Science.gov

Sample records for adjusted hr ahr

  1. The design and performance of a 200 A-hr lithium-metal sulfide cell

    NASA Astrophysics Data System (ADS)

    Askew, B. A.; Dand, P. V.

    The near-term performance goals of 90-100 W-hr/kg specific energy (C/4 rate) and 90-100 W/kg peak specific power are achieved in five-plate 200 A-hr cells using a boron nitride felt separator and wire screen or photoetched electrode constraint systems. Specific energy values greater than 100 W-hr/kg are attained at lower rates (C/6) in cells of similar design using a magnesia powder separator. A marked dependence of temperature on cell capacity is found in cells using lithium chloride-potassium chloride electrolyte over the temperature range 445-470 C. It is thought that an alternative electrolyte composition may be necessary to reduce this effect in the battery.

  2. Student Adjustment Act of 2001 (H.R. 1918 IH). House of Representatives, 107th Congress, 1st Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House.

    The purpose of this bill is to amend the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 to permit states to determine state residency for higher education purposes and to amend the Immigration and Nationality Act to cancel the removal and adjust the status of certain alien college-bound students who are long-term U.S.…

  3. Ahr function in lymphocytes: emerging concepts

    PubMed Central

    Zhou, Liang

    2015-01-01

    The aryl hydrocarbon receptor (Ahr) is an important regulator of the development and function of both innate and adaptive immune cells through roles associated with Ahr's ability to respond to cellular and dietary ligands. Recent findings have revealed tissue and context-specific functions for Ahr in both homeostasis and in during an immune response. I review these findings here, and integrate them into the current understanding of the mechanisms that regulate Ahr transcription and function. I propose a conceptual framework in which Ahr function is determined by three factors: the amount of Ahr in any given cell, the abundance and potency of Ahr ligands within certain tissues, and the tissue microenvironment wherein Ahr+ cells reside. This complexity emphasizes the necessity cell-type specific genetic approaches towards the study of Ahr function. PMID:26700314

  4. HR, Streamlined

    ERIC Educational Resources Information Center

    Ramaswami, Rama

    2008-01-01

    Human Resources (HR) administrators are finding that as software modules are installed to automate various processes, they have more time to focus on strategic objectives. And as compliance with affirmative action and other employment regulations comes under increasing scrutiny, HR staffers are finding that software can deliver and track data with…

  5. AHR-11797: a novel benzodiazepine antagonist

    SciTech Connect

    Johnson, D.N.; Kilpatrick, B.F.; Hannaman, P.K.

    1986-03-01

    AHR-11797(5,6-dihydro-6-methyl-1-phenyl-/sup 3/H-pyrrolo(3,2,1-ij)quinazolin-3-one) displaced /sup 3/H-flunitrazepam (IC/sub 50/ = 82 nM) and /sup 3/H-Ro 15-1877 (IC/sub 50/ = 104 nM) from rat brain synaptosomes. AHR-11797 did not protect mice from seizures induced by maximal electroshock or subcutaneous Metrazol (scMET), nor did it induce seizures in doses up to the lethal dose. However, at 31.6 mg/kg, IP, it significantly increased the anticonvulsant ED/sub 50/ of chlordiazepoxide (CDPX) from 1.9 to 31.6 mg/kg, IP. With 56.7 mg/kg, IP, of AHR-11797, CDPX was inactive in doses up to 100 mg/kg, IP. AHR-11797 did not significantly increase punished responding in the Geller and Seifter conflict procedure, but it did attenuate the effects of diazepam. Although the compound is without anticonvulsant or anxiolytic activity, it did have muscle relaxant properties. AHR-11797 blocked morphine-induced Straub tail in mice (ED/sub 50/ = 31 mg/kg, IP) and it selectively suppressed the polysnaptic linguomandibular reflex in barbiturate-anesthetized cats. The apparent muscle relaxant activity of AHR-11797 suggests that different receptor sites are involved for muscle relaxant vs. anxiolytic/anticonvulsant activities of the benzodiazepines.

  6. The Role of AhR in Breast Cancer Development

    DTIC Science & Technology

    2006-07-01

    other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental carcinogen-responsive transcription factor...constitutively active AhR. Constitutive and environmental chemical-inducible AhR activity was profoundly suppressed by galangin as was cell growth...However, the failure of a-naphthoflavone or FhAhRR transfection to block growth indicated that galangin -mediated AhR inhibition was either insufficient

  7. Feedback control of AHR signalling regulates intestinal immunity.

    PubMed

    Schiering, Chris; Wincent, Emma; Metidji, Amina; Iseppon, Andrea; Li, Ying; Potocnik, Alexandre J; Omenetti, Sara; Henderson, Colin J; Wolf, C Roland; Nebert, Daniel W; Stockinger, Brigitta

    2017-02-09

    The aryl hydrocarbon receptor (AHR) recognizes xenobiotics as well as natural compounds such as tryptophan metabolites, dietary components and microbiota-derived factors, and it is important for maintenance of homeostasis at mucosal surfaces. AHR activation induces cytochrome P4501 (CYP1) enzymes, which oxygenate AHR ligands, leading to their metabolic clearance and detoxification. Thus, CYP1 enzymes have an important feedback role that curtails the duration of AHR signalling, but it remains unclear whether they also regulate AHR ligand availability in vivo. Here we show that dysregulated expression of Cyp1a1 in mice depletes the reservoir of natural AHR ligands, generating a quasi AHR-deficient state. Constitutive expression of Cyp1a1 throughout the body or restricted specifically to intestinal epithelial cells resulted in loss of AHR-dependent type 3 innate lymphoid cells and T helper 17 cells and increased susceptibility to enteric infection. The deleterious effects of excessive AHR ligand degradation on intestinal immune functions could be counter-balanced by increasing the intake of AHR ligands in the diet. Thus, our data indicate that intestinal epithelial cells serve as gatekeepers for the supply of AHR ligands to the host and emphasize the importance of feedback control in modulating AHR pathway activation.

  8. A maternal Ahr null genotype sensitizes embryos to chemical teratogenesis.

    PubMed

    Thomae, Tami L; Glover, Edward; Bradfield, Christopher A

    2004-07-16

    The aryl hydrocarbon receptor (encoded by the Ahr locus) is a ligand-activated transcription factor that mediates the toxicology and teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). In an effort to understand the role of the maternal compartment in dioxin teratology, we designed a breeding strategy that allowed us to compare the teratogenic response in embryos from Ahr(-/-) (null) and Ahr(+/+) (wild-type) dams. Using this strategy, we demonstrate that embryos from the Ahr(-/-) dams are 5-fold more sensitive to dioxin-induced cleft palate and hydronephrosis as compared with embryos from an Ahr(+/+) dam. Moreover, this increased teratogenic sensitivity extends beyond dioxin, because embryos from Ahr(-/-) dams exhibited a 9-fold increase in their sensitivity to the fetotoxic effects of the glucocorticoid, dexamethasone. In searching for an explanation for this increased sensitivity, we found that more dioxin and dexamethasone reached the embryos from Ahr(-/-) dams as compared with embryos from Ahr(+/+) dams. We propose that increased deposition of teratogens/fetotoxicants to the embryonic compartment is the result of porto-systemic shunting and/or blocked P4501A induction in Ahr(-/-) dams. In addition to demonstrating the importance of maternal AHR in teratogenesis, these data may have implications that reach beyond the mechanism of action of dioxin. In this regard, the Ahr(-/-) mouse may provide a system that allows pharmacological agents and toxicants to be more easily studied in a model where first pass clearance is a significant obstacle.

  9. Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options.

    PubMed

    Bock, Karl Walter

    2017-04-01

    Metabolism of aryl hydrocarbons and toxicity of dioxins led to the discovery of the aryl hydrocarbon receptor (AHR). Tremendous advances have been made on multiplicity of AHR signaling and identification of endogenous ligands including the tryptophan metabolites FICZ and kynurenine. However, human AHR functions are still poorly understood due to marked species differences as well as cell-type- and cell context-dependent AHR functions. Observations in dioxin-poisoned individuals may provide hints to physiologic AHR functions in humans. Based on these observations three human AHR functions are discussed: (1) Chemical defence and homeostasis of endobiotics. The AHR variant Val381 in modern humans leads to reduced AHR affinity to aryl hydrocarbons in comparison with Neanderthals and primates expressing the Ala381 variant while affinity to indoles remains unimpaired. (2) Homeostasis of stem/progenitor cells. Dioxins dysregulate homeostasis in sebocyte stem cells. (3) Modulation of immunity. In addition to microbial defence, AHR may be involved in a 'disease tolerance defence pathway'. Further characterization of physiologic AHR functions may lead to therapeutic options.

  10. Parametric and cycle tests of a 40-A-hr bipolar nickel-hydrogen battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R. L.

    1986-01-01

    A series of tests was performed to characterize battery performance relating to certain operating parameters which included charge current, discharge current, temperature and pressure. The parameters were varied to confirm battery design concepts and to determine optimal operating conditions. Spacecraft power requirements are constantly increasing. Special spacecraft such as the Space Station and platforms will require energy storage systems of 130 and 25 kWh, respectively. The complexity of these high power systems will demand high reliability, and reduced mass and volume. A system that uses batteries for storage will require a cell count in excess of 400 units. These cell units must then be assembled into several batteries with over 100 cells in a series connected string. In an attempt to simplify the construction of conventional cells and batteries, the NASA Lewis Research Center battery systems group initiated work on a nickel-hydrogen battery in a bipolar configuration in early 1981. Features of the battery with this bipolar construction show promise in improving both volumetric and gravimetric energy densities as well as thermal management. Bipolar construction allows cooling in closer proximity to the cell components, thus heat removal can be accomplished at a higher rejection temperature than conventional cell designs. Also, higher current densities are achievable because of low cell impedance. Lower cell impedance is achieved via current flow perpendicular to the electrode face, thus reducing voltage drops in the electrode grid and electrode terminals tabs.

  11. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  12. Teratogenic impact of dioxin-activated AHR in laboratory animals

    EPA Science Inventory

    AHR and ARNT are expressed in mouse and human palatal shelves and in the urinary tract of the mouse fetus. AHR expression, translocation to the nucleus, binding to DRE, and activation are required for mediation of TCDD-induction of CP and HN. Although the human palate requires a ...

  13. Green fluorescent protein (GFP) as a marker of aryl hydrocarbon receptor (AhR) function in developing zebrafish (Danio rerio).

    PubMed

    Mattingly, C J; McLachlan, J A; Toscano, W A

    2001-08-01

    We developed an inducible in vivo reporter system to examine expression of the aryl hydrocarbon receptor (AhR) during development in zebrafish (Danio rerio). AhR is a ligand-activated transcription factor that mediates the toxic actions of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Induction of cytochrome P4501A1 (CYP1A1) is an early biomarker of AhR activation. A 1905 base pair region of the human CYP1A1 promoter/enhancer region was regulated by AhR in zebrafish liver cells after exposure to TCDD (10 nM) in a transient transfection assay. This regulatory region was fused to the cDNA sequence encoding green fluorescent protein (GFP) of jellyfish (Aequorea victoria). Transgenic zebrafish were generated to express this AhR-regulated GFP construct. Injected fish exposed to TCDD exhibited induction of GFP in the eye, nose, and vertebrae of zebrafish embryos (48 and 72 hr after fertilization) compared to vehicle controls (DMSO), which did not express GFP. To investigate whether AhR-regulated GFP expression correlated with sites of TCDD toxicity, we exposed wild-type zebrafish to DMSO or TCDD and examined them for morphologic abnormalities. By 5 days after fertilization, TCDD-exposed fish exhibited gross dysmorphogenesis in cranio-facial and vertebral development.

  14. Simulator for SUPO, a Benchmark Aqueous Homogeneous Reactor (AHR)

    SciTech Connect

    Klein, Steven Karl; Determan, John C.

    2015-10-14

    A simulator has been developed for SUPO (Super Power) an aqueous homogeneous reactor (AHR) that operated at Los Alamos National Laboratory (LANL) from 1951 to 1974. During that period SUPO accumulated approximately 600,000 kWh of operation. It is considered the benchmark for steady-state operation of an AHR. The SUPO simulator was developed using the process that resulted in a simulator for an accelerator-driven subcritical system, which has been previously reported.

  15. HR Structure and HR Knowledge Transfer between Subsidiaries in China

    ERIC Educational Resources Information Center

    Wang-Cowham, Cindy

    2008-01-01

    Purpose: This paper attempts to examine the issue concerning human resource (HR) structures and the transfer of HR knowledge to discover whether and how HR structure facilitates the transfer of HR knowledge between subsidiaries of an MNC in China. Design/methodology/approach: The investigation, being of an exploratory nature, follows the tradition…

  16. Role of DNA methylation of AHR1 and AHR2 promoters in differential sensitivity to PCBs in Atlantic Killifish, Fundulus heteroclitus.

    PubMed

    Aluru, Neelakanteswar; Karchner, Sibel I; Hahn, Mark E

    2011-01-17

    Atlantic killifish (Fundulus heteroclitus) inhabiting the PCB-contaminated Superfund site in New Bedford Harbor (MA, USA) have evolved genetic resistance to the toxic effects of these compounds. They also lack induction of cytochrome P4501A (CYP1A) and other aryl hydrocarbon receptor (AHR)-dependent responses after exposure to AHR agonists, suggesting an overall down-regulation of the AHR signaling pathway. In this study, we hypothesized that the genetic resistance is due to altered AHR expression resulting from hypermethylation of DNA in the promoter region of AHR genes in fish inhabiting New Bedford Harbor. To test this hypothesis, we cloned and sequenced AHR1 and AHR2 promoter regions and employed bisulfite conversion-polymerase chain reaction (BS-PCR) followed by clonal analysis to compare the methylation status of CpG islands of AHR1 and AHR2 in livers of adult killifish collected from New Bedford Harbor and a reference site (Scorton Creek, MA). No significant differences in methylation profiles were observed in either AHR1 or AHR2 promoter regions between NBH and SC fish. However, hypermethylation of the AHR1 promoter correlated with low expression of transcripts in the liver in both populations. In comparison to AHR1, hepatic mRNA expression of AHR2 is high and its promoter is hypomethylated. Taken together, our results suggest that genetic resistance to contaminants in NBH fish is not due to altered methylation of AHR promoter regions, but that promoter methylation may control tissue-specific expression of AHR genes in killifish.

  17. Mono-Substituted Isopropylated Triaryl Phosphate, a Major Component of Firemaster 550, is an AHR Agonist that Exhibits AHR-Independent Cardiotoxicity in Zebrafish

    PubMed Central

    Gerlach, Cory V.; Das, Siba R.; Volz, David C.; Bisson, William H.; Kolluri, Siva K.; Tanguay, Robert L.

    2014-01-01

    Firemaster 550 (FM550) is an additive flame retardant mixture used within polyurethane foam and is increasingly found in house dust and the environment due to leaching. Despite the widespread use of FM550, very few studies have investigated the potential toxicity of its ingredients during early vertebrate development. In the current study, we sought to specifically investigate mono-substituted isopropylated triaryl phosphate (mITP), a component comprising approximately 32% of FM550, which has been shown to cause cardiotoxicity during zebrafish embryogenesis. Previous research showed that developmental defects are rescued using an aryl hydrocarbon receptor (AHR) antagonist (CH223191), suggesting that mITP-induced toxicity was AHR-dependent. As zebrafish have three known AHR isoforms, we used a functional AHR2 knockout line along with AHR1A-and AHR1B-specific morpholinos to determine which AHR isoform, if any, mediates mITP-induced cardiotoxicity. As in silico structural homology modeling predicted that mITP may bind favorably to both AHR2 and AHR1B isoforms, we evaluated AHR involvement in vivo by measuring CYP1A mRNA and protein expression following exposure to mITP in the presence or absence of CH223191 or AHR-specific morpholinos. Based on these studies, we found that mITP interacts with both AHR2 and AHR1B isoforms to induce CYP1A expression. However, while CH223191 blocked mITP-induced CYP1A induction and cardiotoxicity, knockdown of all three AHR isoforms failed to block mITP-induced cardiotoxicity in the absence of detectable CYP1A induction. Overall, these results suggest that, while mITP is an AHR agonist, mITP causes AHR-independent cardiotoxicity through a pathway that is also antagonized by CH223191. PMID:24865613

  18. Mono-substituted isopropylated triaryl phosphate, a major component of Firemaster 550, is an AHR agonist that exhibits AHR-independent cardiotoxicity in zebrafish.

    PubMed

    Gerlach, Cory V; Das, Siba R; Volz, David C; Bisson, William H; Kolluri, Siva K; Tanguay, Robert L

    2014-09-01

    Firemaster 550 (FM550) is an additive flame retardant mixture used within polyurethane foam and is increasingly found in house dust and the environment due to leaching. Despite the widespread use of FM550, very few studies have investigated the potential toxicity of its ingredients during early vertebrate development. In the current study, we sought to specifically investigate mono-substituted isopropylated triaryl phosphate (mITP), a component comprising approximately 32% of FM550, which has been shown to cause cardiotoxicity during zebrafish embryogenesis. Previous research showed that developmental defects are rescued using an aryl hydrocarbon receptor (AHR) antagonist (CH223191), suggesting that mITP-induced toxicity was AHR-dependent. As zebrafish have three known AHR isoforms, we used a functional AHR2 knockout line along with AHR1A- and AHR1B-specific morpholinos to determine which AHR isoform, if any, mediates mITP-induced cardiotoxicity. As in silico structural homology modeling predicted that mITP may bind favorably to both AHR2 and AHR1B isoforms, we evaluated AHR involvement in vivo by measuring CYP1A mRNA and protein expression following exposure to mITP in the presence or absence of CH223191 or AHR-specific morpholinos. Based on these studies, we found that mITP interacts with both AHR2 and AHR1B isoforms to induce CYP1A expression. However, while CH223191 blocked mITP-induced CYP1A induction and cardiotoxicity, knockdown of all three AHR isoforms failed to block mITP-induced cardiotoxicity in the absence of detectable CYP1A induction. Overall, these results suggest that, while mITP is an AHR agonist, mITP causes AHR-independent cardiotoxicity through a pathway that is also antagonized by CH223191.

  19. Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation

    PubMed Central

    van den Bogaard, Ellen; Podolsky, Michael; Smits, Jos; Cui, Xiao; John, Christian; Gowda, Krishne; Desai, Dhimant; Amin, Shantu; Schalkwijk, Joost; Perdew, Gary H.

    2015-01-01

    Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis that AHR activation is required for normal keratinocyte differentiation. Using transcriptome analysis of Ahr-/- and Ahr+/+ murine keratinocytes, we found significant enrichment of differentially expressed genes linked to epidermal differentiation. Primary Ahr-/- keratinocytes showed a significant reduction in terminal differentiation gene and protein expression, similar to Ahr+/+ keratinocytes treated with AHR antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM), SGA360. In vitro keratinocyte differentiation led to increased AHR levels and subsequent nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer cultured primary human keratinocytes treated with AHR antagonists also showed an impaired terminal differentiation program. Inactivation of AHR activity during human skin equivalent development severely impaired epidermal stratification, terminal differentiation protein expression and stratum corneum formation. As disturbed epidermal differentiation is a main feature of many skin diseases, pharmacological agents targeting AHR signaling or future identification of endogenous keratinocyte-derived AHR ligands should be considered as potential new drugs in dermatology. PMID:25602157

  20. AHR promoter variant modulates its transcription and downstream effectors by allele-specific AHR-SP1 interaction functioning as a genetic marker for vitiligo.

    PubMed

    Wang, Xiaowen; Li, Kai; Liu, Ling; Shi, Qiong; Song, Pu; Jian, Zhe; Guo, Sen; Wang, Gang; Li, Chunying; Gao, Tianwen

    2015-09-15

    Vitiligo is an acquired depigmentation disorder largely caused by defective melanocyte- or autoimmunity-induced melanocyte destruction. The aryl hydrocarbon receptor (AHR) is essential for melanocyte homeostasis and immune process, and abnormal AHR was observed in vitiligo. We previously identified the T allele of AHR -129C > T variant as a protective factor against vitiligo. However, biological characterization underlying such effects is not fully certain, further validation by mechanistic research is warranted and was conducted in the present study. We showed that -129T allele promoted AHR transcriptional activity through facilitating its interaction with SP1 transcription factor (SP1) compared with -129C allele. We subsequently found reduced peripheral AHR and SP1 transcript expressions in vitiligo and a negative correlation of AHR level with disease duration. We also investigated AHR-related cytokines and observed increased serum TNF-α concentration and diminished serum levels of IL-10 and TGF-β1 in vitiligo. Further genetic analysis showed that -129T carriers possessed higher levels of AHR and IL-10 than -129C carriers. Therefore, our study indicates that the modulation of AHR transcription by a promoter variant has a profound influence on vitiligo, not only advancing our understanding on AHR function but also providing novel insight into the pathogenesis of degenerative or autoimmune diseases including vitiligo.

  1. Design and implementation of SMO for a nonlinear MIMO AHRS

    NASA Astrophysics Data System (ADS)

    Doostdar, Parisa; Keighobadi, Jafar

    2012-10-01

    In a low-cost attitude heading reference system (AHRS), the measurements made by MEMS inertial and magnetic sensors are affected by large parameter uncertainties, stochastic noises and unknown disturbances. In this paper, considering the robustness of the sliding mode observers (SMO) against both structured and unstructured uncertainties as well as exogenous inputs, the process of design and implementation of a nonlinear SMO is proposed for a low-cost AHRS. For simultaneous estimation of orientation variables and calibration biases of gyroscopes, a nonlinear and non-affine model of the AHRS is considered. Therefore, based on the Lie-algebraic method, the estimation algorithm is designed for a general class of non-affine nonlinear MIMO systems. In the proposed observer, owing to decreasing the required assumptions for coordinate transformation in recent literatures, the design process of the SMO is simplified. The gain matrices of the proposed SMO are obtained through ensuring the stability and the convergence of estimation errors based on Lyapunov's direct method. The expected tracking performance of the robust state and parameter estimation algorithm compared to that of the extended Kalman filter (EKF) is evaluated through simulations and real experiments of a strapped AHRS on a ground vehicle.

  2. HR Public meeting

    SciTech Connect

    2010-06-25

    Cher(e)s collègues, En collaboration avec le Département HR, le Directeur général a le plaisir de vous convier à une réunion publique qui se tiendra le vendredi 25 juin 2010 à 9h30 dans l’Amphithéâtre principal (Bâtiment 500)*. Un café d’accueil y sera servi à partir de 9h. Cette réunion abordera les thèmes suivants : • Valeurs de l’Organisation (Directeur général) • Code de Conduite (Directeur général / Anne-Sylvie Catherin) • Création du nouveau rôle d’Ombudsperson (Vincent Vuillemin) Ces présentations seront suivies d’une séance de questions-réponses. Nous espérons vous retrouver nombreux le 25 juin ! Meilleures salutations, Anne-Sylvie Catherin Chef du Département des Ressources humaines *Cette réunion sera retransmise simultanément dans l’Amphithéâtre BE de Prévessin (Bâtiment 864) et également disponible à l’adresse suivante : http://webcast.cern.ch -------------------------------------------------------- Dear colleagues, In collaboration with HR Department, the Director-General would like to invite you to an information meeting which will be held on Friday 25 June 2010 at 9:30 am in the Main Auditorium (Building 500)*. A welcome coffee will be available from 9:00 am. During this meeting, information will be given about: • Organization’s values (Director-General) • Code of Conduct (Director-General / Anne-Sylvie Catherin) • New Ombudsperson role (Vincent Vuillemin) These presentations will be followed by a questions & answers session. We look forward to seeing you all on 25 June! Best regards, Anne-Sylvie Catherin Head, Human Resources Department *This meeting will be simultaneously retransmitted in BE Auditorium (Building 864) and available at the following address: http://webcast.cern.ch.

  3. HR Public meeting

    SciTech Connect

    2010-10-12

    Cher(e)s collègues, En collaboration avec le Département HR, le Directeur général a le plaisir de vous convier à une réunion publique qui se tiendra le vendredi 25 juin 2010 à 9h30 dans l’Amphithéâtre principal (Bâtiment 500)*. Un café d’accueil y sera servi à partir de 9h. Cette réunion abordera les thèmes suivants : • Valeurs de l’Organisation (Directeur général) • Code de Conduite (Directeur général / Anne-Sylvie Catherin) • Création du nouveau rôle d’Ombudsperson (Vincent Vuillemin) Ces présentations seront suivies d’une séance de questions-réponses. Nous espérons vous retrouver nombreux le 25 juin ! Meilleures salutations, Anne-Sylvie Catherin Chef du Département des Ressources humaines *Cette réunion sera retransmise simultanément dans l’Amphithéâtre BE de Prévessin (Bâtiment 864) et également disponible à l’adresse suivante : http://webcast.cern.ch -------------------------------------------------------- Dear colleagues, In collaboration with HR Department, the Director-General would like to invite you to an information meeting which will be held on Friday 25 June 2010 at 9:30 am in the Main Auditorium (Building 500)*. A welcome coffee will be available from 9:00 am. During this meeting, information will be given about: • Organization’s values (Director-General) • Code of Conduct (Director-General / Anne-Sylvie Catherin) • New Ombudsperson role (Vincent Vuillemin) These presentations will be followed by a questions & answers session. We look forward to seeing you all on 25 June! Best regards, Anne-Sylvie Catherin Head, Human Resources Department *This meeting will be simultaneously retransmitted in BE Auditorium (Building 864) and available at the following address: http://webcast.cern.ch.

  4. HR Public meeting

    ScienceCinema

    None

    2016-07-12

    Cher(e)s collègues, En collaboration avec le Département HR, le Directeur général a le plaisir de vous convier à une réunion publique qui se tiendra le vendredi 25 juin 2010 à 9h30 dans l’Amphithéâtre principal (Bâtiment 500)*. Un café d’accueil y sera servi à partir de 9h. Cette réunion abordera les thèmes suivants : • Valeurs de l’Organisation (Directeur général) • Code de Conduite (Directeur général / Anne-Sylvie Catherin) • Création du nouveau rôle d’Ombudsperson (Vincent Vuillemin) Ces présentations seront suivies d’une séance de questions-réponses. Nous espérons vous retrouver nombreux le 25 juin ! Meilleures salutations, Anne-Sylvie Catherin Chef du Département des Ressources humaines *Cette réunion sera retransmise simultanément dans l’Amphithéâtre BE de Prévessin (Bâtiment 864) et également disponible à l’adresse suivante : http://webcast.cern.ch -------------------------------------------------------- Dear colleagues, In collaboration with HR Department, the Director-General would like to invite you to an information meeting which will be held on Friday 25 June 2010 at 9:30 am in the Main Auditorium (Building 500)*. A welcome coffee will be available from 9:00 am. During this meeting, information will be given about: • Organization’s values (Director-General) • Code of Conduct (Director-General / Anne-Sylvie Catherin) • New Ombudsperson role (Vincent Vuillemin) These presentations will be followed by a questions & answers session. We look forward to seeing you all on 25 June! Best regards, Anne-Sylvie Catherin Head, Human Resources Department *This meeting will be simultaneously retransmitted in BE Auditorium (Building 864) and available at the following address: http://webcast.cern.ch.

  5. A Dominant Negative Zebrafish Ahr2 Partially Protects Developing Zebrafish from Dioxin Toxicity

    PubMed Central

    Lanham, Kevin A.; Prasch, Amy L.; Weina, Kasia M.; Peterson, Richard E.; Heideman, Warren

    2011-01-01

    The toxicity by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is thought to be caused by activation of the aryl hydrocarbon receptor (AHR). However, our understanding of how AHR activation by TCDD leads to toxic effects is poor. Ideally we would like to manipulate AHR activity in specific tissues and at specific times. One route to this is expressing dominant negative AHRs (dnAHRs). This work describes the construction and characterization of dominant negative forms of the zebrafish Ahr2 in which the C-terminal transactivation domain was either removed, or replaced with the inhibitory domain from the Drosophila engrailed repressor protein. One of these dnAhr2s was selected for expression from the ubiquitously active e2fα promoter in transgenic zebrafish. We found that these transgenic zebrafish expressing dnAhr2 had reduced TCDD induction of the Ahr2 target gene cyp1a, as measured by 7-ethoxyresorufin-O-deethylase activity. Furthermore, the cardiotoxicity produced by TCDD, pericardial edema, heart malformation, and reduced blood flow, were all mitigated in the zebrafish expressing the dnAhr2. These results provide in vivo proof-of-principle results demonstrating the effectiveness of dnAHRs in manipulating AHR activity in vivo, and demonstrating that this approach can be a means for blocking TCDD toxicity. PMID:22194803

  6. Modeling of the Aryl Hydrocarbon Receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands

    PubMed Central

    Bisson, William; Koch, Daniel; O’Donnell, Edmond; Khalil, Sammy M.; Kerkvliet, Nancy; Tanguay, Robert; Abagyan, Ruben; Kolluri, Siva Kumar

    2012-01-01

    The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor; the AhR Per-AhR/Arnt-Sim (PAS) domain binds ligands. We developed homology models of the AhR PAS domain to characterize previously observed intra- and inter-species differences in ligand binding using Molecular Docking. In silico structure-based virtual ligand screening using our model resulted in the identification of pinocembrin and 5-hydroxy-7-methoxyflavone, which promoted nuclear translocation and transcriptional activation of AhR and AhR-dependent induction of endogenous target genes. PMID:19719119

  7. HR Shared Services and the Realignment of HR.

    ERIC Educational Resources Information Center

    Reilly, P.

    This report examines how adopting the shared services model of human resources (HR) services delivery can help businesses achieve better alignment between their HR service and specific business needs. Chapter 1 provides background information on the research project underlying this report, which included the following data collection activities:…

  8. The Role of AHR in Breast Cancer Development

    DTIC Science & Technology

    2005-07-01

    cancer, AhR, galangin 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18. NUMBER 19a. NAME OF RESPONSIBLE PERSON OF ABSTRACT OF PAGES USAMRMC a. REPORT...Z39.18 ABSTRACT The study described herein was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin , affects growth of...human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon

  9. The emerging roles of AhR in physiology and immunity.

    PubMed

    Hao, Nan; Whitelaw, Murray L

    2013-09-01

    The aryl hydrocarbon receptor (AhR) is traditionally defined as a transcriptional regulator involved in adaptive xenobiotic response, however, emerging evidence supports physiological functions of AhR in normal cell development and immune response. The role of AhR in immunomodulation is multi-dimensional. On the one hand, activation of AhR by TCDD and other ligands leads to profound immunosuppression, potentially via skewed Th1/Th2 cell balance toward Th1 dominance, and boosted Treg cell differentiation. On the other hand, activation of AhR can also induce Th17 cell polarization and increase the severity of autoimmune disease. In addition to T lymphocytes, the AhR also appears to play a vital role in B cell maturation, and regulates the activity of macrophages, dendritic cells and neutrophils following lipopolysaccharide challenge or influenza virus infection. In these scenarios, activation of AhR is associated with decreased host response and reduced survival. Furthermore, gene knock out studies suggest that AhR is indispensable for the postnatal maintenance of intestinal intraepithelial lymphocytes and skin-resident dendritic epidermal gamma delta T cells, providing a potential link between AhR and gut immunity and wound healing. It is well accepted that the magnitude and the type of immune response is dependent on the local cytokine milieu and the AhR appears to be one of the key factors involved in the fine turning of this cytokine balance.

  10. Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions

    SciTech Connect

    Wincent, Emma; Stegeman, John J.; Jönsson, Maria E.

    2015-04-15

    Wnt/β-catenin signaling regulates essential biological functions and acts in developmental toxicity of some chemicals. The aryl hydrocarbon receptor (AHR) is well-known to mediate developmental toxicity of persistent dioxin-like compounds (DLCs). Recent studies indicate a crosstalk between β-catenin and the AHR in some tissues. However the nature of this crosstalk in embryos is poorly known. We observed that zebrafish embryos exposed to the β-catenin inhibitor XAV939 display effects phenocopying those of the dioxin-like 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). This led us to investigate the AHR interaction with β-catenin during development and ask whether developmental toxicity of DLCs involves antagonism of β-catenin signaling. We examined phenotypes and transcriptional responses in zebrafish embryos exposed to XAV939 or to a β-catenin activator, 1-azakenpaullone, alone or with AHR agonists, either PCB126 or 6-formylindolo[3,2-b]carbazole (FICZ). Alone 1-azakenpaullone and XAV939 both were embryo-toxic, and we found that in the presence of FICZ, the toxicity of 1-azakenpaullone decreased while the toxicity of XAV939 increased. This rescue of 1-azakenpaullone effects occurred in the time window of Ahr2-mediated toxicity and was reversed by morpholino-oligonucleotide knockdown of Ahr2. Regarding PCB126, addition of either 1-azakenpaullone or XAV939 led to lower mortality than with PCB126 alone but surviving embryos showed severe edemas. 1-Azakenpaullone induced transcription of β-catenin-associated genes, while PCB126 and FICZ blocked this induction. The data indicate a stage-dependent antagonism of β-catenin by Ahr2 in zebrafish embryos. We propose that the AHR has a physiological role in regulating β-catenin during development, and that this is one point of intersection linking toxicological and physiological AHR-governed processes.

  11. Alloy NASA-HR-1

    NASA Technical Reports Server (NTRS)

    Chen, Po-Shou; Mitchell, Michael

    2005-01-01

    NASA-HR-1 is a high-strength Fe-Ni-base superalloy that resists high-pressure hydrogen environment embrittlement (HEE), oxidation, and corrosion. Originally derived from JBK-75, NASA-HR-1 has exceptional HEE resistance that can be attributed to its gamma-matrix and eta-free (Ni3Ti) grain boundaries. The chemistry was formulated using a design approach capable of accounting for the simultaneous effects of several alloy additions. This approach included: (1) Systematically modifying gamma-matrix compositions based on JBK-75; (2) Increasing gamma (Ni3(Al,Ti)) volume fraction and adding gamma-matrix strengthening elements to obtain higher strength; and (3) Obtaining precipitate-free grain boundaries. The most outstanding attribute of NASA-HR-1 is its ability to resist HEE while showing much improved strength. NASA-HR-1 has approximately 25% higher yield strength than JXK-75 and exhibits tensile elongation of more than 20% with no ductility loss in a hydrogen environment at 5 ksi, an achievement unparalleled by any other commercially available alloy. Its Cr and Ni contents provide exceptional resistance to environments that promote oxidation and corrosion. Microstructural stability was maintained by improved solid solubility of the gamma-matrix, along with the addition of alloying elements to retard eta (Ni3Ti) precipitation. NASA-HR-1 represents a new system that greatly extends the compositional ranges of existing HEE-resistant Fe-Ni-base superalloys.

  12. 76 FR 80447 - Eighth Meeting: RTCA Special Committee 219: Attitude and Heading Reference Systems (AHRS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ... Special Committee 219: Attitude and Heading Reference Systems (AHRS) AGENCY: Federal Aviation...: Attitude and Heading Reference Systems (AHRS). SUMMARY: The FAA is issuing this notice to advise the public of the eighth meeting of RTCA Special Committee 219: Attitude and Heading Reference Systems...

  13. The Mystery of HR 6815

    NASA Astrophysics Data System (ADS)

    Thompson, Raymond R.

    The catalogue data for HR 6815 (V669 Herculis) are very incomplete. A literature search was carried out in an attempt to find the missing parameters, and a possible source for the single catalogued datum was found. Further suggested elements are provided, based on 105 photoelectric observations made between 1991 and 1996.

  14. Putting HR outsourcing into practice.

    PubMed

    Berger, Michael

    2007-01-01

    Faced with the time-consuming responsibility of human resources (HR) management, a growing number of medical practices are outsourcing their HR to professional employer organizations (PEOs) so they can concentrate on their core business. A PEO functions as an HR department-minus the high overhead-managing daily administrative tasks such as payroll processing and related tax filings, employee benefits, and workers' compensation coverage and claims resolution. PEOs help physicians' offices keep up with the piles of paperwork that never seem to shrink, freeing doctors to focus on patient care and building their practice. Because of their volume buying power, PEOs are able to offer employees of small medical practices big-company benefits-everything from health, dental, and vision coverage to long-term disability insurance and tuition assistance. A fledgling industry only a decade ago, HR outsourcing has morphed into a blossoming industry. Enlisting the services of a PEO is now considered de rigueur in many small business circles.

  15. HR Positions on the Internet.

    ERIC Educational Resources Information Center

    Coghill, Carey Cox; Kirk, James J.

    The question of whether the online job market reflects the trends predicted for the job market was examined in a study of a random sample of 690 Internet job postings over a 6-month period. Each listing was categorized by type of position, desired qualifications, salary, and job specifications. Of the human resources (HR) jobs posted, 7.2% were…

  16. The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90

    PubMed Central

    Tsuji, Noriko; Fukuda, Kana; Nagata, Yuhtaroh; Okada, Hirotaka; Haga, Asami; Hatakeyama, Shiori; Yoshida, Shiho; Okamoto, Tomoya; Hosaka, Miki; Sekine, Kazuhiro; Ohtaka, Kei; Yamamoto, Soh; Otaka, Michiro; Grave, Ewa; Itoh, Hideaki

    2014-01-01

    The aryl hydrocarbon receptor is a member of the nuclear receptor superfamily that associates with the molecular chaperone HSP90 in the cytoplasm. The activation mechanism of the AhR is not yet fully understood. It has been proposed that after binding of ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3methylcholanthrene (3-MC), or β-naphthoflavone (β-NF), the AhR dissociates from HSP90 and translocates to the nucleus. It has also been hypothesized that the AhR translocates to the nucleus and forms a complex with HSP90 and other co-chaperones. There are a few reports about the direct association or dissociation of AhR and HSP90 due to difficulties in purifying AhR. We constructed and purified the PAS domain from AhR. Binding of the AhR-PAS domain to β-NF affinity resin suggested that it possesses ligand-binding affinity. We demonstrated that the AhR-PAS domain binds to HSP90 and the association is not affected by ligand binding. The ligand 17-DMAG inhibited binding of HSP90 to GST-PAS. In an immunoprecipitation assay, HSP90 was co-immunoprecipitated with AhR both in the presence or absence of ligand. Endogenous AhR decreased in the cytoplasm and increased in the nucleus of HeLa cells 15 min after treatment with ligand. These results suggested that the ligand-bound AhR is translocated to nucleus while in complex with HSP90. We used an in situ proximity ligation assay to confirm whether AhR was translocated to the nucleus alone or together with HSP90. HSP90 was co-localized with AhR after the nuclear translocation. It has been suggested that the ligand-bound AhR was translocated to the nucleus with HSP90. Activated AhR acts as a transcription factor, as shown by the transcription induction of the gene CYP1A1 8 h after treatment with β-NF. PMID:25349783

  17. Dioxin-dependent and dioxin-independent gene batteries: comparison of liver and kidney in AHR-null mice.

    PubMed

    Boutros, Paul C; Bielefeld, Kirsten A; Pohjanvirta, Raimo; Harper, Patricia A

    2009-11-01

    The aryl hydrocarbon receptor (AHR) is a widely expressed ligand-dependent transcription factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Ahr-null mice are refractory to the toxic effects of dioxin exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. To address the latter issue, we defined and compared transcriptional responses to dioxin exposure in the liver and kidney of wild-type and Ahr-null adult C57BL/6J mice treated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin or corn-oil vehicle. In both tissues, essentially all effects of dioxin on hepatic mRNA levels were mediated by the AHR. Although 297 genes were altered by dioxin exposure in the liver, only 17 were changed in the kidney, including a number of well-established AHR target genes. Ahr genotype had a large effect in both tissues, profoundly remodeling both the renal and hepatic transcriptomes. Surprisingly, a large number of genes were affected by Ahr genotype in both tissues, suggesting the presence of a basal AHR gene battery. Alterations of the renal transcriptome in Ahr-null animals were associated with perturbation of specific functional pathways and enrichment of specific DNA motifs. Our results demonstrate the importance of intertissue comparisons, highlight the basal role of the AHR in liver and kidney, and support a role in development or normal physiology.

