiler. The samples were installed on air-cooled, retractable corrosion probes, installed in the reheater cavity, controlled to the operating metal temperatures of an existing and advanced-cycle, coal-fired boiler. Samples of each alloy are being exposed for 4,000, 12,000, and 16,000 hours of operation. The present results are for the metallurgical examination of the corrosion probe samples after approximately 4,400 hours of exposure.

  11. Four-flavour leading-order hadronic contribution to the muon anomalous magnetic moment

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Burger, Florian; Feng, Xu; Hotzel, Grit; Jansen, Karl; Petschlies, Marcus; Renner, Dru B.

    2014-02-24

    We present a four-flavour lattice calculation of the leading-order hadronic vacuum polarisation contribution to the anomalous magnetic moment of the muon, aμhvp, arising from quark-connected Feynman graphs. It is based on ensembles featuring Nf=2+1+1 dynamical twisted mass fermions generated by the European Twisted Mass Collaboration (ETMC). Several light quark masses are used in order to yield a controlled extrapolation to the physical pion mass. We employ three lattice spacings to examine lattice artefacts and several different volumes to check for finite-size effects. Including the complete first two generations of quarks allows for a direct comparison with phenomenological determinations of amore » μhvp. The final result involving an estimate of the systematic uncertainty aμhvp=6.74 (21)(18) 10-8 shows a good overall agreement with these computations.« less

  12. Detailed optical characterization of a near diffraction limited xenon fluoride laser

    SciTech Connect (OSTI)

    Londono, C. ); Smith, M.J.; Trainor, D.W.; Itzkan, I. ); Berggren, R. ); Fulghum, S.F. )

    1988-12-01

    A 1 m gain length, electron beam pumped xenon fluoride laser (lambda = 353, 351 nm) utilizing two laser mixtures of lean and rich NF/sub 3/, with Xe and balance Ne, was operated with a confocal unstable resonator with magnification of 2.24. The resultant beam quality was diagnosed with both shearing interferometry to measure near-field phase and far-field focal spot evaluation techniques. These measurements resulted in a beam quality of <1.15 times the diffraction limit with no evidence of the wide angle energy loss. This laser device was fully characterized with regard to electron beam deposition uniformity, transient refractive index effects, and optical quality of the resonator and diagnostic components.

  13. Imision, Sohmso~ operatlonr Offloe

    Office of Legacy Management (LM)

    " c:.' ; ' : w. A. f9riokron, ohlrrf, Researoh and ojmrat1onr Imision, Sohmso~ operatlonr Offloe W/6. 1950 8taal.y Et. Roboff, harlatant Dbeotor, Speulal bfatarlalo lmlqioa, mu To* opwatfoar Offiue L I!t?Qm m AToWfZrn URAXIUW - %lb-fiNf---~" ;' RlmisiM \ \ sxlmoLr aO:arr Rafermoa 18 sada to your manozvmd~ datad April uhioh pOU &' @qtuStOd dncbolf pOuad Of SbOUt x)0 uranha powder meida b;r 3$Waaia Eleotrlo Produoto, ho., 3ayslde, Long fElti, 8. Y. Sylvaaia'o prooorr for pa-oduofng

  14. 100 Area D4 Project Building Completion Report - July 2007 to December 2008

    SciTech Connect (OSTI)

    M. T. Stankovich

    2009-04-15

    This report documents the decontamination, decommissioning, and demolition of the 105-NB, 163-N, 183-N, 183-NA, 183-NB, 183-NC, 184-N, 184-NA, 184-NB, 184-NC, 184-ND, 184-NE, 184-NF, 1312-N, 1330-N, 1705-N, 1705-NA, 1706-N, 1712-N, 1714-N, 1714-NA, 1714-NB, 1802-N, MO-050, MO-055, MO-358, MO-390, MO-900, MO-911, and MO-950 facilities in the 100 Area of the Hanford Site. The D4 activities for these facilities include utility disconnection, planning, characterization, engineering, removal of hazardous and radiological contaminated materials, equipment removal, decommissioning, deactivation, decontamination, demolition of the structure, and removal of the remaining slabs.

  15. Helicity evolution at small-x

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Kovchegov, Yuri V.; Pitonyak, Daniel; Sievert, Matthew D.