  18. INSIGHTS FROM AHR AND ARNT GENE KNOCKOUT STUDIES REGARDING RESPONSES TO TCDD AND REGULATION OF NORMAL EMBRYONIC DEVELOPMENT

    EPA Science Inventory

    The aryl hydrocarbon receptor (AhR) and the AhR nuclear translocator (ARNT) are members of the Per-ARNT-Sim (PAS) family of proteins. The AhR binds members of the chemical family that includes dioxins, furans and coplanar polychlorinated biphenyls (PCBs). A ligand-AhR-ARNT comp...

  19. Estimation of weekly 99Mo production by AHR 200 kW

    NASA Astrophysics Data System (ADS)

    Siregar, I. H.; Suharyana; Khakim, A.; Siregar, D.; Frida, A. R.

    2016-11-01

    The estimation of weekly 99Mo production by AHR 200 kW fueled with Low Enriched Uranium Uranyl Nitrate solution has been simulated by using MCNPX computer code. We have employed the AHR design of Babcock & Wilcox Medical Isotope Production System with 9Be Reflector and Stainless steel vessel. We found that when the concentration of uranium in the fresh fuel was 108 gr U/L of UO2(NO3)2 fuel solution, the multiplication factor was 1.0517. The 99Mo concentration reached saturated at tenth day operation. The AHR can produce approximately 1.96×103 6-day-Ci weekly.

  20. The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin.

    PubMed

    Hidaka, Takanori; Ogawa, Eisaku; Kobayashi, Eri H; Suzuki, Takafumi; Funayama, Ryo; Nagashima, Takeshi; Fujimura, Taku; Aiba, Setsuya; Nakayama, Keiko; Okuyama, Ryuhei; Yamamoto, Masayuki

    2017-01-01

    Atopic dermatitis is increasing worldwide in correlation with air pollution. Various organic components of pollutants activate the transcription factor AhR (aryl hydrocarbon receptor). Through the use of AhR-CA mice, whose keratinocytes express constitutively active AhR and that develop atopic-dermatitis-like phenotypes, we identified Artn as a keratinocyte-specific AhR target gene whose product (the neurotrophic factor artemin) was responsible for epidermal hyper-innervation that led to hypersensitivity to pruritus. The activation of AhR via air pollutants induced expression of artemin, alloknesis, epidermal hyper-innervation and inflammation. AhR activation and ARTN expression were positively correlated in the epidermis of patients with atopic dermatitis. Thus, AhR in keratinocytes senses environmental stimuli and elicits an atopic-dermatitis pathology. We propose a mechanism of air-pollution-induced atopic dermatitis via activation of AhR.

  1. Identification and expression of aryl hydrocarbon receptors (AhR1 and AhR2) provide insight in an evolutionary context regarding sensitivity of white sturgeon (Acipenser transmontanus) to dioxin-like compounds.

    PubMed

    Doering, Jon A; Wiseman, Steve; Beitel, Shawn C; Giesy, John P; Hecker, Markus

    2014-05-01

    Sturgeons are ancient fishes, which are endangered in many parts of the world. Due to their benthic nature and longevity, sturgeon are at great risk of exposure to bioaccumulative contaminants such as dioxin-like compounds (DLCs). Despite their endangered status, little research has been conducted to characterize the relative sensitivity of sturgeons to DLCs. Proper assessment of risk of DLCs posed to these fishes therefore, requires a better understanding of this sensitivity and the factors that are driving it. Adverse effects associated with exposure to DLCs are mediated by the aryl hydrocarbon receptor (AhR). This study identified and characterized two distinct AhRs, AhR1 and AhR2, in white sturgeon (Acipenser transmontanus) for the first time as a first step in studying the relative sensitivities of sturgeons to DLCs. Furthermore, tissue-specific expression of both AhRs under basal conditions and in response to exposure to the model DLC, β-naphthoflavone (βNF), was determined. The sequence of amino acids of AhR1 of white sturgeon had greater similarity to AhRs of tetrapods, including amphibians, birds, and mammals, than to AhR1s of other fishes. The sequence of amino acids in the ligand binding domain of the AhR1 had greater than 80% similarity to AhRs known to bind DLCs and was less similar to AhRs not known to bind DLCs. AhR2 of white sturgeon had greatest similarity to AhR2 of other fishes. Profiles of expression of AhR1 and AhR2 in white sturgeon were distinct from those known in other fishes and appear more similar to profiles observed in birds. Expressions of both AhR1 and AhR2 of white sturgeon were greatest in liver and heart, which are target organs for DLCs. Furthermore, abundances of transcripts of AhR1 and AhR2 in all tissues from white sturgeon were greater than controls (up to 35-fold) following exposure to βNF. Based upon both AhRs having similar abundances of transcript in target organs of DLC toxicity, both AhRs being up-regulated following

  2. Specific Ligand Binding Domain Residues Confer Low Dioxin Responsiveness to AHR1β of Xenopus laevis

    PubMed Central

    Odio, Camila; Holzman, Sarah A.; Denison, Michael S.; Fraccalvieri, Domenico; Bonati, Laura; Franks, Diana G.; Hahn, Mark E.; Powell, Wade H.

    2013-01-01

    The aryl hydrocarbon receptor (AHR) is a PAS-family protein that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vertebrates. Frogs are remarkably insensitive to TCDD, and AHRs from Xenopus laevis bind TCDD with low affinity. We sought to identify structural features of X. laevis AHR1β associated with low TCDD sensitivity. Substitution of the entire ligand-binding domain (LBD) with the corresponding sequence from mouse AHRb-1 dramatically increased TCDD responsiveness in transactivation assays. To identify amino acid residues responsible, we constructed a comparative model of the AHR1β LBD using homologous domains of PAS proteins HIF2α and ARNT. The model revealed an internal cavity of similar dimensions to the putative binding cavity of mouse AHRb-1, suggesting the importance of side-chain interactions over cavity size. Of residues with side chains clearly pointing into the cavity, only two differed from the mouse sequence. When A354, located within a conserved β-strand, was changed to serine, the corresponding mouse residue, the EC50 for TCDD decreased more than 15-fold. When N325 was changed to serine, EC50 declined 3-fold. When the mutations were combined, the EC50 declined from 18.6 nM to 0.8 nM, nearly matching mouse AHR for TCDD sensitivity. Velocity sedimentation analysis confirmed that mutant frog AHRs exhibited correspondingly increased TCDD binding. We also assayed mutant AHRs for responsiveness to a candidate endogenous ligand, 6-formylindolo[3,2b]carbazole (FICZ). Mutations that increased TCDD sensitivity also increased sensitivity to FICZ. This comparative study represents a novel approach to discerning fundamental information about the structure of AHR and its interactions with biologically important agonists. PMID:23394719

  3. Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast.

    PubMed

    Mexia, Nikitia; Gaitanis, Georgios; Velegraki, Aristea; Soshilov, Anatoly; Denison, Michael S; Magiatis, Prokopios

    2015-04-01

    Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in the human skin and are highly potent activators of the aryl hydrocarbon receptor (AhR) and AhR-dependent gene expression. Chemical analysis of an EtOAc extract of a M. furfur strain obtained from diseased human skin and grown on l-tryptophan agar revealed several known AhR active tryptophan metabolites along with a previously unidentified compound, pityriazepin. While its structure resembled that of the known alkaloid pityriacitrin, the comprised pyridine ring had been transformed into an azepinone. The indoloazepinone scaffold of pityriazepin is extremely rare in nature and has only been reported once previously. Pityriazepin, like the other isolated compounds, was found to be a potent activator of the AhR-dependent reporter gene assay in recombinant cell lines derived from four different species, although significant species differences in relative potency were observed. The ability of pityriazepin to competitively bind to the AhR and directly stimulate AhR DNA binding classified it as a new naturally-occurring potent AhR agonist. M. furfur produces an expanded collection of extremely potent naturally occurring AhR agonists, which produce their biological effects in a species-specific manner.

  4. A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC

    PubMed Central

    Regazzo, Daniela; Bertazza, Loris; Galuppini, Francesca; Guzzardo, Vincenza; Jaffrain-Rea, Marie Lise; Vianello, Federica; Ciato, Denis; Ceccato, Filippo; Watutantrige-Fernando, Sara; Bisognin, Andrea; Bortoluzzi, Stefania; Pennelli, Gianmaria; Boscaro, Marco; Scaroni, Carla; Mian, Caterina

    2015-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAFV600E may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice. PMID:26392334

  5. A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC.

    PubMed

    Occhi, Gianluca; Barollo, Susi; Regazzo, Daniela; Bertazza, Loris; Galuppini, Francesca; Guzzardo, Vincenza; Jaffrain-Rea, Marie Lise; Vianello, Federica; Ciato, Denis; Ceccato, Filippo; Watutantrige-Fernando, Sara; Bisognin, Andrea; Bortoluzzi, Stefania; Pennelli, Gianmaria; Boscaro, Marco; Scaroni, Carla; Mian, Caterina

    2015-10-13

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAFV600E may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice.

  6. Characterization testing of a 40 Ahr bipolar nickel hydrogen battery

    NASA Technical Reports Server (NTRS)

    Brewer, Jeffrey C.; Manzo, Michelle A.; Gahn, Randall F.

    1989-01-01

    In a continuing effort to develop NiH2 bipolar technology to a point where it can be used efficiently in space flight, testing of a second 40 Ahr, 10-cell bipolar battery has begun. This battery has undergone extensive characterization testing to determine the effects of such operating parameters as charge and discharge rates, temperature, and pressure. The fundamental design of this actively cooled bipolar battery is the same as the first battery. Most of the individual components, however, are from different manufacturers. Different testing procedures as well as certain unique battery characteristics make it difficult to directly compare the two sets of results. In general, the performance of this battery throughout characterization produced expected results. The main differences seen between the first and second batteries occurred during the high-rate discharge portion of the test matrix. The first battery also had poor high-rate discharge results, although better than those of the second battery. Minor changes were made to the battery frame design used for the first battery in an attempt to allow better gas access to the reaction sites for the second build and hopefully improve performance. The changes, however, did not improve the performance of the second battery and could have possibly contributed to the poorer performance that was observed. There are other component differences that could have contributed to the poorer performance of the second battery. The H2 electrode in the second battery was constructed with a Goretex backing which could have limited the high-rate current flow. The gas screen in the second battery had a larger mesh which again could have limited the high-rate current flow. Small scale 2 x 2 batteries are being tested to evaluate the effects of the component variations.

  7. eHR: An Introduction. IES Report.

    ERIC Educational Resources Information Center

    Kettley, P.; Reilly, P.

    This document introduces the concept of electronic human resources (eHR) and its application. Chapter 1 presents a brief overview of the guide's development, purpose, and structure. Chapter 2 defines the concept of eHR as "the application of conventional, Web, and voice technologies to improve HR administration, transactions, and process…

  8. The aryl hydrocarbon receptor (AhR) inhibits vanadate-induced vascular endothelial growth factor (VEGF) production in TRAMP prostates

    PubMed Central

    Fritz, Wayne A.; Lin, Tien-Min; Peterson, Richard E.

    2008-01-01

    Hypoxia-inducible factor-1 alpha (HIF-1α) and aryl hydrocarbon receptor nuclear translocator (ARNT) are basic helix-loop-helix/per-arnt-sim (PAS) family transcription factors. During angiogenesis and tumor growth, HIF-1α dimerizes with ARNT, inducing expression of many genes, including vascular endothelial growth factor (VEGF). ARNT also dimerizes with the aryl hydrocarbon receptor (AhR). AhR-null (Ahr−/−) transgenic adenocarcinoma of the mouse prostate (TRAMP) mice develop prostate tumors with greater frequency than AhR wild-type (Ahr+/+) TRAMP mice, even though prevalence of prostate epithelial hyperplasia is not inhibited. This suggests that Ahr inhibits prostate carcinogenesis. In TRAMP mice, prostatic epithelial hyperplasia results in stabilized HIF-1α, inducing expression of VEGF, a prerequisite for tumor growth and angiogenesis. Since ARNT is a common dimerization partner of AhR and HIF-1α, we hypothesized that the AhR inhibits prostate tumor formation by competing with HIF-1α for ARNT, thereby limiting VEGF production. Prostates from Ahr+/+, Ahr+/− and Ahr−/− C57BL/6J TRAMP mice were cultured in the presence of graded concentrations of vanadate, an inducer of VEGF through the HIF-1α–ARNT pathway. Vanadate induced VEGF protein in a dose-dependent fashion in Ahr+/− and Ahr−/− TRAMP cultures, but not in Ahr+/+ cultures. However, vanadate induced upstream proteins in the phosphatidylinositol 3-kinase-signaling cascade to a similar extent in TRAMPs of each Ahr genotype, evidenced by v-akt murine thymoma viral oncogene homolog (Akt) phosphorylation. These findings suggest that AhR sequesters ARNT, decreasing interaction with HIF-1α reducing VEGF production. Since VEGF is required for tumor vascularization and growth, these studies further suggest that reduction in VEGF correlates with inhibited prostate carcinogenesis in Ahr+/+ TRAMP mice. PMID:18359762

  9. FCAPT uvby Photometry of the mCP Stars HD 86592, HR 4330, HR 6958, and HR 7786

    NASA Astrophysics Data System (ADS)

    Adelman, Saul J.

    2008-04-01

    New differential Strömgren uvby Four College Automated Photoelectric Telescope (FCAPT) observations of four magnetic CP stars HD 86592, HR 4330, HR 6958, and HR 7786 are presented. These observations are analyzed along with published FCAPT data to improve the periods and the light curves. The period of HD 86592 is that of Babel & North, 2.886669 days. The new periods of HR 4330, HR 6958, and HR 7786 are 3.152, 18.0642, and 8.5295 days, respectively, almost the same as their previous values from FCAPT data. The first three stars can be characterized as having constant light curves and periods. However, the small differences among the seasonal light curves of HR 7786 indicate it is a star whose rotational axis is precessing about its magnetic axis.

  10. Réunion publique HR

    SciTech Connect

    2010-04-30

    Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanée de cette réunion sera assurée dans l'Amphithéâtre BE de Prévessin et également disponible à l'adresse suivante: http://webcast.cern.chJe me réjouis de votre participation!Meilleures salutations,Anne-Sylvie CatherinChef du Département des Ressources humaines__________________________________________________________________________________Dear Colleagues,I should like to remind you that a plublic meeting organised by HR Department will be held today:Friday 30 April 2010 at 9:30 am in the Main Auditorium (coffee from 9:00 am).During this meeting, general information will be given about:the CERN Admin e-guide which is a new guide to the Organization's administrative procedures, drawn up to facilitate the retrieval of practical information and to offer a user-friendly format;the CERN Health Insurance System (presentation by Philippe Charpentier, President of the CHIS Board) and;the Pension Fund (presentation by Theodore Economou, Administrator of the CERN Pension Fund).A simultaneous transmission of this meeting will be broadcast in the BE Auditorium at Prévessin and will also be available at the following address. http://webcast.cern.chI look forward to your participation!Best regards,Anne-Sylvie Catherin

  11. Asteroseismology Across the HR Diagram

    NASA Astrophysics Data System (ADS)

    Thompson, M. J.; Cunha, M. S.; Monteiro, M. J. P. F. G.

    2003-05-01

    Ground-based observations have detected solar-like oscillations on Sun-like stars, and diagnostics similar to those used in helioseismology are now being used to test and constrain the physics and evolutionary state of these stars. Multi-mode oscillations are being observed in an abundance of other stars, including slowly pulsating B stars (SPB stars), delta-Scuti stars, Ap stars and the pulsating white dwarfs. New classes of pulsators continue to be discovered across the Herzsprung-Russell diagram. Yet the chances still to be faced to make asteroseismology across the HR diagram a reality are formidable. Observation, data analysis and theory all pose hard problems to be overcome. This book, reflecting the goal of the meeting, aims to facilitate a cross-fertilisation of ideas and approaches between fields covering different pulsators and with different areas of expertise. The book successfully covers most known types of pulsators, reflecting a highly productive and far reaching interchange of ideas which we believe is conveyed by the papers and posters published, making it a reference for researchers and postgraduate students working on stellar structure and evolution. Link: http://www.wkap.nl/prod/b/1-4020-1173-3

  12. An altered hydrotropic response (ahr1) mutant of Arabidopsis recovers root hydrotropism with cytokinin

    PubMed Central

    Saucedo, Manuel; Ponce, Georgina; Campos, María Eugenia; Eapen, Delfeena; García, Edith; Luján, Rosario; Sánchez, Yoloxóchitl; Cassab, Gladys I.

    2012-01-01

    Roots are highly plastic and can acclimate to heterogeneous and stressful conditions. However, there is little knowledge of the effect of moisture gradients on the mechanisms controlling root growth orientation and branching, and how this mechanism may help plants to avoid drought responses. The aim of this study was to isolate mutants of Arabidopsis thaliana with altered hydrotropic responses. Here, altered hydrotropic response 1 (ahr1), a semi-dominant allele segregating as a single gene mutation, was characterized. ahr1 directed the growth of its primary root towards the source of higher water availability and developed an extensive root system over time. This phenotype was intensified in the presence of abscisic acid and was not observed if ahr1 seedlings were grown in a water stress medium without a water potential gradient. In normal growth conditions, primary root growth and root branching of ahr1 were indistinguishable from those of the wild type (wt). The altered hydrotropic growth of ahr1 roots was confirmed when the water-rich source was placed at an angle of 45° from the gravity vector. In this system, roots of ahr1 seedlings grew downward and did not display hydrotropism; however, in the presence of cytokinins, they exhibited hydrotropism like those of the wt, indicating that cytokinins play a critical role in root hydrotropism. The ahr1 mutant represents a valuable genetic resource for the study of the effects of cytokinins in the differential growth of hydrotropism and control of lateral root formation during the hydrotropic response. PMID:22442413

  13. AHR2-Mediated Transcriptomic Responses Underlying the Synergistic Cardiac Developmental Toxicity of PAHs

    PubMed Central

    Jayasundara, Nishad; Van Tiem Garner, Lindsey; Meyer, Joel N.; Erwin, Kyle N.; Di Giulio, Richard T.

    2015-01-01

    Polycyclic aromatic hydrocarbons (PAHs) induce developmental defects including cardiac deformities in fish. The aryl hydrocarbon receptor (AHR) mediates the toxicity of some PAHs. Exposure to a simple PAH mixture during embryo development consisting of an AHR agonist (benzo(a)pyrene-BaP) with fluoranthene (FL), an inhibitor of cytochrome p450 1(CYP1)—a gene induced by AHR activation—results in cardiac deformities. Exposure to BaP or FL alone at similar concentrations alters heart rates, but does not induce morphological deformities. Furthermore, AHR2 knockdown prevents the toxicity of BaP + FL mixture. Here, we used a zebrafish microarray analysis to identify heart-specific transcriptomic changes during early development that might underlie cardiotoxicity of BaP + FL. We used AHR2 morphant embryos to determine the role of this receptor in mediating toxicity. Control and knockdown embryos at 36 h post-fertilization were exposed to DMSO, 100 μg/l BaP, 500 μg/l FL, or 100 μg/l BaP + 500 μg/l FL, and heart tissues for RNA were extracted at 2, 6, 12, and 18 h-post-exposure (hpe), prior to the appearance of cardiac deformities. Data show AHR2-dependent BaP + FL effects on expression of genes involved in protein biosynthesis and neuronal development in addition to signaling molecules and their associated molecular pathways. Ca2+-cycling and muscle contraction genes were the most significantly differentially expressed category of transcripts when comparing BaP + FL-treated AHR2 morphant and control embryos. These differences were most prominent at 2 and 6 hpe. Therefore, we postulate that BaP + FL may affect cellular Ca2+ levels and subsequently cardiac muscle function, potentially underlying BaP + FL cardiotoxicity. PMID:25412620

  14. Tetrachlorodibenzo-p-dioxin exposure alters radial arm maze performance and hippocampal morphology in female AhR mice.

    PubMed

    Powers, B E; Lin, T-M; Vanka, A; Peterson, R E; Juraska, J M; Schantz, S L

    2005-02-01

    Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter spatial learning in rats tested on a radial arm maze (RAM). TCDD is believed to exert most of its effects through binding to the aryl hydrocarbon receptor (AhR). To determine whether the AhR mediates TCDD-induced alterations in spatial learning, we tested male and female AhR-knockout (AhR-/-), heterozygous (AhR+/-) and wild-type (AhR+/+) mice on the RAM. AhR+/- male and female mice were time mated, and treated dams were dosed with 5 microg TCDD/kg body weight on day 13 of gestation. When offspring reached adulthood, male and female AhR+/+, AhR+/- and AhR-/- mice from TCDD-exposed and unexposed litters were tested on the eight-arm RAM. After testing, we examined hippocampal morphology as visualized by the Timm's silver sulfide stain. TCDD-exposed female AhR+/- mice made more errors than their respective controls on the RAM and exhibited a decrease in the size of the intra- and infrapyramidal mossy fiber (IIP-MF) field of the hippocampus. None of the other TCDD-exposed groups differed from their respective control groups with regard to maze performance or hippocampal morphology. The reduction of IIP-MF field indicates a possible morphological basis for the learning deficit that was observed in the female AhR+/- mice. It is hypothesized that the effect of TCDD exposure is AhR dependent and that TCDD may alter GABAergic activity in the hippocampus of female mice during development.

  15. Dioxin-Dependent and Dioxin-Independent Gene Batteries: Comparison of Liver and Kidney in AHR-Null Mice

    PubMed Central

    Boutros, Paul C.; Bielefeld, Kirsten A.; Pohjanvirta, Raimo; Harper, Patricia A.

    2009-01-01

    The aryl hydrocarbon receptor (AHR) is a widely expressed ligand-dependent transcription factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Ahr-null mice are refractory to the toxic effects of dioxin exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. To address the latter issue, we defined and compared transcriptional responses to dioxin exposure in the liver and kidney of wild-type and Ahr-null adult C57BL/6J mice treated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin or corn-oil vehicle. In both tissues, essentially all effects of dioxin on hepatic mRNA levels were mediated by the AHR. Although 297 genes were altered by dioxin exposure in the liver, only 17 were changed in the kidney, including a number of well-established AHR target genes. Ahr genotype had a large effect in both tissues, profoundly remodeling both the renal and hepatic transcriptomes. Surprisingly, a large number of genes were affected by Ahr genotype in both tissues, suggesting the presence of a basal AHR gene battery. Alterations of the renal transcriptome in Ahr-null animals were associated with perturbation of specific functional pathways and enrichment of specific DNA motifs. Our results demonstrate the importance of intertissue comparisons, highlight the basal role of the AHR in liver and kidney, and support a role in development or normal physiology. PMID:19759094

  16. Regulation of zebrafish CYP3A65 transcription by AHR2

    SciTech Connect

    Chang, Chin-Teng; Chung, Hsin-Yu; Su, Hsiao-Ting; Tseng, Hua-Pin; Tzou, Wen-Shyong; Hu, Chin-Hwa

    2013-07-15

    CYP3A proteins are the most abundant CYPs in the liver and intestines, and they play a pivotal role in drug metabolism. In mammals, CYP3A genes are induced by various xenobiotics through processes mediated by PXR. We previously identified zebrafish CYP3A65 as a CYP3A ortholog that is constitutively expressed in gastrointestinal tissues, and is upregulated by treatment with dexamethasone, rifampicin or tetrachlorodibenzo-p-dioxin (TCDD). However, the underlying mechanism of TCDD-mediated CYP3A65 transcription is unclear. Here we generated two transgenic zebrafish, Tg(CYP3A65S:EGFP) and Tg(CYP3A65L:EGFP), which contain 2.1 and 5.4 kb 5′ flanking sequences, respectively, of the CYP3A65 gene upstream of EGFP. Both transgenic lines express EGFP in larval gastrointestinal tissues in a pattern similar to that of the endogenous CYP3A65 gene. Moreover, EGFP expression can be significantly induced by TCDD exposure during the larval stage. In addition, EGFP expression can be stimulated by kynurenine, a putative AHR ligand produced during tryptophan metabolism. AHRE elements in the upstream regulatory region of the CYP3A65 gene are indispensible for basal and TCDD-induced transcription. Furthermore, the AHR2 DNA and ligand-binding domains are required to mediate effective CYP3A65 transcription. AHRE sequences are present in the promoters of many teleost CYP3 genes, but not of mammalian CYP3 genes, suggesting that AHR/AHR2-mediated transcription is likely a common regulatory mechanism for teleost CYP3 genes. It may also reflect the different environments that terrestrial and aquatic organisms encounter. - Highlights: • Tg(CYP3A65:EGFP) and CYP3A65 exhibits identical expression pattern. • CYP3A65 can be significantly induced by TCDD or kynurenine. • The AHRE elements are required to mediate CYP3A65 transcription. • The AHR2 DNA and ligand-binding domains are required for CYP3A65 transcription. • AHRE elements are present in many teleost CYP3 genes, but not in

  17. Genetic variation at aryl hydrocarbon receptor (AHR) loci in populations of Atlantic killifish (Fundulus heteroclitus) inhabiting polluted and reference habitats

    PubMed Central

    2014-01-01

    Background The non-migratory killifish Fundulus heteroclitus inhabits clean and polluted environments interspersed throughout its range along the Atlantic coast of North America. Several populations of this species have successfully adapted to environments contaminated with toxic aromatic hydrocarbon pollutants such as polychlorinated biphenyls (PCBs). Previous studies suggest that the mechanism of resistance to these and other “dioxin-like compounds” (DLCs) may involve reduced signaling through the aryl hydrocarbon receptor (AHR) pathway. Here we investigated gene diversity and evidence for positive selection at three AHR-related loci (AHR1, AHR2, AHRR) in F. heteroclitus by comparing alleles from seven locations ranging over 600 km along the northeastern US, including extremely polluted and reference estuaries, with a focus on New Bedford Harbor (MA, USA), a PCB Superfund site, and nearby reference sites. Results We identified 98 single nucleotide polymorphisms within three AHR-related loci among all populations, including synonymous and nonsynonymous substitutions. Haplotype distributions were spatially segregated and F-statistics suggested strong population genetic structure at these loci, consistent with previous studies showing strong population genetic structure at other F. heteroclitus loci. Genetic diversity at these three loci was not significantly different in contaminated sites as compared to reference sites. However, for AHR2 the New Bedford Harbor population had significant FST values in comparison to the nearest reference populations. Tests for positive selection revealed ten nonsynonymous polymorphisms in AHR1 and four in AHR2. Four nonsynonymous SNPs in AHR1 and three in AHR2 showed large differences in base frequency between New Bedford Harbor and its reference site. Tests for isolation-by-distance revealed evidence for non-neutral change at the AHR2 locus. Conclusion Together, these data suggest that F. heteroclitus populations in reference

  18. Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis

    PubMed Central

    van den Bogaard, Ellen H.; Bergboer, Judith G.M.; Vonk-Bergers, Mieke; van Vlijmen-Willems, Ivonne M.J.J.; Hato, Stanleyson V.; van der Valk, Pieter G.M.; Schröder, Jens Michael; Joosten, Irma; Zeeuwen, Patrick L.J.M.; Schalkwijk, Joost

    2013-01-01

    Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte–mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine–mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD. PMID:23348739

  19. Tissue specificity of aryl hydrocarbon receptor (AhR) mediated responses and relative sensitivity of white sturgeon (Acipenser transmontanus) to an AhR agonist.

    PubMed

    Doering, Jon A; Wiseman, Steve; Beitel, Shawn C; Tendler, Brett J; Giesy, John P; Hecker, Markus

    2012-06-15

    Sturgeons are endangered in some parts of the world. Due to their benthic nature and longevity sturgeon are at greater risk of exposure to bioaccumulative contaminants such as dioxin-like compounds that are associated with sediments. Despite their endangered status, little research has been conducted to characterize the relative responsiveness of sturgeon to dioxin-like compounds. In an attempt to study the biological effects and possible associated risks of exposure to dioxin-like compounds in sturgeon, the molecular and biochemical responses of white sturgeon (Acipenser transmontanus) to a model aryl hydrocarbon receptor (AhR) agonist, β-naphthoflavone (βNF) were investigated. White sturgeon were injected intraperitoneally with one of three doses of βNF (0, 50, or 500mg/kg, bw). Rainbow trout (Oncorhynchus mykiss) were used as a reference species since their responses have been well characterized in the past. Three days following injection with βNF, fish were euthanized and livers, gills, and intestines collected for biochemical and molecular analyses. White sturgeon exposed to βNF had significantly greater ethoxyresorufin O-deethylase (EROD) activity in liver (up to 37-fold), gill (up to 41-fold), and intestine (up to 36-fold) than did unexposed controls. Rainbow trout injected with βNF exhibited EROD activity that was significantly greater in liver (88-fold), than that of controls, but was undetectable in gills or intestine. Abundance of CYP1A transcript displayed a comparable pattern of tissue-specific induction with intestine (up to 189-fold), gills (up to 53-fold), and liver (up to 21-fold). Methoxyresorufin O-deethylase (MROD) and pentoxyresorufin O-deethylase (PROD) activities were undetectable in unexposed white sturgeon tissues while exposed tissues displayed MROD activity that was only moderately greater than the activity that could be detected. Differential inducibility among liver, gill, and intestine following exposure to an AhR agonist is

  20. In silico predictive studies of mAHR congener binding using homology modelling and molecular docking.

    PubMed

    Panda, Roshni; Cleave, A Suneetha Susan; Suresh, P K

    2014-09-01

    The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic, nuclear receptor that is responsible for the early events involved in the transcription of a complex set of genes comprising the CYP450 gene family. In the present computational study, homology modelling and molecular docking were carried out with the objective of predicting the relationship between the binding efficiency and the lipophilicity of different polychlorinated biphenyl (PCB) congeners and the AHR in silico. Homology model of the murine AHR was constructed by several automated servers and assessed by PROCHECK, ERRAT, VERIFY3D and WHAT IF. The resulting model of the AHR by MODWEB was used to carry out molecular docking of 36 PCB congeners using PatchDock server. The lipophilicity of the congeners was predicted using the XLOGP3 tool. The results suggest that the lipophilicity influences binding energy scores and is positively correlated with the same. Score and Log P were correlated with r = +0.506 at p = 0.01 level. In addition, the number of chlorine (Cl) atoms and Log P were highly correlated with r = +0.900 at p = 0.01 level. The number of Cl atoms and scores also showed a moderate positive correlation of r = +0.481 at p = 0.01 level. To the best of our knowledge, this is the first study employing PatchDock in the docking of AHR to the environmentally deleterious congeners and attempting to correlate structural features of the AHR with its biochemical properties with regards to PCBs. The result of this study are consistent with those of other computational studies reported in the previous literature that suggests that a combination of docking, scoring and ranking organic pollutants could be a possible predictive tool for investigating ligand-mediated toxicity, for their subsequent validation using wet lab-based studies.

  1. AHR2 mediates cardiac teratogenesis of polycyclic aromatic hydrocarbons and PCB-126 in Atlantic killifish (Fundulus heteroclitus).

    PubMed

    Clark, Bryan W; Matson, Cole W; Jung, Dawoon; Di Giulio, Richard T

    2010-08-15

    Exposure of developing fish to polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) results in a suite of defects including cardiac malformation, pericardial and yolk sac edema, craniofacial defects, and hemorrhaging. Several populations of Atlantic killifish or mummichog (Fundulus heteroclitus) on the Atlantic coast of the United States are resistant to the developmental and acute toxicity caused by PAHs and HAHs; this has made Fundulus a valuable model for studying aryl hydrocarbon sensitivity and adaptation. In order to further increase the utility of Fundulus, better understanding of the components of the molecular pathways governing aryl hydrocarbon response in Fundulus is required. The aryl hydrocarbon receptor (AHR) is known to mediate many of the toxic responses to PAHs and HAHs. A single AHR has been identified in mammals, but Fundulus has two AHRs and their relative roles are not clear. In the current study, translation-blocking and splice-junction morpholino gene knockdown was used to determine the roles of AHR1 and AHR2 in mediating cardiac teratogenesis induced by beta-naphthoflavone (BNF), benzo[k]fluoranthene (BkF), and 3,3',4,4',5-pentachlorobiphenyl (PCB-126). Here we report that AHR2 and not AHR1 knockdown resulted in rescue of teratogenicity induced by BNF, BkF, and PCB-126. These data demonstrate that AHR2 is the primary mediator of cardiac teratogenesis caused by multiple aryl hydrocarbons in Fundulus and suggest that suppression of the AHR pathway through modulation of AHR2 is a plausible mechanism for PAH resistance in adapted fish. Additionally, this is the first reported use of splice-junction morpholinos in Fundulus.

  2. Progesterone, as well as 17β-estradiol, is important for regulating AHR battery homoeostasis in the rat uterus.

    PubMed

    Rataj, Felicitas; Möller, Frank Josef; Jähne, Maria; Hönscheid, Pia; Zierau, Oliver; Vollmer, Günter; Kretzschmar, Georg

    2015-03-01

    Several studies indicate that the aryl hydrocarbon receptor (AHR), which plays an important role in mediating the toxicity of many industrial chemicals, plays an important role in the physiology of female reproductive tract organs. This makes it likely that the AHR and additional components of the AHR signalling pathway are under the control of female sex steroids. In a previous study, we could already demonstrate the regulation of many members of the AHR battery by 17β-estradiol (E2) in the uterus of rats. In this study, we addressed the potential role of progesterone (P4) in this context. In a comparative approach using ovariectomized rats which were treated for 3 days with either vehicle control, E2, progesterone (P4) or the combination of both hormones in addition to sham-operated animals, we could demonstrate that in addition to E2, P4 is also an important factor in regulating AHR signalling in the rat uterus. P4 has effects similar to E2 on uterine Ahr, Arnt and Arnt2 mRNA levels, resulting in a downregulation of these genes, while the E2-mediated downregulation of key AHR response genes Cyp1a1, Gsta2 and Ugt1 is completely antagonized by P4. As with E2, P4 leads to an increase in uterine AHR levels, especially in the endometrial epithelium despite the decrease in corresponding mRNA levels. This indicates a complex gene-specific regulatory network involving E2, P4 and possibly AHR itself to maintain all components of the AHR signalling cascade at the required levels during all stages of the oestrous cycle and pregnancy.

  3. In vivo characterization of an AHR-dependent long non-coding RNA required for proper Sox9b expression.

    PubMed

    Garcia, Gloria R; Goodale, Britton C; Wiley, Michelle W; La Du, Jane K; Hendrix, David A; Tanguay, Robert L

    2017-04-06

    Xenobiotic activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the proper formation of craniofacial cartilage and the heart in developing zebrafish. Downstream molecular targets responsible for AHR-dependent adverse effects remain largely unknown; however, in zebrafish sox9b has been identified as one of the most reduced transcripts in several target organs and is hypothesized to have a causal role in TCDD-induced toxicity. The reduction of sox9b expression in TCDD-exposed zebrafish embryos has been shown to contribute to heart and jaw malformation phenotypes. The mechanisms by which AHR2 (functional ortholog of mammalian AHR) activation leads to reduced sox9b expression levels and subsequent target organ toxicity are unknown. We have identified a novel long non-coding RNA (slincR) that is upregulated by strong AHR ligands and is located adjacent to the sox9b gene. We hypothesize that slincR is regulated by AHR2 and transcriptionally represses sox9b. The slincR transcript functions as an RNA macromolecule, and slincR expression is AHR2-dependent. Antisense knockdown of slincR results in an increase in sox9b expression during both normal development and AHR2 activation, which suggests a relief in repression. During development, slincR was expressed in tissues with sox9 essential functions, including the jaw/snout region, otic vesicle, eye, and brain. Reducing the levels of slincR resulted in altered neurological and/or locomotor behavioral responses. Our results place slincR as an intermediate between AHR2 activation and the reduction of sox9b mRNA in the AHR2 signaling pathway.

  4. 75 FR 49550 - Fifth Meeting: RTCA Special Committee 219: Attitude and Heading Reference System (AHRS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... Federal Aviation Administration Fifth Meeting: RTCA Special Committee 219: Attitude and Heading Reference...: Notice of RTCA Special Committee 219: Attitude and Heading Reference System (AHRS). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of ] RTCA Special Committee 219: Attitude...

  5. RELATIONSHIPS BETWEEN RESIDUES OF AHR AGONISTS IN FISH AND CONCENTRATIONS IN WATER AND SEDIMENTS

    EPA Science Inventory

    Relationships between Residues of AhR Agonists in Fish and Concentrations in Water and Sediment. Cook, PM*, Burkhard, LP, Mount, DR, US-EPA, NHEERL, MED, Duluth, MN. The bioaccumulation visualization approach of Burkhard et al. (2002) can be effectively used to describe the bioa...

  6. EXPRESSION OF AHR AND ARNT MRNA IN CULTURED HUMAN ENDOMETRIAL EXPLANTS EXPOSED TO TCDD

    EPA Science Inventory

    Expression of AhR and ARNT mRNA in cultured human endometrial explants exposed to TCDD.

    Pitt JA, Feng L, Abbott BD, Schmid J, Batt RE, Costich TG, Koury ST, Bofinger DP.

    Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA.

    Endom...

  7. Intersection of AHR and Wnt Signaling in Development, Health, and Disease

    PubMed Central

    Schneider, Andrew J.; Branam, Amanda M.; Peterson, Richard E.

    2014-01-01

    The AHR (aryl hydrocarbon receptor) and Wnt (wingless-related MMTV integration site) signaling pathways have been conserved throughout evolution. Appropriately regulated signaling through each pathway is necessary for normal development and health, while dysregulation can lead to developmental defects and disease. Though both pathways have been vigorously studied, there is relatively little research exploring the possibility of crosstalk between these pathways. In this review, we provide a brief background on (1) the roles of both AHR and Wnt signaling in development and disease, and (2) the molecular mechanisms that characterize activation of each pathway. We also discuss the need for careful and complete experimental evaluation of each pathway and describe existing research that explores the intersection of AHR and Wnt signaling. Lastly, to illustrate in detail the intersection of AHR and Wnt signaling, we summarize our recent findings which show that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced disruption of Wnt signaling impairs fetal prostate development. PMID:25286307

  8. Building HR capability in health care organizations.

    PubMed

    Khatri, Naresh

    2006-01-01

    The current human resource (HR) management practices in health care are consistent with the industrial model of management. However, health care organizations are not factories. They are highly knowledge-intensive and service-oriented entities and thus require a different set of HR practices and systems to support them. Drawing from the resource-based theory, I argue that HRs are a potent weapon of competitive advantage for health care organizations and propose a five-dimensional conception of HR capability for harnessing HRs in health care organizations. The significant complementarities that exist between HRs and information technologies for delivering safer and better quality of patient care are also discussed.

  9. The genome-wide transcriptional response to neonatal hyperoxia identifies Ahr as a key regulator

    PubMed Central

    Bhattacharya, Soumyaroop; Zhou, Zhongyang; Yee, Min; Chu, Chin-Yi; Lopez, Ashley M.; Lunger, Valerie A.; Solleti, Siva Kumar; Resseguie, Emily; Buczynski, Bradley; O'Reilly, Michael A.

    2014-01-01

    Premature infants requiring supplemental oxygen are at increased risk for developing bronchopulmonary dysplasia (BPD). Rodent models involving neonatal exposure to excessive oxygen concentrations (hyperoxia) have helped to identify mechanisms of BPD-associated pathology. Genome-wide assessments of the effects of hyperoxia in neonatal mouse lungs could identify novel BPD-related genes and pathways. Newborn C57BL/6 mice were exposed to 100% oxygen for 10 days, and whole lung tissue RNA was used for high-throughput, sequencing-based transcriptomic analysis (RNA-Seq). Significance Analysis of Microarrays and Ingenuity Pathway Analysis were used to identify genes and pathways affected. Expression patterns for selected genes were validated by qPCR. Mechanistic relationships between genes were further tested in cultured mouse lung epithelial cells. We identified 300 genes significantly and substantially affected following acute neonatal hyperoxia. Canonical pathways dysregulated in hyperoxia lungs included nuclear fctor (erythryoid-derived-2)-like 2-mediated oxidative stress signaling, p53 signaling, eNOS signaling, and aryl hydrocarbon receptor (Ahr) pathways. Cluster analysis identified Ccnd1, Cdkn1a, and Ahr as critical regulatory nodes in the response to hyperoxia, with Ahr serving as the major effector node. A mechanistic role for Ahr was assessed in lung epithelial cells, and we confirmed its ability to regulate the expression of multiple hyperoxia markers, including Cdkn1a, Pdgfrb, and A2m. We conclude that a global assessment of gene regulation in the acute neonatal hyperoxia model of BPD-like pathology has identified Ahr as one driver of gene dysregulation. PMID:25150061

  10. AHR2 morpholino knockdown reduces the toxicity of total particulate matter to zebrafish embryos.

    PubMed

    Massarsky, Andrey; Bone, Audrey J; Dong, Wu; Hinton, David E; Prasad, G L; Di Giulio, Richard T

    2016-10-15

    The zebrafish embryo has been proposed as a 'bridge model' to study the effects of cigarette smoke on early development. Previous studies showed that exposure to total particulate matter (TPM) led to adverse effects in developing zebrafish, and suggested that the antioxidant and aryl hydrocarbon receptor (AHR) pathways play important roles. This study investigated the roles of these two pathways in mediating TPM toxicity. The study consisted of four experiments. In experiment I, zebrafish embryos were exposed from 6h post fertilization (hpf) until 96hpf to TPM0.5 and TPM1.0 (corresponding to 0.5 and 1.0μg/mL equi-nicotine units) in the presence or absence of an antioxidant (N-acetyl cysteine/NAC) or a pro-oxidant (buthionine sulfoximine/BSO). In experiment II, TPM exposures were performed in embryos that were microinjected with nuclear factor erythroid 2-related factor 2 (Nrf2), AHR2, cytochrome P450 1A (CYP1A), or CYP1B1 morpholinos, and deformities were assessed. In experiment III, embryos were exposed to TPM, and embryos/larvae were collected at 24, 48, 72, and 96hpf to assess several genes associated with the antioxidant and AHR pathways. Lastly, experiment IV assessed the activity and protein levels of CYP1A and CYP1B1 after exposure to TPM. We demonstrate that the incidence of TPM-induced deformities was generally not affected by NAC/BSO treatments or Nrf2 knockdown. In contrast, AHR2 knockdown reduced, while CYP1A or CYP1B1 knockdowns elevated the incidence of some deformities. Moreover, as shown by gene expression the AHR pathway, but not the antioxidant pathway, was induced in response to TPM exposure, providing further evidence for its importance in mediating TPM toxicity.

  11. HR8844: a new hot Am star?

    NASA Astrophysics Data System (ADS)

    Monier, R.; Gebran, M.; Royer, F.

    2016-12-01

    Using one archival high dispersion high quality spectrum of HR8844 (A0V) obtained with the echelle spectrograph SOPHIE at Observatoire de Haute Provence, we show that this star is not a superficially normal A0V star as hitherto thought. The model atmosphere and spectrum synthesis modeling of the spectrum of HR8844 reveals large departures of its abundances from the solar composition. We report here on our first determinations of the elemental abundances of 41 elements in the atmosphere of HR8844. Most of the light elements are underabundant whereas the very heavy elements are overabundant in HR8844. This interesting new chemically peculiar star could be a hybrid object between the HgMn stars and the Am stars.

  12. Alternative in vitro approach for assessing AHR-mediated CYP1A induction by dioxins in wild cormorant (Phalacrocorax carbo) population.

    PubMed

    Thuruthippallil, Leena Mol; Kubota, Akira; Kim, Eun-Young; Iwata, Hisato

    2013-06-18

    Our line of papers revealed that the common (great) cormorant (Phalacrocorax carbo) possesses two isoforms of the aryl hydrocarbon receptor (ccAHR1 and ccAHR2). This paper addresses in vitro tests of the ccAHR signaling pathways to solve two questions: (1) whether there are functional differences in the two ccAHR isoforms, and (2) whether a molecular perturbation, cytochrome P450 1A (ccCYP1A) induction, in the population-level can be predicted from the in vitro tests. The transactivation potencies mediated by ccAHR1 and ccAHR2 were measured in COS-7 cells treated with 15 selected dioxins and related compounds (DRCs), where ccAHR1 or ccAHR2 expression plasmid and ccCYP1A5 promoter/enhancer-linked luciferase reporter plasmid were transfected. For congeners that exhibited dose-dependent luciferase activities, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) and induction equivalency factors (IEFs) were estimated. ccAHR1-IEF profile was similar to WHO avian TCDD toxic equivalency factor (TEF) profile except for dioxin-like polychlorinated biphenyls that showed lower IEFs in ccAHR1-driven reporter assay. ccAHR2-IEF profile was different from WHO TEFs and ccAHR1-IEFs. Notably, 2,3,4,7,8-PeCDF was more potent than TCDD for ccAHR2-mediated response. Using ccAHR1- and ccAHR2-IEFs and hepatic DRC concentrations in the Lake Biwa cormorant population, total TCDD induction equivalents (IEQs) were calculated for each ccAHR-mediated response. Nonlinear regression analyses provided significant sigmoidal relationships of ccAHR1- and ccAHR2-derived IEQs with hepatic ccCYP1A5 mRNA levels, supporting the results of in vitro ccAHR-mediated TCDD dose-response curves. Collectively, our in vitro AHR reporter assay potentially could be an alternative to molecular epidemiology of the species of concern regarding CYP1A induction by AHR ligands.

  13. The aryl hydrocarbon receptor (AhR) pathway as a regulatory pathway for cell adhesion and matrix metabolism

    PubMed Central

    Kung, Tiffany; Murphy, K.A.; White, L.A.

    2009-01-01

    The aryl hydrocarbon receptor (AhR) is an orphan receptor in the basic-helix-loop-helix PAS family of transcriptional regulators. Although the endogenous regulator of this pathway has not been identified, the AhR is known to bind and be activated by a variety of compounds ranging from environmental contaminants to flavanoids. The function of this receptor is still unclear; however, animal models indicate that the AhR is important for normal development. One hypothesis is that the AhR senses cellular stress and initiates the cellular response by altering gene expression and inhibiting cell cycle progression and that activation of the AhR by exogenous environmental chemicals results in the dysregulation of this normal function. In this review we will examine the role of the AhR in the regulation of genes and proteins involved in cell adhesion and matrix remodeling, and discuss the implications of these changes in development and disease. In addition, we will discuss evidence suggesting that the AhR pathway is responsive to changes in matrix composition as well as cell-cell and cell-matrix interactions. PMID:18940186

  14. DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells.

    PubMed

    Gaspar-Ramírez, Octavio; Pérez-Vázquez, Francisco J; Salgado-Bustamante, Mariana; González-Amaro, Roberto; Hernandez-Castro, Berenice; Pérez-Maldonado, Ivan N

    2015-01-01

    Recent studies have demonstrated that compounds inducing pro-inflammatory cytokines enhance AhR expression. The aim of this study was 2-fold: (1) to determine if two pro-inflammatory compounds, dichlorodiphenyldichloroethylene (DDE) and 2,2',4,4',5,5'-hexa-chlorobiphenyl (PCB 153), independently affect AhR gene expression in peripheral blood mononuclear cells (PBMC); and (2) if affected, to determine whether the mechanism involved was due to AhR activation or to a pro-inflammatory effect of the chemicals. PBMC isolated from healthy individuals were incubated in the presence of DDE (10 µg/ml) and PCB 153 (20 ng/ml) over time and AhR and CYP1A1 expression was assessed with a real-time PCR technique. The results indicated there was over-expression of the AhR mRNA in PBMC when the cells were treated with DDE and PCB 153. No changes in expression levels of CYP1A1 mRNA were found. Importantly, when the cells were exposed to DDE and PCB 153 in the presence of an antagonist of tumor necrosis factor (TNF)-α, the over-expression of AhR was abolished; as expected, the expression of CYP1A1 was unaffected. In conclusion, these studies demonstrated for the first time an increment of AhR expression "in vitro" in PBMC treated with two pro-inflammatory environmental pollutants, DDE and PCB153. Moreover, the over-expression of AhR was dependent of TNFα induced by DDE and PCB 153 and was independent of AhR activation.

  15. AIP mutations impair AhR signaling in pituitary adenoma patients fibroblasts and in GH3 cells.

    PubMed

    Lecoq, Anne-Lise; Viengchareun, Say; Hage, Mirella; Bouligand, Jérôme; Young, Jacques; Boutron, Audrey; Zizzari, Philippe; Lombès, Marc; Chanson, Philippe; Kamenický, Peter

    2016-05-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas through unknown molecular mechanisms. The best-known interacting partner of AIP is the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the effects of xenobiotics implicated in carcinogenesis. As 75% of AIP mutations disrupt the physical and/or functional interaction with AhR, we postulated that the tumorigenic potential of AIP mutations might result from altered AhR signaling. We evaluated the impact of AIP mutations on the AhR signaling pathway, first in fibroblasts from AIP-mutated patients with pituitary adenomas, by comparison with fibroblasts from healthy subjects, then in transfected pituitary GH3 cells. The AIP protein level in mutated fibroblasts was about half of that in cells from healthy subjects, but AhR expression was unaffected. Gene expression analyses showed significant modifications in the expression of the AhR target genes CYP1B1 and AHRR in AIP-mutated fibroblasts, both before and after stimulation with the endogenous AhR ligand kynurenine. Kynurenine increased Cyp1b1 expression to a greater extent in GH3 cells overexpressing wild type compared with cells expressing mutant AIP Knockdown of endogenous Aip in these cells attenuated Cyp1b1 induction by the AhR ligand. Both mutant AIP expression and knockdown of endogenous Aip affected the kynurenine-dependent GH secretion of GH3 cells. This study of human fibroblasts bearing endogenous heterozygous AIP mutations and transfected pituitary GH3 cells shows that AIP mutations affect the AIP protein level and alter AhR transcriptional activity in a gene- and tissue-dependent manner.

  16. A binding site for activation by the Bacillus subtilis AhrC protein, a repressor/activator of arginine metabolism.

    PubMed

    Klingel, U; Miller, C M; North, A K; Stockley, P G; Baumberg, S

    1995-08-21

    In Bacillus subtilis, the AhrC protein represses genes encoding enzymes of arginine biosynthesis and activates those mediating its catabolism. To determine how this repressor also functions as an activator, we attempted to clone catabolic genes by searching for insertions of the Tn917-lacZ transposon that express AhrC-dependent, arginine-inducible beta-galactosidase activity. One such isolate was obtained. The region upstream of lacZ was subcloned in Escherichia coli in such a way that it could be replaced in the B. subtilis chromosome after appropriate manipulation. Analysis of exonuclease III-derived deletions located an AhrC-dependent, arginine-inducible promoter to within a ca. 1.9 kb fragment. The sequence revealed: the 3' end of an ORF homologous to gdh genes encoding glutamate dehydrogenase, with highest homology to the homologue from Clostridium difficile; the 5' end of an ORF homologous to a Saccharomyces cerevisiae gene encoding delta 1-pyrroline 5-carboxylate dehydrogenase (P5CDH), an enzyme of arginine catabolism; and just upstream of the latter, a sequence with homology to known AhrC binding sites in the upstream part of the biosynthetic argCJBD-cpa-F cluster. The same region has also been sequenced by others as part of the B. subtilis genome sequencing project, revealing that the P5CDH gene is the first in a cluster termed rocABC. Restriction fragments containing the putative AhrC-binding sequence, but not those lacking it, showed retarded electrophoretic mobility in the presence of purified AhrC. A 277 bp AhrC-binding fragment also showed anomalous mobility in the absence of AhrC, consistent with its being intrinsically bent. DNAse I footprinting localized AhrC binding to bp -16/-22 to +1 (the transcription startpoint). Such a location for an activator binding site, i.e. overlapping the transcription start, is unusual.

  17. Cancer-promoting and Inhibiting Effects of Dietary Compounds: Role of the Aryl Hydrocarbon Receptor (AhR)

    PubMed Central

    Powell, Joann B.; Ghotbaddini, Maryam

    2014-01-01

    Polyaromatic hydrocarbons, heterocyclic aromatic amines and dioxin-like compounds are environmental carcinogens shown to initiate cancer in a number of tissue types including prostate and breast. These environmental carcinogens elicit their effects through interacting with the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. Naturally occurring compounds found in fruits and vegetables shown to have anti-carcinogenic effects also interact with the AhR. This review explores dietary and environmental exposure to chemical carcinogens and beneficial natural compounds whose effects are elicited by the AhR. PMID:25258701

  18. Characterization testing of a 40 AHR bipolar nickel-hydrogen battery

    NASA Technical Reports Server (NTRS)

    Brewer, Jeffrey C.; Manzo, Michelle A.; Gemeiner, Russel P.

    1989-01-01

    Extensive characterization testing has been done on a second 40 amp-hour (Ahr), 10-cell bipolar nickel-hydrogen (Ni-H2) battery to study the effects of such operating parameters as charge and discharge rates, temperature, and pressure, on capacity, Ahr and watt-hour (Whr) efficiencies, end-of-charge (EOC) and mid-point discharge voltages. Testing to date has produced many interesting results, with the battery performing well throughout all of the test matrix except during the high-rate (5C and 10C) discharges, where poorer than expected results were observed. The exact cause of this poor performance is, as yet, unknown. Small scale 2 x 2 inch battery tests are to be used in studying this problem. Low earth orbit (LEO) cycle life testing at a 40 percent depth of discharge (DOD) and 10 C is scheduled to follow the characterization testing.

  19. Binarity of the LBV HR Car

    NASA Astrophysics Data System (ADS)

    Rivinius, Th.; Boffin, H. M. J.; de Wit, W. J.; Mehner, A.; Martayan, Ch.; Guieu, S.; Le Bouquin, J.-B.

    2015-01-01

    VLTI/AMBER and VLTI/PIONIER observations of the LBV HR Car show an interferometric signature that could not possibly be explained by an extended wind, more or less symmetrically distributed around a single object. Instead, observations both in the Brγ line and the H-band continuum are best explained by two point sources (or alternatively one point source and one slightly extended source) at about 2 mas separation and a contrast ratio of about 1:5. These observations establish that HR Car is a binary, but further interpretation will only be possible with future observations to constrain the orbit. Under the assumption that the current separation is close to the maximum one, the orbital period can be estimated to be of the order of 5 years, similar as in the η Car system. This would make HR Car the second such LBV binary.

  20. Acromegaly Is More Severe in Patients With AHR or AIP Gene Variants Living in Highly Polluted Areas.

    PubMed

    Cannavo, S; Ragonese, M; Puglisi, S; Romeo, P D; Torre, M L; Alibrandi, A; Scaroni, C; Occhi, G; Ceccato, F; Regazzo, D; De Menis, E; Sartorato, P; Arnaldi, G; Trementino, L; Trimarchi, F; Ferrau, F

    2016-04-01

    In this multicentric study, we aimed to correlate the occurrence of AHR and/or AIP. genes variants in acromegalic patients with the disease severity and/or with the response to somatostatin analogs (SSa) treatment, according to pollution exposition.

  1. A novel AhR ligand, 2AI, protects the retina from environmental stress

    PubMed Central

    Gutierrez, Mark A.; Davis, Sonnet S.; Rosko, Andrew; Nguyen, Steven M.; Mitchell, Kylie P.; Mateen, Samiha; Neves, Joana; Garcia, Thelma Y.; Mooney, Shaun; Perdew, Gary H.; Hubbard, Troy D.; Lamba, Deepak A.; Ramanathan, Arvind

    2016-01-01

    Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2′-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice. PMID:27364765

  2. The thymus of the hairless rhino-j (hr/hr-j) mice

    PubMed Central

    SAN JOSE, I.; GARCÍA-SUÁREZ, O.; HANNESTAD, J.; CABO, R.; GAUNA, L.; REPRESA, J.; VEGA, J. A.

    2001-01-01

    The hairless (hr) gene is expressed in a large number of tissues, primarily the skin, and a mutation in the hr gene is responsible for the typical cutaneous phenotype of hairless mice. Mutant hr mouse strains show immune defects involving especially T cells and macrophages, as well as an age-related immunodeficiency and an accelerated atrophy of the thymus. These data suggest that the hr mutation causes a defect of this organ, although hr transcripts have not been detected in fetal or adult mice thymus. The present study analyses the thymus of young (3 mo) and adult (9 mo) homozygous hr-rh-j mice (a strain of hairless mice) by means of structural techniques and immunohistochemistry to selectively identify thymic epithelial cells, dendritic cells, and macrophages. There were structural alterations in the thymus of both young and adult rh-rh-j mice, which were more severe in older animals. These alterations consisted of relative cortical atrophy, enlargement of blood vessels, proliferation of perivascular connective tissue, and the appearance of cysts. hr-rh-j mice also showed a decrease in the number of epithelial and dendritic cells, and macrophages. Taken together, present results strongly suggest degeneration and accelerated age-dependent regression of the thymus in hr-rh-j mice, which could explain at least in part the immune defects reported in hairless mouse strains. PMID:11327202

  3. An Assessment of Technical and Production Risks of Candidate Low-Cost Attitude/Heading Reference Systems(AHRS)

    NASA Technical Reports Server (NTRS)

    Yuchnovicz, Daniel; Burgess, Malcolm; Hammers, William

    1999-01-01

    This report provides an assessment of technical and production risks of candidate low-cost attitude/heading reference systems (AHRS) for use in the Advanced General Aviation Transport Experiments (AGATE) airplanes. A low-cost AHRS is a key component of modem "glass cockpit" flight displays for General Aviation (GA) aircraft. The technical capabilities of several candidate low-cost AHRS were examined and described along with the technical issues involved with using all solid-state components for attitude measurement. An economic model was developed which describes the expected profit, rate of return, and volume requirements for the manufacture of low-cost AHRS for GA aircraft in the 2000 to 2020 time frame. The model is the result of interviews with GA airframe manufacturers, avionics manufacturers and historical analysis of avionics of similar complexity. The model shows that a manufacturer will break even after three years of AHRS production, realizing an 18 percent rate of return (23 percent profit) on an investment of $3.5M over the 20 year period. A start-up production estimate showed costs of $6-12M for a new company to build and certify an AHRS from scratch, considered to be a high-risk proposition, versus $0.25-0.75M for an experienced avionics manufacturer to manufacture a design under license, a low-risk proposition.

  4. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity

    PubMed Central

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-01-01

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity. PMID:27068235

  5. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity.

    PubMed

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-04-12

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity.

  6. Matching Effective HR Practices with Competitive Strategy.

    ERIC Educational Resources Information Center

    Schuler, Randall S.; And Others

    1987-01-01

    Examines links between three competitive strategies (cost reduction, quality improvement, and innovation) and human resources (HR) practices. Describes a framework for ensuring that the two are made compatible and illustrates the process by showing how one $20 million business wrestled with these compatibility issues. (CH)

  7. AhR activation underlies the CYP1A autoinduction by A-998679 in rats

    PubMed Central

    Liguori, Michael J.; Lee, Chih-Hung; Liu, Hong; Ciurlionis, Rita; Ditewig, Amy C.; Doktor, Stella; Andracki, Mark E.; Gagne, Gerard D.; Waring, Jeffrey F.; Marsh, Kennan C.; Gopalakrishnan, Murali; Blomme, Eric A. G.; Yang, Yi

    2012-01-01

    Xenobiotic-mediated induction of cytochrome P450 (CYP) drug metabolizing enzymes (DMEs) is frequently encountered in drug discovery and can influence disposition, pharmacokinetic, and toxicity profiles. The CYP1A subfamily of DMEs plays a central role in the biotransformation of several drugs and environmental chemicals. Autoinduction of drugs through CYP3A enzymes is a common mechanism for their enhanced clearance. However, autoinduction via CYP1A is encountered less frequently. In this report, an experimental compound, A-998679 [3-(5-pyridin-3-yl-1,2,4-oxadiazol-3-yl) benzonitrile], was shown to enhance its own clearance via induction of Cyp1a1 and Cyp1a2. Rats were dosed for 5 days with 30, 100, and 200 mg/kg/day A-998679. During the dosing period, the compound's plasma AUC decreased at 30 mg/kg (95%) and 100 mg/kg (80%). Gene expression analysis and immunohistochemistry of the livers showed a large increase in the mRNA and protein levels of Cyp1a, which was involved in the biotransformation of A-998679. Induction of CYP1A was confirmed in primary rat, human, and dog hepatocytes. The compound also weakly inhibited CYP1A2 in human liver microsomes. A-998679 activated the aryl hydrocarbon receptor (AhR) in a luciferase gene reporter assay in HepG2 cells, upregulated expression of genes associated with AhR activation in rat liver and enhanced nuclear migration of AhR in HepG2 cells. Collectively these results demonstrate that A-998679 is an AhR activator that induces Cyp1a1 and Cyp1a2 expression, resulting in an autoinduction phenomenon. The unique properties of A-998679, along with its novel structure distinct from classical polycyclic aromatic hydrocarbons (PAHs), may warrant its further evaluation as a tool compound for use in studies involving AhR biology and CYP1A-related mechanisms of drug metabolism and toxicity. PMID:23112805

  8. Functionality of aryl hydrocarbon receptors (AhR1 and AhR2) of white sturgeon (Acipenser transmontanus) and implications for the risk assessment of dioxin-like compounds.

    PubMed

    Doering, Jon A; Farmahin, Reza; Wiseman, Steve; Kennedy, Sean W; Giesy, John P; Hecker, Markus

    2014-07-15

    Worldwide, populations of sturgeons are endangered, and it is hypothesized that anthropogenic chemicals, including dioxin-like compounds (DLCs), might be contributing to the observed declines in populations. DLCs elicit their toxic action through activation of the aryl hydrocarbon receptor (AhR), which is believed to regulate most, if not all, adverse effects associated with exposure to these chemicals. Currently, risk assessment of DLCs in fishes uses toxic equivalency factors (TEFs) developed for the World Health Organization (WHO) that are based on studies of embryo-lethality with salmonids. However, there is a lack of knowledge of the sensitivity of sturgeons to DLCs, and it is uncertain whether TEFs developed by the WHO are protective of these fishes. Sturgeons are evolutionarily distinct from salmonids, and the AhRs of sturgeons differ from those of salmonids. Therefore, this study investigated the sensitivity of white sturgeon (Acipenser transmontanus) to DLCs in vitro via the use of luciferase reporter gene assays using COS-7 cells transfected with AhR1 or AhR2 of white sturgeon. Specifically, activation and relative potencies (RePs) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachloro-dibenzofuran, 2,3,7,8-tetrachloro-dibenzofuran, 3,3',4,4',5-pentachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, and 2,3,3',4,4'-pentachlorobiphenyl were determined for each AhR. It was demonstrated that white sturgeon expresses AhR1s and AhR2s that are both activated by DLCs with EC50 values for 2,3,7,8-TCDD that are lower than those of any other AhR of vertebrates tested to date. Both AhRs of white sturgeon had RePs for polychlorinated dibenzofurans more similar to TEFs for birds, while RePs for polychlorinated biphenyls were most similar to TEFs for fishes. Measured concentrations of select DLCs in tissues of white sturgeon from British Columbia, Canada, were used to calculate toxic equivalents (TEQs) by use of TEFs for fishes used by the WHO and TCDD

  9. NcoA2-Dependent Inhibition of HIF-1α Activation Is Regulated via AhR.

    PubMed

    Tsai, Chi-Hao; Li, Ching-Hao; Liao, Po-Lin; Cheng, Yu-Wen; Lin, Cheng-Hui; Huang, Shih-Hsuan; Kang, Jaw-Jou

    2015-12-01

    High endogenous levels of aryl hydrocarbon receptor (AhR) contribute to hypoxia signaling pathway inhibition following exposure to the potent AhR ligand benzo[a]pyrene (B[a]P) and could alter cellular homeostasis and disease condition. Increasing evidence indicates that AhR might compete with AhR nuclear translocator (ARNT) for complex formation with hypoxia-inducible factor-1α (HIF-1α) for transactivation, which could alter several physiological variables. Nuclear receptor coactivator 2 (NcoA2) is a transcription coactivator that regulates transcription factor activation and inhibition of basic helix-loop-helix Per (Period)-ARNT-SIM (single-minded) (bHLH-PAS) family proteins, such as HIF-1α, ARNT, and AhR, through protein-protein interactions. In this study, we demonstrated that both hypoxia and hypoxia-mimic conditions decreased NcoA2 protein expression in HEK293T cells. Hypoxia response element (HRE) and xenobiotic-responsive element (XRE) transactivation also were downregulated with NcoA2 knockdown under hypoxic conditions. In addition, B[a]P significantly decreased NcoA2 protein expression be accompanied with AhR degradation. We next evaluated whether the absence of AhR could affect NcoA2 protein function under hypoxia-mimetic conditions. NcoA2 and HIF-1α nuclear localization decreased in both B[a]P-pretreated and AhR-knockdown HepG2 cells under hypoxia-mimic conditions. Interestingly, NcoA2 overexpression downregulated HRE transactivation by competing with HIF-1α and AhR to form protein complexes with ARNT. Both NcoA2 knockdown and overexpression inhibited endothelial cell tube formation in vitro. We also demonstrated using the in vivo plug assay that NcoA2-regulated vascularization decreased in mice. Taken together, these results revealed a biphasic role of NcoA2 between AhR and hypoxic conditions, thus providing a novel mechanism underlying the cross talk between AhR and hypoxia that affects disease development and progression.

  10. Classification of ischaemic episodes with ST/HR diagrams.

    PubMed

    Faganeli Pucer, Jana; Demšar, Janez; Kukar, Matjaž

    2012-01-01

    Coronary artery disease is the developed world's premier cause of mortality and the most probable cause of myocardial ischaemia. More advanced diagnostic tests aside, in electrocardiogram (ECG) analysis it manifests itself as a ST segment deviation, targeted by both exercise ECG and ambulatory ECG. In ambulatory ECG, besides ischaemic ST segment deviation episodes there are also non-ischaemic heart rate related episodes which aggravate real ischaemia detection. We present methods to transform the features developed for the heart rate adjustment of ST segment depression in exercise ECG for use in ambulatory ECG. We use annotations provided by the Long-Term ST Database to plot the ST/HR diagrams and then estimate the overall and maximal slopes of the diagrams in the exercise and recovery phase for each ST segment deviation episode. We also estimate the angle at the extrema of the ST/HR diagrams. Statistical analysis shows that ischaemic ST segment deviation episodes have significantly steeper overall and maximal slopes than heart rate related episodes, which indicates the explored features' utility for distinguishing between the two types of episodes. This makes the proposed features very useful in automated ECG analysis.

  11. THE DEBRIS DISK AROUND HR 8799

    SciTech Connect

    Su, K. Y. L.; Rieke, G. H.; Smith, P. S.; Misselt, K. A.; Stapelfeldt, K. R.; Bryden, G.; Moro-Martin, A.; Williams, J. P.

    2009-11-01

    We have obtained a full suite of Spitzer observations to characterize the debris disk around HR 8799 and to explore how its properties are related to the recently discovered set of three massive planets orbiting the star. We distinguish three components to the debris system: (1) warm dust (T approx 150 K) orbiting within the innermost planet; (2) a broad zone of cold dust (T approx 45 K) with a sharp inner edge orbiting just outside the outermost planet and presumably sculpted by it; and (3) a dramatic halo of small grains originating in the cold dust component. The high level of dynamical activity implied by this halo may arise due to enhanced gravitational stirring by the massive planets. The relatively young age of HR 8799 places it in an important early stage of development and may provide some help in understanding the interaction of planets and planetary debris, an important process in the evolution of our own solar system.

  12. HR 7275 - A new variable star

    NASA Technical Reports Server (NTRS)

    Fried, R. E.; Lovell, L. P.; Krisciunas, K.; Chamblis, C. R.; Detterline, P. K.; Landis, H. J.; Louth, H.; Eaton, J. A.; Hall, D. S.; Henry, G. W.

    1982-01-01

    Three years of photometry in V and B of the UBV system are presented to confirm the suspicion of Herbst (1973) that HR 7275 is a variable star. The photometry is used to derive the photometric period, which proves to be about 3% shorter than the spectroscopically determined optical period of 28.59 d. Total variation observed during the three years was 0.22 m in the V, and the light curve was always asymmetrical.

  13. Chiropractic Adjustment

    MedlinePlus

    ... structural alignment and improve your body's physical function. Low back pain, neck pain and headache are the most common ... treated. Chiropractic adjustment can be effective in treating low back pain, although much of the research done shows only ...

  14. Adjustment disorder

    MedlinePlus

    ... from other people Skipped heartbeats and other physical complaints Trembling or twitching To have adjustment disorder, you ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  15. Instability Regions in the Upper HR Diagram

    NASA Technical Reports Server (NTRS)

    deJager, Cornelis; Lobel, Alex; Nieuwenhuijzen, Hans; Stothers, Richard; Hansen, James E. (Technical Monitor)

    2001-01-01

    The following instability regions for blueward evolving supergiants are outlined and compared: (1) Areas in the Hertzsprung-Russell(HR) diagram where stars are dynamically unstable. (2) Areas where the effective acceleration in the upper part of the photospheres is negative, hence directed outward. (3) Areas where the sonic points of the stellar wind (Where wind velocity = sound velocity) are situated inside the photospheres, at a level deeper than tau(sub Ross) = 0.01. We compare the results with the positions of actual stars in the HR diagram and we find evidence that the recent strong contraction of the yellow hypergiant HR8752 was initiated in a period during which (g(sub eff)) is less than 0, whereupon the star became dynamically unstable. The instability and extreme shells around IRC+10420 are suggested to be related to three factors: (g(sub eff)) is less than 0; the sonic point is situated inside the photosphere; and the star is dynamically unstable.

  16. Nonthermal Radio Emission and the HR Diagram

    NASA Technical Reports Server (NTRS)

    Gibson, D. M.

    1985-01-01

    Perhaps the most reliable indicator of non-radiative heating/momentum in a stellar atmosphere is the presence of nonthermal radio emission. To date, 77 normal stellar objects have been detected and identified as nonthermal sources. These stellar objects are tabulated herein. It is apparent that non-thermal radio emission is not ubiquitous across the HR diagram. This is clearly the case for the single stars; it is not as clear for the binaries unless the radio emission is associated with their late-type components. Choosing to make this association, the single stars and the late-type components are plotted together. The following picture emerges: (1) there are four locations on the HR diagram where non-thermal radio stars are found; (2) the peak incoherent 5 GHz luminosities show a suprisingly small range for stars within each class; (3) the fraction of stellar energy that escapes as radio emission can be estimated by comparing the integrated maximum radio luminosity to the bolometric luminosity; (4) there are no apparent differences in L sub R between binaries with two cool components, binaries with one hot and one cool component, and single stars for classes C and D; and (5) The late-type stars (classes B, C, and D) are located in parts of the HR diagram where there is reason to suspect that the surfaces of the stars are being braked with respect to their interiors.

  17. Enabling quaternion derivatives: the generalized HR calculus

    PubMed Central

    Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C.; Mandic, Danilo P.

    2015-01-01

    Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis. PMID:26361555

  18. Enabling quaternion derivatives: the generalized HR calculus.

    PubMed

    Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C; Mandic, Danilo P

    2015-08-01

    Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis.

  19. Effects of scorched food leachates with or without activated charcoal pretreatment on AhR activation in cultured cells.

    PubMed

    Takahashi, Satoshi; Morita, Koji; Kinoshita, Makoto; Fujimori, Shin; Ishikawa, Toshio

    2015-12-01

    Aryl hydrocarbon receptor (AhR) is a transcription factor activated by xenobiotics, including dioxins and polycyclic aromatic hydrocarbons (PAHs). Although AhR is also activated by some dietary constituents, it has not been completely clarified in what circumstances AhR ligands are ingested in our daily life. Because PAHs are formed by the incomplete combustion of organic materials, we hypothesized that scorched foods might contain and leach out AhR ligands sufficient to stimulate AhR in vitro. To test this hypothesis, scorched foods (bread, cheese, etc.) were mixed vigorously with water, and the supernatants were retrieved as samples. The samples were added to HepG2 cells stably expressing an AhR-responsive reporter gene. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was analyzed by RT-PCR in different cell lines treated with the samples. We further tested whether pretreatment of the samples with activated charcoal would alter their AhR-stimulating activity. All the supernatant samples tested induced AhR-dependent reporter gene activity and CYP1A1 mRNA expression. In some samples, these inductions were inhibited by pretreatment with activated charcoal. Our findings indicate that scorched food leachates stimulate AhR in cultured cells and that activated charcoal adsorbs the AhR-stimulating substances in some leachates. Thus, people who habitually eat scorched foods are exposed to AhR ligands on a regular basis. Further studies are needed to elucidate whether burnt foods actually exert biological effects on our health.

  20. TCDD dysregulation of 13 AHR-target genes in rat liver

    SciTech Connect

    Watson, John D.; Prokopec, Stephenie D.; Smith, Ashley B.; Okey, Allan B.; Pohjanvirta, Raimo; Boutros, Paul C.

    2014-02-01

    Despite several decades of research, the complete mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been shown that the AHR is required for all major manifestations of toxicity, the specific downstream changes involved in the development of toxic phenotypes remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in many species and tissues. We profiled their hepatic mRNA abundances in two rat strains with very different sensitivities to TCDD: the TCDD-sensitive Long–Evans (Turku/AB; L–E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated doses ranging from 0 to 3000 μg/kg at 19 h after TCDD exposure and time points ranging from 1.5 to 384 h after exposure to 100 μg/kg TCDD. Twelve of 13 genes responded to TCDD in at least one strain, and seven of these showed statistically significant inter-strain differences in the time course analysis (Aldh3a1, Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr, Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as association with additional transcriptional modulators. Of the 12 genes that responded to TCDD during the dose–response analysis, none had an ED{sub 50} equivalent to that of Cyp1a1, the most sensitive gene in this study, while nine genes responded to doses at least 10–100 fold higher, in at least one strain (Ahrr (L–E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L–E), Inmt (both), Nfe2l2 (L–E), Nqo1 (L–E) and Tiparp (both)). These data shed new light on the association of the AHR target genes with TCDD toxicity, and in particular the seven genes exhibiting strain-specific differences represent strong candidate mediators of Type-II toxicities. - Highlights: • NanoString measured hepatic mRNA molecules

  1. Cytochrome P450s in human immune cells regulate IL-22 and c-Kit via an AHR feedback loop

    PubMed Central

    Effner, Renate; Hiller, Julia; Eyerich, Stefanie; Traidl-Hoffmann, Claudia; Brockow, Knut; Triggiani, Massimo; Behrendt, Heidrun; Schmidt-Weber, Carsten B.; Buters, Jeroen T. M.

    2017-01-01

    The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AHR) has immune-modulating functions and responds to small molecules. Cytochrome P4501 enzymes (CYP1) act downstream of the AHR and metabolize small molecules. However, it is currently unknown whether CYP1 activity is relevant for immune modulation. We studied the interdependence of CYP1 and AHR in human primary immune cells using pharmacological methods. CYP1 inhibition increased the expression levels of the stem cell factor receptor (c-Kit) and interleukin (IL)-22 but decreased IL-17. Single cell analyses showed that CYP1 inhibition especially promoted CD4+ helper T (Th) cells that co-express c-Kit and IL-22 simultaneously. The addition of an AHR antagonist reversed all these effects. In addition to T cells, we screened other human immune cells for CYP and found cell-specific fingerprints, suggesting that similar mechanisms are present in multiple immune cells. We describe a feedback loop yet unknown in human immune cells where CYP1 inhibition resulted in an altered AHR-dependent immune response. This mechanism relates CYP1-dependent metabolism of environmental small molecules to human immunity. PMID:28276465

  2. NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice.

    PubMed

    Long, Xiaoru; Xie, Jun; Zhao, Keting; Li, Wei; Tang, Wei; Chen, Sisi; Zang, Na; Ren, Luo; Deng, Yu; Xie, Xiaohong; Wang, Lijia; Fu, Zhou; Liu, Enmei

    2016-10-01

    RSV can lead to persistent airway inflammation and AHR and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. There are high numbers of NK cells in the lung, which not only play important roles in the acute stage of RSV infection, but also are pivotal in regulating the pathogenesis of asthma. Therefore, in this study, we assumed that NK cells might contribute to persistent airway disease during the later stage of RSV infection. Mice were killed at serial time points after RSV infection to collect samples. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, lung histopathology was examined, and airway hyperresponsiveness (AHR) was measured by whole-body plethysmography. Cytokines were detected by ELISA, and NK cells were determined by flow cytometry. Rabbit anti-mouse asialo-GM-1 antibodies and resveratrol were used to deplete or suppress NK cells. Inflammatory cells in BALF, lung tissue damage and AHR were persistent for 60 days post-RSV infection. Type 2 cytokines and NK cells were significantly increased during the later stage of infection. When NK cells were decreased by the antibodies or resveratrol, type 2 cytokines, the persistent airway inflammation and AHR were all markedly reduced. NK cells can contribute to the RSV-associated persistent airway inflammation and AHR at least partially by promoting type 2 cytokines. Therefore, therapeutic targeting of NK cells may provide a novel approach to alleviating the recurrent wheezing subsequent to RSV infection.