    2016-01-13

    We construct small-x evolution equations which can be used to calculate quark and anti-quark helicity TMDs and PDFs, along with the g1 structure function. These evolution equations resum powers of αs ln2(1/x) in the polarization-dependent evolution along with the powers of αs ln(1/x) in the unpolarized evolution which includes saturation efects. The equations are written in an operator form in terms of polarization-dependent Wilson line-like operators. While the equations do not close in general, they become closed and self-contained systems of non-linear equations in the large-Nc and large-Nc & Nf limits. As a cross-check, in the ladder approximation, our equationsmore » map onto the same ladder limit of the infrared evolution equations for g1 structure function derived previously by Bartels, Ermolaev and Ryskin.« less

  16. Activation of IL-2 receptor {alpha}-chain gene by individual members of the rel oncogene family in association with serum response factor

    SciTech Connect (OSTI)

    Pierce, J.W.; Jamieson, C.A.; Ross, J.L.

    1995-08-15

    Expression of the IL-2R{alpha} gene is regulated by members of the c-Rel/NF-{kappa}B family of transcription factors binding to the {kappa}B site in the promoter. Previous work has not defined the role of individual members of the c-Rel family in the activation of the IL-2R{alpha} gene. Using the COS cell system, we were able to reconstitute the regulation of the IL-2R{alpha} promoter by expressing cloned Rel family members with serum response factor (SRF). We found that c-rel alone activated the IL-2R{alpha} promoter only weakly but worked with the p50 subunit of NF-{kappa}B (NFKB1) to give a higher level of expression. We showed that c-rel heterodimerizes with p50 and the amount of this heterodimer correlated with the level of IL-2R{alpha} gene expression. Our results provide evidence that c-rel/p50 heterodimers activate gene expression in the context of a cellular promoter. We show that c-rel or p65 can cooperate with SRF in the activation of this promoter and the transactivation by c-rel with SRF was enhanced by p50. Synergistic activation required both {kappa}B an CArG sites, and binding studies show that these that these adjacent sites can be occupied simultaneously. The transactivation observed with cloned transcription factors mimics the physiologic induction of the IL-2R{alpha} gene since multiple sequence elements cooperate to give gene activation. The data support the model that c-rel/p50 or p65 can cooperate with SRF to specifically target the expression of the IL-2R{alpha} gene in activated T cells.

  17. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    SciTech Connect (OSTI)

    Miyata, Ryohei; Eeden, Stephan F. van

    2011-12-15

    Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 {mu}m or less, PM{sub 10}) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 {mu}m or less, PM{sub 2.5}) and ultrafine particles (0.1 {mu}m or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-{kappa}B and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1{beta}, IL-6, and tumor necrosis factor-{alpha}] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-{kappa}B pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.

  18. Welding and performance of advanced high temperature alloys

    SciTech Connect (OSTI)

    Prager, M.; Masuyama, F.

    1995-12-31

    The last decade has witnessed the development of many new alloys for elevated temperature service and recognition of a large number of them in the form of allowable stresses by the ASME Boiler and Pressure Vessel Code. These alloys offer considerable advantages in terms of higher tensile and stress rupture strengths, lower thermal stresses, superior corrosion resistance and, in one case, weldability. The improvements are obtained through additions of tungsten, vanadium, columbium, copper, nitrogen and other elements which significantly affect microstructure and weldability. The paper will discuss where introduction of these advanced materials may be warranted, the properties to be expected in comparison to conventional alloys, PWHT requirements and concerns regarding weld failure modes. Higher performance in operation of power plants is achieved by use of tungsten alloyed advanced 9--12%Cr ferritic steels, NF616 (9Cr-0.5 Mo-1.8W-V-Nb) and HCM12A (12Cr-0.4Mo-2W-1 Cu-V-Nb), which exhibit over 30% higher creep strength than T91/P91 (Mod. 9Cr-1 Mo) at 600 C. Thick-walled and large-diameter pipes of NF616 and HCM12A were subjected to fabrication tests such as joint welding and induction bending, and it was shown that the properties of the fabricated parts were satisfactory for the practical application of those steels. HCM2S, a newly developed low alloy steel (0.06C-2.25Cr-1.6W-0.25V0.05Nb) is approximately 1.8 times stronger than conventional T22 (2.25Cr-1 Mo) at around 600 C. The weldability of this low carbon content steel is much improved, as it needs no pre-weld nor postweld heat treatment. HCM2S was installed in a large capacity utility boiler.