  3. Deletion of Aryl Hydrocarbon Receptor AHR in Mice Leads to Subretinal Accumulation of Microglia and RPE Atrophy

    PubMed Central

    Kim, Soo-Young; Yang, Hyun-Jin; Chang, Yi-Sheng; Kim, Jung-Woong; Brooks, Matthew; Chew, Emily Y.; Wong, Wai T.; Fariss, Robert N.; Rachel, Rivka A.; Cogliati, Tiziana; Qian, Haohua; Swaroop, Anand

    2014-01-01

    Purpose. The aryl hydrocarbon receptor (AHR) is a ligand-activated nuclear receptor that regulates cellular response to environmental signals, including UV and blue wavelength light. This study was undertaken to elucidate AHR function in retinal homeostasis. Methods. RNA-seq data sets were examined for Ahr expression in the mouse retina and rod photoreceptors. The Ahr−/− mice were evaluated by fundus imaging, optical coherence tomography, histology, immunohistochemistry, and ERG. For light damage experiments, adult mice were exposed to 14,000 to 15,000 lux of diffuse white light for 2 hours. Results. In mouse retina, Ahr transcripts were upregulated during development, with continued increase in aging rod photoreceptors. Fundus examination of 3-month-old Ahr−/− mice revealed subretinal autofluorescent spots, which increased in number with age and following acute light exposure. Ahr−/− retina also showed subretinal microglia accumulation that correlated with autofluorescence changes, RPE abnormalities, and reactivity against immunoglobulin, complement factor H, and glial fibrillary acidic protein. Functionally, Ahr−/− mice displayed reduced ERG c-wave amplitudes. Conclusions. The Ahr−/− mice exhibited subretinal accumulation of microglia and focal RPE atrophy, phenotypes observed in AMD. Together with a recently published report on another Ahr−/− mouse model, our study suggests that AHR has a protective role in the retina as an environmental stress sensor. As such, its altered function may contribute to human AMD progression and provide a target for pharmacological intervention. PMID:25159211

  4. Constitutive AhR activation leads to concomitant ABCG2-mediated multidrug resistance in cisplatin-resistant esophageal carcinoma cells.

    PubMed

    To, Kenneth K W; Yu, Le; Liu, Shuwen; Fu, Jianhua; Cho, Chi Hin

    2012-06-01

    Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease that is generally not responding to chemotherapy. It is particularly predominant in China. Although ESCC is significantly associated with cigarette smoking, the relationship between its molecular pathogenesis and responsiveness to chemotherapy and cigarette smoke remains elusive. This study reported the constitutive activation of aryl hydrocarbon receptor (AhR), leading to ABCG2 upregulation and the multidrug resistance (MDR) phenotype, in ESCC cell lines with acquired cisplatin resistance. Reporter gene assay, chromatin immunoprecipitation analysis and specific gene knockdown confirmed that the enhanced AhR binding to a xenobiotic response element (XRE) within the ABCG2 promoter is responsible for ABCG2 overexpression. A HSP90 inhibitor (17-AAG) and two AhR antagonists (kaempferol and salicylamide) were shown to inhibit ABCG2 upregulation, thereby reversing the ABCG2-mediated MDR. Our data therefore advocate the use of these inhibitors as novel chemosensitizers for the treatment of esophageal cancer.

  5. Characterizing HR 3549 B using SPHERE

    NASA Astrophysics Data System (ADS)

    Mesa, D.; Vigan, A.; D'Orazi, V.; Ginski, C.; Desidera, S.; Bonnefoy, M.; Gratton, R.; Langlois, M.; Marzari, F.; Messina, S.; Antichi, J.; Biller, B.; Bonavita, M.; Cascone, E.; Chauvin, G.; Claudi, R. U.; Curtis, I.; Fantinel, D.; Feldt, M.; Garufi, A.; Galicher, R.; Henning, Th.; Incorvaia, S.; Lagrange, A.-M.; Millward, M.; Perrot, C.; Salasnich, B.; Scuderi, S.; Sissa, E.; Wahhaj, Z.; Zurlo, A.

    2016-10-01

    Aims: In this work, we characterize the low-mass companion of the A0 field star HR 3549. Methods: We observed HR 3549B in imaging mode with the near-infrared branch (IFS and IRDIS) of SPHERE at the VLT, with IFS in YJ mode and IRDIS in the H band. We also acquired a medium-resolution spectrum with the IRDIS long-slit spectroscopy mode. The data were reduced using the dedicated SPHERE GTO pipeline, which is custom-designed for this instrument. We employed algorithms such as PCA and TLOCI to reduce the speckle noise. Results: The companion was clearly visible with both IRDIS and IFS. We obtained photometry in four different bands and also the astrometric position for the companion. Based on our astrometry, we confirm that it is a bound object and set constraints on its orbit. Although several uncertainties still remain, we estimate an age of ~100-150 Myr for this system, yielding a most probable mass for the companion of 40-50 MJup and Teff ~ 2300-2400 K. Compared with template spectra, this points to a spectral type between M9 and L0 for the companion, commensurate with its position on the color-magnitude diagram.

  6. Benzo[ghi]perylene activates the AHR pathway to exert biological effects on the NL-20 human bronchial cell line.

    PubMed

    Zaragoza-Ojeda, Montserrat; Eguía-Aguilar, Pilar; Perezpeña-Díazconti, Mario; Arenas-Huertero, Francisco

    2016-08-10

    Polycyclic aromatic hydrocarbons (PAH) are produced by incomplete combustion of organic material. In the Mexico City atmosphere, the most abundant PAH is benzo[ghi]perylene (BghiP), a gasoline combustion marker. At present, there are no reports of the effects of BghiP on human bronchial cells, so the aim of the study was to evaluate the effects in vitro of BghiP on the NL-20 cell line. Results showed that BghiP induced the formation of small vesicles throughout the cytoplasm, with absence of nuclear fragmentation. At 48h exposition, damage in cell membrane increased significantly at 1.24μg/mL of BghiP (p<0.05). Immunocytochemistry revealed that BghiP provokes nuclear translocation of AhR receptor, which indicates that this compound can induce transcription of genes via receptor binding (AhR pathway activation). BghiP induced a two-fold increase (p<0.05) in the expression of AhR and CYP4B1 (a lung-specific pathway effector). In the presence of the receptor antagonist CH-223191, the loss of viability, the nuclear translocation and the overexpression of genes decreased, though this did not prevent the formation of vesicles. BghiP induced oxidative stress and in presence of the receptor antagonist this increased significantly. In conclusion, BghiP can activate the overexpression of AhR and CYP4B1, and the effects are abated by the AhR receptor antagonist. This is the first report to prove that BghiP utilizes the AhR pathway to exert its toxic effects on the NL-20 human bronchial cell line .

  7. Inhibition of AHR transcription by NF1C is affected by a single-nucleotide polymorphism, and is involved in suppression of human uterine endometrial cancer.

    PubMed

    Li, D; Takao, T; Tsunematsu, R; Morokuma, S; Fukushima, K; Kobayashi, H; Saito, T; Furue, M; Wake, N; Asanoma, K

    2013-10-10

    Involvement of the aryl hydrocarbon receptor (AHR) in carcinogenesis has been suggested in many studies. Upregulation of AHR has been reported in some cancer species, and an association between single-nucleotide polymorphisms (SNPs) of AHR and cancer risk or cancer development has also been reported. This evidence suggests the involvement of some specific SNPs in AHR transcriptional regulation in the process of carcinogenesis or cancer development, but there have been no studies to elucidate the mechanism involved. In this study, we identified the transcription factor Nuclear Factor 1-C (NF1C) as a candidate to regulate AHR transcription in a polymorphism-dependent manner. SNP rs10249788 was included in a consensus binding site for NF1C. Our results suggested that NF1C preferred the C allele to the T allele at rs10249788 for binding. Forced expression of NF1C suppressed the activity of the AHR promoter with C at rs10249788 stronger than that with T. Moreover, expression analysis of human uterine endometrial cancer (HEC) specimens showed greater upregulation of AHR and downregulation of NF1C than those of normal endometrium specimens. Sequence analysis showed HEC patients at advanced stages tended to possess T/T alleles more frequently than healthy women. We also demonstrated that NF1C suppressed proliferation, motility and invasion of HEC cells. This function was at least partially mediated by AHR. This study is the first to report that a polymorphism on the AHR regulatory region affected transcriptional regulation of the AHR gene in vitro. Because NF1C is a tumor suppressor, our new insights into AHR deregulation and its polymorphisms could reveal novel mechanisms of genetic susceptibility to cancer.

  8. Shaft adjuster

    DOEpatents

    Harry, H.H.

    1988-03-11

    Abstract and method for the adjustment and alignment of shafts in high power devices. A plurality of adjacent rotatable angled cylinders are positioned between a base and the shaft to be aligned which when rotated introduce an axial offset. The apparatus is electrically conductive and constructed of a structurally rigid material. The angled cylinders allow the shaft such as the center conductor in a pulse line machine to be offset in any desired alignment position within the range of the apparatus. 3 figs.

  9. Shaft adjuster

    DOEpatents

    Harry, Herbert H.

    1989-01-01

    Apparatus and method for the adjustment and alignment of shafts in high power devices. A plurality of adjacent rotatable angled cylinders are positioned between a base and the shaft to be aligned which when rotated introduce an axial offset. The apparatus is electrically conductive and constructed of a structurally rigid material. The angled cylinders allow the shaft such as the center conductor in a pulse line machine to be offset in any desired alignment position within the range of the apparatus.

  10. Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver

    NASA Astrophysics Data System (ADS)

    Amenya, Hesbon Z.; Tohyama, Chiharu; Ohsako, Seiichiroh

    2016-10-01

    The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24 hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress.

  11. Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver

    PubMed Central

    Amenya, Hesbon Z.; Tohyama, Chiharu; Ohsako, Seiichiroh

    2016-01-01

    The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24 hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress. PMID:27713569

  12. Characterization of AhR agonists reveals antagonistic activity in European herring gull (Larus argentatus) eggs.

    PubMed

    Muusse, Martine; Christensen, Guttorm; Gomes, Tânia; Kočan, Anton; Langford, Katherine; Tollefsen, Knut Erik; Vaňková, Lenka; Thomas, Kevin V

    2015-05-01

    European herring gull (Larus argentatus) eggs from two Norwegian islands, Musvær in the south east and Reiaren in Northern Norway, were screened for dioxins, furans, and dioxin-like and selected non-dioxin-like polychlorinated biphenyls (PCBs), and subjected to non-target analysis to try to identify the aryl hydrocarbon receptor (AhR) agonists, responsible for elevated levels measured using the dioxin responsive chemically activated luciferase expression (DR-CALUX) assay. Eggs from Musvær contained chemically calculated toxic equivalent (WHO TEQ) levels of between 109 and 483 pg TEQ/g lw, and between 82 and 337 pg TEQ/g lw was determined in eggs from Reiaren. In particular PCB126 contributed highly to the total TEQ (69-82%). In 19 of the 23 samples the calculated WHO TEQ was higher than the TEQCALUX. Using CALUX specific relative effect potencies (REPs), the levels were lower at between 77 and 292 pg/g lw in eggs from Musvær and between 55 and 223 pg/g lw in eggs from Reiaren, which was higher than the TEQCALUX in 16 of the 23 samples. However, the means of the REP values and the TEQCALUX were not significantly different. This suggests the presence of compounds that can elicit antagonist effects, with a low binding affinity to the AhR. Non-target analysis identified the presence of hexachlorobenzene (HCB) (quantified at 9.6-185 pg/g lw) but neither this compound nor high concentrations of PCB126 and non-dioxin-like PCBs could explain the differences between the calculated TEQ or REP values and the TEQCALUX. Even though, for most AhR agonists, the sensitivity of herring gulls is not known, the reported levels can be considered to represent a risk for biological effects in the developing embryo, compared to LC50 values in chicken embryos. For human consumers of herring gull eggs, these eggs contain TEQ levels up to four times higher than the maximum tolerable weekly intake.

  13. VizieR Online Data Catalog: HR 8799e and HR 8799d spectra (Zurlo+, 2016)

    NASA Astrophysics Data System (ADS)

    Zurlo, A.; Vigan, A.; Galicher, R.; Maire, A.-L.; Mesa, D.; Gratton, R.; Chauvin, G.; Kasper, M.; Moutou, C.; Bonnefoy, M.; Desidera, S.; Abe, L.; Apai, D.; Baruffolo, A.; Baudoz, P.; Baudrand, J.; Beuzit, J.-L.; Blancard, P.; Boccaletti, A.; Cantalloube, F.; Carle, M.; Cascone, E.; Charton, J.; Claudi, R. U.; Costille, A.; de Caprio, V.; Dohlen, K.; Dominik, C.; Fantinel, D.; Feautrier, P.; Feldt, M.; Fusco, T.; Gigan, P.; Girard, J. H.; Gisler, D.; Gluck, L.; Gry, C.; Henning, T.; Hugot, E.; Janson, M.; Jaquet, M.; Lagrange, A.-M.; Langlois, M.; Llored, M.; Madec, F.; Magnard, Y.; Martinez, P.; Maurel, D.; Mawet, D.; Meyer, M. R.; Milli, J.; Moeller-Nilsson, O.; Mouillet, D.; Origne, A.; Pavlov, A.; Petit, C.; Puget, P.; Quanz, S. P.; Rabou, P.; Ramos, J.; Rousset, G.; Roux, A.; Salasnich, B.; Salter, G.; Sauvage, J.-F.; Schmid, H. M.; Soenke, C.; Stadler, E.; Suarez, M.; Turatto, M.; Udry, S.; Vakili, F.; Wahhaj, Z.; Wildi, F.; Antichi, J.

    2015-11-01

    The files contain the wavelength in micrometers in the first column, the flux in W/m2/mum in the second column and the corresponding error in the third. We refer to the text for more informations /Users/alice/paper_hr8799/readme.txt. Any further question can be addressed to alice.zurlo@mail.udp.cl (2 data files).

  14. Improved calibration of IMU biases in analytic coarse alignment for AHRS

    NASA Astrophysics Data System (ADS)

    Lu, Jiazhen; Lei, Chaohua; Li, Baoguo; Wen, Ting

    2016-07-01

    An improved method for the inertial measurement unit (IMU) calibration of coarse alignment for the low-accuracy attitude heading reference system (AHRS) is proposed in this paper. The sensitivities of the Euler angles with respect to the inertial sensor biases are studied based on the analytic coarse alignment principle, and the errors of earth rotation rate and local gravity in the body frame caused by initial attitude error are analyzed. Then, an improved analytic coarse alignment algorithm with accelerometer and gyro bias calibration in an arbitrary three-position is proposed. Simulation and experiment results show that the novel method can calibrate accelerometer and gyro biases, reduce Euler angle attitude error, and improve navigation precision in practical applications. Moreover, this method can be applied to other low-accuracy inertial navigation systems.

  15. Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: role of the proximal promoter GC-rich region

    PubMed Central

    Englert, Neal A.; Turesky, Robert J.; Han, Weiguo; Bessette, Erin E.; Spivack, Simon D.; Caggana, Michele; Spink, David C.; Spink, Barbara C.

    2014-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, contributes to carcinogenesis through its role in the regulation of cytochrome P450 1 (CYP1)-catalyzed metabolism of carcinogens. Here, we investigated genetic and epigenetic mechanisms that affect AhR expression. Analyses of the human AHR proximal promoter in MCF-7 human breast cancer cells using luciferase assays and electrophoretic mobility shift assays revealed multiple specificity protein (Sp) 1 binding sequences that are transcriptional activators in vitro. The regulation of AhR expression was evaluated in long-term estrogen exposed (LTEE) MCF-7 cells, which showed increased AhR expression, enhanced CYP1 inducibility, and increased capacity to form DNA adducts when exposed to the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. The increased AhR expression in LTEE cells was found not to result from increased mRNA stability, differential RNA processing, or decreased DNA methylation. Analysis of the AHR proximal promoter region using chromatin immunoprecipitation confirmed that enhanced expression of AhR in LTEE cells involves changes in histone modifications, notably decreased trimethylation of histone 3, lysine 27. Upon further examination of the GC-rich Sp1-binding region, we confirmed that it contains a polymorphic (GGGGC)n repeat. In a population of newborns from New York State, the allele frequency of (GGGGC)n was n = 4>5≫6, 2. Circular dichroism spectroscopy revealed the ability of sequences of this GC-rich region to form guanine-quadruplex structures in vitro. These studies revealed multiple levels at which AhR expression may be controlled, and offer additional insights into mechanisms regulating AhR expression that can ultimately impact carcinogenesis. PMID:22728919

  16. Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: role of the proximal promoter GC-rich region.

    PubMed

    Englert, Neal A; Turesky, Robert J; Han, Weiguo; Bessette, Erin E; Spivack, Simon D; Caggana, Michele; Spink, David C; Spink, Barbara C

    2012-09-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, contributes to carcinogenesis through its role in the regulation of cytochrome P450 1 (CYP1)-catalyzed metabolism of carcinogens. Here, we investigated genetic and epigenetic mechanisms that affect AhR expression. Analyses of the human AHR proximal promoter in MCF-7 human breast cancer cells using luciferase assays and electrophoretic mobility shift assays revealed multiple specificity protein (Sp) 1 binding sequences that are transcriptional activators in vitro. The regulation of AhR expression was evaluated in long-term estrogen exposed (LTEE) MCF-7 cells, which showed increased AhR expression, enhanced CYP1 inducibility, and increased capacity to form DNA adducts when exposed to the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. The increased AhR expression in LTEE cells was found not to result from increased mRNA stability, differential RNA processing, or decreased DNA methylation. Analysis of the AHR proximal promoter region using chromatin immunoprecipitation confirmed that enhanced expression of AhR in LTEE cells involves changes in histone modifications, notably decreased trimethylation of histone 3, lysine 27. Upon further examination of the GC-rich Sp1-binding region, we confirmed that it contains a polymorphic (GGGGC)(n) repeat. In a population of newborns from New York State, the allele frequency of (GGGGC)(n) was n = 4 > 5 ≫ 6, 2. Circular dichroism spectroscopy revealed the ability of sequences of this GC-rich region to form guanine-quadruplex structures in vitro. These studies revealed multiple levels at which AhR expression may be controlled, and offer additional insights into mechanisms regulating AhR expression that can ultimately impact carcinogenesis.

  17. The Role of AhR in Autoimmune Regulation and Its Potential as a Therapeutic Target against CD4 T Cell Mediated Inflammatory Disorder

    PubMed Central

    Zhu, Conghui; Xie, Qunhui; Zhao, Bin

    2014-01-01

    AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently. PMID:24905409

  18. The role of AhR in autoimmune regulation and its potential as a therapeutic target against CD4 T cell mediated inflammatory disorder.

    PubMed

    Zhu, Conghui; Xie, Qunhui; Zhao, Bin

    2014-06-05

    AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently.

  19. Predicting the sensitivity of fishes to dioxin-like compounds: possible role of the aryl hydrocarbon receptor (AhR) ligand binding domain.

    PubMed

    Doering, Jon A; Giesy, John P; Wiseman, Steve; Hecker, Markus

    2013-03-01

    Dioxin-like compounds are chronically toxic to most vertebrates. However, dramatic differences in sensitivity to these chemicals exist both within and among vertebrate classes. A recent study found that in birds, critical amino acid residues in the aryl hydrocarbon receptor (AhR) ligand binding domain are predictive of sensitivity to dioxin-like compounds in a range of species. It is currently unclear whether similar predictive relationships exist for fishes, a group of animals at risk of exposure to dioxin-like compounds. Effects of dioxin-like compounds are mediated through the AhR in fishes and birds. However, AhR dynamics are more complex among fishes. Fishes possess AhRs that can be grouped within at least three distinct clades (AhR1, AhR2, AhR3) with each clade possibly containing multiple isoforms. AhR2 has been shown to be the active form in most teleosts, with AhR1 not binding dioxin-like compounds. The role of AhR3 in dioxin-like toxicity has not been established to date and this clade is only known to be expressed in some cartilaginous fishes. Furthermore, multiple mechanisms of sensitivity to dioxin-like compounds that are not relevant in birds could exist among fishes. Although, at this time, deficiencies exist for the development of such a predictive relationship for application to fishes, successfully establishing such relationships would offer a substantial improvement in assessment of risks of dioxin-like compounds for this class of vertebrates. Elucidation of such relationships would provide a mechanistic foundation for extrapolation among species to allow the identification of the most sensitive fishes, with the ultimate goal of the prediction of risk posed to endangered species that are not easily studied.

  20. 4-Nitrophenol exposure alters the AhR signaling pathway and related gene expression in the rat liver.

    PubMed

    Li, Ruonan; Song, Meiyan; Li, Zhi; Li, Yansen; Watanabe, Gen; Nagaoka, Kentaro; Taya, Kazuyoshi; Li, Chunmei

    2017-02-01

    4-Nitrophenol (PNP) is well known as an environmental endocrine disruptor. The aim of this study was to clarify the mechanism of PNP-induced liver damage and determine the regulatory involvement of the aryl hydrocarbon receptor (AhR) signaling pathway and associated gene expression. Immature male Wistar-Imamichi rats (28 days old) were randomly divided into control and PNP groups, which consisted of 1- and 3-day exposure (1 DE and 3 DE, respectively) and 3-day exposure followed by 3-day recovery (3 DE + 3 DR), groups. Each group was administered the vehicle or PNP (200 mg kg(-1) body weight). The body and liver weight were significantly decreased in the 3 DE group. The mRNA expression levels of estrogen receptor-α (ERα), glutathione S-transferase (GST) and AhR exhibited a significant increase in the 1 DE group whereas, in contrast, that of cytochrome P450 (CYP) 1A1 decreased significantly in the 3 DE +3 DR group. AhR and CYP1A1 proteins were detected in the cytoplasm of hepatocytes of the 1 DE and 3 DE +3 DR groups whereas the ERα protein was found in the hepatocyte nuclei of the 1 DE and 3 DE groups. The present study demonstrates that PNP activated the AhR signaling pathway and regulated related CYP1A1 and GST gene expression in the liver. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Access Path to the Ligand Binding Pocket May Play a Role in Xenobiotics Selection by AhR

    PubMed Central

    Szöllősi, Dániel; Erdei, Áron; Gyimesi, Gergely; Magyar, Csaba; Hegedűs, Tamás

    2016-01-01

    Understanding of multidrug binding at the atomic level would facilitate drug design and strategies to modulate drug metabolism, including drug transport, oxidation, and conjugation. Therefore we explored the mechanism of promiscuous binding of small molecules by studying the ligand binding domain, the PAS-B domain of the aryl hydrocarbon receptor (AhR). Because of the low sequence identities of PAS domains to be used for homology modeling, structural features of the widely employed HIF-2α and a more recent suitable template, CLOCK were compared. These structures were used to build AhR PAS-B homology models. We performed molecular dynamics simulations to characterize dynamic properties of the PAS-B domain and the generated conformational ensembles were employed in in silico docking. In order to understand structural and ligand binding features we compared the stability and dynamics of the promiscuous AhR PAS-B to other PAS domains exhibiting specific interactions or no ligand binding function. Our exhaustive in silico binding studies, in which we dock a wide spectrum of ligand molecules to the conformational ensembles, suggest that ligand specificity and selection may be determined not only by the PAS-B domain itself, but also by other parts of AhR and its protein interacting partners. We propose that ligand binding pocket and access channels leading to the pocket play equally important roles in discrimination of endogenous molecules and xenobiotics. PMID:26727491

  2. Musashi-2 Attenuates AHR Signaling to Expand Human Hematopoietic Stem Cells

    PubMed Central

    Rentas, Stefan; Voisin, Veronique; Wilhelm, Brian T; Bader, Gary D; Yeo, Gene W; Hope, Kristin J

    2016-01-01

    Umbilical cord blood (CB)-derived hematopoietic stem cells (HSCs) are essential in many life saving regenerative therapies, but their low number in CB units has significantly restricted their clinical use despite the advantages they provide during transplantation1. Select small molecules that enhance hematopoietic stem and progenitor cell (HSPC) expansion in culture have been identified2,3, however, in many cases their mechanisms of action or the nature of the pathways they impinge on are poorly understood. A greater understanding of the molecular pathways that underpin the unique human HSC self-renewal program will facilitate the development of targeted strategies that expand these critical cell types for regenerative therapies. Whereas transcription factor networks have been shown to influence the self-renewal and lineage decisions of human HSCs4,5, the post-transcriptional mechanisms guiding HSC fate have not been closely investigated. Here we show that overexpression of the RNA-binding protein (RBP) Musashi-2 (MSI2) induces multiple pro-self-renewal phenotypes, including a 17-fold increase in short-term repopulating cells and a net 23-fold ex vivo expansion of long-term repopulating HSCs. By performing a global analysis of MSI2-RNA interactions, we determined that MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signaling through post-transcriptional downregulation of canonical AHR pathway components in CB HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and give evidence that manipulating such networks ex vivo can provide a novel means to enhance the regenerative potential of human HSCs. PMID:27121842

  3. Réunion publique HR

    ScienceCinema

    None

    2016-07-12

    Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanée de cette réunion sera assurée dans l'Amphithéâtre BE de Prévessin et également disponible à l'adresse suivante: http://webcast.cern.chJe me réjouis de votre participation!Meilleures salutations,Anne-Sylvie CatherinChef du Département des Ressources humaines__________________________________________________________________________________Dear Colleagues,I should like to remind you that a plublic meeting organised by HR Department will be held today:Friday 30 April 2010 at 9:30 am in the Main Auditorium (coffee from 9:00 am).During this meeting, general information will be given about:the CERN Admin e-guide which is a new guide to the Organization's administrative procedures, drawn up to facilitate the retrieval of practical information and to offer a user-friendly format;the CERN Health Insurance System (presentation by Philippe Charpentier, President of the CHIS Board) and;the Pension Fund (presentation by Theodore Economou, Administrator of the CERN Pension Fund).A simultaneous transmission of this meeting will be broadcast in the BE Auditorium at Prévessin and will also be available at the following address. http://webcast.cern.chI look forward to your participation!Best regards,Anne-Sylvie Catherin

  4. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    SciTech Connect

    Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  5. AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels

    SciTech Connect

    Barrett, R.J.; Appell, K.C.; Kilpatrick, B.F.; Proakis, A.G.; Nolan, J.C.; Walsh, D.A. )

    1991-01-01

    In vivo and in vitro methods were used to characterize AHR-16303B, a novel compound with antagonistic action at 5-HT2 receptors and voltage-sensitive calcium channels. The 5-HT2 receptor-antagonistic properties of AHR-16303B were demonstrated by inhibition of (a) (3H)ketanserin binding to rat cerebral cortical membranes (IC50 = 165 nM); (b) 5-hydroxytryptamine (5-HT)-induced foot edema in rats (minimum effective dose, (MED) = 0.32 mg/kg orally, p.o.); (c) 5-HT-induced vasopressor responses in spontaneously hypertensive rats (SHR) (ID50 = 0.18 mg/kg intravenously (i.v.), 1.8 mg/kg p.o.), (d) 5-HT-induced antidiuresis in rats (MED = 1 mg/kg p.o.), and (e) platelet aggregation induced by 5-HT + ADP (IC50 = 1.5 mM). The calcium antagonist properties of AHR-16303B were demonstrated by inhibition of (a) (3H)nimodipine binding to voltage-sensitive calcium channels on rabbit skeletal muscle membranes (IC50 = 15 nM), (b) KCl-stimulated calcium flux into cultured PC12 cells (IC50 = 81 nM), and (c) CaCl2-induced contractions of rabbit thoracic aortic strips (pA2 = 8.84). AHR-16303B had little or no effect on binding of radioligands to dopamine2 (DA2) alpha 1, alpha 2, H1, 5-HT1 alpha, beta 2, muscarinic M1, or sigma opioid receptors; had no effect on 5-HT3 receptor-mediated vagal bradycardia; and had only minor negative inotropic, chronotropic, and dromotropic effects on isolated guinea pig atria. In conscious SHR, 30 mg/kg p.o. AHR-16303B completely prevented the vasopressor responses to i.v. 5-HT, and decreased blood pressure (BP) by 24% 3 h after dosing.

  6. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer.

    PubMed

    Spink, Barbara C; Bloom, Michael S; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n=2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n=4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility.

  7. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    PubMed Central

    Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n = 4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. PMID:25447411

  8. The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction

    PubMed Central

    Vacca, Margherita; Nardelli, Claudia; Castegna, Alessandra; Arnesano, Fabio; Carella, Nicola; Depalo, Raffaella

    2016-01-01

    Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR). Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy), an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs) retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group), who were undergoing in vitro fertilization (IVF) protocol. In follicular fluids (FFs) of both groups the toxic and essential heavy metals, such as chromiun (Cr), Manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1 (PGRMC1), a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins) or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb. PMID:27008165

  9. The hot white-dwarf companions of HR 1608, HR 8210, and HD 15638

    NASA Technical Reports Server (NTRS)

    Landsman, Wayne; Simon, Theodore; Bergeron, P.

    1993-01-01

    We have obtained low-dispersion IUE spectra of the late-type stars HD 15638 (F3 V), HR 1608 (=63 Eridani, KO IV), and HR 8210 (A8m). Each of these stars had been detected as a strong EUV source with the Wide Field Camera aboard the ROSAT satellite. The short-wavelength IUE spectrum of each star reveals the presence of a hot white-dwarf companion. We have fit the Lyman-alpha profile and UV continuum of each white dwarf using pure hydrogen models. The excellent fit of the data to the models provides confirmation of the Finley and Koester absolute calibration of the SWP camera of IUE. The UV data alone are insufficient to constrain the model gravity, but an additional constraint is provided by the photometric distance to the late-type primary. The most interesting of the three white dwarfs is the companion to HR 8210 for which our results imply a mass of 1.15 +0.05/-0.15 solar mass. This result is in good agreement with the lower limit on the mass derived from the spectroscopic orbit (greater than 1.1 solar mass), provided that the inclination is close to 90 deg.

  10. The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells

    PubMed Central

    Ghotbaddini, Maryam; Powell, Joann B.

    2015-01-01

    The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR) expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models. PMID:26154658

  11. Genome Editing of the CYP1A1 Locus in iPSCs as a Platform to Map AHR Expression throughout Human Development

    PubMed Central

    Smith, Brenden W.; Stanford, Elizabeth A.; Sherr, David H.; Murphy, George J.

    2016-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that increases the expression of detoxifying enzymes upon ligand stimulation. Recent studies now suggest that novel endogenous roles of the AHR exist throughout development. In an effort to create an optimized model system for the study of AHR signaling in several cellular lineages, we have employed a CRISPR/CAS9 genome editing strategy in induced pluripotent stem cells (iPSCs) to incorporate a reporter cassette at the transcription start site of one of its canonical targets, cytochrome P450 1A1 (CYP1A1). This cell line faithfully reports on CYP1A1 expression, with luciferase levels as its functional readout, when treated with an endogenous AHR ligand (FICZ) at escalating doses. iPSC-derived fibroblast-like cells respond to acute exposure to environmental and endogenous AHR ligands, and iPSC-derived hepatocytes increase CYP1A1 in a similar manner to primary hepatocytes. This cell line is an important innovation that can be used to map AHR activity in discrete cellular subsets throughout developmental ontogeny. As further endogenous ligands are proposed, this line can be used to screen for safety and efficacy and can report on the ability of small molecules to regulate critical cellular processes by modulating the activity of the AHR. PMID:27148368

  12. The Nuclear Receptor AhR Controls Bone Homeostasis by Regulating Osteoclast Differentiation via the RANK/c-Fos Signaling Axis

    PubMed Central

    Izawa, Takashi; Arakaki, Rieko; Mori, Hiroki; Tsunematsu, Takaaki; Kudo, Yasusei; Tanaka, Eiji

    2016-01-01

    The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)–mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow–derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1. In response to RANKL, bone marrow macrophages isolated from AhR−/− mice exhibited impaired phosphorylation of Akt and MAPK as well as NF-κB, whereas their response to M-CSF remained unchanged. Osteoclast differentiation mediated by the AhR signaling pathway was also regulated in an RANKL/c-Fos–dependent manner. Furthermore, ligand activation of AhR by the smoke toxin benzo[a]pyrene accelerated osteoclast differentiation in a receptor-dependent manner, and AhR-dependent regulation of mitochondrial biogenesis in osteoclasts was observed. Moreover, AhR−/− mice exhibited impaired bone healing with delayed endochondral ossification. Taken together, the present results suggest that the RANKL/AhR/c-Fos signaling axis plays a critical role in osteoclastogenesis, thereby identifying the potential of AhR in treating pathological, inflammatory, or metabolic disorders of the bone. PMID:27849171

  13. Starspots on V711 Tauri /HR 1099/

    NASA Astrophysics Data System (ADS)

    Dorren, J. D.; Siah, M. J.; Guinan, E. F.; McCook, G. P.

    1981-04-01

    Hα (λ6563) intermediate- and narrowband light curves of the RS CVn-type binary system V711 Tau (HR 1099) were obtained in 1977-1978 at Biruni Observatory and in 1977-1978 and late 1979 at Villanova Observatory, where a λ7790 light curve was also obtained in 1977-1978. The light curves are quasisinusoidal, with a period approximately equal to the spectroscopic period. A significant change in the λ6585 light curve occurred between the two observing seasons, with an increase in amplitude from 0.075 to 0.125 mag, a change of shape, and an advance in the phases of maximum and minimum light by 0.3 phase. Flaring activity in Hα was observed, on time scales from minutes to days. We fitted our light curves and V-band light curves obtained at the same time using the starspot model of Torres and Ferraz Mello. We the observed light variations are due to the synchronous rotation of spots on the heavier member of the binary system, which has been shown to be the chromospherically active star. The orbital inclination was assumed to be 35°. Radiant fluxes were taken from spectrophotometric tables. Owing to the broad wavelength coverage in 1977-1978, it was possible to determine the spot temperature to be ˜1800 K cooler than the photosphere, and hence to fix the spot area. A simple model with two circular spots of 26° radius at the same latitude, +48°, adequately reproduces the 1977-1978 light curves. The 1979 observations can be reproduced in detail by a model with two slightly larger circular spots of 31°.5 radius at latitude +15°. The spots cover about 14% of the total stellar surface in 1979. The fits also provide an explanation of the presence of an observed phase dependence in the Hα emission in 1979 but not in 1977-1978. There is a strong suggestion that a spot cycle is in progress in V711 Tau.

  14. Elemental abundances of the B and A stars Gamma Geminorum, 7 Sextantis, HR 4817, and HR 5780

    NASA Technical Reports Server (NTRS)

    Adelman, Saul J.; Philip, A. G. D.

    1992-01-01

    Fine analyses of the B and A stars, Gamma Geminorum, 7 Sextantis, HR 4817, and HR 5780 are performed. Although the data cover rather limited spectral regions, still useful results were obtained. The data were mostly obtained at the KPNO coude feed telescope with CCD TI No. 3, camera 5, and grating A. The He/H ratio of HR 4817 confirms the similarity of many abundance values with those of the peculiar Mn star 53 Tauri. For the most part Gamma Gem, 7 Sex, and HR 5780 have derived abundances similar to those of other normal sharp-lined stars of similar effective temperature.

  15. Zebrafish Cardiotoxicity: The Effects of CYP1A Inhibition and AHR2 Knockdown Following Exposure to Weak Aryl Hydrocarbon Receptor Agonists

    PubMed Central

    Clark, Bryan William; Van Tiem Garner, Lindsey; Di Giulio, Richard Thomas

    2014-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates many of the toxic effects of dioxin-like compounds (DLCs) and some polycyclic aromatic hydrocarbons (PAHs). Strong AHR agonists, such as certain polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), cause severe cardiac teratogenesis in fish embryos. Moderately strong AHR agonists, such as benzo[a]pyrene and β-naphthoflavone, have been shown to cause similar cardiotoxic effects when coupled with a cytochrome P450 1A (CYP1A) inhibitor, such as fluoranthene (FL). We sought to determine if weak AHR agonists, when combined with a CYP1A inhibitor (FL) or CYP1A morpholino gene knockdown, are capable of causing cardiac deformities similar to moderately strong AHR agonists (Wassenberg and Di Giulio 2004; Wassenberg and Di Giulio 2004; Billiard, Timme-Laragy et al. 2006; Van Tiem and Di Giulio 2011). The weak AHR agonists included the following: carbaryl, phenanthrene, 2-methylindole, 3-methylindole, indigo, and indirubin. The results showed a complex pattern of cardiotoxic response to weak agonist inhibitor exposure and morpholino-knockdown. Danio rerio (zebrafish) embryos were first exposed to weak AHR agonists at equimolar concentrations. The agonists were assessed for their relative potency as inducers of CYP1 enzyme activity, measured by the ethoxyresorufin-o-deethylase (EROD) assay, and cardiac deformities. Carbaryl, 2-methylindole, and 3-methylindole induced the highest CYP1A activity in zebrafish. Experiments were then conducted to determine the individual cardiotoxicity of each compound. Next, zebrafish were co-exposed to each agonist (at concentrations below those determined to be cardiotoxic) and FL in combination to assess if CYP1A inhibition could induce cardiac deformities. Carbaryl, 2-methylindole, 3-methylindole, and phenanthrene significantly increased pericardial edema relative to controls when combined with FL. To further evaluate the

  16. Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5

    SciTech Connect

    Oshima, Motohiko; Mimura, Junsei; Yamamoto, Masayuki; Fujii-Kuriyama, Yoshiaki

    2007-12-14

    The Aryl hydrocarbon receptor repressor (AhRR) has been proposed to inhibit Aryl hydrocarbon receptor (AhR) activity by competing with AhR for forming a heterodimer with AhR nuclear translocator (Arnt) and subsequently binding to the xenobiotic responsive elements (XRE). However, the precise mechanism of AhRR inhibitory activity remains unknown. Analysis of the inhibitory activity of AhRR on the expression of a TK promoter-driven reporter has localized a core repressor domain in the sequence of amino acid residue 555-701. The inhibitory activity of AhRR is sensitive to a histone deacetylase (HDAC) inhibitor, trichostatin A. By using the yeast two-hybrid screening method with the C-terminal sequence of AhRR as bait, we identified a binding partner, Ankyrin-repeat protein2 (ANKRA2), a protein known to interact with HDAC4 and HDAC5. RNA interference experiments using ANKRA2 and AhRR siRNAs indicate that ANKRA2 is important for transcriptional repression by AhRR. We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors.

  17. AhR signaling activation disrupts migration and dendritic growth of olfactory interneurons in the developing mouse

    PubMed Central

    Kimura, Eiki; Ding, Yunjie; Tohyama, Chiharu

    2016-01-01

    Perinatal exposure to a low level of dioxin, a ubiquitous environmental pollutant, has been shown to induce abnormalities in learning and memory, emotion, and sociality in laboratory animals later in adulthood. However, how aryl hydrocarbon receptor (AhR) signaling activation disrupts the higher brain function remains unclear. Therefore, we studied the possible effects of excessive activation of AhR signaling on neurodevelopmental processes, such as cellular migration and neurite growth, in mice. To this end, we transfected a constitutively active-AhR plasmid into stem cells in the lateral ventricle by in vivo electroporation on postnatal day 1. Transfection was found to induce tangential migration delay and morphological abnormalities in neuronal precursors in the rostral migratory stream at 6 days post-electroporation (dpe) as well as disrupt radial migration in the olfactory bulb and apical and basal dendritic growth of the olfactory interneurons in the granule cell layer at 13 and 20 dpe. These results suggest that the retarded development of interneurons by the excessive AhR signaling may at least in part explain the dioxin-induced abnormal behavioral alterations previously reported in laboratory animals. PMID:27197834

  18. Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

    PubMed Central

    2011-01-01

    Background The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate) at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS). AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR), extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'). Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t) > 0.999). Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation. PMID:21762485

  19. Outsourcing HR Services: The Role of Human Resource Intermediaries

    ERIC Educational Resources Information Center

    Kock, Henrik; Wallo, Andreas; Nilsson, Barbro; Hoglund, Cecilia

    2012-01-01

    Purpose: In this article, the area of interest is an emerging type of organisation called human resource intermediaries (HRIs), which focus on delivering human resource (HR) services to public sector organisations and private companies. The purpose of this article is, thus, to explore HRIs as deliverers of HR services. More specifically, the…

  20. African American Accounting Majors and the 150-hr Requirement

    ERIC Educational Resources Information Center

    Booker, Quinton; Hill, Cecil L.; Wright, Carl

    2010-01-01

    The study provides information on African American accounting majors' views regarding 150-hr issues. The authors collected data from 152 students at two schools. Students at one school supported the requirement while those at the other school did not. However, students believed that the 150-hr requirement enhances the quality of certified public…

  1. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice

    SciTech Connect

    Lund, Amie K.; Goens, M. Beth; Nunez, Bethany A.; Walker, Mary K. . E-mail: mkwalker@unm.edu

    2006-04-15

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy and fibrosis, associated with elevated plasma angiotensin II (Ang II) and endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular homeostasis. In these studies, we tested the hypothesis that ET-1 mediates cardiovascular pathology in AhR null mice via ET{sub A} receptor activation. First, we determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1 expression in AhR wildtype and null mice. AhR null mice exhibited increases in heart-to-body weight ratio and age-related expression of cardiac hypertrophy markers, {beta}-myosin heavy chain ({beta}-MHC), and atrial natriuretic factor (ANF), which were significant at 2 months. Similarly, plasma and tissue ET-1 expression was significantly elevated at 2 months and increased further with age. Second, AhR null mice were treated with ET{sub A} receptor antagonist, BQ-123 (100 nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28 days significantly reduced the histological appearance of cardiac fibrosis. Treatment for 58 days significantly reduced cardiac mass, assessed by heart weight, echocardiography, and {beta}-MHC and ANF expression; and reduced cardiac fibrosis as determined by osteopontin and collagen I mRNA expression. These findings establish ET-1 and the ET{sub A} receptor as primary determinants of hypertension and cardiac pathology in AhR null mice.

  2. Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with caffeine consumption.

    PubMed

    McMahon, George; Taylor, Amy E; Davey Smith, George; Munafò, Marcus R

    2014-01-01

    Two genetic loci, one in the cytochrome P450 1A1 (CYP1A1) and 1A2 (CYP1A2) gene region (rs2472297) and one near the aryl-hydrocarbon receptor (AHR) gene (rs6968865), have been associated with habitual caffeine consumption. We sought to establish whether a more refined and comprehensive assessment of caffeine consumption would provide stronger evidence of association, and whether a combined allelic score comprising these two variants would further strengthen the association. We used data from between 4,460 and 7,520 women in the Avon Longitudinal Study of Parents and Children, a longitudinal birth cohort based in the United Kingdom. Self-report data on coffee, tea and cola consumption (including consumption of decaffeinated drinks) were available at multiple time points. Both genotypes were individually associated with total caffeine consumption, and with coffee and tea consumption. There was no association with cola consumption, possibly due to low levels of consumption in this sample. There was also no association with measures of decaffeinated drink consumption, indicating that the observed association is most likely mediated via caffeine. The association was strengthened when a combined allelic score was used, accounting for up to 1.28% of phenotypic variance. This was not associated with potential confounders of observational association. A combined allelic score accounts for sufficient phenotypic variance in caffeine consumption that this may be useful in Mendelian randomization studies. Future studies may therefore be able to use this combined allelic score to explore causal effects of habitual caffeine consumption on health outcomes.

  3. Deficiency in Aryl Hydrocarbon Receptor (AHR) Expression throughout Aging Alters Gene Expression Profiles in Murine Long-Term Hematopoietic Stem Cells

    PubMed Central

    Bennett, John A.; Singh, Kameshwar P.; Unnisa, Zeenath; Welle, Stephen L.; Gasiewicz, Thomas A.

    2015-01-01

    Dysregulation of hematopoietic stem cell (HSC) signaling can contribute to the development of diseases of the blood system. Lack of aryl hydrocarbon receptor (AhR) has been associated with alterations in gene expression related to HSC function and the subsequent development of a myeloproliferative disorder in aging female mice. We sorted the most primitive population of HSCs with the highest stem cell potential (Long-term, or LT-HSCs) from 18-month-old AhR-null-allele (AhR-KO) and WT mice and analyzed gene expression using microarray to determine alterations in gene expression and cell signaling networks in HSCs that could potentially contribute to the aging phenotype of AhR-KO mice. Comparisons with previous array data from 8-week old mice indicated that aging alone is sufficient to alter gene expression. In addition, a significant number of gene expression differences were observed in aged LT-HSCs that are dependent on both aging and lack of AhR. Pathway analysis of these genes revealed networks related to hematopoietic stem cell activity or function. qPCR was used to confirm the differential expression of a subset of these genes, focusing on genes that may represent novel AhR targets due to the presence of a putative AhR binding site in their upstream regulatory region. We verified differential expression of PDGF-D, Smo, Wdfy1, Zbtb37 and Zfp382. Pathway analysis of this subset of genes revealed overlap between cellular functions of the novel AhR targets and AhR itself. Lentiviral-mediated knockdown of AhR in lineage-negative hematopoietic cells was sufficient to induce changes in all five of the candidate AhR targets identified. Taken together, these data suggest a role for AhR in HSC functional regulation, and identify novel HSC AhR target genes that may contribute to the phenotypes observed in AhR-KO mice. PMID:26208102

  4. Constitutive IDO expression in human cancer is sustained by an autocrine signaling loop involving IL-6, STAT3 and the AHR

    PubMed Central

    Sahm, Felix; Rauschenbach, Katharina J.; Trump, Saskia; Winter, Marcus; Ott, Martina; Ochs, Katharina; Lutz, Christian; Liu, Xiangdong; Anastasov, Natasa; Lehmann, Irina; Höfer, Thomas; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael

    2014-01-01

    Indoleamine-2,3-dioxygenase (IDO) inhibitors have entered clinical trials based on their ability to restore anti-tumor immunity in preclinical studies. However, the mechanisms leading to constitutive expression of IDO in human tumors are largely unknown. Here we analyzed the pathways mediating constitutive IDO expression in human cancer. IDO-positive tumor cells and tissues showed basal phosphorylation and acetylation of STAT3 as evidenced by western blotting and immunoprecipitation. Inhibition of IL-6 or STAT3 using siRNA and/or pharmacological inhibitors reduced IDO mRNA and protein expression as well as kynurenine formation. In turn, IDO enzymatic activity activated the AHR as shown by the induction of AHR target genes. IDO-mediated AHR activation induced IL-6 expression, while inhibition or knockdown of the AHR reduced IL-6 expression. IDO activity thus sustains its own expression via an autocrine AHR–IL-6–STAT3 signaling loop. Inhibition of the AHR–IL-6–STAT3 signaling loop restored T-cell proliferation in mixed leukocyte reactions performed in the presence of IDO-expressing human cancer cells. Identification of the IDO-AHR-IL-6-STAT3 signaling loop maintaining IDO expression in human cancers reveals novel therapeutic targets for the inhibition of this core pathway promoting immunosuppression of human cancers. The relevance of the IDO-AHR-IL-6-STAT3 transcriptional circuit is underscored by the finding that high expression of its members IDO, STAT3 and the AHR target gene CYP1B1 is associated with reduced relapse-free survival in lung cancer patients. PMID:24657910

  5. Sequence and in vitro function of chicken, ring-necked pheasant, and Japanese quail AHR1 predict in vivo sensitivity to dioxins.

    PubMed

    Farmahin, Reza; Wu, Dongmei; Crump, Doug; Hervé, Jessica C; Jones, Stephanie P; Hahn, Mark E; Karchner, Sibel I; Giesy, John P; Bursian, Steven J; Zwiernik, Matthew J; Kennedy, Sean W

    2012-03-06

    There are large differences in sensitivity to the toxic and biochemical effects of dioxins and dioxin-like compounds (DLCs) among vertebrates. Previously, we demonstrated that the difference in sensitivity between domestic chicken (Gallus gallus domesticus) and common tern (Sterna hirundo) to aryl hydrocarbon receptor 1 (AHR1)-dependent changes in gene expression following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is based upon the identities of the amino acids at two sites within the ligand binding domain of AHR1 (chicken--highly sensitive; Ile324_Ser380 vs common tern--250-fold less sensitive than chicken; Val325_Ala381). Here, we tested the hypotheses that (i) the sensitivity of other avian species to TCDD, 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) is also determined by the amino acids at sites that are equivalent to sites 324 and 380 in chicken, and (ii) Ile324_Ala380 and Val324_Ser380 genotypes confer intermediate sensitivity to DLCs in birds. We compared ligand-induced transactivation function of full-length AHR1s from chicken, common tern, ring-necked pheasant (Phasianus colchicus; Ile324_Ala380) and Japanese quail (Coturnix japonica; Val324_Ala380), and three Japanese quail AHR1 mutants. The results support our hypothesis that avian species can be grouped into three general classes of sensitivity to DLCs. Both AHR1 genotype and in vitro transactivation assays predict in vivo sensitivity. Contrary to the assumption that TCDD is the most potent DLC, PeCDF was more potent than TCDD at activating Japanese quail (13- to 26-fold) and common tern (23- to 30-fold) AHR1. Our results support and expand previous in vitro and in vivo work that demonstrated ligand-dependent species differences in AHR1 affinity. The findings and methods will be of use for DLC risk assessments.

  6. Chemical abundance analysis of π Dra and HR 7545

    NASA Astrophysics Data System (ADS)

    Elmaslı, Aslı; Nasolo, Yahya

    2017-02-01

    We carried out detailed abundance analysis of two A-type stars; π Dra and HR 7545. High resolution echelle spectra of these stars were obtained at the TÜBİTAK National Observatory. We determined the fundamental parameters of each target star using traditional methods. We also plotted the stars on the H-R diagram and calculated the masses from evolutionary tracks and ages from isochrones.

  7. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)

    SciTech Connect

    Cheng, Xingguo; Vispute, Saurabh G.; Liu, Jie; Cheng, Christine; Kharitonenkov, Alexei; Klaassen, Curtis D.

    2014-07-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression.

  8. Elemental abundances of the B and A stars. 2: Gamma Geminorum, HD 60825, 7 Sextantis, HR 4817, and HR 5780

    NASA Technical Reports Server (NTRS)

    Adelman, Saul J.; Philip, A. G. Davis

    1994-01-01

    We extend fine analyses of the B and A stars, gamma Geminorum, 7 Sextantis, HR 4817, and HR 5780 using additional spectroscopic data from the Kitt Peak National Observatory (KPNO) coude feed telescope with a TI CCD, camera 5, and grating A, and ATLAS9 model atmospheres. In addition we study HD 60825, which had colors similar to the FHB A stars, but was found to be a Population I star. HD 60825, as is gamma Gem, is a sharp-lined early-A star with nearly solar derived abundances. HR 5780 and 7 Sex are also examples of stars which for the most part have solar abundances. The newly derived abundances for HR 4817 reveal important differences with respect to 53 Tau, a somewhat similar HgMn star.

  9. Developmental Activation of the AHR Increases Effector CD4+ T Cells and Exacerbates Symptoms in Autoimmune Disease-Prone Gnaq+/− Mice

    PubMed Central

    Boule, Lisbeth A.; Burke, Catherine G.; Fenton, Bruce M.; Thevenet-Morrison, Kelly; Jusko, Todd A.; Lawrence, B. Paige

    2015-01-01

    Perinatal environmental exposures are potentially important contributors to the increase in autoimmune diseases. Yet, the mechanisms by which these exposures increase self-reactive immune responses later in life are poorly understood. Autoimmune diseases require CD4+ T cells for initiation, progression, and/or clinical symptoms; thus, developmental exposures that cause durable changes in CD4+ T cells may play a role. Early life activation of the aryl hydrocarbon receptor (AHR) causes persistent changes in the response of CD4+ T cells to infection later in life but whether CD4+ T cells are affected by developmental exposure in the context of an autoimmune disease is unknown. Gnaq+/− mice develop symptoms of autoimmune disease similar to those measured clinically, and therefore can be used to evaluate gene-environment interactions during development on disease progression. Herein, we examined the effect of AHR activation in utero and via lactation, or solely via lactation, on disease onset and severity in adult Gnaq+/− offspring. Developmental activation of the AHR-accelerated disease in Gnaq+/− mice, and this correlates with increases in effector CD4+ T-cell populations. Increased symptom onset and cellular changes due to early life AHR activation were more evident in female Gnaq+/− mice compared with males. These observations suggest that developmental AHR activation by pollutants, and other exogenous ligands, may increase the likelihood that genetically predisposed individuals will develop clinical symptoms of autoimmune disease later in life. PMID:26363170

  10. Developmental Activation of the AHR Increases Effector CD4+ T Cells and Exacerbates Symptoms in Autoimmune Disease-Prone Gnaq+/- Mice.

    PubMed

    Boule, Lisbeth A; Burke, Catherine G; Fenton, Bruce M; Thevenet-Morrison, Kelly; Jusko, Todd A; Lawrence, B Paige

    2015-12-01

    Perinatal environmental exposures are potentially important contributors to the increase in autoimmune diseases. Yet, the mechanisms by which these exposures increase self-reactive immune responses later in life are poorly understood. Autoimmune diseases require CD4(+) T cells for initiation, progression, and/or clinical symptoms; thus, developmental exposures that cause durable changes in CD4(+) T cells may play a role. Early life activation of the aryl hydrocarbon receptor (AHR) causes persistent changes in the response of CD4(+) T cells to infection later in life but whether CD4(+) T cells are affected by developmental exposure in the context of an autoimmune disease is unknown. Gnaq(+/-) mice develop symptoms of autoimmune disease similar to those measured clinically, and therefore can be used to evaluate gene-environment interactions during development on disease progression. Herein, we examined the effect of AHR activation in utero and via lactation, or solely via lactation, on disease onset and severity in adult Gnaq(+/-) offspring. Developmental activation of the AHR-accelerated disease in Gnaq(+/-) mice, and this correlates with increases in effector CD4(+) T-cell populations. Increased symptom onset and cellular changes due to early life AHR activation were more evident in female Gnaq(+/-) mice compared with males. These observations suggest that developmental AHR activation by pollutants, and other exogenous ligands, may increase the likelihood that genetically predisposed individuals will develop clinical symptoms of autoimmune disease later in life.

  11. Modelling the inner debris disc of HR 8799

    NASA Astrophysics Data System (ADS)

    Contro, B.; Horner, J.; Wittenmyer, R. A.; Marshall, J. P.; Hinse, T. C.

    2016-11-01

    In many ways, the HR 8799 planetary system strongly resembles our own. It features four giant planets and two debris belts, analogues to the Asteroid and Edgeworth-Kuiper belts. Here, we present the results of dynamical simulations of HR8799's inner debris belt, to study its structure and collisional environment. Our results suggest that HR 8799's inner belt is highly structured, with gaps between regions of dynamical stability. The belt is likely constrained between sharp inner and outer edges, located at ˜6 and ˜8 au, respectively. Its inner edge coincides with a broad gap cleared by the 4:1 mean-motion resonance with HR 8799e. Within the belt, planetesimals are undergoing a process of collisional attrition like that observed in the Asteroid belt. However, whilst the mean collision velocity in the Asteroid belt exceeds 5 km s-1, the majority of collisions within HR 8799's inner belt occur with velocities of order 1.2 km s-1, or less. Despite this, they remain sufficiently energetic to be destructive - giving a source for the warm dust detected in the system. Interior to the inner belt, test particles remain dynamically unstirred, aside from narrow bands excited by distant high-order resonances with HR 8799e. This lack of stirring is consistent with earlier thermal modelling of HR 8799's infrared excess, which predicted little dust inside 6 au. The inner system is sufficiently stable and unstirred that the formation of telluric planets is feasible, although such planets would doubtless be subject to a punitive impact regime, given the intense collisional grinding required in the inner belt to generate the observed infrared excess.

  12. Afghanistan and Pakistan Reconstruction Opportunity Zones (ROZs), H.R. 1318/H.R. 1886/H.R. 2410 and S. 496: Issues and Arguments

    DTIC Science & Technology

    2009-07-09

    such they are self-contained islands of infrastructure necessary to support manufacturing , often located in relatively undeveloped geographic...President Obama in his March 27 announcement of a new U.S. strategy for Afghanistan and Pakistan. Proponents of the legislation see it as a way of promoting...Figures Figure 1. Areas of Afghanistan and Pakistan Eligible for Designation of Reconstruction Opportunity Zones (ROZs) as Provided for in H.R. 1318

  13. HR 7355 - another rapidly braking He-strong CP star?

    NASA Astrophysics Data System (ADS)

    Mikulášek, Z.; Krtička, J.; Henry, G. W.; de Villiers, S. N.; Paunzen, E.; Zejda, M.

    2010-02-01

    Context. Strong meridional mixing induced by rapid rotation is one reason why all hot main-sequence stars are not chemically peculiar. However, the finding that the He-strong CP star HR 7355 is a rapid rotator complicates this concept. Aims: Our goal is to explain the observed behaviour of HR 7355 based on period analysis of all available photometry. Methods: Over two years, we acquired 114 new BV observations of HR 7355 at observatories in Arizona, U.S.A and Cape Town, South Africa. We performed period analyses of the new observations along with new analyses of 732 archival measurements from the Hipparcos and ASAS projects. Results: We find that the light curves of HR 7355gt; in various filters are quite similar, with amplitudes 0.035(4), 0.036(4), and 0.038(3) mag in B, Hp, and V, respectively. The light curves are double-peaked, with unevenly deep minima. We substantially refine the rotational period to be P = 0.5214410(4)d, indicating that HR 7355gt; is the most rapidly rotating CP star known. Our period analyses reveal a possible lengthening of the rotational period with dot{P}/P = 2.4(8)×10-6 yr-1. Conclusions: We conclude that the shape and amplitude of HR 7355gt; light curves are typical of magnetic He-strong CP stars, for which light variations are the result of photospheric spots on the surface of a rotating star. We hypothesise that the light variations are caused mainly by an uneven distribution of overabundant helium on the star's surface. We briefly describe and discuss the cause of the rapid rotational braking of the star. Photometric data are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/511/L7

  14. Measured and predicted affinities of binding and relative potencies to activate the AhR of PAHs and their alkylated analogues.

    PubMed

    Lee, Sangwoo; Shin, Woong-Hee; Hong, Seongjin; Kang, Habyeong; Jung, Dawoon; Yim, Un Hyuk; Shim, Won Joon; Khim, Jong Seong; Seok, Chaok; Giesy, John P; Choi, Kyungho

    2015-11-01

    Polycyclic aromatic hydrocarbons (PAHs) and their alkylated forms are important components of crude oil. Both groups of PAHs have been reported to cause dioxin-like responses, mediated by aryl hydrocarbon receptor (AhR). Thus, characterization of binding affinity to the AhR of unsubstituted or alkylated PAHs is important to understand the toxicological consequences of oil contamination on ecosystems. We investigated the potencies of major PAHs of crude oil, e.g., chrysene, phenanthrene and dibenzothiophene, and their alkylated forms (n=17) to upregulate expression of AhR-mediated processes by use of the H4IIE-luc transactivation bioassay. In addition, molecular descriptors of different AhR activation potencies among PAHs were investigated by use of computational molecular docking models. Based on responses of the H4IIE-luc in vitro assay, it was shown that potencies of PAHs were determined by alkylation in addition to the number and conformation of rings. Potencies of AhR-mediated processes were generally greater when a chrysene group was substituted, especially in 1-methyl-chrysene. Significant negative correlations were observed between the in vitro dioxin-like potency measured in H4IIE-luc cells and the binding distance estimated from the in silico modeling. The difference in relative potency for AhR activation observed among PAHs and their alkylated forms could be explained by differences among binding distances in the ligand binding domain of the AhR caused by alkylation. The docking model developed in the present study may have utility in predicting risks of environmental contaminants of which toxicities are mediated by AhR binding.

  15. Disruption of period gene expression alters the inductive effects of dioxin on the AhR signaling pathway in the mouse liver

    SciTech Connect

    Qu Xiaoyu; Metz, Richard P.; Porter, Weston W.; Cassone, Vincent M.; Earnest, David J.

    2009-02-01

    The aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) are transcription factors that express Per-Arnt-Sim (PAS) DNA-binding motifs and mediate the metabolism of drugs and environmental toxins in the liver. Because these transcription factors interact with other PAS genes in molecular feedback loops forming the mammalian circadian clockworks, we determined whether targeted disruption or siRNA inhibition of Per1 and Per2 expression alters toxin-mediated regulation of the AhR signaling pathway in the mouse liver and Hepa1c1c7 hepatoma cells in vitro. Treatment with the prototypical Ahr ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), had inductive effects on the primary targets of AhR signaling, Cyp1A1 and Cyp1B1, in the liver of all animals, but genotype-based differences were evident such that the toxin-mediated induction of Cyp1A1 expression was significantly greater (2-fold) in mice with targeted disruption of Per1 (Per1{sup ldc} and Per1{sup ldc}/Per2{sup ldc}). In vitro experiments yielded similar results demonstrating that siRNA inhibition of Per1 significantly increases the TCDD-induced expression of Cyp1A1 and Cyp1B1 in Hepa1c1c7 cells. Per2 inhibition in siRNA-infected Hepa1c1c7 cells had the opposite effect and significantly decreased both the induction of these p450 genes as well as AhR and Arnt expression in response to TCDD treatment. These findings suggest that Per1 may play a distinctive role in modulating AhR-regulated responses to TCDD in the liver.

  16. Effects of 4-nitrophenol on expression of the ER-α and AhR signaling pathway-associated genes in the small intestine of rats.

    PubMed

    Tang, Juan; Song, Meiyan; Watanabe, Gen; Nagaoka, Kentaro; Rui, Xiaoli; Li, ChunMei

    2016-09-01

    4-Nitrophenol (PNP) is a persistent organic pollutant that was proven to be an environmental endocrine disruptor. The aim of this study was to evaluate the role of the estrogen receptor-α (ER-α) and aryl hydrocarbon receptor (AhR) signaling pathway in regulating the damage response to PNP in the small intestine of rats. Wistar-Imamichi male rats (21 d) were randomly divided into two groups: the control group and PNP group. Each group had three processes that were gavaged with PNP or vehicle daily: single dose (1 d), repeated dose (3 consecutive days) (3 d), and repeated dose with recovery (3 consecutive days and 3 recovery days) (6 d). The weight of the body, the related viscera, and small intestine were examined. Histological parameters of the small intestine and the quantity of mucus proteins secreted by small goblet cells were determined using HE staining and PAS staining. The mRNA expression of AhR, ER-α, CYP1A1, and GST was measured by real-time qPCR. In addition, we also analyzed the AhR, ER-α, and CYP1A1 expression in the small intestine by immunohistochemical staining. The small intestines histologically changed in the PNP-treated rat and the expression of AhR, CYP1A1, and GST was increased. While ER-α was significantly decreased in the small intestine, simultaneously, when rats were exposed to a longer PNP treatment, the damages disappeared. Our results demonstrate that PNP has an effect on the expression of AhR signaling pathway genes, AhR, CYP1A1, and GST, and ER-α in the rat small intestine.

  17. Combined chemical and toxicological long-term monitoring for AhR agonists with SPMD-based virtual organisms in drinking water Danjiangkou Reservoir, China.

    PubMed

    Wang, Jingxian; Song, Guoqiang; Li, Aimin; Henkelmann, Bernhard; Pfister, Gerd; Tong, Anthony Z; Schramm, Karl-Werner

    2014-08-01

    SPMD-based virtual organisms (VOs) were employed for time-integrating, long-term sampling combined biological and chemical analyses for exposure assessment of hydrophobic organic pollutants (HOPs) in a drinking water reservoir, China. The SPMDs were deployed at four and five sites in the Danjiangkou (DJK) reservoir over two periods of 26 and 31 d to sequester the hydrophobic contaminants in water. The chosen bioassay response for the extracts of the SPMDs, the induction of 7-ethoxyresorufin-o-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The known aryl hydrocarbon receptor (AhR) agonists PAHs and PCBs were analyzed by HRGC/HRMS instrument. The cause-effect relationship between the observed AhR activities and chemical concentrations of detected AhR agonists was examined. The results show that the extracts from the SPMD samples could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) was not correlated with the bioassay-derived TCDD equivalent (TEQbio). The known AhR agonists could only account for 2-10% of the observed AhR responses among which the contribution of PCBs could almost be neglected. Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent (TCDD-EQ) in SPMD samples from DJK. Based on the first assessment, the VO followed by the combination of chemical and biological analyses emerges as a resource efficient water monitoring device in ecotoxicological assessment for toxicologically relevant compounds which are readily available for uptake by resident aquatic biota in drinking water resources.

  18. The fate of the solid matter orbiting HR 4796A

    NASA Technical Reports Server (NTRS)

    Jura, M.; Ghez, A. M.; White, Russell J.; Mccarthy, D. W.; Smith, R. C.; Martin, P. G.

    1995-01-01

    We have obtained optical spectra, 2 micrometers speckle images, and an upper limit to the 800 micrometers flux for HR 4796A, and optical spectra for its physical companion separated by 7.7 arcsecs, HR 4796B. We detect H-beta, H-gamma, and the calcium H and K lines in emission from HR 4796B; these data are consistent with the hypothesis that it is later than spectral type M2 and lies substantially above the main-sequence. From the location of HR 4796B on the H-R diagram, the estimated age of this star is 3 x 10(exp 6) yr, and assuming this age for the entire system, we find from our 2 micrometers speckle data that there is no close stellar companion to HR 4796A (M greater than 0.125 solar mass) between 11 and 120 AU from the star. From the IRAS and ground-based photometry, it seems that there is a hole in the dust distribution around HR 4796A with an inner radius of between approximately 40 and approximately 200 AU. The observed circumstellar dust grains, which lie at D greater than 40 AU from the star, are likely to be at least 3 micrometers in radius in order to be gravitationally bound to HR 4796A, if the circumstellar dust cloud is optically thin. Since they are larger than almost all interstellar grains, the circumstellar dust grains probably grew by coalescence. Because the existing grains at D greater than 40 AU have undergone measurable coalescence, it is possible that particles that presumably once existed at D less than 40 AU, where the collision times were shorter than at D greater than 40 AU, grew into macroscopic objects. A likely explanation for the dust hole is that there is a companion located at about half the inner radius of the dust hole, or between 20 and 100 AU from the star. If such a companion exists, it must have a mass less than 0.125 solar mass. Since grain coalescence has occurred, this putative companion possibly could be a planet.

  19. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    SciTech Connect

    Cheng, Ya-Hsin; Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan; Hung, Chein-Hui; Chang, Nai Wen; Lin, Chingju

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  20. Robust root growth in altered hydrotropic response1 (ahr1) mutant of Arabidopsis is maintained by high rate of cell production at low water potential gradient.

    PubMed

    Salazar-Blas, Amed; Noriega-Calixto, Laura; Campos, María E; Eapen, Delfeena; Cruz-Vázquez, Tania; Castillo-Olamendi, Luis; Sepulveda-Jiménez, Gabriela; Porta, Helena; Dubrovsky, Joseph G; Cassab, Gladys I

    2017-01-01

    Hydrotropism is the directional root growth response determined by water stimulus. In a water potential gradient system (WPGS) the roots of the Arabidopsis wild type have a diminished root growth compared to normal medium (NM). In contrast, the altered hydrotropic response1 (ahr1) mutant roots maintain their robust growth in the same WPGS. The aims of this work were to ascertain how ahr1 roots could sustain growth in the WPGS, with a special focus on the integration of cellular processes involved in the signaling that determines root growth during abiotic stress and their relation to hydrotropism. Cellular analysis of the root apical meristem of ahr1 mutant contrary to the wild type showed an absence of changes in the meristem length, the elongation zone length, the length of fully elongated cells, and the cell cycle duration. The robust and steady root growth of ahr1 seedlings in the WPGS is explained by the mutant capacity to maintain cell production and cell elongation at the same level as in the NM. Analysis of auxin response at a transcriptional level showed that roots of the ahr1 mutant had a lower auxin response when grown in the WPGS, compared to wild type, indicating that auxin signaling participates in attenuation of root growth under water stress conditions. Also, wild type plants exhibited a high increase in proline content while ahr1 mutants showed minimum changes in the Normal Medium→Water Stress Medium (NM→WSM), a lower water potential gradient system than the WPGS. Accordingly, in this condition, gene expression of Δ1-6 Pyrroline-5-Carboxylate Synthetase1 (P5CS1) involved in proline synthesis strongly increased in wild type but not in ahr1 seedlings. The ahr1 phenotype shows unique features since the mutant root cells continue to proliferate and grow in the presence of a progressively negative water potential gradient at a level comparable to wild type growing in the NM. As such, it represents an exceptional resource for understanding

  1. In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

    PubMed Central

    Curran, Christine P.; Genter, Mary Beth; Patel, Krishna V.; Schaefer, Tori L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

    2011-01-01

    Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response. Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs. Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors. Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on

  2. Teaching HR Professionals: The Classroom as a Community of Practice

    ERIC Educational Resources Information Center

    Rowlands, Kate; Avramenko, Alex

    2013-01-01

    This paper introduces an innovative course design incorporating both communities of practice and reflective practice as a learning strategy for part-time learners in higher education. The new design has been applied to teaching HR practitioners in a UK-based business school. Findings indicate that the suggested way of organizing teaching and…

  3. Learning Culture, Line Manager and HR Professional Practice

    ERIC Educational Resources Information Center

    Harrison, Patricia

    2011-01-01

    Purpose: This paper aims to focus on the role of line management and learning culture in the development of professional practice for the human resource (HR) practitioner. Design/methodology/approach: Three-year longitudinal, matched-pair study involving five participants and their line managers. Findings: Two of the five participants experienced…

  4. An Ounce of Prevention: The Benefits of an HR Audit

    ERIC Educational Resources Information Center

    Seals, Brenda

    2011-01-01

    During her 13 years leading a school district human resources office, the author came to recognize that managing human capital is much more than recruiting, hiring, managing personnel records, and handling performance issues. In addition to implementing initiatives to increase the efficiency with which HR officers and staff perform those tasks,…

  5. DISCOVERY OF A LOW-MASS COMPANION AROUND HR 3549

    SciTech Connect

    Mawet, D.; David, T.; Bottom, M.; Hinkley, S.; Stapelfeldt, K.; Padgett, D.; Mennesson, B.; Serabyn, E.; Morales, F.; Kuhn, J.

    2015-10-01

    We report the discovery of a low-mass companion to HR 3549, an A0V star surrounded by a debris disk with a warm excess detected by WISE at 22 μm (10σ significance). We imaged HR 3549 B in the L band with NAOS-CONICA, the adaptive optics infrared camera of the Very Large Telescope, in January 2013 and confirmed its common proper motion in 2015 January. The companion is at a projected separation of ≃80 AU and position angle of ≃157°, so it is orbiting well beyond the warm disk inner edge of r > 10 AU. Our age estimate for this system corresponds to a companion mass in the range 15–80 M{sub J}, spanning the brown dwarf regime, and so HR 3549 B is another recent addition to the growing list of brown dwarf desert objects with extreme mass ratios. The simultaneous presence of a warm disk and a brown dwarf around HR 3549 provides interesting empirical constraints on models of the formation of substellar companions.

  6. HR Manager Leadership in Quality Improvement in a College Environment

    ERIC Educational Resources Information Center

    Sharabi, Moshe

    2010-01-01

    Purpose: The purpose of this paper is to present the influence of the human resource (HR) manager on the quality of service in an academic college, and the human resource management (HRM) outcomes of the process. Design/methodology/approach: The paper relates to a customer satisfaction survey. More than 120 questionnaires were completed by the…

  7. Bumping HR: Giving Principals More Say over Staffing

    ERIC Educational Resources Information Center

    National Council on Teacher Quality, 2010

    2010-01-01

    In what may come as a surprise to many, principals have remarkably little control over who teaches in their schools. For the most part, the human resources (HR) department in a district's central office, not individual school principals, makes the final call about when to hire teachers, whom to hire and in which schools they are placed.…

  8. USE OF THE TEQ MODEL FOR ASSESSING AHR MEDIATED TOXICITY RISKS TO POPULATIONS OF LAKE TROUT AND OTHER SPECIES IN LAKE ONTARIO

    EPA Science Inventory

    The toxicity equivalence (TEQ) model for assessing aryl hydrocarbon receptor (AHR) mediated toxicity risks associated with polyhalogenated aromatic chemicals structurally similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been applied to human health risks for more than 15...

  9. Effect of TBT and PAHs on CYP1A, AhR and Vitellogenin Gene Expression in the Japanese Eel, Anguilla japonica.

    PubMed

    Choi, Min Seop; Kwon, Se Ryun; Choi, Seong Hee; Kwon, Hyuk Chu

    2012-12-01

    Gene expressions of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor (AhR) and vitellogenin (Vg) by endocrine disruptors, benzo[α]pyrene (B[a]P) and tributyltin (TBT) were examined in cultured eel hepatocytes which were isolated from eels treated previously with B[a]P (10 mg/kg) or estradiol-17β (20 mg/kg) in vivo, and the relationship between CYP1A, AhR and Vg genes were studied. When the cultured eel hepatocytes were treated with B[a]P (10(-6)-10(-5) M) the gene expressions of CYP1A and AhR were enhanced in a concentration-dependent manner. However, when treated with TBT (10(-9)-10(-5) M) the gene expressions of CYP1A and AhR were suppressed at high concentrations (10(-6)-10(-5) M), while having no effects at low concentrations (10(-9)-10(-7) M). Gene expression of Vg was also suppressed by TBT in a concentration-dependent manner in cultured eel hepatocytes which was previously treated in vivo with estradiol-17β.

  10. Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.

    PubMed

    Kamenickova, Alzbeta; Pecova, Michaela; Bachleda, Petr; Dvorak, Zdenek

    2013-12-01

    Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1.

  11. Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish

    SciTech Connect

    Jönsson, Maria E.; Kubota, Akira; Timme-Laragy, Alicia R.; Woodin, Bruce; Stegeman, John J.

    2012-12-01

    The teleost swim bladder is assumed a homolog of the tetrapod lung. Both swim bladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR) agonists; in zebrafish (Danio rerio) the swim bladder fails to inflate with exposure to 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P450 1 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swim bladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependence of the effect of PCB126 on swim bladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24 h and then held in clean water until day 4, a normal time for swim bladder inflation. The effects of PCB126 were concentration-dependent with EC{sub 50} values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swim bladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swim bladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2 nM PCB126 approximately 30% of eleutheroembryos failed to inflate the swim bladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swim bladder. Our results indicate that PCB126 blocks swim bladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swim bladder cells. -- Highlights: ► PCB126 caused cellular changes in the developing swim bladder. ► Swim bladder inflation was not related to expression of CYP1 or cox

  12. Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation

    PubMed Central

    Corrada, Dario; Soshilov, Anatoly A.; Denison, Michael S.

    2016-01-01

    The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the

  13. Abundance Analysis of the Silicon Star HR 6958

    NASA Astrophysics Data System (ADS)

    Kato, Ken-Ichi

    2003-12-01

    The elemental composition of the chemically peculiar star HR6958 has been studied with emphasis on doubly ionized rare earths. A visual region spectrum taken with the ELODIE spectrograph at the Haute-Provence Observatory was analyzed. A total of 40 elements including Pr III, Nd III, Tb III, Dy III, Ho III, and Er III were identified and their abundances computed. He is deficient by over 1dex with respect to the Sun; the light elements (C-Ca), except for Si, have solar abundances; the iron group elements (Sc-Fe) are overabundant by 1 dex to 2dex, with Ti and Cr highly overabundant; and the lanthanide rare earths are overabundant by 3dex to 4dex. This abundance pattern with He deficient, Si, Ti, Cr, Sr, and Pr overabundant indicates that HR6958 is a member of Si stars.

  14. Regulation of Ahr signaling by Nrf2 during development: Effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio).

    PubMed

    Rousseau, Michelle E; Sant, Karilyn E; Borden, Linnea R; Franks, Diana G; Hahn, Mark E; Timme-Laragy, Alicia R

    2015-10-01

    The embryotoxicity of co-planar PCBs is regulated by the aryl hydrocarbon receptor (Ahr), and has been reported to involve oxidative stress. Ahr participates in crosstalk with another transcription factor, Nfe2l2, or Nrf2. Nrf2 binds to antioxidant response elements to regulate the adaptive response to oxidative stress. To explore aspects of the crosstalk between Nrf2 and Ahr and its impact on development, we used zebrafish (Danio rerio) with a mutated DNA binding domain in Nrf2a (nrf2a(fh318/fh318)), rendering these embryos more sensitive to oxidative stress. Embryos were exposed to 2 nM or 5 nM PCB126 at 24 h post fertilization (prim-5 stage of pharyngula) and examined for gene expression and morphology at 4 days post fertilization (dpf; protruding - mouth stage). Nrf2a mutant eleutheroembryos were more sensitive to PCB126 toxicity at 4 dpf, and in the absence of treatment also displayed some subtle developmental differences from wildtype embryos, including delayed inflation of the swim bladder and smaller yolk sacs. We used qPCR to measure changes in expression of the nrf gene family, keap1a, keap1b, the ahr gene family, and known target genes. cyp1a induction by PCB126 was enhanced in the Nrf2a mutants (156-fold in wildtypes vs. 228-fold in mutants exposed to 5 nM). Decreased expression of heme oxygenase (decycling) 1 (hmox1) in the Nrf2a mutants was accompanied by increased nrf2b expression. Target genes of Nrf2a and AhR2, NAD(P)H:quinone oxidoreductase 1 (nqo1) and glutathione S-transferase, alpha-like (gsta1), showed a 2-5-fold increase in expression in the Nrf2a mutants as compared to wildtype. This study elucidates the interaction between two important transcription factor pathways in the developmental toxicity of co-planar PCBs.

  15. Evaluation of the Enterococcus faecalis Biofilm-Associated Virulence Factors AhrC and Eep in Rat Foreign Body Osteomyelitis and In Vitro Biofilm-Associated Antimicrobial Resistance

    PubMed Central

    Frank, Kristi L.; Vergidis, Paschalis; Brinkman, Cassandra L.; Greenwood Quaintance, Kerryl E.; Barnes, Aaron M. T.; Mandrekar, Jayawant N.; Schlievert, Patrick M.; Dunny, Gary M.; Patel, Robin

    2015-01-01

    Enterococcus faecalis can cause healthcare-associated biofilm infections, including those of orthopedic devices. Treatment of enterococcal prosthetic joint infection is difficult, in part, due to biofilm-associated antimicrobial resistance. We previously showed that the E. faecalis OG1RF genes ahrC and eep are in vitro biofilm determinants and virulence factors in animal models of endocarditis and catheter-associated urinary tract infection. In this study, we evaluated the role of these genes in a rat acute foreign body osteomyelitis model and in in vitro biofilm-associated antimicrobial resistance. Osteomyelitis was established for one week following the implantation of stainless steel orthopedic wires inoculated with E. faecalis strains OG1RF, ΩahrC, and ∆eep into the proximal tibiae of rats. The median bacterial loads recovered from bones and wires did not differ significantly between the strains at multiple inoculum concentrations. We hypothesize that factors present at the infection site that affect biofilm formation, such as the presence or absence of shear force, may account for the differences in attenuation in the various animal models we have used to study the ΩahrC and ∆eep strains. No differences among the three strains were observed in the planktonic and biofilm antimicrobial susceptibilities to ampicillin, vancomycin, daptomycin, linezolid, and tetracycline. These findings suggest that neither ahrC nor eep directly contribute to E. faecalis biofilm-associated antimicrobial resistance. Notably, the experimental evidence that the biofilm attachment mutant ΩahrC displays biofilm-associated antimicrobial resistance suggests that surface colonization alone is sufficient for E. faecalis cells to acquire the biofilm antimicrobial resistance phenotype. PMID:26076451

  16. Mixed-ligand copper(II) complexes activate aryl hydrocarbon receptor AhR and induce CYP1A genes expression in human hepatocytes and human cell lines.