  19. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    SciTech Connect (OSTI)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan Cui, Yong-Yao

    2012-07-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  20. Separation of metallic residues from the dissolution of a high-burnup BWR fuel using nitrogen trifluoride

    SciTech Connect (OSTI)

    McNamara, Bruce K.; Buck, Edgar C.; Soderquist, Chuck Z.; Smith, Frances N.; Mausolf, Edward J.; Scheele, Randall D.

    2014-02-10

    Nitrogen trifluoride (NF3) was used to fluorinate the metallic residue from the dissolution of a high burnup, boiling water reactor fuel (?70 MWd/kgU). The metallic residue included the noble metal phase (containing ruthenium, rhodium, palladium, technetium, and molybdenum), and smaller amounts of zirconium, selenium, tellurium, and silver. Exposing the noble metal phase to 10% NF3 in argon between 400 and 550?C, removed molybdenum and technetium near 400?C as their volatile fluorides, and ruthenium near 500?C as its volatile fluoride. The events were thermally and temporally distinct and the conditions specified are a recipe to separate these transition metals from each other and from the noble metal phase nonvolatile residue. Depletion of the volatile fluorides resulted in substantial exothermicity. Thermal excursion behavior was recorded under non-adiabatic, isothermal conditions that typically minimize heat release. Physical characterization of the metallic noble phase and its thermal behavior are consistent with high kinetic velocity reactions encouraged by the nanoparticulate phase or perhaps catalytic influences of the mixed platinum metals with nearly pure phase structure. Post-fluorination, only two phases were present in the residual nonvolatile fraction. These were identified as a nano-crystalline, metallic palladium cubic phase and a hexagonal rhodium trifluoride (RhF3) phase. The two phases were distinct as the sub-m crystallites of metallic palladium were in contrast to the RhF3 phase, which grew from the parent nano-crystalline noble-metal phase during fluorination, to acicular crystals exceeding 20-m in length.

  1. Spent nuclear fuel reprocessing modeling

    SciTech Connect (OSTI)

    Tretyakova, S.; Shmidt, O.; Podymova, T.; Shadrin, A.; Tkachenko, V.; Makeyeva, I.; Tkachenko, V.; Verbitskaya, O.; Schultz, O.; Peshkichev, I.

    2013-07-01

    The long-term wide development of nuclear power requires new approaches towards the realization of nuclear fuel cycle, namely, closed nuclear fuel cycle (CNFC) with respect to fission materials. Plant nuclear fuel cycle (PNFC), which is in fact the reprocessing of spent nuclear fuel unloaded from the reactor and the production of new nuclear fuel (NF) at the same place together with reactor plant, can be one variant of CNFC. Developing and projecting of PNFC is a complicated high-technology innovative process that requires modern information support. One of the components of this information support is developed by the authors. This component is the programme conducting calculations for various variants of process flow sheets for reprocessing SNF and production of NF. Central in this programme is the blocks library, where the blocks contain mathematical description of separate processes and operations. The calculating programme itself has such a structure that one can configure the complex of blocks and correlations between blocks, appropriate for any given flow sheet. For the ready sequence of operations balance calculations are made of all flows, i.e. expenses, element and substance makeup, heat emission and radiation rate are determined. The programme is open and the block library can be updated. This means that more complicated and detailed models of technological processes will be added to the library basing on the results of testing processes using real equipment, in test operating mode. The development of the model for the realization of technical-economic analysis of various variants of technologic PNFC schemes and the organization of 'operator's advisor' is expected. (authors)

  2. Sirt2 suppresses inflammatory responses in collagen-induced arthritis

    SciTech Connect (OSTI)

    Lin, Jiangtao; Sun, Bing; Jiang, Chuanqiang; Hong, Huanyu; Zheng, Yanping

    2013-11-29

    Highlights: •Sirt2 expression decreases in collagen-induced arthritis (CIA). •Sirt2 knockout aggravates severity of arthritis in mice with CIA. •Sirt2 knockout increases levels of pro-inflammatory factors in the serum. •Sirt2 deacetylates p65 and inhibits pro-inflammatory factors expression. •Sirt2 rescue abates severity of arthritis in mice with CIA. -- Abstract: Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD{sup +}-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.