    PubMed

    Kubešová, Kateřina; Dořičáková, Aneta; Trávníček, Zdeněk; Dvořák, Zdeněk

    2016-07-25

    The effects of four copper(II) mixed-ligand complexes [Cu(qui1)(L)]NO3·H2O (1-3) and [Cu(qui2)(phen)]NO3 (4), where qui1=2-phenyl-3-hydroxy-4(1H)-quinolinone, Hqui2=2-(4-amino-3,5-dichlorophenyl)-N-propyl-3-hydroxy-4(1H)-quinolinone-7-carboxamide, L=1,10-phenanthroline (phen) (1), 5-methyl-1,10-phenanthroline (mphen) (2), bathophenanthroline (bphen) (3), on transcriptional activities of steroid receptors, nuclear receptors and xenoreceptors have been studied. The complexes (1-4) did not influence basal or ligand-inducible activities of glucocorticoid receptor, androgen receptor, thyroid receptor, pregnane X receptor and vitamin D receptor, as revealed by gene reporter assays. The complexes 1 and 2 dose-dependently induced luciferase activity in stable gene reporter AZ-AhR cell line, and this induction was reverted by resveratrol, indicating involvement of aryl hydrocarbon receptor (AhR) in the process. The complexes 1, 2 and 3 induced CYP1A1 mRNA in LS180 cells and CYP1A1/CYP1A2 in human hepatocytes through AhR. Electrophoretic mobility shift assay EMSA showed that the complexes 1 and 2 transformed AhR in its DNA-binding form. Collectively, we demonstrate that the complexes 1 and 2 activate AhR and induce AhR-dependent genes in human hepatocytes and cancer cell lines. In conclusion, the data presented here might be of toxicological importance, regarding the multiple roles of AhR in human physiology and pathophysiology.

  17. Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma.

    PubMed

    Gil Del Alcazar, Carlos Rodrigo; Todorova, Pavlina Krasimirova; Habib, Amyn A; Mukherjee, Bipasha; Burma, Sandeep

    2016-10-01

    Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults and is universally fatal. The DNA alkylating agent temozolomide is part of the standard-of-care for GBM. However, these tumors eventually develop therapy-driven resistance and inevitably recur. While loss of mismatch repair (MMR) and re-expression of MGMT have been shown to underlie chemoresistance in a fraction of GBMs, resistance mechanisms operating in the remaining GBMs are not well understood. To better understand the molecular basis for therapy-driven temozolomide resistance, mice bearing orthotopic GBM xenografts were subjected to protracted temozolomide treatment, and cell lines were generated from the primary (untreated) and recurrent (temozolomide-treated) tumors. As expected, the cells derived from primary tumors were sensitive to temozolomide, whereas the cells from the recurrent tumors were significantly resistant to the drug. Importantly, the acquired resistance to temozolomide in the recurrent lines was not driven by re-expression of MGMT or loss of MMR but was due to accelerated repair of temozolomide-induced DNA double-strand breaks (DSB). Temozolomide induces DNA replication-associated DSBs that are primarily repaired by the homologous recombination (HR) pathway. Augmented HR appears to underpin temozolomide resistance in the recurrent lines, as these cells were cross-resistant to other agents that induced replication-associated DSBs, exhibited faster resolution of damage-induced Rad51 foci, and displayed higher levels of sister chromatid exchanges (SCE). Furthermore, in light of recent studies demonstrating that CDK1 and CDK2 promote HR, it was found that CDK1/2 inhibitors countered the heightened HR in recurrent tumors and sensitized these therapy-resistant tumor cells to temozolomide.

  18. The Dynamical Structure of HR 8799's Inner Debris Disk.

    PubMed

    Contro, B; Wittenmyer, Robert A; Horner, J; Marshall, Jonathan P

    2015-06-01

    The HR 8799 system, with its four giant planets and two debris belts, has an architecture closely mirroring that of our Solar system where the inner, warm asteroid belt and outer, cool Edgeworth-Kuiper belt bracket the giant planets. As such, it is a valuable laboratory for examining exoplanetary dynamics and debris disk-exoplanet interactions. Whilst the outer debris belt of HR 8799 has been well resolved by previous observations, the spatial extent of the inner disk remains unknown. This leaves a significant question mark over both the location of the planetesimals responsible for producing the belt's visible dust and the physical properties of those grains. We have performed the most extensive simulations to date of the inner, unresolved debris belt around HR 8799, using UNSW Australia's Katana supercomputing facility to follow the dynamical evolution of a model inner disk comprising 300,298 particles for a period of 60 Ma. These simulations have enabled the characterisation of the extent and structure of the inner disk in detail, and will in future allow us to provide a first estimate of the small-body impact rate and water delivery prospects for possible (as-yet undetected) terrestrial planet (s) in the inner system.

  19. PHF11 promotes DSB resection, ATR signaling, and HR.

    PubMed

    Gong, Yi; Handa, Naofumi; Kowalczykowski, Stephen C; de Lange, Titia

    2017-01-01

    Resection of double-strand breaks (DSBs) plays a critical role in their detection and appropriate repair. The 3' ssDNA protrusion formed through resection activates the ATR-dependent DNA damage response (DDR) and is required for DSB repair by homologous recombination (HR). Here we report that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5' end resection, ATR signaling, and HR. PHF11 was identified based on its association with deprotected telomeres and localized to sites of DNA damage in S phase. Depletion of PHF11 diminished the ATR signaling response to telomere dysfunction and genome-wide DNA damage, reduced end resection at sites of DNA damage, resulted in compromised HR and misrejoining of S-phase DSBs, and increased the sensitivity to DNA-damaging agents. PHF11 interacted with the ssDNA-binding protein RPA and was found in a complex with several nucleases, including the 5' dsDNA exonuclease EXO1. Biochemical experiments demonstrated that PHF11 stimulates EXO1 by overcoming its inhibition by RPA, suggesting that PHF11 acts (in part) by promoting 5' end resection at RPA-bound sites of DNA damage. These findings reveal a role for PHF11 in DSB resection, DNA damage signaling, and DSB repair.

  20. PHF11 promotes DSB resection, ATR signaling, and HR

    PubMed Central

    Gong, Yi; Handa, Naofumi; Kowalczykowski, Stephen C.; de Lange, Titia

    2017-01-01

    Resection of double-strand breaks (DSBs) plays a critical role in their detection and appropriate repair. The 3′ ssDNA protrusion formed through resection activates the ATR-dependent DNA damage response (DDR) and is required for DSB repair by homologous recombination (HR). Here we report that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5′ end resection, ATR signaling, and HR. PHF11 was identified based on its association with deprotected telomeres and localized to sites of DNA damage in S phase. Depletion of PHF11 diminished the ATR signaling response to telomere dysfunction and genome-wide DNA damage, reduced end resection at sites of DNA damage, resulted in compromised HR and misrejoining of S-phase DSBs, and increased the sensitivity to DNA-damaging agents. PHF11 interacted with the ssDNA-binding protein RPA and was found in a complex with several nucleases, including the 5′ dsDNA exonuclease EXO1. Biochemical experiments demonstrated that PHF11 stimulates EXO1 by overcoming its inhibition by RPA, suggesting that PHF11 acts (in part) by promoting 5′ end resection at RPA-bound sites of DNA damage. These findings reveal a role for PHF11 in DSB resection, DNA damage signaling, and DSB repair. PMID:28115467

  1. HR4EU--A Web-Portal for E-Learning of Croatian

    ERIC Educational Resources Information Center

    Filko, Matea; Farkaš, Daša; Hriberski, Diana

    2016-01-01

    In this paper, we present the HR4EU--a web portal for e-learning of Croatian. HR4EU is the first portal that offers Croatian language courses which are free-of-charge and developed by language professionals. Moreover, HR4EU also integrates bidirectional interaction with some of the previously developed language resources for Croatian. The HR4EU…

  2. NEW PRECISION ORBITS OF BRIGHT DOUBLE-LINED SPECTROSCOPIC BINARIES. IV. 66 ANDROMEDAE, HR 6979, AND HR 9059

    SciTech Connect

    Fekel, Francis C.; Williamson, Michael H.; Tomkin, Jocelyn E-mail: jt@alexis.as.utexas.edu

    2010-04-15

    We have determined improved spectroscopic orbits for three double-lined binaries, 66 And (F4 V), HR 6979 (Am), and HR 9059 (F5 IV) using radial velocities from the 2.1 m telescope at McDonald Observatory, the coude feed telescope at Kitt Peak National Observatory, and 2 m telescope at Fairborn Observatory. The orbital periods range from 11.0 to 14.3 days, and all three systems have eccentric orbits. The new orbital dimensions (a {sub 1} sin i and a {sub 2} sin i) and minimum masses (m {sub 1} sin{sup 3} i and m {sub 2} sin{sup 3} i) have accuracies of 0.2% or better. All six components of the three binary systems are rotating more slowly than their predicted pseudosynchronous rotational velocities. Hipparcos photometry of HR 9059 shows that this system has partial eclipses. Its components are nearly identical in mass and are at the very end of their main-sequence lifetimes or perhaps have just begun to traverse the Hertsprung gap.

  3. Everolimus-Based Therapy versus Chemotherapy among Patients with HR+/HER2- Metastatic Breast Cancer: Comparative Effectiveness from a Chart Review Study.

    PubMed

    Li, Nanxin; Hao, Yanni; Xie, Jipan; Lin, Peggy L; Koo, Valerie; Ohashi, Erika; Wu, Eric Q

    2015-01-01

    Objective. To compare the real-world effectiveness of everolimus-based therapy and chemotherapy in postmenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC). Methods. This retrospective chart review examined a nationwide sample of postmenopausal HR+/HER2- mBC women in community-based oncology practices. Patients received everolimus-based therapy or chemotherapy for mBC between 07/01/2012 and 04/15/2013, after failure of a non-steroidal aromatase inhibitor. Overall survival (OS), progression-free survival (PFS), and time on treatment (TOT) were compared using Kaplan-Meier analysis and Cox proportional hazards models adjusting for line of therapy and baseline characteristics. Results. 234 and 137 patients received everolimus-based therapy and chemotherapy. Patients treated with everolimus-based therapy tended to have less aggressive mBC than patients treated with chemotherapy. Multivariate-adjusted Cox models showed that everolimus-based therapy was associated with significantly longer OS [hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.22-0.63], PFS (HR = 0.70, 95% CI = 0.50-0.97), and TOT (HR = 0.34, 95% CI: 0.25-0.45) than chemotherapy. Adjusted comparative effectiveness results were generally consistent across lines of therapy. Conclusion. In this retrospective chart review of postmenopausal HR+/HER2- mBC patients, treatment with everolimus-based therapy was associated with longer OS, PFS, and TOT than chemotherapy.

  4. Benzimidazoisoquinolines: A New Class of Rapidly Metabolized Aryl Hydrocarbon Receptor (AhR) Ligands that Induce AhR-Dependent Tregs and Prevent Murine Graft-Versus-Host Disease

    PubMed Central

    Punj, Sumit; Kopparapu, Prasad; Jang, Hyo Sang; Phillips, Jessica L.; Pennington, Jamie; Rohlman, Diana; O’Donnell, Edmond; Iversen, Patrick L.; Kolluri, Siva Kumar; Kerkvliet, Nancy I.

    2014-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays multiple roles in regulation of immune and inflammatory responses. The ability of certain AhR ligands to induce regulatory T cells (Tregs) has generated interest in developing AhR ligands for therapeutic treatment of immune-mediated diseases. To this end, we designed a screen for novel Treg-inducing compounds based on our understanding of the mechanisms of Treg induction by the well-characterized immunosuppressive AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We screened a ChemBridge small molecule library and identified 10-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (10-Cl-BBQ) as a potent AhR ligand that was rapidly metabolized and not cytotoxic to proliferating T cells. Like TCDD,10-Cl-BBQ altered donor CD4+ T cell differentiation during the early stages of a graft versus host (GVH) response resulting in expression of high levels of CD25, CTLA-4 and ICOS, as well as several genes associated with Treg function. The Treg phenotype required AhR expression in the donor CD4+ T cells. Foxp3 was not expressed in the AhR-induced Tregs implicating AhR as an independent transcription factor for Treg induction. Structure-activity studies showed that unsubstituted BBQ as well as 4, 11-dichloro-BBQ were capable of inducing AhR-Tregs. Other substitutions reduced activation of AhR. Daily treatment with 10-Cl-BBQ during the GVH response prevented development of GVH disease in an AhR-dependent manner with no overt toxicity. Together, our data provide strong support for development of select BBQs that activate the AhR to induce Tregs for treatment of immune-mediated diseases. PMID:24586378

  5. Hepatoprotective and antioxidant effects of dietary Glycyrrhiza polysaccharide against TCDD-induced hepatic injury and RT-PCR quantification of AHR2, ARNT2, CYP1A mRNA in Jian Carp (Cyprinus carpio var. Jian).

    PubMed

    Du, Jinliang; Cao, Liping; Jia, Rui; Yin, Guojun

    2017-01-01

    To evaluate the protective effects of Glycyrrhiza polysaccharide (GPS) against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hepatotoxicity in Jian carp, the fish were fed diets containing GPS at doses of 0.1, 0.5 and 1.0g/kg for 60days before an intraperitoneal injection of 0.6μg/kg TCDD at a volume of 0.05mL/10g body weight. At 72hr post-injection, blood and liver samples were taken for biochemical analysis and the fish liver samples were used for the preparation of pathological slices. The results showed that increases in alanine aminotransferase (GPT), aspartate aminotransferase (GOT), lactate dehydrogenase (LDH), and alkaline phosphatase (AKP) in serum induced by TCDD were significantly inhibited by pre-treatment with 1.0g/kg GPS. Following the 1.0g/kg GPS pre-treatment, total protein (TP), albumin (Alb), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activities in liver tissue increased significantly, malondialdehyde (MDA) formation (P<0.05 or P<0.01) was significantly inhibited, and the expression of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor 2 (AHR2) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) mRNA (P<0.05) was significantly enhanced. Histological observations on fish liver were obtained by preparing paraffin tissue sections via HE staining, and the results showed that histological changes were obviously reduced by 0.5 and 1.0g/kg GPS. GPS significantly reduced liver tissue damage caused by TCDD. Overall, these results proved the hepatoprotective effect of GPS in protecting against fish liver injury induced by TCDD, and supported the use of GPS (1.0g/kg) as a hepatoprotective and antioxidant agent in fish.

  6. Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish.

    PubMed

    Jönsson, Maria E; Kubota, Akira; Timme-Laragy, Alicia R; Woodin, Bruce; Stegeman, John J

    2012-12-01

    The teleost swim bladder is assumed a homolog of the tetrapod lung. Both swim bladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR(2)) agonists; in zebrafish (Danio rerio) the swim bladder fails to inflate with exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P450 1 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swim bladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependence of the effect of PCB126 on swim bladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24h and then held in clean water until day 4, a normal time for swim bladder inflation. The effects of PCB126 were concentration-dependent with EC(50) values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swim bladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swim bladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2nM PCB126 approximately 30% of eleutheroembryos(3) failed to inflate the swim bladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swim bladder. Our results indicate that PCB126 blocks swim bladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swim bladder cells.

  7. 10 MMBt/Hr AFBC Commercial Demonstration Cedar Lane Farms

    SciTech Connect

    Harold M. Keener; Mary H. Wicks; Tom Machamer; Dave Hoecke; Don Bonk; Bob Brown

    2005-10-31

    The objective of this project was to demonstrate and promote the commercialization of coal-fired atmospheric fluidized bed combustion (AFBC) systems, with limestone addition for SO2 emissions control and a baghouse for particulate emissions control. This AFBC system was targeted for small scale industrial-commercial-institutional space and process heat applications in the 4-40 MMBtu/hr size range. A cost effective and environmentally acceptable AFBC technology in this size range could displace a considerable amount of heating gas and oil with coal, while resulting in significant total cost savings to the owner/operators.

  8. Is the HR8799 extrasolar system destined for planetary scattering?

    NASA Astrophysics Data System (ADS)

    Goździewski, Krzysztof; Migaszewski, Cezary

    2009-07-01

    The recent discovery of a three-planet extrasolar system of HR8799 by Marois et al. is a breakthrough in the field of the direct imaging. This great achievement raises questions on the formation and dynamical stability of the system, because Keplerian fits to astrometric data disrupt during ~0.2Myr. We search for stable, self-consistent N-body orbits with the so-called GAMP (genetic algorithm with MEGNO penalty) method that incorporates stability constraints into the optimization algorithm. Our searches reveal only small regions of stable motions in the phase space of three-planet, coplanar configurations. Most likely, if the planetary masses are in 10MJ range, they may be stable only if the planets are involved in two- or three-body mean motion resonances (MMRs). We found that 80 per cent systems found by GAMP that survived 30Myr backwards integrations, eventually become unstable after 100Myr. It could mean that the HR8799 system undergo a phase of planet-planet scattering. We test a hypothesis that the less certain detection of the innermost object is due to a blending effect. In such a case, two-planet best-fitting systems are mostly stable, on quasi-circular orbits and close to the 5:2 MMR, resembling the Jupiter-Saturn pair.

  9. Images of a fourth planet orbiting HR 8799.

    PubMed

    Marois, Christian; Zuckerman, B; Konopacky, Quinn M; Macintosh, Bruce; Barman, Travis

    2010-12-23

    High-contrast near-infrared imaging of the nearby star HR 8799 has shown three giant planets. Such images were possible because of the wide orbits (>25 astronomical units, where 1 au is the Earth-Sun distance) and youth (<100 Myr) of the imaged planets, which are still hot and bright as they radiate away gravitational energy acquired during their formation. An important area of contention in the exoplanet community is whether outer planets (>10 au) more massive than Jupiter form by way of one-step gravitational instabilities or, rather, through a two-step process involving accretion of a core followed by accumulation of a massive outer envelope composed primarily of hydrogen and helium. Here we report the presence of a fourth planet, interior to and of about the same mass as the other three. The system, with this additional planet, represents a challenge for current planet formation models as none of them can explain the in situ formation of all four planets. With its four young giant planets and known cold/warm debris belts, the HR 8799 planetary system is a unique laboratory in which to study the formation and evolution of giant planets at wide (>10 au) separations.

  10. Modeling the Asteroseismic Surface Term across the HR Diagram

    NASA Astrophysics Data System (ADS)

    Schmitt, Joseph R.; Basu, Sarbani

    2015-08-01

    Asteroseismology is a powerful tool that can precisely characterize the mass, radius, and other properties of field stars. However, our inability to properly model the near-surface layers of stars creates a frequency-dependent frequency difference between the observed and the modeled frequencies, usually referred to as the “surface term.” This surface term can add significant errors to the derived stellar properties unless removed properly. In this paper, we simulate surface terms across a significant portion of the HR diagram, exploring four different masses (M=0.8,1.0,1.2, and 1.5 {M}⊙ ) at five metallicities ([{Fe}/{{H}}]=0.5,0.0,-0.5,-1.0, and -1.5) from the main sequence to red giants for stars with {T}{eff}\\lt 6500 K and explore how well the most common ways of fitting and removing the surface term actually perform. We find that the two-term model proposed by Ball & Gizon works much better than other models across a large portion of the HR diagram, including the red giants, leading us to recommend its use for future asteroseismic analyses.

  11. The Dusty Environment of the Warm Hypergiant HR 5171A

    NASA Astrophysics Data System (ADS)

    Humphreys, Roberta

    HR 5171A is one of a few stars that define the upper luminosity boundary in the HR Diagram for evolved stars. It is a high luminosity warm hypergiant with a peculiar visual and near-infrared light curve and a complex, asymmetric nebulosity in the near-infrared which has been attributed to the presence of a low mass companion. The proposed long wavelength imaging with SOFIA/FORCAST will be used to map the spatial distribution and extent of the cold dust to provide a more complete picture of its dusty environment and its mass loss history. We will use FORCAST at a range of wavelengths from 6.6 to 37 microns to map the spatial extent of the cold dust. We are also proposing spectroscopy with the grisms to investigate the nature of the grains producing its strong silicate emission features. The proposed imaging and spectroscopy will provide critical missing information on the role of dust formation and circumstellar extinction on its peculiar variability.

  12. Bringing human resources to the table: utilization of an HR balanced scorecard at Mayo Clinic.

    PubMed

    Fottler, Myron D; Erickson, Eric; Rivers, Patrick A

    2006-01-01

    Rather than viewing HR as a critical driver of organizational strategy and outcomes, most health care organizations see HR as a drain on the organization's bottom line. Only by aligning HR with the organizational strategy will HR leaders truly get a seat at the leadership table. HR professionals can overcome impediments and gain a seat at the table by learning the language of business and the ways in which organizational leaders use data to drive their decisions. This article shows how Mayo Clinic uses the popular Balanced Scorecard approach to align its measures of HR performance to the organization's strategic plan.

  13. Polycyclic aromatic hydrocarbons (PAHs) mediate transcriptional activation of the ATP binding cassette transporter ABCB6 gene via the aryl hydrocarbon receptor (AhR).

    PubMed

    Chavan, Hemantkumar; Krishnamurthy, Partha

    2012-09-14

    Liver is endowed with a mechanism to induce hepatic cytochromes P450 (CYP450s) in response to therapeutic drugs and environmental contaminants, leading to increased detoxification and elimination of the xenobiotics. Each CYP450 is composed of an apoprotein moiety and a heme prosthetic group, which is required for CYP450 activity. Thus, under conditions of CYP450 induction, there is a coordinate increase in heme biosynthesis to compensate for the increased expression of CYP450s. ABCB6, a mitochondrial ATP binding cassette transporter, which regulates coproporphyrinogen transport from the cytoplasm into the mitochondria to complete heme biosynthesis, represents a previously unrecognized rate-limiting step in heme biosynthesis. However, it is not known if exposure to drugs and environmental contaminants induces ABCB6 expression, to assure an adequate and apparently coordinated supply of heme for the generation of functional cytochrome holoprotein. In the present study, we demonstrate that polycyclic aromatic hydrocarbons (PAHs), the widely distributed environmental toxicants shown to induce porphyrin accumulation causing hepatic porphyria, up-regulate ABCB6 expression in both mice and humans. Using siRNA technology and Abcb6 knock-out mice, we demonstrate that PAH-mediated increase in hepatic porphyrins is compromised in the absence of ABCB6. Moreover, in vivo studies in aryl hydrocarbon receptor (AhR) knock-out mice demonstrate that PAH induction of ABCB6 is mediated by AhR. Promoter activation studies combined with electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrate direct interactions between the AhR binding sites in the ABCB6 promoter and the AhR receptor, implicating drug activation mechanisms for ABCB6 similar to those found in inducible cytochrome P450s. These studies are the first to describe direct transcriptional activation of both mouse and human ABCB6 by xenobiotics.

  14. AHR Over-Expression in Papillary Thyroid Carcinoma: Clinical and Molecular Assessments in a Series of Italian Acromegalic Patients with a Long-Term Follow-Up

    PubMed Central

    Mian, Caterina; Ceccato, Filippo; Barollo, Susi; Watutantrige-Fernando, Sara; Albiger, Nora; Regazzo, Daniela; de Lazzari, Paola; Pennelli, Gianmaria; Rotondi, Sandra; Nacamulli, Davide; Pelizzo, Maria Rosa; Jaffrain-Rea, Marie-Lise; Grimaldi, Franco; Occhi, Gianluca; Scaroni, Carla

    2014-01-01

    Aim Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3–7%. Germline mutations in the aryl-hydrocarbon receptor (AHR) interacting protein (AIP) have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC) in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer. Methods Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied. Results 12 DTCs (10 papillary and 2 follicular carcinomas) were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status. Conclusions The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma. PMID:25019383

  15. Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines

    SciTech Connect

    Dumont, Julie Josse, Rozenn Lambert, Carine Antherieu, Sebastien Laurent, Veronique Loyer, Pascal Robin, Marie-Anne Guillouzo, Andre

    2010-11-15

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA produce different tumor profiles in rodents and are suspected to be carcinogenic in humans. In order to better understand the molecular basis of HAA toxicity, we have analyzed gene expression profiles in the metabolically competent human HepaRG cells using pangenomic oligonucleotide microarrays, after either a single (24-h) or a repeated (28-day) exposure to 10 {mu}M PhIP or MeIQx. The most responsive genes to both HAA were downstream targets of the arylhydrocarbon receptor (AhR): CYP1A1 and CYP1A2 after both time points and CYP1B1 and ALDH3A1 after 28 days. Accordingly, CYP1A1/1A2 induction in HAA-treated HepaRG cells was prevented by chemical inhibition or small interference RNA-mediated down-regulation of the AhR. Consistently, HAA induced activity of the CYP1A1 promoter, which contains a consensus AhR-related xenobiotic-responsive element (XRE). In addition, several other genes exhibited both time-dependent and compound-specific expression changes with, however, a smaller magnitude than previously reported for the prototypical AhR target genes. These changes concerned genes mainly related to cell growth and proliferation, apoptosis, and cancer. In conclusion, these results identify the AhR gene battery as the preferential target of PhIP and MeIQx in HepaRG cells and further support the hypothesis that intake of HAA in diet might increase human cancer risk.

  16. Exposure to Diesel Exhaust Particle Extracts (DEPe) Impairs Some Polarization Markers and Functions of Human Macrophages through Activation of AhR and Nrf2

    PubMed Central

    Jaguin, Marie; Fardel, Olivier; Lecureur, Valérie

    2015-01-01

    Macrophages (MΦ), well-known to play an important role in immune response, also respond to environmental toxic chemicals such as diesel exhaust particles (DEP). Potential effects of DEPs towards MΦ polarization, a key hall-mark of MΦ physiology, remain however poorly documented. This study was therefore designed to evaluate the effects of a reference DEP extract (DEPe) on human MΦ polarization. Human blood monocytes-derived MΦ were incubated with IFNγ+LPS or IL-4 to obtain M1 and M2 subtypes, respectively; a 24 h exposure of polarizing MΦ to 10 μg/ml DEPe was found to impair expression of some macrophagic M1 and M2 markers, without however overall inhibition of M1 and M2 polarization processes. Notably, DEPe treatment increased the secretion of the M1 marker IL-8 and the M2 marker IL-10 in both MΦ subtypes, whereas it reduced lipopolysaccharide-induced IL-6 and IL-12p40 secretion in M1 MΦ. In M2 MΦ, DEPe exposure led to a reduction of CD200R expression and of CCL17, CCL18 and CCL22 secretion, associated with a lower chemotaxis of CCR4-positive cells. DEPe activated the Nrf2 and AhR pathways and induced expression of their reference target genes such as Hmox-1 and cytochrome P-4501B1 in M1 and M2 MΦ. Nrf2 or AhR silencing through RNA interference prevented DEPe-related down-regulation of IL-6. AhR silencing also inhibited the down-secretion of IL-12p40 and CCL18 in M1- and M2-DEPe-exposed MΦ, respectively. DEPs are therefore likely to alter expression of some M1 and M2 markers in an AhR- and Nrf2-dependent manner; such regulations may contribute to deleterious immune effects of atmospheric DEP. PMID:25710172

  17. Fast trabecular bone strength predictions of HR-pQCT and individual trabeculae segmentation-based plate and rod finite element model discriminate postmenopausal vertebral fractures.

    PubMed

    Liu, X Sherry; Wang, Ji; Zhou, Bin; Stein, Emily; Shi, Xiutao; Adams, Mark; Shane, Elizabeth; Guo, X Edward

    2013-07-01

    Although high-resolution peripheral quantitative computed tomography (HR-pQCT) has advanced clinical assessment of trabecular bone microstructure, nonlinear microstructural finite element (µFE) prediction of yield strength using a HR-pQCT voxel model is impractical for clinical use due to its prohibitively high computational costs. The goal of this study was to develop an efficient HR-pQCT-based plate and rod (PR) modeling technique to fill the unmet clinical need for fast bone strength estimation. By using an individual trabecula segmentation (ITS) technique to segment the trabecular structure into individual plates and rods, a patient-specific PR model was implemented by modeling each trabecular plate with multiple shell elements and each rod with a beam element. To validate this modeling technique, predictions by HR-pQCT PR model were compared with those of the registered high-resolution micro-computed tomography (HR-µCT) voxel model of 19 trabecular subvolumes from human cadaveric tibia samples. Both the Young's modulus and yield strength of HR-pQCT PR models strongly correlated with those of µCT voxel models (r²  = 0.91 and 0.86). Notably, the HR-pQCT PR models achieved major reductions in element number (>40-fold) and computer central processing unit (CPU) time (>1200-fold). Then, we applied PR model µFE analysis to HR-pQCT images of 60 postmenopausal women with (n = 30) and without (n = 30) a history of vertebral fracture. HR-pQCT PR model revealed significantly lower Young's modulus and yield strength at the radius and tibia in fracture subjects compared to controls. Moreover, these mechanical measurements remained significantly lower in fracture subjects at both sites after adjustment for areal bone mineral density (aBMD) T-score at the ultradistal radius or total hip. In conclusion, we validated a novel HR-pQCT PR model of human trabecular bone against µCT voxel models and demonstrated its ability to discriminate vertebral fracture

  18. Direct imaging of multiple planets orbiting the star HR 8799

    SciTech Connect

    Marois, C; Macintosh, B; Barman, T; Zuckerman, B; Song, I; Patience, J; Lafreniere, D; Doyon, R

    2008-10-14

    Direct imaging of exoplanetary systems is a powerful technique that can reveal Jupiter-like planets in wide orbits, can enable detailed characterization of planetary atmospheres, and is a key step towards imaging Earth-like planets. Imaging detections are challenging due to the combined effect of small angular separation and large luminosity contrast between a planet and its host star. High-contrast observations with the Keck and Gemini telescopes have revealed three planets orbiting the star HR 8799, with projected separations of 24, 38, and 68 astronomical units. Multi-epoch data show counter-clockwise orbital motion for all three imaged planets. The low luminosity of the companions and the estimated age of the system imply planetary masses between 5 and 13 times that of Jupiter. This system resembles a scaled-up version of the outer portion of our Solar System.

  19. RADIO ASTROMETRY OF THE CLOSE ACTIVE BINARY HR 5110

    SciTech Connect

    Abbuhl, E.; Mutel, R. L.; Lynch, C.; Güedel, M.

    2015-09-20

    The close active binary HR 5110 was observed at six epochs over 26 days using a global very long baseline interferometry array at 15.4 GHz. We used phase referencing to determine the position of the radio centroid at each epoch with an uncertainty significantly smaller than the component separation. After correcting for proper motion and parallax, we find that the centroid locations of all six epochs have barycenter separations consistent with an emission source located on the KIV secondary, and not in an interaction region between the stars or on the F primary. We used a homogeneous power-law gyrosynchrotron emission model to reproduce the observed flux densities and fractional circular polarization. The resulting ranges of mean magnetic field strength and relativistic electron densities are of the order of 10 G and 10{sup 5} cm{sup −3}, respectively, in the source region.

  20. Improved practices, synthetic mud drive record 24-hr drilling

    SciTech Connect

    Collins, G.J.; White, W.W.

    1995-05-01

    Revised and improved drilling practices resulted in increased rate of penetration (ROP), improved hole cleaning, decreased circulating time, fewer instances of stuck pipe and reduced total drilling days. Rig equipment modifications and optimized techniques, combined with olefin-based synthetic fluid, produced significant efficiency improvements and cost reductions. Total-project strategy allows best technologies to be used, even if they are not low bid. In the Gulf of Mexico, a total-project concept helped Marathon drill back-to-back record 24-hr footages. Methods and philosophy described in this article allow drillers to choose optimum technologies, tools, materials and service performance for achieving optimum or lowest cost per foot rather than always using low bid.

  1. Complete genome sequence of Desulfohalobium retbaense type strain (HR(100)).

    PubMed

    Spring, Stefan; Nolan, Matt; Lapidus, Alla; Glavina Del Rio, Tijana; Copeland, Alex; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Land, Miriam; Chen, Feng; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Ivanova, Natalia; Mavromatis, Konstantinos; Mikhailova, Natalia; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Hauser, Loren; Chang, Yun-Juan; Jeffries, Cynthia D; Munk, Christine; Kiss, Hajnalka; Chain, Patrick; Han, Cliff; Brettin, Thomas; Detter, John C; Schüler, Esther; Göker, Markus; Rohde, Manfred; Bristow, Jim; Eisen, Jonathan A; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter

    2010-01-28

    Desulfohalobium retbaense (Ollivier et al. 1991) is the type species of the polyphyletic genus Desulfohalobium, which comprises, at the time of writing, two species and represents the family Desulfohalobiaceae within the Deltaproteobacteria. D. retbaense is a moderately halophilic sulfate-reducing bacterium, which can utilize H(2) and a limited range of organic substrates, which are incompletely oxidized to acetate and CO(2), for growth. The type strain HR(100) (T) was isolated from sediments of the hypersaline Retba Lake in Senegal. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the family Desulfohalobiaceae. The 2,909,567 bp genome (one chromosome and a 45,263 bp plasmid) with its 2,552 protein-coding and 57 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

  2. Remotely Adjustable Hydraulic Pump

    NASA Technical Reports Server (NTRS)

    Kouns, H. H.; Gardner, L. D.

    1987-01-01

    Outlet pressure adjusted to match varying loads. Electrohydraulic servo has positioned sleeve in leftmost position, adjusting outlet pressure to maximum value. Sleeve in equilibrium position, with control land covering control port. For lowest pressure setting, sleeve shifted toward right by increased pressure on sleeve shoulder from servovalve. Pump used in aircraft and robots, where hydraulic actuators repeatedly turned on and off, changing pump load frequently and over wide range.

  3. Adjustable Pitot Probe

    NASA Technical Reports Server (NTRS)

    Ashby, George C., Jr.; Robbins, W. Eugene; Horsley, Lewis A.

    1991-01-01

    Probe readily positionable in core of uniform flow in hypersonic wind tunnel. Formed of pair of mating cylindrical housings: transducer housing and pitot-tube housing. Pitot tube supported by adjustable wedge fairing attached to top of pitot-tube housing with semicircular foot. Probe adjusted both radially and circumferentially. In addition, pressure-sensing transducer cooled internally by water or other cooling fluid passing through annulus of cooling system.

  4. Weighted triangulation adjustment

    USGS Publications Warehouse

    Anderson, Walter L.

    1969-01-01

    The variation of coordinates method is employed to perform a weighted least squares adjustment of horizontal survey networks. Geodetic coordinates are required for each fixed and adjustable station. A preliminary inverse geodetic position computation is made for each observed line. Weights associated with each observed equation for direction, azimuth, and distance are applied in the formation of the normal equations in-the least squares adjustment. The number of normal equations that may be solved is twice the number of new stations and less than 150. When the normal equations are solved, shifts are produced at adjustable stations. Previously computed correction factors are applied to the shifts and a most probable geodetic position is found for each adjustable station. Pinal azimuths and distances are computed. These may be written onto magnetic tape for subsequent computation of state plane or grid coordinates. Input consists of punch cards containing project identification, program options, and position and observation information. Results listed include preliminary and final positions, residuals, observation equations, solution of the normal equations showing magnitudes of shifts, and a plot of each adjusted and fixed station. During processing, data sets containing irrecoverable errors are rejected and the type of error is listed. The computer resumes processing of additional data sets.. Other conditions cause warning-errors to be issued, and processing continues with the current data set.

  5. Black–White Latino Racial Disparities in HIV Survival, Florida, 2000–2011

    PubMed Central

    Sheehan, Diana M.; Trepka, Mary Jo; Fennie, Kristopher P.; Prado, Guillermo; Cano, Miguel Ángel; Maddox, Lorene M.

    2015-01-01

    This research aimed to estimate Black/White racial disparities in all-cause mortality risk among HIV-positive Latinos. Florida surveillance data for Latinos diagnosed with HIV (2000–2008) were merged with 2007–2011 American Community Survey data. Crude and adjusted hazard ratios (aHR) were calculated using multi-level Cox regression. Of 10,903 HIV-positive Latinos, 8.2% were Black and 91.9% White. Black Latinos were at increased mortality risk compared with White Latinos after controlling for individual and neighborhood factors (aHR 1.40, 95% confidence interval (CI) 1.21–1.62). In stratified analyses, risk factors for Black Latinos included: age ≥60 years compared with ages 13–19 (aHR 4.63, 95% CI 1.32–16.13); US birth compared with foreign birth (aHR 1.56, 95% CI 1.16–2.11); diagnosis of AIDS within three months of HIV diagnosis (aHR 3.53, 95% CI 2.64–4.74); residence in the 3rd (aHR 1.82, 95% CI 1.13–2.94) and 4th highest quartiles (aHR 1.79, 95% CI 1.12–2.86) of neighborhood poverty compared with the lowest quartile; and residence in neighborhood with 25%–49% (aHR 1.59, 95% CI 1.07–2.42) and ≥50% Latinos compared with <25% Latinos (aHR 1.58, 95% CI 1.03–2.42). Significant racial disparities in HIV survival exist among Latinos. Differential access to—and quality of—care and perceived/experienced racial discrimination may be possible explanations. PMID:26703656

  6. Role of zebrafish cytochrome P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2

    SciTech Connect

    Kubota, Akira; Stegeman, John J.; Woodin, Bruce R.; Iwanaga, Toshihiko; Harano, Ryo; Peterson, Richard E.; Hiraga, Takeo; Teraoka, Hiroki

    2011-06-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various signs of toxicity in early life stages of vertebrates through activation of the aryl hydrocarbon receptor (AHR). We previously reported a sensitive and useful endpoint of TCDD developmental toxicity in zebrafish, namely a decrease in blood flow in the dorsal midbrain, but downstream genes involved in the effect are not known. The present study addressed the role of zebrafish cytochrome P450 1C (CYP1C) genes in association with a decrease in mesencephalic vein (MsV) blood flow. The CYP1C subfamily was recently discovered in fish and includes the paralogues CYP1C1 and CYP1C2, both of which are induced via AHR2 in zebrafish embryos. We used morpholino antisense oligonucleotides (MO or morpholino) to block initiation of translation of the target genes. TCDD-induced mRNA expression of CYP1Cs and a decrease in MsV blood flow were both blocked by gene knockdown of AHR2. Gene knockdown of CYP1C1 by two different morpholinos and CYP1C2 by two different morpholinos, but not by their 5 nucleotide-mismatch controls, was effective in blocking reduced MsV blood flow caused by TCDD. The same CYP1C-MOs prevented reduction of blood flow in the MsV caused by {beta}-naphthoflavone (BNF), representing another class of AHR agonists. Whole-mount in situ hybridization revealed that mRNA expression of CYP1C1 and CYP1C2 was induced by TCDD most strongly in branchiogenic primordia and pectoral fin buds. In situ hybridization using head transverse sections showed that TCDD increased the expression of both CYP1Cs in endothelial cells of blood vessels, including the MsV. These results indicate a potential role of CYP1C1 and CYP1C2 in the local circulation failure induced by AHR2 activation in the dorsal midbrain of the zebrafish embryo. - Research Highlights: > We examine the roles of zebrafish CYP1C1 and CYP1C2 in TCDD developmental toxicity. > TCDD induces mRNA expression of both CYP1Cs in the mesencephalic vein. > Knockdown of each

  7. Regulation of Ahr signaling by Nrf2 during development: Effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio)

    PubMed Central

    Rousseau, Michelle E.; Sant, Karilyn E.; Borden, Linnea R.; Franks, Diana G.; Hahn, Mark E.; Timme-Laragy, Alicia R.

    2015-01-01

    The embryotoxicity of co-planar PCBs is regulated by the aryl hydrocarbon receptor (Ahr), and has been reported to involve oxidative stress. Ahr participates in crosstalk with another transcription factor, Nfe2l2, or Nrf2. Nrf2 binds to antioxidant response elements to regulate the adaptive response to oxidative stress. To explore aspects of the crosstalk between Nrf2 and Ahr and its impact on development, we used zebrafish (Danio rerio) with a mutated DNA binding domain in Nrf2a (nrf2afh318/fh318), rendering these embryos more sensitive to oxidative stress. Embryos were exposed to 2 nM or 5 nM PCB126 at 24 hours post fertilization (prim-5 stage of pharyngula) and examined for gene expression and morphology at 4 days post fertilization (dpf; protruding –mouth stage). Nrf2a mutant eleutheroembryos were more sensitive to PCB126 toxicity at 4 dpf, and in the absence of treatment also displayed some subtle developmental differences from wildtype embryos, including delayed inflation of the swim bladder and smaller yolk sacs. We used qPCR to measure changes in expression of the nrf gene family, keap1a, keap1b, the ahr gene family, and known target genes. cyp1a induction by PCB126 was enhanced in the Nrf2a mutants (156-fold in wildtypes vs. 228-fold in mutants exposed to 5 nM). Decreased expression of heme oxygenase (decycling) 1 (hmox1) in the Nrf2a mutants was accompanied by increased nrf2b expression. Target genes of Nrf2a and AhR2, NAD(P)H:quinone oxidoreductase 1 (nqo1) and glutathione S-transferase, alpha-like (gsta1), showed a 2-5-fold increase in expression in the Nrf2a mutants as compared to wildtype. This study elucidates the interaction between two important transcription factor pathways in the developmental toxicity of co-planar PCBs. PMID:26325326

  8. Employee Returns: Linking HR Performance Indicators to Business Strategy. IES Report 365.

    ERIC Educational Resources Information Center

    Carter, Alison; Robinson, Dilys

    This document is a practical guide that demonstrates how human resource (HR) professionals can use performance measurement to link HR to organizational strategy and business objectives, and thereby raise the profile of HR within their organization. The following are among the topics examined: (1) the strategic context of measurement (the role…

  9. Recirculating valve lash adjuster

    SciTech Connect

    Stoody, R.R.

    1987-02-24

    This patent describes an internal combustion engine with a valve assembly of the type including overhead valves supported by a cylinder head for opening and closing movements in a substantially vertical direction and a rotatable overhead camshaft thereabove lubricated by engine oil pumped by an engine oil pump. A hydraulic lash adjuster with an internal reservoir therein is solely supplied with run-off lubricating oil from the camshaft which oil is pumped into the internal reservoir of the lash adjuster by self-pumping operation of the lash adjuster produced by lateral forces thereon by the rotative operation of the camshaft comprising: a housing of the lash adjuster including an axially extending bore therethrough with a lower wall means of the housing closing the lower end thereof; a first plunger member being closely slidably received in the bore of the housing and having wall means defining a fluid filled power chamber with the lower wall means of the housing; and a second plunger member of the lash adjuster having a portion being loosely slidably received and extending into the bore of the housing for reciprocation therein. Another portion extends upwardly from the housing to operatively receive alternating side-to-side force inputs from operation of the camshaft.

  10. Masses, Radii, and Cloud Properties of the HR 8799 Planets

    NASA Technical Reports Server (NTRS)

    Marley, Mark S.; Saumon, Didier; Cushing, Michael; Ackerman, Andrew S.; Fortney, Jonathan J.; Freedman, Richard

    2012-01-01

    The near-infrared colors of the planets directly imaged around the A star HR 8799 are much redder than most field brown dwarfs of the same effective temperature. Previous theoretical studies of these objects have compared the photometric and limited spectral data of the planets to the predictions of various atmosphere and evolution models and concluded that the atmospheres of planets b, c, and d are unusually cloudy or have unusual cloud properties. Most studies have also found that the inferred radii of some or all of the planets disagree with expectations of standard giant planet evolution models. Here we compare the available data to the predictions of our own set of atmospheric and evolution models that have been extensively tested against field L and T dwarfs, including the reddest L dwarfs. Unlike almost all previous studies we specify mutually self-consistent choices for effective temperature, gravity, cloud properties, and planetary radius. This procedure yields plausible and self-consistent values for the masses, effective temperatures, and cloud properties of all three planets. We find that the cloud properties of the HR 8799 planets are in fact not unusual but rather follow previously recognized trends including a gravity dependence on the temperature of the L to T spectral transition, some reasons for which we discuss. We find that the inferred mass of planet b is highly sensitive to the H and K band spectrum. Solutions for planets c and particularly d are less certain but are consistent with the generally accepted constraints on the age of the primary star and orbital dynamics. We also confirm that as for L and T dwarfs and solar system giant planets, non-equilibrium chemistry driven by atmospheric mixing is also important for these objects. Given the preponderance of data suggesting that the L to T spectral type transition is gravity dependent, we present a new evolution calculation that predicts cooling tracks on the near-infrared color

  11. Capping risk adjustment?

    PubMed

    Eugster, Patrick; Sennhauser, Michèle; Zweifel, Peter

    2010-07-01

    When premiums are community-rated, risk adjustment (RA) serves to mitigate competitive insurers' incentive to select favorable risks. However, unless fully prospective, it also undermines their incentives for efficiency. By capping its volume, one may try to counteract this tendency, exposing insurers to some financial risk. This in term runs counter the quest to refine the RA formula, which would increase RA volume. Specifically, the adjuster, "Hospitalization or living in a nursing home during the previous year" will be added in Switzerland starting 2012. This paper investigates how to minimize the opportunity cost of capping RA in terms of increased incentives for risk selection.

  12. Influence of initial angiotensin receptor blockers on treatment persistence in uncomplicated hypertension: A nation-wide population-based study.

    PubMed

    Ah, Young-Mi; Lee, Ju-Yeun; Choi, Yun-Jung; Kong, Jisun; Kim, Baegeum; Choi, Kyung Hee; Han, Nayoung; Yu, Yun Mi; Oh, Jung Mi; Shin, Wan Gyoon; Lee, Hae-Young

    2016-01-01

    We identified 55 504 uncomplicated, treatment-naïve hypertensive patients who started angiotensin II receptor blockers (ARBs) in 2012 from national claims data. The proportion of patients remaining on any hypertension treatment at 12 months and the adherence rate were similar between the losartan cohort (66.82% and 68.25%) and the nonlosartan ARB cohort (67.48% and 69.01%). After adjusting for confounding factors, there was no difference in persistence (aHR 0.98, 95% confidence interval (CI) 0.95-1.01) on hypertension treatment between losartan and nonlosartan ARB cohort. Post hoc analysis showed that patients initially prescribed eprosartan, irbesartan (both, aHR 1.33), and telmisartan (aHR 1.11) were more likely to discontinue the initial drug, whereas valsartan initiators (aHR 0.96) were less likely compared with losartan initiators.

  13. Resolving the planetesimal belt of HR 8799 with ALMA

    NASA Astrophysics Data System (ADS)

    Booth, Mark; Jordán, Andrés; Casassus, Simon; Hales, Antonio S.; Dent, William R. F.; Faramaz, Virginie; Matrà, Luca; Barkats, Denis; Brahm, Rafael; Cuadra, Jorge

    2016-07-01

    The star HR 8799 hosts one of the largest known debris discs and at least four giant planets. Previous observations have found evidence for a warm belt within the orbits of the planets, a cold planetesimal belt beyond their orbits and a halo of small grains. With the infrared data, it is hard to distinguish the planetesimal belt emission from that of the grains in the halo. With this in mind, the system has been observed with ALMA in band 6 (1.34 mm) using a compact array format. These observations allow the inner edge of the planetesimal belt to be resolved for the first time. A radial distribution of dust grains is fitted to the data using an MCMC method. The disc is best fitted by a broad ring between 145^{+12}_{-12} au and 429^{+37}_{-32} au at an inclination of 40^{+5}_{-6}° and a position angle of 51^{+8}_{-8}°. A disc edge at ˜145 au is too far out to be explained simply by interactions with planet b, requiring either a more complicated dynamical history or an extra planet beyond the orbit of planet b.

  14. HR 1362 - A test case for stellar dynamo theories

    NASA Technical Reports Server (NTRS)

    Strassmeier, Klaus G.; Hall, Douglas S.; Barksdale, William S.; Jusick, Anthony T.; Henry, Gregory W.

    1990-01-01

    An analysis of 11 yr of photometry of HR 1362 = EK Eri has shown a well-established photometric period of 335 days. This confirms an earlier period determination of about 310 days from 3 yr of APT data and is consistent with a new v sin i determination of 2 + or - 2 km/s. Recent Ca II H and K observations show moderately strong H and K emission lines at a flux level of log F prime (K) of about 6.5 ergs sq m/s. If the photometric period is interpreted as the rotation period, this surface flux is more than one order of magnitude larger than what can be expected from empirical activity versus rotation relationships. The spectrum and the U-B and B-V colors are consistent with a single G8 III-IV spectral classification, while the V-R and V-I values indicate a small color excess, typical of chromospherically active stars.

  15. Copper Bronze Powder Surface Studied by XPS and HR SEM

    NASA Astrophysics Data System (ADS)

    Shvab, R.; Hryha, E.; Tahir, A. M.; Nyborg, L.

    2016-10-01

    The state of the powder surface represents one of the main interests in the whole cycle of components' production using powder metallurgy (PM) route. Large specific surface area of the powder in combination with often alloying with oxygen sensitive elements results in oxidation of the powder surface in most of the cases. The information about surface chemistry of the powder is of vital importance for further consolidation and sintering steps. Surface sensitive analytical techniques - X-ray photoelectron spectroscopy (XPS) and high-resolution scanning electron microscopy combined with energy dispersive X-ray analysis (HR SEM+EDX) were used for surface chemical analysis of the 60Cu-40Sn bronze powder. Determination of the compositional profiles and estimation of the surface oxide layer thickness was done by altering of ion etching and XPS analysis. The results showed tin oxide enrichment and presence of copper hydroxide on the surface of the powder particles. The impurities of P, Zn and Ca were also detected on the top surface of the powder in trace amounts.

  16. Psychological Adjustment and Homosexuality.

    ERIC Educational Resources Information Center

    Gonsiorek, John C.

    In this paper, the diverse literature bearing on the topic of homosexuality and psychological adjustment is critically reviewed and synthesized. The first chapter discusses the most crucial methodological issue in this area, the problem of sampling. The kinds of samples used to date are critically examined, and some suggestions for improved…

  17. Self Adjusting Sunglasses

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Corning Glass Works' Serengeti Driver sunglasses are unique in that their lenses self-adjust and filter light while suppressing glare. They eliminate more than 99% of the ultraviolet rays in sunlight. The frames are based on the NASA Anthropometric Source Book.

  18. Self adjusting inclinometer

    DOEpatents

    Hunter, Steven L.

    2002-01-01

    An inclinometer utilizing synchronous demodulation for high resolution and electronic offset adjustment provides a wide dynamic range without any moving components. A device encompassing a tiltmeter and accompanying electronic circuitry provides quasi-leveled tilt sensors that detect highly resolved tilt change without signal saturation.

  19. Gestational exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin induces BRCA-1 promoter hypermethylation and reduces BRCA-1 expression in mammary tissue of rat offspring: preventive effects of resveratrol.

    PubMed

    Papoutsis, Andreas J; Selmin, Ornella I; Borg, Jamie L; Romagnolo, Donato F

    2015-04-01

    Studies with murine models suggest that maternal exposure to aromatic hydrocarbon receptor (AhR) agonists may impair mammary gland differentiation and increase the susceptibility to mammary carcinogenesis in offspring. However, the molecular mechanisms responsible for these perturbations remain largely unknown. Previously, we reported that the AhR agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced CpG methylation of the breast cancer-1 (BRCA-1) gene and reduced BRCA-1 expression in breast cancer cell lines. Based on the information both the human and rat BRCA-1 genes harbor xenobiotic responsive elements (XRE = 5'-GCGTG-3'), which are binding targets for the AhR, we extended our studies to the analysis of offspring of pregnant Sprague-Dawley rats treated during gestation with TCDD alone or in combination with the dietary AhR antagonist resveratrol (Res). We report that the in utero exposure to TCDD increased the number of terminal end buds (TEB) and reduced BRCA-1 expression in mammary tissue of offspring. The treatment with TCDD induced occupancy of the BRCA-1 promoter by DNA methyltransferase-1 (DNMT-1), CpG methylation of the BRCA-1 promoter, and expression of cyclin D1 and cyclin-dependent kinase-4 (CDK4). These changes were partially overridden by pre-exposure to Res, which stimulated the expression of the AhR repressor (AhRR) and its recruitment to the BRCA-1 gene. These findings point to maternal exposure to AhR agonists as a risk factor for breast cancer in offspring through epigenetic inhibition of BRCA-1 expression, whereas dietary antagonists of the AhR may exert protective effects.

  20. The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1 and UGT1A1 on urine 1-hydroxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil.

    PubMed

    Abnet, Christian C; Fagundes, Renato B; Strickland, Paul T; Kamangar, Farin; Roth, Mark J; Taylor, Philip R; Dawsey, Sanford M

    2007-01-01

    Polymorphisms in genes encoding polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes may alter metabolism of these carcinogens and contribute to inter-individual difference in urine concentrations. We investigated the influence of genetic polymorphism on PAH metabolism in urine from 199 healthy subjects from Southern Brazil. We measured urine 1-hydroxypyrene glucuronide (1-OHPG) concentrations using immunoaffinity chromatography and synchronous fluorescence spectroscopy and genotyped subjects using standard methods. Genetic variants in CYP1B1 (rs1056827, rs1800440, rs10012) were strongly associated with urine 1-OHPG with P-values < 0.010. Variants in aryl hydrocarbon receptor (Ahr) (rs4986826), CYP1A1 (rs1799814) and CYP1A2 (rs2069514) were also, although less strongly, associated with changes in urine 1-OHPG concentrations. These variants had P-values of 0.074, 0.040 and 0.025, respectively. The median urine 1-OHPG concentrations (pmol/ml) in the homozygous wild-type and homozygous variants for CYP1B1 (rs10012) and the Ahr, CYP1A1 and CYP1A2 variants listed above were 2.16 and 0.10, 2.16 and 0.41, 2.03 and 0.46, 2.19 and 2.79, respectively. We found no effect of deletions in GST M1 or GST T1, or different alleles of UGT1A1*28. Adjusting for age, sex, place of residence, tobacco smoke exposure, maté drinking, cachaça and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r2 of 0.21; a model with single genotypes for Ahr, CYP1A1, CYP1A2 and CYP1B1 had an r2 of 0.10; and a model combining both exposure and genotype information had a total r2 of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population.

  1. Health-related quality of life and life satisfaction in colorectal cancer survivors: trajectories of adjustment

    PubMed Central

    2013-01-01

    Background This longitudinal study describes the five year trajectories of health-related quality of life (HR-QOL) and life satisfaction in long term colorectal cancer survivors. Patients and methods A population-based sample of 1966 colorectal cancer survivors were surveyed at six time points from five months to five years post-diagnosis. Predictor variables were: socio-demographic variables, optimism; cancer threat appraisal; perceived social support. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Colorectal (HR-QOL); and the Satisfaction with Life Scale. Growth mixture models were applied to identify trajectory classes and their predictors. Results Distinct adjustment trajectories were identified for HR-QOL and life satisfaction. Lower optimism, poorer social support, a more negative cognitive appraisal, and younger age were associated with poorer life satisfaction, while survivors with less than 8 years of education had higher life satisfaction. This pattern was similar for overall HR-QOL except that educational level was not a significant predictor and later stage disease and female gender emerged as related to poorer outcomes. One in five survivors reported poorer constant HR-QOL (19.2%) and a small group had poor life satisfaction (7.2%); 26.2% reported constant high HR-QOL and 48.8% had high constant life satisfaction. Socioeconomic disadvantage and remoteness of residence uniquely predicted poorer outcomes in the colorectal cancer specific HR-QOL sub domain. Conclusion Although HR-QOL and subjective cognitive QOL share similar antecedents their trajectory patterns suggested they are distinct adjustment outcomes; with life satisfaction emerging as temporally stable phenomenon. Unique patterns of risk support suggest the need to account for heterogeneity in adjustment in longitudinal QOL studies with cancer survivors. PMID:23497387

  2. Resolved imaging of the HR 8799 Debris disk with Herschel

    SciTech Connect

    Matthews, Brenda; Booth, Mark; Broekhoven-Fiene, Hannah; Marois, Christian; Kennedy, Grant; Wyatt, Mark; Sibthorpe, Bruce; Macintosh, Bruce

    2014-01-01

    We present Herschel far-infrared and submillimeter maps of the debris disk associated with the HR 8799 planetary system. We resolve the outer disk emission at 70, 100, 160, and 250 μm and detect the disk at 350 and 500 μm. A smooth model explains the observed disk emission well. We observe no obvious clumps or asymmetries associated with the trapping of planetesimals that is a potential consequence of planetary migration in the system. We estimate that the disk eccentricity must be <0.1. As in previous work by Su et al., we find a disk with three components: a warm inner component and two outer components, a planetesimal belt extending from 100 to 310 AU, with some flexibility (±10 AU) on the inner edge, and the external halo that extends to ∼2000 AU. We measure the disk inclination to be 26° ± 3° from face-on at a position angle of 64° E of N, establishing that the disk is coplanar with the star and planets. The spectral energy distribution of the disk is well fit by blackbody grains whose semi-major axes lie within the planetesimal belt, suggesting an absence of small grains. The wavelength at which the spectrum steepens from blackbody, 47 ± 30 μm, however, is short compared with other A star debris disks, suggesting that there are atypically small grains likely populating the halo. The PACS longer wavelength data yield a lower disk color temperature than do MIPS data (24 and 70 μm), implying two distinct halo dust-grain populations.

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

    SciTech Connect

    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.

  4. Resveratrol and its methoxy derivatives modulate the expression of estrogen metabolism enzymes in breast epithelial cells by AhR down-regulation.

    PubMed

    Licznerska, Barbara; Szaefer, Hanna; Wierzchowski, Marcin; Sobierajska, Hanna; Baer-Dubowska, Wanda

    2017-01-01

    Our earlier studies have shown that compared to resveratrol, its analogs with ortho-methoxy substituents exert stronger antiproliferative and proapoptotic activity. Since estrogens are considered the major risk factors of breast carcinogenesis, the aim of this study was to evaluate the effect of 3,4,2'-trimethoxy (3MS), 3,4,2',4'-tetramethoxy (4MS), and 3,4,2',4',6'-pentamethoxy (5MS) trans-stilbenes on the constitutive expression of the enzymes involved in estrogen metabolism, as well as receptors: AhR and HER2 in breast epithelial cell line MCF10A. The results showed different effect of resveratrol and its methoxy derivatives on the expression of genes encoding key enzymes of estrogen synthesis and catabolism. Resveratrol at the doses of 1 and 5 µmol/L increased the level of CYP19 transcript and protein level, while 5MS reduced mRNA transcript of both CYP19 and STS genes. Resveratrol and all its derivatives reduced also SULT1E1 mRNA transcript level. The reduced expression of AhR, CYP1A1, and 1B1 was also found as a result of treatment with these compounds. The most significant changes were found in the case of AhR. The most potent inhibitor of CYP1A1 and 1B1 genes expression was 5MS, which reduced the levels of mRNA transcript and protein of both CYPs from 31 to 89% of the initial levels. These results indicate that methoxy derivatives of resveratrol might be efficient modulators of estrogen metabolism. Moreover, the number of methoxy groups introduced to stilbene structure may play a certain role in this effect.

  5. The constitutively active Ah receptor (CA-Ahr) mouse as a potential model for dioxin exposure--effects in vital organs.

    PubMed

    Brunnberg, Sara; Andersson, Patrik; Lindstam, Maria; Paulson, Ivar; Poellinger, Lorenz; Hanberg, Annika

    2006-07-25

    The dioxin/aryl hydrocarbon receptor (AhR) mediates most, if not all, toxic effects of dioxins and functions as a ligand-activated transcription factor regulating transcription of a battery of genes. In order to study the mechanisms behind the toxicity of ligands of the Ah receptor we have created a transgenic mouse model expressing a constitutively active Ah receptor (CA-AhR). The mutant Ah receptor is expressed and functionally active in all organs studied. The purpose of the present study was to characterize histopathologically, the phenotype of the CA-AhR with regard to the liver, kidney, lung, heart, spleen and thymus of male and female transgenic CA-AhR mice. Moreover, cell-specific activity of the CA-AhR using up-regulation of the AhR target gene CYP1A1 as a marker, was also examined. The relative weight of liver, kidney and heart were increased while relative thymus weight was decreased. Furthermore, slight morphological lesions of the liver, kidney and spleen was seen. Expression of CYP1A1 was found in cells corresponding to endothelial cells in all of the organs studied. In some tissues additional cell types, such as hepatocytes, renal tubuli cell and Clara cells expressed CYP1A1. Both the effects on organ weights and the cellular expression of CYP1A1 in CA-AhR mice correspond well to observations in TCDD-exposed mice. In conclusion, this characterization further support that the CA-AhR mouse is a useful model for life-long continuous low-level activity of the AhR, i.e. the dioxin exposure situation of humans of the general population.

  6. New CYP1 genes in the frog Xenopus (Silurana) tropicalis: Induction patterns and effects of AHR agonists during development

    SciTech Connect

    Joensson, Maria E.; Berg, Cecilia; Goldstone, Jared V.; Stegeman, John J.

    2011-01-15

    The Xenopus tropicalis genome shows a single gene in each of the four cytochrome P450 1 (CYP1) subfamilies that occur in vertebrates, designated as CYP1A, CYP1B1, CYP1C1, and CYP1D1. We cloned the cDNAs of these genes and examined their expression in untreated tadpoles and in tadpoles exposed to waterborne aryl hydrocarbon receptor agonists, 3,3',4,4',5-pentachlorobiphenyl (PCB126), {beta}-naphthoflavone ({beta}NF), or indigo. We also examined the effects of PCB126 on expression of genes involved in stress response, cell proliferation, thyroid homeostasis, and prostaglandin synthesis. PCB126 induced CYP1A, CYP1B1, and CYP1C1 but had little effect on CYP1D1 (77-, 1.7-, 4.6- and 1.4-fold induction versus the control, respectively). {beta}NF induced CYP1A and CYP1C1 (26- and 2.5-fold), while, under conditions used, indigo tended to induce only CYP1A (1.9-fold). The extent of CYP1 induction by PCB126 and {beta}NF was positively correlated to the number of putative dioxin response elements 0-20 kb upstream of the start codons. No morphological effect was observed in tadpoles exposed to 1 nM-10 {mu}M PCB126 at two days post-fertilization (dpf) and screened 20 days later. However, in 14-dpf tadpoles a slight up-regulation of the genes for PCNA, transthyretin, HSC70, Cu-Zn SOD, and Cox-2 was observed two days after exposure to 1 {mu}M PCB126. This study of the full suite of CYP1 genes in an amphibian species reveals gene- and AHR agonist-specific differences in response, as well as a much lower sensitivity to CYP1 induction and short-term toxicity by PCB126 compared with in fish larvae. The single genes in each CYP1 subfamily may make X. tropicalis a useful model for mechanistic studies of CYP1 functions.

  7. New CYP1 genes in the frog Xenopus (Silurana) tropicalis: Induction patterns and effects of AHR agonists during development

    PubMed Central

    Jönsson, Maria E.; Berg, Cecilia; Goldstone, Jared V.; Stegeman, John J.

    2010-01-01

    The Xenopus tropicalis genome shows a single gene in each of the four cytochrome P450 1 (CYP1) subfamilies that occur in vertebrates, designated as CYP1A, CYP1B1, CYP1C1, and CYP1D1. We cloned the cDNAs of these genes and examined their expression in untreated tadpoles and in tadpoles exposed to waterborne aryl hydrocarbon receptor agonists, 3,3',4,4',5-pentachlorobiphenyl (PCB126), β-naphthoflavone (βNF), or indigo. We also examined the effects of PCB126 on expression of genes involved in stress response, cell proliferation, thyroid homeostasis, and prostaglandin synthesis. PCB126 induced CYP1A, CYP1B1, and CYP1C1 but had little effect on CYP1D1 (77-, 1.7-, 4.6- and 1.4-fold induction versus the control, respectively). βNF induced CYP1A and CYP1C1 (26- and 2.5-fold), while, under conditions used, indigo tended to induce only CYP1A (1.9-fold). The extent of CYP1 induction by PCB126 and βNF was positively correlated to the number of putative dioxin response elements 0–20 kb upstream of the start codons. No morphological effect was observed in tadpoles exposed to 1 nM-10 µM PCB126 at two days post-fertilization (dpf) and screened 20 days later. However, in 14-dpf tadpoles a slight up-regulation of the genes for PCNA, transthyretin, HSC70, Cu-Zn SOD, and Cox-2 was observed two days after exposure to 1 µM PCB126. This study of the full suite of CYP1 genes in an amphibian species reveals gene- and AHR agonist-specific differences in response, as well as a much lower sensitivity to CYP1 induction and short-term toxicity by PCB126 compared with in fish larvae. The single genes in each CYP1 subfamily may make X. tropicalis a useful model for mechanistic studies of CYP1 functions. PMID:20965207

  8. The AhR and NF-κB/Rel Proteins Mediate the Inhibitory Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the 3' Immunoglobulin Heavy Chain Regulatory Region.

    PubMed

    Salisbury, Richard L; Sulentic, Courtney E W

    2015-12-01

    Transcriptional regulation of the murine immunoglobulin (Ig) heavy chain gene (Igh) involves several regulatory elements including the 3'Igh regulatory region (3'IghRR), which is composed of at least 4 enhancers (hs3A, hs1.2, hs3B, and hs4). The hs1.2 and hs4 enhancers exhibit the greatest transcriptional activity and contain binding sites for several transcription factors including nuclear factor kappaB/Rel (NF-κB/Rel) proteins and the aryl hydrocarbon receptor (AhR). Interestingly, the environmental immunosuppressant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which potently inhibits antibody secretion, also profoundly inhibits 3'IghRR and hs1.2 enhancer activation induced by the B-lymphocyte activator lipopolysaccharide (LPS), but enhances LPS-induced activation of the hs4 enhancer. Within the hs1.2 and hs4 enhancers, the AhR binding site is in close proximity or overlaps an NF-κB/Rel binding site suggesting a potential reciprocal modulation of the 3'IghRR by AhR and NF-κB/Rel. The objective of the current study was to evaluate the role of NF-κB/Rel and the AhR on the 3'IghRR and its enhancers using the AhR ligand TCDD, the AhR antagonist CH223191, and toll-like receptor agonists LPS, Resiquimod (R848), or cytosine-phosphate-guanine-oligodeoxynucleotides (CpG). Utilizing the CH12.LX B-lymphocyte cell line and variants expressing either a 3'IghRR-regulated transgene reporter or an inducible IκBα (inhibitor kappa B-alpha protein) superrepressor (IκBαAA), we demonstrate an AhR- and NF-κB/Rel-dependent modulation of 3'IghRR and hs4 activity. Additionally, in mouse splenocytes or CH12.LX cells, binding within the hs1.2 and hs4 enhancer of the AhR and the NF-κB/Rel proteins RelA and RelB was differentially altered by the cotreatment of LPS and TCDD. These results suggest that the AhR and NF-κB/Rel protein binding profile within the 3'IghRR mediates the inhibitory effects of TCDD on Ig expression and therefore antibody levels.

  9. The AhR and NF-κB/Rel Proteins Mediate the Inhibitory Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the 3′ Immunoglobulin Heavy Chain Regulatory Region

    PubMed Central

    Salisbury, Richard L.; Sulentic, Courtney E. W.

    2015-01-01

    Transcriptional regulation of the murine immunoglobulin (Ig) heavy chain gene (Igh) involves several regulatory elements including the 3′Igh regulatory region (3′IghRR), which is composed of at least 4 enhancers (hs3A, hs1.2, hs3B, and hs4). The hs1.2 and hs4 enhancers exhibit the greatest transcriptional activity and contain binding sites for several transcription factors including nuclear factor kappaB/Rel (NF-κB/Rel) proteins and the aryl hydrocarbon receptor (AhR). Interestingly, the environmental immunosuppressant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which potently inhibits antibody secretion, also profoundly inhibits 3′IghRR and hs1.2 enhancer activation induced by the B-lymphocyte activator lipopolysaccharide (LPS), but enhances LPS-induced activation of the hs4 enhancer. Within the hs1.2 and hs4 enhancers, the AhR binding site is in close proximity or overlaps an NF-κB/Rel binding site suggesting a potential reciprocal modulation of the 3′IghRR by AhR and NF-κB/Rel. The objective of the current study was to evaluate the role of NF-κB/Rel and the AhR on the 3′IghRR and its enhancers using the AhR ligand TCDD, the AhR antagonist CH223191, and toll-like receptor agonists LPS, Resiquimod (R848), or cytosine-phosphate-guanine-oligodeoxynucleotides (CpG). Utilizing the CH12.LX B-lymphocyte cell line and variants expressing either a 3′IghRR-regulated transgene reporter or an inducible IκBα (inhibitor kappa B-alpha protein) superrepressor (IκBαAA), we demonstrate an AhR- and NF-κB/Rel-dependent modulation of 3′IghRR and hs4 activity. Additionally, in mouse splenocytes or CH12.LX cells, binding within the hs1.2 and hs4 enhancer of the AhR and the NF-κB/Rel proteins RelA and RelB was differentially altered by the cotreatment of LPS and TCDD. These results suggest that the AhR and NF-κB/Rel protein binding profile within the 3′IghRR mediates the inhibitory effects of TCDD on Ig expression and therefore antibody levels. PMID:26377645

  10. Adjustable Autonomy Testbed

    NASA Technical Reports Server (NTRS)

    Malin, Jane T.; Schrenkenghost, Debra K.

    2001-01-01

    The Adjustable Autonomy Testbed (AAT) is a simulation-based testbed located in the Intelligent Systems Laboratory in the Automation, Robotics and Simulation Division at NASA Johnson Space Center. The purpose of the testbed is to support evaluation and validation of prototypes of adjustable autonomous agent software for control and fault management for complex systems. The AA T project has developed prototype adjustable autonomous agent software and human interfaces for cooperative fault management. This software builds on current autonomous agent technology by altering the architecture, components and interfaces for effective teamwork between autonomous systems and human experts. Autonomous agents include a planner, flexible executive, low level control and deductive model-based fault isolation. Adjustable autonomy is intended to increase the flexibility and effectiveness of fault management with an autonomous system. The test domain for this work is control of advanced life support systems for habitats for planetary exploration. The CONFIG hybrid discrete event simulation environment provides flexible and dynamically reconfigurable models of the behavior of components and fluids in the life support systems. Both discrete event and continuous (discrete time) simulation are supported, and flows and pressures are computed globally. This provides fast dynamic simulations of interacting hardware systems in closed loops that can be reconfigured during operations scenarios, producing complex cascading effects of operations and failures. Current object-oriented model libraries support modeling of fluid systems, and models have been developed of physico-chemical and biological subsystems for processing advanced life support gases. In FY01, water recovery system models will be developed.

  11. Precision adjustable stage

    DOEpatents

    Cutburth, Ronald W.; Silva, Leonard L.

    1988-01-01

    An improved mounting stage of the type used for the detection of laser beams is disclosed. A stage center block is mounted on each of two opposite sides by a pair of spaced ball bearing tracks which provide stability as well as simplicity. The use of the spaced ball bearing pairs in conjunction with an adjustment screw which also provides support eliminates extraneous stabilization components and permits maximization of the area of the center block laser transmission hole.

  12. Protective effects of levamisole, acetylsalicylic acid, and α-tocopherol against dioxin toxicity measured as the expression of AhR and COX-2 in a chicken embryo model.

    PubMed

    Gostomska-Pampuch, Kinga; Ostrowska, Alicja; Kuropka, Piotr; Dobrzyński, Maciej; Ziółkowski, Piotr; Kowalczyk, Artur; Łukaszewicz, Ewa; Gamian, Andrzej; Całkosiński, Ireneusz

    2017-04-01

    Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are classed as persistent organic pollutants and have adverse effects on multiple functions within the body. Dioxins are known carcinogens, immunotoxins, and teratogens. Dioxins are transformed in vivo, and interactions between the products and the aryl hydrocarbon receptor (AhR) lead to the formation of proinflammatory and toxic metabolites. The aim of this study was to determine whether α-tocopherol (vitamin E), acetylsalicylic acid (ASA), and levamisole can decrease the amount of damage caused by dioxins. Fertile Hubbard Flex commercial line chicken eggs were injected with solutions containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or containing TCDD and the test compounds. The chicken embryos and organs were analyzed after 7 and 13 days. The levels at which AhR and cyclooxygenase-2 (COX-2) proteins (which are induced during inflammation) were expressed were evaluated by performing immunohistochemical analyses on embryos treated with TCDD alone or with TCDD and the test compounds. TCDD caused developmental disorders and increased AhR and COX-2 expression in the chicken embryo tissues. Vitamin E, levamisole, ASA, and ASA plus vitamin E inhibited AhR and COX-2 expression in embryos after 7 days and decreased AhR and COX-2 expression in embryos after 13 days. ASA, levamisole, and ASA plus vitamin E weakened the immune response and prevented multiple organ changes. Vitamin E was not fully protective against developmental changes in the embryos.

  13. Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women.

    PubMed

    Kobayashi, Sumitaka; Sata, Fumihiro; Sasaki, Seiko; Ban, Susumu; Miyashita, Chihiro; Okada, Emiko; Limpar, Mariko; Yoshioka, Eiji; Kajiwara, Jumboku; Todaka, Takashi; Saijo, Yasuaki; Kishi, Reiko

    2013-06-07

    Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1048963), CYP1 subfamily A polypeptide 2 (CYP1A2; rs762551), and CYP1 subfamily B polypeptide 1 (CYP1B1; rs1056836) in pregnant Japanese women. These six polymorphisms were detected in 421 healthy pregnant Japanese women. Differences in dioxin exposure concentrations in maternal blood among the genotypes were investigated. Comparisons among the GG, GA, and AA genotypes of AHR showed a significant difference (genotype model: P=0.016 for the mono-ortho polychlorinated biphenyl concentrations and toxicity equivalence quantities [TEQs]). Second, we found a significant association with the dominant genotype model ([TT+TC] vs. CC: P=0.048 for the polychlorinated dibenzo-p-dioxin TEQs; P=0.035 for polychlorinated dibenzofuran TEQs) of CYP1A1 (rs4646903). No significant differences were found among blood dioxin concentrations and polymorphisms in AHRR, CYP1A1 (rs1048963), CYP1A2, and CYP1B1. Thus, polymorphisms in AHR and CYP1A1 (rs4646903) were associated with maternal dioxin concentrations. However, differences in blood dioxin concentrations were relatively low.

  14. Studies on the intracellular localization of hHR23B

    SciTech Connect

    Katiyar, Samiksha; Lennarz, William J. . E-mail: wlennarz@notes.cc.sunysb.edu

    2005-12-02

    Yeast Rad23, originally identified as a DNA repair protein, has been proposed to participate in other cellular functions, i.e., the proteasome-degradation pathway, the process of spindle pole body duplication and as a component of the anaphase checkpoint. Two human homologs of yeast Rad23, hHR23A and hHR23B, exhibit high sequence homology with yRad23 and also have been shown to be involved in DNA repair and proteasome-dependent degradation. Previous studies on the intracellular localization of hHR23A and hHR23B revealed their predominant localization in the nucleus during interphase and in the cytoplasm during mitosis. We have analyzed the localization of hHR23B during all the phases of the cell cycle using immunofluorescence. Unlike previous studies, our results suggest localization of hHR23B in the nucleus as well as in the cytoplasm during G1 phase. The nuclear levels of hHR23B decrease during S-phase of the cell cycle. When the cell enters mitosis, hHR23B relocalizes in the cytoplasm without association with chromatin. These results indicate that the intracellular distribution hHR23B is cell cycle dependent.

  15. AhR ligands, malassezin, and indolo[3,2-b]carbazole are selectively produced by Malassezia furfur strains isolated from seborrheic dermatitis.

    PubMed

    Gaitanis, George; Magiatis, Prokopios; Stathopoulou, Konstantina; Bassukas, Ioannis D; Alexopoulos, Evangelos C; Velegraki, Aristea; Skaltsounis, Alexios-Leandros

    2008-07-01

    Malassezia yeasts are connected with seborrheic dermatitis (SD) whereas M. furfur pathogenicity is associated with the production of bioactive indoles. In this study, the production of indoles by M. furfur isolates from healthy and diseased skin was compared, the respective HPLC patterns were analyzed, and substances that are preferentially synthesized by strains isolated from SD lesions were isolated and characterized. Malassezin, pityriacitrin, indole-3-carbaldehyde, and indolo[3,2-b]carbazole (ICZ) were isolated by HPLC from extracts of M. furfur grown in L-tryptophan agar, and identified by nuclear magnetic resonance and mass spectroscopy. Of these, ICZ, a potent ligand of the aryl hydrocarbon receptor (AhR), is described for the first time to our knowledge as a M. furfur metabolite. HPLC-photodiode array detection analysis of strain extracts from 7 healthy subjects and 10 SD patients showed that M. furfur isolates from only SD patients consistently produce malassezin and ICZ. This discriminatory production of AhR agonists provides initial evidence for a previously unreported mechanism triggering development of SD and indicates that the variable pathogenicity patterns recorded for M. furfur-associated SD conditions may be attributed to selective production (P<0.001) of measurable bioactive indoles.

  16. Polychlorinated biphenyls (PCBs) contamination and aryl hydrocarbon receptor (AhR) agonist activity of Omega-3 polyunsaturated fatty acid supplements: implications for daily intake of dioxins and PCBs.

    PubMed

    Bourdon, J A; Bazinet, T M; Arnason, T T; Kimpe, L E; Blais, J M; White, P A

    2010-11-01

    Omega-3 polyunsaturated fatty acid (n-3 PUFA) rich oils derived primarily from fish are frequently consumed as supplements. Due to the tendency of persistent organic pollutants (POPs) to accumulate in exposed organisms, n-3 PUFA supplements can contain sufficient POPs to present a risk to consumers. Here we investigated PCB concentrations and aryl hydrocarbon receptor (AhR) agonist activity in 17 n-3 PUFA supplements available in Canada. PCBs ranged from <0.8 to 793 ng g(-1) oil, with salmon- and seal-derived products yielding the highest values. AhR agonist activity from a reporter gene assay ranged from 1.3 to 72.2 pg TEQ g(-1) oil, with salmon and tuna yielding the highest values. When consumed at the recommended doses and as a supplement to the average Canadian diet, seal-derived oil can contribute to exceedance of the tolerable daily intake of 20 ng PCBs kg-BW(-1)day(-1), and salmon-, tuna-, and sea herring-derived oils can contribute to exceedance of the tolerable daily intake limit of 2.3 pg TEQ kg-BW(-1)day(-1). The beneficial properties of fish and n-3 PUFA supplements, and the results of this study suggest that it is prudent to consume supplements derived from small, cold-water fatty fish. Further research will be necessary to draw firm conclusions.