  3. Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression

    SciTech Connect (OSTI)

    Wang, Lei; Kuang, Lisha; Hitron, John Andrew; Son, Young-Ok; Wang, Xin; Budhraja, Amit; Lee, Jeong-Chae; Pratheeshkumar, Poyil; Chen, Gang; Zhang, Zhuo; Luo, Jia; Shi, Xianglin

    2013-10-01

    Environmental exposure to arsenic is known to cause various cancers. There are some potential relationships between cell malignant transformation and C-X-C chemokine receptor type 4 (CXCR4) expressions. Metastasis, one of the major characteristics of malignantly transformed cells, contributes to the high mortality of cells. CXCR4 and its natural chemokine ligand C-X-C motif ligand 12 (CXCL12) play a critical role in metastasis. Therefore, identification of nutritional factors which are able to inhibit CXCR4 is important for protection from environmental arsenic-induced carcinogenesis and for abolishing metastasis of malignantly transformed cells. The present study demonstrates that apigenin (4′,5,7-trihydroxyflavone), a natural dietary flavonoid, suppressed CXCR4 expression in arsenic-transformed Beas-2B cells (B-AsT) and several other types of transformed/cancer cells in a dose- and time-dependent manner. Neither proteasome nor lysosome inhibitor had any effect in reducing the apigenin-induced down-regulation of CXCR4, indicating that apigenin-induced down-regulation of CXCR4 is not due to proteolytic degradation. The down-regulation of CXCR4 is mainly due to the inhibition of nuclear factor κB (NF-κB) transcriptional activity. Apigenin also abolished migration and invasion of transformed cells induced by CXCL12. In a xenograft mouse model, apigenin down-regulated CXCR4 expression and suppressed tumor growth. Taken together, our results show that apigenin is a novel inhibitor of CXCR4 expression. This dietary flavonoid has the potential to suppress migration and invasion of transformed cells and prevent environmental arsenic-induced carcinogenesis. - Highlights: • Apigenin has a potential in preventing environmental arsenic induced carcinogenesis. • Apigenin suppresses CXCR4 in malignant transformed cells in vitro and in vivo. • The down-regulation of CXCR4 is mainly due to inhibition of NF-κB activity.

  4. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    SciTech Connect (OSTI)

    Hamdy, Nadia; El-Demerdash, Ebtehal

    2012-06-15

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-?B). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-?B expression and finally HSC activation. -- Highlights: ? Carvedilol is a beta blocker with antioxidant and antifibrotic properties

  5. Real-time Molecular Study of Bystander Effects of Low dose Low LET radiation Using Living Cell Imaging and Nanoparticale Optics

    SciTech Connect (OSTI)

    Natarajan, Mohan; Xu, Nancy R; Mohan, Sumathy

    2013-06-03

    cGy on coverslips will be examined for (a) low LET radiation-induced alterations of cellular function and its physiological relevance in real time; and (b) radiation damage triggered bystander effect on the neighboring unirradiated cells. First, to determine the low LET radiation induced alteration of cellular function we will examine: (i) the real time transformation of single membrane transporters in single living cells; (ii) the pump efficiency of membrane efflux pump of live cells in real time at the molecular level; (iii) the kinetics of single-ligand receptor interaction on single live cell surface (Figure C); and (iv) alteration in chromosome replication in living cell. Second, to study the radiation triggered bystander responses, we will examine one of the key signaling pathway i.e. TNF- alpha/NF-kappa B mediated signaling. TNF-alpha specific nano particle sensors (green) will be developed to detect the releasing dynamics, transport mechanisms and ligand-receptor binding on live cell surface in real time. A second sensor (blue) will be developed to simultaneously monitor the track of NF-kB inside the cell. The proposed nano-particle optics approach would complement our DOE funded study on biochemical mechanisms of TNF-alpha- NF-kappa B-mediated bystander effect.

  6. Microscale Immune Studies Laboratory.

    SciTech Connect (OSTI)

    Poschet, Jens Fredrich; Carroll-Portillo, Amanda; Wu, Meiye; Manginell, Ronald Paul; Herr, Amy Elizabeth; Martino, Anthony A.; Perroud, Thomas D.; Branda, Catherine; Srivastava, Nimisha; Sinclair, Michael B.; Moorman, Matthew Wallace; Apblett, Christopher Alan; Sale, Kenneth L.; James, Conrad D.; Carles, Elizabeth L.; Lidke, Diane S.; Van Benthem, Mark Hilary; Rebeil, Roberto; Kaiser, Julie; Seaman, William; Rempe, Susan; Brozik, Susan Marie; Jones, Howland D. T.; Gemperline, Paul; Throckmorton, Daniel J.; Misra, Milind; Murton, Jaclyn K.; Carson, Bryan D.; Zhang, Zhaoduo; Plimpton, Steven James; Renzi, Ronald F.; Lane, Todd W.; Ndiaye-Dulac, Elsa; Singh, Anup K.; Haaland, David Michael; Faulon, Jean-Loup Michel; Davis, Ryan W.; Ricken, James Bryce; Branda, Steven S.; Patel, Kamlesh D.; Joo, Jaewook; Kubiak, Glenn D.; Brennan, James S.; Martin, Shawn Bryan; Brasier, Allan

    2009-01-01

    The overarching goal is to develop novel technologies to elucidate molecular mechanisms of the innate immune response in host cells to pathogens such as bacteria and viruses including the mechanisms used by pathogens to subvert/suppress/obfuscate the immune response to cause their harmful effects. Innate immunity is our first line of defense against a pathogenic bacteria or virus. A comprehensive 'system-level' understanding of innate immunity pathways such as toll-like receptor (TLR) pathways is the key to deciphering mechanisms of pathogenesis and can lead to improvements in early diagnosis or developing improved therapeutics. Current methods for studying signaling focus on measurements of a limited number of components in a pathway and hence, fail to provide a systems-level understanding. We have developed a systems biology approach to decipher TLR4 pathways in macrophage cell lines in response to exposure to pathogenic bacteria and their lipopolysaccharide (LPS). Our approach integrates biological reagents, a microfluidic cell handling and analysis platform, high-resolution imaging and computational modeling to provide spatially- and temporally-resolved measurement of TLR-network components. The Integrated microfluidic platform is capable of imaging single cells to obtain dynamic translocation data as well as high-throughput acquisition of quantitative protein expression and phosphorylation information of selected cell populations. The platform consists of multiple modules such as single-cell array, cell sorter, and phosphoflow chip to provide confocal imaging, cell sorting, flow cytomtery and phosphorylation assays. The single-cell array module contains fluidic constrictions designed to trap and hold single host cells. Up to 100 single cells can be trapped and monitored for hours, enabling detailed statistically-significant measurements. The module was used to analyze translocation behavior of transcription factor NF-kB in macrophages upon activation by E

  7. Fresh Water Generation from Aquifer-Pressured Carbon Storage: Interim Progress Report

    SciTech Connect (OSTI)

    Aines, R D; Wolery, T J; Hao, Y; Bourcier, W L

    2009-07-22

    This project is establishing the potential for using brine pressurized by Carbon Capture and Storage (CCS) operations in saline formations as the feedstock for desalination and water treatment technologies including nanofiltration (NF) and reverse osmosis (RO). The aquifer pressure resulting from the energy required to inject the carbon dioxide provides all or part of the inlet pressure for the desalination system. Residual brine would be reinjected into the formation at net volume reduction. This process provides additional storage space (capacity) in the aquifer, reduces operational risks by relieving overpressure in the aquifer, and provides a source of low-cost fresh water to offset costs or operational water needs. Computer modeling and laboratory-scale experimentation are being used to examine mineral scaling and osmotic pressure limitations for brines typical of CCS sites. Computer modeling is being used to evaluate processes in the aquifer, including the evolution of the pressure field. This progress report deals mainly with our geochemical modeling of high-salinity brines and covers the first six months of project execution (September, 2008 to March, 2009). Costs and implementation results will be presented in the annual report. The brines typical of sequestration sites can be several times more concentrated than seawater, requiring specialized modeling codes typical of those developed for nuclear waste disposal calculations. The osmotic pressure developed as the brines are concentrated is of particular concern, as are precipitates that can cause fouling of reverse osmosis membranes and other types of membranes (e.g., NF). We have now completed the development associated with tasks (1) and (2) of the work plan. We now have a contract with Perlorica, Inc., to provide support to the cost analysis and nanofiltration evaluation. We have also conducted several preliminary analyses of the pressure effect in the reservoir in order to confirm that reservoir

  8. Near-field/altered-zone models report

    SciTech Connect (OSTI)

    Hardin, E. L., LLNL

    1998-03-01

    lithophysal units. These units are made up of moderately to densely welded, devitrified, fractured tuff. The rock's chemical composition is comparable to that of typical granite, but has textural features and mineralogical characteristics of large-scale, silicic volcanism. Because the repository horizon will be approximately 300 m below the ground surface and 200 m above the water table, the repository will be partially saturated. The welded tuff matrix in the host units is highly impermeable, but water and gas flow readily through fractures. The degree of fracturing in these units is highly variable, and the hydrologic significance of fracturing is an important aspect of site investigation. This report describes the characterization and modeling of a region around the potential repository--the altered zone--a region in which the temperature will be increased significantly by waste-generated heat. Numerical simulation has shown that, depending on the boundary conditions, rock properties, and repository design features incorporated in the models, the altered zone (AZ) may extend from the water table to the ground surface. This report also describes models of the near field, the region comprising the repository emplacement drifts and the surrounding rock, which are critical to the performance of engineered components. Investigations of near-field and altered-zone (NF/AZ) processes support the design of underground repository facilities and engineered barriers and also provide constraint data for probabilistic calculations of waste-isolation performance (i.e., performance assessment). The approach to investigation, which is an iterative process involving hypothesis testing and experimentation, has relied on conceptualizing engineered barriers and on performance analysis. This report is a collection, emphasizing conceptual and numerical models, of the recent results contributed from studies of NF/AZ processes and of quantitative measures of NF/AZ performance. The selection and

  9. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

    SciTech Connect (OSTI)

    Jackson, Anna Francina; Williams, Andrew; Recio, Leslie; Waters, Michael D.; Lambert, Iain B.; Yauk, Carole L.

    2014-01-01

    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: Global gene expression changes in furan-exposed mouse livers were analyzed. A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. Key pathways include NRF2, SAPK, ERK and death receptor signaling. Important roles for TNF-alpha, c-Jun, and NF-?B in

  10. MiR-138 promotes smooth muscle cells proliferation and migration in db/db mice through down-regulation of SIRT1

    SciTech Connect (OSTI)

    Xu, Juan; Li, Li; Yun, Hui-fang; Han, Ye-shan

    2015-08-07

    Background: Diabetic vascular smooth muscle cells (VSMCs) exhibit significantly increased rates of proliferation and migration, which was the most common pathological change in atherosclerosis. In addition, the study about the role for miRNAs in the regulation of VSMC proliferation is just beginning to emerge and additional miRNAs involved in VSMC proliferation modulation should be identified. Methods: The expression of miR-138 and SIRT1 were examined in SMCs separated from db/db mice and in SMC lines C-12511 exposed to high glucose with qRT-PCR and western blot. The regulation of miR-138 on the expression of SMCs was detected with luciferase report assay. VSMCs proliferation and migration assays were performed to examine the effect of miR-138 inhibitor on VSMCs proliferation and migration. Results: We discovered that higher mRNA level of miR-138 and reduced expression of SIRT1 were observed in SMCs separated from db/db mice and in SMC lines C-12511. Moreover, luciferase report assay showed that the activity of SIRT1 3′-UTR was highly increased by miR-138 inhibitor and reduced by miR-138 mimic. In addition, we examined that the up-regulation of NF-κB induced by high glucose in SMCs was reversed by resveratrol and miR-138 inhibitor. MTT and migration assays showed that miR-138 inhibitor attenuated the proliferation and migration of smooth muscle cells. Conclusion: In this study, we revealed that miR-138 might promote proliferation and migration of SMC in db/db mice through suppressing the expression of SIRT1. - Highlights: • Higher mRNA level of miR-138 was observed in SMCs from db/db mice. • The mRNA and protein level of SIRT1 in SMCs from db/db mice were greatly reduced. • miR-138 could regulate the expression of SIRT1 in SMCs. • SIRT1 overexpression reversed the up-regulation of acetylized p65 and NF-κB induced by high glucose. • MiR-138 inhibitor reversed VSMCs proliferation and migration induced by high glucose.