  17. Adjustable Reeds For Weaving

    NASA Technical Reports Server (NTRS)

    Farley, Gary L.

    1994-01-01

    Local characteristics of fabrics varied to suit special applications. Adjustable reed machinery proposed for use in weaving fabrics in various net shapes, widths, yarn spacings, and yarn angles. Locations of edges of fabric and configuration of warp and filling yarns varied along fabric to obtain specified properties. In machinery, reed wires mounted in groups on sliders, mounted on lengthwise rails in reed frame. Mechanisms incorporated to move sliders lengthwise, parallel to warp yarns, by sliding them along rails; move sliders crosswise by translating reed frame rails perpendicular to warp yarns; and crosswise by spreading reed rails within group. Profile of reed wires in group on each slider changed.

  18. Genome-Wide RNAi High-Throughput Screen Identifies Proteins Necessary for the AHR-Dependent Induction of CYP1A1 by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

    PubMed Central

    Hankinson, Oliver

    2013-01-01

    The aryl hydrocarbon receptor (AHR) has a plethora of physiological roles, and upon dysregulation, carcinogenesis can occur. One target gene of AHR encodes the xenobiotic and drug-metabolizing enzyme CYP1A1, which is inducible by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via the AHR. An siRNA library targeted against over 5600 gene candidates in the druggable genome was used to transfect mouse Hepa-1 cells, which were then treated with TCDD, and subsequently assayed for CYP1A1-dependent ethoxyresorufin-o-deethylase (EROD) activity. Following redundant siRNA activity (RSA) statistical analysis, we identified 93 hits that reduced EROD activity with a p value ≤ .005 and substantiated 39 of these as positive hits in a secondary screening using endoribonuclease-prepared siRNAs (esiRNAs). Twelve of the corresponding gene products were subsequently confirmed to be necessary for the induction of CYP1A1 messenger RNA by TCDD. None of the candidates were deficient in aryl hydrocarbon nuclear translocator expression. However 6 gene products including UBE2i, RAB40C, CRYGD, DCTN4, RBM5, and RAD50 are required for the expression of AHR as well as for induction of CYP1A1. We also found 2 gene products, ARMC8 and TCF20, to be required for the induction of CYP1A1, but our data are ambiguous as to whether they are required for the expression of AHR. In contrast, SIN3A, PDC, TMEM5, and CD9 are not required for AHR expression but are required for the induction of CYP1A1, implicating a direct role in Cyp1a1 transcription. Our methods, although applied to Cyp1a1, could be modified for identifying proteins that regulate other inducible genes. PMID:23997114

  19. Continuously adjustable Pulfrich spectacles

    NASA Astrophysics Data System (ADS)

    Jacobs, Ken; Karpf, Ron

    2011-03-01

    A number of Pulfrich 3-D movies and TV shows have been produced, but the standard implementation has inherent drawbacks. The movie and TV industries have correctly concluded that the standard Pulfrich 3-D implementation is not a useful 3-D technique. Continuously Adjustable Pulfrich Spectacles (CAPS) is a new implementation of the Pulfrich effect that allows any scene containing movement in a standard 2-D movie, which are most scenes, to be optionally viewed in 3-D using inexpensive viewing specs. Recent scientific results in the fields of human perception, optoelectronics, video compression and video format conversion are translated into a new implementation of Pulfrich 3- D. CAPS uses these results to continuously adjust to the movie so that the viewing spectacles always conform to the optical density that optimizes the Pulfrich stereoscopic illusion. CAPS instantly provides 3-D immersion to any moving scene in any 2-D movie. Without the glasses, the movie will appear as a normal 2-D image. CAPS work on any viewing device, and with any distribution medium. CAPS is appropriate for viewing Internet streamed movies in 3-D.

  20. Potent, Persistent Induction and Modulation of Cellular Immune Responses in Rhesus Macaques Primed with Ad5hr-Simian Immunodeficiency Virus (SIV) env/rev, gag, and/or nef Vaccines and Boosted with SIV gp120

    PubMed Central

    Patterson, L. Jean; Malkevitch, Nina; Pinczewski, Joel; Venzon, David; Lou, Yuanmei; Peng, Bo; Munch, Cindy; Leonard, Melissa; Richardson, Ersell; Aldrich, Kristine; Kalyanaraman, V. S.; Pavlakis, George N.; Robert-Guroff, Marjorie

    2003-01-01

    Immunity elicited by multicomponent vaccines delivered by replication-competent Ad5hr-simian immunodeficiency virus (SIV) recombinants was systematically investigated. Rhesus macaques were immunized mucosally at weeks 0 and 12 with Ad5hr-SIVsmH4 env/rev, with or without Ad5hr-SIVmac239 gag or Ad5hr-SIVmac239 nef, or with all three recombinants. The total Ad5hr dosage was comparably adjusted among all animals with empty Ad5hr-ΔE3 vector. The macaques were boosted with SIV gp120 in monophosphoryl A-stable emulsion adjuvant at 24 and 36 weeks. Controls received Ad5hr-ΔE3 vector or adjuvant only. By ELISPOT analysis, all four SIV gene products elicited potent cellular immune responses that persisted 42 weeks post-initial immunization. Unexpectedly, modulation of this cellular immune response was observed among macaques receiving one, two, or three Ad5hr-SIV recombinants. Env responses were significantly enhanced throughout the immunization period in macaques immunized with Ad5hr-SIV env/rev plus Ad5hr-SIV gag and tended to be higher in macaques that also received Ad5hr-SIV nef. Macaques primed with all three recombinants displayed significant down-modulation in numbers of gamma interferon (IFN-γ)-secreting cells specific for SIV Nef, and the Env- and Gag-specific responses were also diminished. Modulation of antibody responses was not observed. Down-modulation was seen only during the period of Ad5hr-recombinant priming, not during subunit boosting, although SIV-specific IFN-γ-secreting cells persisted. The effect was not attributable to Ad5hr replication differences among immunization groups. Vaccine delivery via replication-competent live vectors, which can persistently infect new cells and continuously present low-level antigen, may be advantageous in overcoming competition among complex immunogens for immune recognition. Effects of current multicomponent vaccines on individual immune responses should be evaluated with regard to future vaccine design. PMID

  1. Gender differences in prognostic factors for oral cancer.

    PubMed

    Honorato, J; Rebelo, M S; Dias, F L; Camisasca, D R; Faria, P A; Azevedo e Silva, G; Lourenço, S Q C

    2015-10-01

    The aim of this study was to assess gender differences in prognostic factors among patients treated surgically for oral squamous cell carcinoma (OSCC). The medical records of 477 eligible patients (345 males, 132 females) obtained from the Brazilian Cancer Institute were reviewed. Survival was calculated by Kaplan-Meier method. Cox regression models were used to obtain adjusted hazard ratios (aHR) for males and females. Multivariate analysis showed that past tobacco use (aHR 0.2, 95% confidence interval (CI) 0.1-0.7) and regional metastasis (aHR 2.3, 95% CI 1.5-3.5) in males, and regional metastasis (aHR 2.2, 95% CI 1.2-4.3), distant metastasis (aHR 6.7, 95% CI 1.3-32.7), and hard palate tumours (aHR 11.8, 95% CI 3.3-47.7) in females, were associated with a higher risk of death. There were no differences in survival between males and females. Regional metastasis was found to be a negative prognostic factor in OSCC for both genders. Past tobacco use was an independent prognostic factor for worse survival among males, while distant metastasis and hard palate tumours were independent prognostic factors for worse survival among females. Further studies are necessary to corroborate the relationships found in this study.

  2. Risk and impact of tuberculosis in patients with chronic myeloid leukemia: a nationwide population-based study in Taiwan.

    PubMed

    Liu, Chia-Jen; Hong, Ying-Chung; Teng, Chung-Jen; Hung, Man-Hsin; Hu, Yu-Wen; Ku, Fan-Chen; Chen, Yung-Tai; Chien, Sheng-Hsuan; Yeh, Chiu-Mei; Chen, Tzeng-Ji; Chiou, Tzeon-Jye; Gau, Jyh-Pyng; Tzeng, Cheng-Hwai

    2015-04-15

    The relationship between chronic myeloid leukemia (CML) and tuberculosis (TB) has not been determined. We conducted a national survey including 1,082 CML patients identified from the Taiwan National Health Insurance database covering a period between 1998 and 2011; the matched non-exposed cohort included 10,820 subjects without CML that were matched for age, sex and comorbidities. The impact of TB was measured by the overall mortality, and the risk factors were identified by a multivariate Cox proportional hazards model. We found the risk of TB was higher in the CML cohort, with an adjusted hazard ratio (aHR) of 3.76 (p = 0.001) for both pulmonary (aHR 3.23, p < 0.001) and extrapulmonary (aHR 9.77, p = 0.001) TB. Specific risk factors were: aged ≥ 60 (aHR 3.24, p = 0.022), being male (aHR 13.49, p = 0.012), receiving stem cell transplantation (aHR 10.50, p = 0.001) and interferon-α therapy (aHR 3.34, p = 0.011). CML patients with TB had a higher mortality rate than those without (aHR 2.04, p = 0.043). We conclude that the incidence of TB is significantly higher in CML patients of male sex, aged ≥ 60, having received either stem cell transplantation or interferon-α treatment. Careful screening strategies for TB should be considered for CML patients with high risk of the infection.

  3. Policy, Professionalism, Professionality and the Development of HR Practitioners in the UK

    ERIC Educational Resources Information Center

    Bailey, Moira

    2011-01-01

    Purpose: The aim of this paper is to explore the role of relevant policies in the professional development of HR practitioners in the UK. Design/methodology/approach: A review of literature was carried out on the subject of the role of relevant policies in the professional development of HR practitioners in the UK. In doing so, the issues of…

  4. From Admin to Strategy: The Changing Face of the HR Function. IES Report 332.

    ERIC Educational Resources Information Center

    Tamkin, Penny; And Others

    Evidence from academic research and management experts in the United Kingdom and elsewhere confirms that the recent focus in work organizations on cost reductions through downsizing has changed the roles and structures of many human resources (HR) units. HR units have had to prove their contribution to the organization's bottom line, raise their…

  5. The HR96 activator, atrazine, reduces sensitivity of D. magna to triclosan and DHA

    PubMed Central

    Sengupta, Namrata; Litoff, Elizabeth J.; Baldwin, William S.

    2015-01-01

    HR96 is a CAR/PXR/VDR ortholog in invertebrates, and a promiscuous endo- and xenobiotic nuclear receptor involved in acclimation to toxicants. Daphnia HR96 is activated by chemicals such as atrazine and linoleic acid (LA) (n-6 fatty acid), and inhibited by triclosan and docosahexaenoic acid (DHA)(n-3 fatty acid). We hypothesized that inhibitors of HR96 may block the protective responses of HR96 based on previously performed luciferase assays. Therefore, we performed acute toxicity tests with two-chemical mixtures containing a HR96 inhibitor (DHA or triclosan) and a HR96 activator (LA or atrazine). Surprisingly, results demonstrate that triclosan and DHA are less toxic when co-treated with 20–80 μM atrazine. Atrazine provides concentration-dependent protection as lower concentrations have no effect and higher concentrations cause toxicity. LA, a weaker HR96 activator, did not provide protection from triclosan or DHA. Atrazine’s protective effects are presumably due to its ability to activate HR96 or other toxicologically relevant transcription factors and induce protective enzymes. Atrazine did not significantly induce glucosyltransferase, a crucial enzyme in triclosan detoxification. However, atrazine did increase antioxidant activities, crucial pathways in triclosan’s toxicity, as measured through GST activity and the TROLOX equivalence assay. The increase in antioxidant capacity is consistent with atrazine providing protection from a wide range of toxicants that induce ROS, including triclosan and unsaturated fatty acids predisposed to lipid peroxidation. PMID:25747156

  6. The HR96 activator, atrazine, reduces sensitivity of D. magna to triclosan and DHA.

    PubMed

    Sengupta, Namrata; Litoff, Elizabeth J; Baldwin, William S

    2015-06-01

    HR96 is a CAR/PXR/VDR ortholog in invertebrates, and a promiscuous endo- and xenobiotic nuclear receptor involved in acclimation to toxicants. Daphnia HR96 is activated by chemicals such as atrazine and linoleic acid (LA) (n-6 fatty acid), and inhibited by triclosan and docosahexaenoic acid (DHA) (n-3 fatty acid). We hypothesized that inhibitors of HR96 may block the protective responses of HR96 based on previously performed luciferase assays. Therefore, we performed acute toxicity tests with two-chemical mixtures containing a HR96 inhibitor (DHA or triclosan) and a HR96 activator (LA or atrazine). Surprisingly, results demonstrate that triclosan and DHA are less toxic when co-treated with 20-80 μM atrazine. Atrazine provides concentration-dependent protection as lower concentrations have no effect and higher concentrations cause toxicity. LA, a weaker HR96 activator, did not provide protection from triclosan or DHA. Atrazine's protective effects are presumably due to its ability to activate HR96 or other toxicologically relevant transcription factors and induce protective enzymes. Atrazine did not significantly induce glucosyltransferase, a crucial enzyme in triclosan detoxification. However, atrazine did increase antioxidant activities, crucial pathways in triclosan's toxicity, as measured through GST activity and the TROLOX equivalence assay. The increase in antioxidant capacity is consistent with atrazine providing protection from a wide range of toxicants that induce ROS, including triclosan and unsaturated fatty acids predisposed to lipid peroxidation.

  7. Legislative Hearing: Regulations on the Solomon Amendment to the Defense Act of 1983. Hearings before the Subcommittee on Postsecondary Education of the Committee on Education and Labor. House of Representatives, Ninety-Eighth Congress, First Session on H.R. 1286 and H.R. 1567, and H.R. 1622 and H.R. 2145 (February 23, 24; March 23, 1983).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    Hearings on the Solomon amendment regulations proposed by the U.S. Department of Education are presented. The Solomon amendment requires that any student be registered under the military's Selective Service Act in order to receive Title IV federal student assistance. H.R. 1286 and H.R. 1567 would repeal the provision of the Military Selective…

  8. Multi-wavelength observations of the peculiar red giant HR 3126

    NASA Technical Reports Server (NTRS)

    Pesce, Joseph E.; Stencel, Robert E.; Walter, Frederick M.; Doggett, Jesse; Dachs, Joachim; Whitelock, Patricia A.; Mundt, Reinhard

    1988-01-01

    Ultraviolet observations of the red giant HR 3126 are combined with multi-wavelength data in order to provide a firmer basis for explaining the arc-minute sized nebula surrounding the object. Possibilities as to the location of HR 3126 on the Hertzsprung-Russel diagram, and to the formation mechanisms of the reflection nebula IC 2220 associated with it, are summarized.

  9. Heritability of HR and BP Response To Exercise Training in the HERITAGE Family Study.

    ERIC Educational Resources Information Center

    Rice, Treva; Gagnon, Jacques; Leon, Arthur S.; Skinner, James S.; Wilmore, Jack H.; Bouchard, Claude; Rao, D. C.

    2002-01-01

    Assessed the heritability of response to exercise training in resting blood pressure (BP) and heart rate (HR) among sedentary Caucasians comprising 98 families who completed an exercise training program. Results indicated that the trainability of systolic BP and HR in families with elevated BP was partially determined by genetic factors. Diastolic…

  10. Bone Microarchitecture Assessed by HR-pQCT as Predictor of Fracture Risk in Postmenopausal Women: The OFELY Study.

    PubMed

    Sornay-Rendu, Elisabeth; Boutroy, Stephanie; Duboeuf, François; Chapurlat, Roland D

    2017-03-09

    Several cross-sectional studies have shown that impairment of bone microarchitecture contributes to skeletal fragility. The aim of this study was to prospectively investigate the prediction of fracture (Fx) by bone microarchitecture assessed by high-resolution peripheral computed tomography (HR- pQCT) in postmenopausal women. We measured microarchitecture at the distal radius and tibia with HR-pQCT in the OFELY study, in addition to areal BMD with dual-energy X-ray absorptiometry (DXA) in 589 women, mean ± SD age 68 ± 9 years. During a median [IQ] 9.4 [1.0] years of follow-up, 135 women sustained an incident fragility Fx, including 81 women with a major osteoporotic Fx (MOP Fx). After adjustment for age, women who sustained Fx had significantly lower total and trabecular volumetric densities (vBMD) at both sites, cortical parameters (area and thickness at the radius, vBMD at the tibia), trabecular number (Tb.N), connectivity density (Conn.D), stiffness, and estimated failure load at both sites, compared with control women. After adjustment for age, current smoking, falls, prior Fx, use of osteoporosis-related drugs, and total hip BMD, each quartile decrease of several baseline values of bone microarchitecture at the radius was associated with significant change of the risk of Fx (HR of 1.39 for Tb.BMD [p = 0.001], 1.32 for Tb.N [p = 0.01], 0.76 for Tb.Sp.SD [p = 0.01], 1.49 [p = 0.01] for Conn.D, and 1.27 for stiffness [p = 0.02]). At the tibia, the association remained significant for stiffness and failure load in the multivariate model for all fragility Fx and for Tt.BMD, stiffness, and failure load for MOP Fx. We conclude that impairment of bone microarchitecture-essentially in the trabecular compartment of the radius-predict the occurrence of incident fracture in postmenopausal women. This assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement

  11. Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

    SciTech Connect

    Lucas, John T.; Colmer, Hentry G.; White, Lance; Fitzgerald, Nora; Isom, Scott; Bourland, John D.; Laxton, Adrian W.; Tatter, Stephen B.; Chan, Michael D.

    2015-08-01

    Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model. Patients and Methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultant model was converted into an online calculator for ease of clinical use. Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death. Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes.

  12. H-BAND IMAGE OF A PLANETARY COMPANION AROUND HR 8799 IN 2002

    SciTech Connect

    Fukagawa, Misato; Fujita, Yutaka; Shibai, Hiroshi; Itoh, Yoichi; Oasa, Yumiko; Tamura, Motohide; Hayashi, Saeko S.; Hayashi, Masahiko

    2009-05-01

    The discovery of three planetary companions around HR 8799 marked a significant epoch in direct imaging of extrasolar planets. Given the importance of this system, we re-analyzed H-band images of HR 8799 obtained with the Subaru 36-elements adaptive optics (AO) in 2002 July. The low-order AO imaging combined with the classical point-spread function (PSF) subtractions even revealed the extrasolar planet, HR 8799b. Our observations in 2002 confirmed that it has been orbiting HR 8799 in a counterclockwise direction. The flux of HR 8799b was consistent with those in the later epochs within the uncertainty of 0.25 mag, further supporting the planetary mass estimate by Marois et al.

  13. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity

    SciTech Connect

    Manning, Gillian E.; Mundy, Lukas J.; Crump, Doug; Jones, Stephanie P.; Chiu, Suzanne; Klein, Jeff; Konstantinov, Alex; Potter, Dave; Kennedy, Sean W.

    2013-01-01

    Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species. -- Highlights: ► The chicken isn't the most sensitive species to CYP1A induction by PCB 105 and 118. ► The relative potency of PCBs differs between avian species. ► EROD activity was correlated with luciferase activity from the LRG assay. ► EROD activity was a better predictor of toxicity than CYP

  14. Tumorigenic effects of endocrine-disrupting chemicals are alleviated by licorice (Glycyrrhiza glabra) root extract through suppression of AhR expression in mammalian cells.

    PubMed

    Chu, Xiao Ting; de la Cruz, Joseph; Hwang, Seong Gu; Hong, Heeok

    2014-01-01

    Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, 400 μg/mL) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

  15. High-resolution peripheral quantitative computed tomography (HR-pQCT) can assess microstructural and biomechanical properties of both human distal radius and tibia: Ex vivo computational and experimental validations.

    PubMed

    Zhou, Bin; Wang, Ji; Yu, Y Eric; Zhang, Zhendong; Nawathe, Shashank; Nishiyama, Kyle K; Rosete, Fernando Rey; Keaveny, Tony M; Shane, Elizabeth; Guo, X Edward

    2016-05-01

    High-resolution peripheral quantitative computed tomography (HR-pQCT) provides in vivo three-dimensional (3D) imaging at the distal radius and tibia and has been increasingly used to characterize cortical and trabecular bone morphology in clinical studies. In this study, we comprehensively examined the accuracy of HR-pQCT and HR-pQCT based micro finite element (μFE) analysis predicted bone elastic stiffness and strength through comparisons with gold-standard micro computed tomography (μCT) based morphological/μFE measures and direct mechanical testing results. Twenty-six sets of human cadaveric distal radius and tibia segments were imaged by HR-pQCT and μCT. Microstructural analyses were performed for the registered HR-pQCT and μCT images. Bone stiffness and yield strength were determined by both HR-pQCT and μCT based linear and nonlinear μFE predictions and mechanical testing. Our results suggested that strong and significant correlations existed between the HR-pQCT standard, model-independent and corresponding μCT measurements. HR-pQCT based nonlinear μFE overestimated stiffness and yield strength while the linear μFE underestimated yield strength, but both were strongly correlated with those predicted by μCT μFE and measured by mechanical testing at both radius and tibia (R(2)>0.9). The microstructural differences between HR-pQCT and μCT were also examined by the Bland-Altman plots. Our results showed HR-pQCT morphological measurements of BV/TV(d), Tb.Th, and Tb.Sp, can be adjusted by correction values to approach true values measured by gold-standard μCT. In addition, we observed moderate correlations of HR-pQCT biomechanical and microstructural parameters between the distal radius and tibia. We concluded that morphological and mechanical properties of human radius and tibia bone can be assessed by HR-pQCT based measures.

  16. Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells.

    PubMed

    Bermejo, Daniela A; Jackson, Shaun W; Gorosito-Serran, Melisa; Acosta-Rodriguez, Eva V; Amezcua-Vesely, Maria C; Sather, Blythe D; Singh, Akhilesh K; Khim, Socheath; Mucci, Juan; Liggitt, Denny; Campetella, Oscar; Oukka, Mohamed; Gruppi, Adriana; Rawlings, David J

    2013-05-01

    Here we identified B cells as a major source of rapid, innate-like production of interleukin 17 (IL-17) in vivo in response to infection with Trypanosoma cruzi. IL-17(+) B cells had a plasmablast phenotype, outnumbered cells of the TH17 subset of helper T cells and were required for an optimal response to this pathogen. With both mouse and human primary B cells, we found that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell-surface mucin CD45, which led to signaling dependent on the kinase Btk and production of IL-17A or IL-17F via a transcriptional program independent of the transcription factors RORγt and Ahr. Our combined data suggest that the generation of IL-17(+) B cells may be a previously unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.

  17. Delay Adjusted Incidence

    Cancer.gov

    This Infographic shows the National Cancer Institute SEER Incidence Trends. The graphs show the Average Annual Percent Change (AAPC) 2002-2011. For Men, Thyroid: 5.3*,Liver & IBD: 3.6*, Melanoma: 2.3*, Kidney: 2.0*, Myeloma: 1.9*, Pancreas: 1.2*, Leukemia: 0.9*, Oral Cavity: 0.5, Non-Hodgkin Lymphoma: 0.3*, Esophagus: -0.1, Brain & ONS: -0.2*, Bladder: -0.6*, All Sites: -1.1*, Stomach: -1.7*, Larynx: -1.9*, Prostate: -2.1*, Lung & Bronchus: -2.4*, and Colon & Rectum: -3/0*. For Women, Thyroid: 5.8*, Liver & IBD: 2.9*, Myeloma: 1.8*, Kidney: 1.6*, Melanoma: 1.5, Corpus & Uterus: 1.3*, Pancreas: 1.1*, Leukemia: 0.6*, Brain & ONS: 0, Non-Hodgkin Lymphoma: -0.1, All Sites: -0.1, Breast: -0.3, Stomach: -0.7*, Oral Cavity: -0.7*, Bladder: -0.9*, Ovary: -0.9*, Lung & Bronchus: -1.0*, Cervix: -2.4*, and Colon & Rectum: -2.7*. * AAPC is significantly different from zero (p<.05). Rates were adjusted for reporting delay in the registry. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  18. Nonlinear Hydrostatic Adjustment.

    NASA Astrophysics Data System (ADS)

    Bannon, Peter R.

    1996-12-01

    The final equilibrium state of Lamb's hydrostatic adjustment problem is found for finite amplitude heating. Lamb's problem consists of the response of a compressible atmosphere to an instantaneous, horizontally homogeneous heating. Results are presented for both isothermal and nonisothermal atmospheres.As in the linear problem, the fluid displacements are confined to the heated layer and to the region aloft with no displacement of the fluid below the heating. The region above the heating is displaced uniformly upward for heating and downward for cooling. The amplitudes of the displacements are larger for cooling than for warming.Examination of the energetics reveals that the fraction of the heat deposited into the acoustic modes increases linearly with the amplitude of the heating. This fraction is typically small (e.g., 0.06% for a uniform warming of 1 K) and is essentially independent of the lapse rate of the base-state atmosphere. In contrast a fixed fraction of the available energy generated by the heating goes into the acoustic modes. This fraction (e.g., 12% for a standard tropospheric lapse rate) agrees with the linear result and increases with increasing stability of the base-state atmosphere.The compressible results are compared to solutions using various forms of the soundproof equations. None of the soundproof equations predict the finite amplitude solutions accurately. However, in the small amplitude limit, only the equations for deep convection advanced by Dutton and Fichtl predict the thermodynamic state variables accurately for a nonisothermal base-state atmosphere.

  19. PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model

    PubMed Central

    Larsen, Michele Campaigne; N'jai, Alhaji; Czuprynski, Charles J.

    2016-01-01

    7,12-Dimethylbenz(a)anthracene (DMBA) rapidly suppresses hematopoietic progenitors, measured as colony forming units (CFU), in mouse bone marrow (BM) leading to mature cell losses as replenishment fails. These losses are mediated by Cyp1b1, independent of the AhR, despite induction of Cyp1b1. BM mesenchymal progenitor cells (MPC) may mediate these responses since basal Cyp1b1 is minimally induced. PreB colony forming unit activity (PreB CFU) is lost within 24 hours in isolated BM cells (BMC) unless cocultured with cells derived from primary MPC (BMS2 line). The mouse embryonic OP9 line, which provides more efficient coculture support, shares similar induction-resistant Cyp1b1 characteristics. This OP9 support is suppressed by DMBA, which is then prevented by Cyp1b1 inhibitors. OP9-enriched medium partially sustains CFU activities but loses DMBA-mediated suppression, consistent with mediation by OP9 Cyp1b1. PreB CFU activity in BMC from Cyp1b1-ko mice has enhanced sensitivity to DMBA. BMC gene expression profiles identified cytokines and developmental factors that are substantially changed in Cyp1b1-ko mice. DMBA had few effects in WT mice but systematically modified many clustered responses in Cyp1b1-ko mice. Typical BMC AhR-responsive genes were insensitive to Cyp1b1 deletion. TCDD replicated Cyp1b1 interventions, suggesting alternative AhR mediation. Cyp1b1 also diminishes oxidative stress, a key cause of stem cell instability. PMID:27891153

  20. Hepatic stellate cells increase the immunosuppressive function of natural Foxp3+ regulatory T cells via IDO-induced AhR activation.

    PubMed

    Kumar, Sudhir; Wang, Jiang; Thomson, Angus W; Gandhi, Chandrashekhar R

    2017-02-01

    Immunosuppressive, naturally occurring CD4(+)CD25(+)forkhead box p3(+) (Foxp3(+)) regulatory T cells (nTregs) offer potential for the treatment of immune-mediated inflammatory disorders. However, potential instability of ex vivo-expanded nTregs following their adoptive transfer may be a significant limitation. LPS-stimulated hepatic stellate cells (HSCs) induce expansion and enhance the suppressive function and stability of allogeneic nTregs We aimed to delineate mechanisms underlying HSC-induced expansion and increased potency of nTregs HSCs and nTregs were isolated from mouse livers and spleens, respectively. Following coculture with LPS-pretreated allogeneic HSCs (LPS/HSCs), proliferation of nTregs was measured by CFSE dilution, and Foxp3 expression and acetylation were determined by immunoprecipitation (IP) and Western blotting analysis. Expression of various genes associated with immunologic tolerance was determined by quantitative RT-PCR (qRT-PCR). LPS stimulation increased the expression and activity of the immunoregulatory enzyme IDO1 in HSCs, and LPS/HSCs stimulated aryl hydrocarbon receptor (AhR) signaling in cocultured nTregs Reciprocally, Tregs increased IDO1 expression in HSCs. IDO1(-/-) LPS/HSCs were inferior to WT LPS/HSCs in stimulating nTreg expansion. Pharmacologic inhibition of IDO1 in HSCs by 1-methyltryptophan (1MT) inhibited LPS/HSC-induced AhR signaling in nTregs, which was responsible for their expansion, Foxp3 expression, and stabilization of Foxp3 by increasing acetylation of lysine residues. Finally, HSCs cryopreserved, following 2-3 passages, were as potent as primary-cultured HSCs in expanding nTregs In conclusion, LPS/HSCs expand allogeneic nTregs through an IDO-dependent, AhR-mediated mechanism and increase their stability through lysine-acetylation of Foxp3. nTregs expanded by cryopreserved HSCs may have potential for clinical use.

  1. Spatial shell structure of the novas DQ Her and HR Del

    SciTech Connect

    Pilyogin, L.S.

    1986-03-01

    This paper considers the formation of the spatial shell structure of the novas DQ Her (1934) and HR Del (1967). It is shown that the existence of polar caps is due to the influence of the second component of the system on the angular distribution of the mass shell depth of the mainshell. The ratio of the mass shell depth in the equatorial ring and in the polar caps is 1.13 for DQ Her and 2.7 for HR Del. The ratio of the maximal densities in the equatorial ring and the polar caps is of order 3 for DQ Her and of order 70 for HR Del.

  2. AHR-related activities in a creosote-adapted population of adult atlantic killifish, Fundulus heteroclitus, two decades post-EPA superfund status at the Atlantic Wood Site, Portsmouth, VA USA.

    PubMed

    Wojdylo, Josephine V; Vogelbein, Wolfgang; Bain, Lisa J; Rice, Charles D

    2016-08-01

    Atlantic killifish, Fundulus heteroclitus, are adapted to creosote-based PAHs at the US EPA Superfund site known as Atlantic Wood (AW) on the southern branch of the Elizabeth River, VA USA. Subsequent to the discovery of the AW population in the early 1990s, these fish were shown to be recalcitrant to CYP1A induction by PAHs under experimental conditions, and even to the time of this study, killifish embryos collected from the AW site are resistant to developmental deformities typically associated with exposure to PAHs in reference fish. Historically, however, 90 +% of the adult killifish at this site have proliferative hepatic lesions including cancer of varying severity. Several PAHs at this site are known to be ligands for the aryl hydrocarbon receptor (AHR). In this study, AHR-related activities in AW fish collected between 2011 and 2013 were re-examined nearly 2 decades after first discovery. This study shows that CYP1A mRNA expression is three-fold higher in intestines of AW killifish compared to a reference population. Using immunohistochemistry, CYP1A staining in intestines was uniformly positive compared to negative staining in reference fish. Livers of AW killifish were examined by IHC to show that CYP1A and AHR2 protein expression reflect lesions-specific patterns, probably representing differences in intrinsic cellular physiology of the spectrum of proliferative lesions comprising the hepatocarcinogenic process. We also found that COX2 mRNA expression levels were higher in AW fish livers compared to those in the reference population, suggesting a state of chronic inflammation. Overall, these findings suggest that adult AW fish are responsive to AHR signaling, and do express CYP1A and AHR2 proteins in intestines at a level above what was observed in the reference population.

  3. Promoter analysis of TCDD-inducible genes in a thymic epithelial cell line indicates the potential for cell-specific transcription factor crosstalk in the AhR response

    SciTech Connect

    Frericks, Markus; Burgoon, Lyle D.; Zacharewski, Timothy R.; Esser, Charlotte

    2008-10-15

    Activation of the aryl hydrocarbon receptor (AhR{sup 1}) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elicits severe immunosuppression accompanied by thymic atrophy. Previous evidence suggests that TCDD targets both thymocytes and thymic epithelial cells. The AhR induces cell-specific changes in gene transcription via binding to the dioxin response element DRE; however, the underlying specificity-mechanisms, in particular with regard to the role of promoter element context, and possible transcription factor crosstalk remain poorly understood. Global gene expression in the cortical thymic epithelial cell line ET at 2, 4, and 6 h following 5 nM TCDD exposure resulted in differential regulation of 201 genes. JASPAR and TRANSFAC mapped the statistically over-represented promoter elements in the regulated genes to specific transcription factor binding sites, suggesting a regulatory role in AhR signaling. Over-represented elements included the xenobiotic response element XRE, NF{kappa}B-Rel, HRE, PPAR{gamma}, GR, PAX-4 and estrogen receptor binding sites. Co-treatment experiments with TCDD and CoCl{sub 2}, to induce hypoxia, or TCDD and 17-{beta}-estradiol (E2) indicated crosstalk between AhR and Hif or ER, in agreement with other experimental models. The computational identification of TFBS and the demonstration of interaction confirm their interactions with AhR signaling and suggest that the other over-represented elements may also be important in the immunosuppressive effects elicited by TCDD. In conclusion, we demonstrated the importance of promoter element cooperation in the shaping of a cell-specific AhR response. Our findings regarding the transcriptional changes in cortical epithelial cells are congruent with the well-known thymotoxic TCDD-phenotype, and useful in new hypothesis generation of the role of cortical TECs in TCDD toxicity.

  4. Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer.

    PubMed

    Dalmau, Elsa; Armengol-Alonso, Alejandra; Muñoz, Montserrat; Seguí-Palmer, Miguel Ángel

    2014-12-01

    The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease. The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy. However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research. This review focuses on current and emerging treatments for HR+ metastatic breast cancer.

  5. The Dust and Gas Content of a Disk Around Young Star HR 4796A

    NASA Technical Reports Server (NTRS)

    Mannings, V.; Greaves, J.; Holland, W.

    1999-01-01

    We have used the James Clerk Maxwell Telescope (JCMT) in Hawaii to search at submillimeter wavelengths for continuum emission from dust, and spectral line emission from carbon monoxide (CO) gas, in the neighborhood of HR 4796A.

  6. Determination of the light ion abundances in the strong-helium star HR 3089

    NASA Technical Reports Server (NTRS)

    Lester, J. B.

    1975-01-01

    Using line blanketed model stellar atmospheres and a spectrum synthesis approach, a differential abundance study of the ultraviolet spectrum of HR 3089 relative to the normal star lambda Sco was performed. Both stars were found to have the same abundances of carbon and silicon, but the helium and nitrogen are significantly enhanced in HR 3089. The atmospheric parameters and the distribution of abundances found for HR 3089 agree well with the results of Osmer and Peterson on sharp-lined helium-rich stars. The rotational velocity of 160 km/sec found for HR 3089 places a constraint on the role of diffusion in producing the abundance anomalies. Examination of the resonance lines of C II, N II, Si III and Si IV shows no evidence for mass loss in either star.

  7. STIRLING BOILER BY BABCOCK & WILCOX CO. (45,000 LB/HR CAPACITY), ...

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

    STIRLING BOILER BY BABCOCK & WILCOX CO. (45,000 LB/HR CAPACITY), INSIDE BOILER HOUSE NO. 2. - Pittsburgh Steel Company, Monessen Works, Open Hearth Plant, Donner Avenue, Monessen, Westmoreland County, PA

  8. IUE spectra of a flare in HR 5110: A flaring RS CVn or Algol system?

    NASA Technical Reports Server (NTRS)

    Simon, T.; Linsky, J. L.; Schiffer, F. H., III

    1981-01-01

    Ultraviolet spectra of the RS CVn type binary system HR 5110 were obtained with IUE on May 31, 1979 during a period of intense radio flaring of this star. High temperature transition region lines are present, but are not enhanced above observed quiescent strengths. The similarities of HR 5110 to the Algol system, As Eri, suggest that the 1979 May to June flare may involve mass exchange rather than annihilation of coronal magnetic fields.

  9. Spectroscopy and photometry of HR Lyr (Nova Lyr 1919) during one of its mysterious dimming episodes

    NASA Astrophysics Data System (ADS)

    Munari, U.; Siviero, A.; Ochner, P.; Dallaporta, S.

    2016-08-01

    An alert posted to the BAA-VSS newsgroup on Aug 24 by J. Shears informs about a new excursion down to V~17 of old nova HR Lyr (Nova Lyr 1919). A few other such episodes were catch by Honeycutt et al (2014, AJ 147, 105) in their intensive 1991-2012 V-band monitoring of HR Lyr, usually between V=15.5 and 16.0.

  10. Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in Klinefelter syndrome.

    PubMed

    Shanbhogue, Vikram V; Hansen, Stinus; Jørgensen, Niklas Rye; Brixen, Kim; Gravholt, Claus H

    2014-11-01

    Although the expected skeletal manifestations of testosterone deficiency in Klinefelter's syndrome (KS) are osteopenia and osteoporosis, the structural basis for this is unclear. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with KS. Thirty-one patients with KS confirmed by lymphocyte chromosome karyotyping aged 35.8 ± 8.2 years were recruited consecutively from a KS outpatient clinic and matched with respect to age and height with 31 healthy subjects aged 35.9 ± 8.2 years. Dual-energy X-ray absorptiometry (DXA) and HR-pQCT were performed in all participants, and blood samples were analyzed for hormonal status and bone biomarkers in KS patients. Twenty-one KS patients were on long-term testosterone-replacement therapy. In weight-adjusted models, HR-pQCT revealed a significantly lower cortical area (p < 0.01), total and trabecular vBMD (p = 0.02 and p = 0.04), trabecular bone volume fraction (p = 0.04), trabecular number (p = 0.05), and estimates of bone strength, whereas trabecular spacing was higher (p = 0.03) at the tibia in KS patients. In addition, cortical thickness was significantly reduced, both at the radius and tibia (both p < 0.01). There were no significant differences in indices of bone structure, estimated bone strength, or bone biomarkers in KS patients with and without testosterone therapy. This study showed that KS patients had lower total vBMD and a compromised trabecular compartment with a reduced trabecular density and bone volume fraction at the tibia. The compromised trabecular network integrity attributable to a lower trabecular number with relative preservation of trabecular thickness is similar to the picture found in women with aging. KS patients also displayed a reduced cortical area and thickness at the tibia, which in

  11. Spousal Adjustment to Myocardial Infarction.

    ERIC Educational Resources Information Center

    Ziglar, Elisa J.

    This paper reviews the literature on the stresses and coping strategies of spouses of patients with myocardial infarction (MI). It attempts to identify specific problem areas of adjustment for the spouse and to explore the effects of spousal adjustment on patient recovery. Chapter one provides an overview of the importance in examining the…

  12. International Child Abduction Act. Hearing before the Subcommittee on Administrative Law and Governmental Relations of the Committee on the Judiciary. House of Representatives, One Hundredth Congress, Second Session on H.R. 2673 and H.R. 3971.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on the Judiciary.

    This document contains witnesses' testimonies and prepared statements from the Congressional hearing called to consider enactment of H.R. 2673, a bill to facilitate implementation of the 1980 Hague Convention on the Civil Aspects of International Child Abduction. The text of H.R. 2673 is included in the document as is the text of H.R. 3971, a bill…

  13. Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis

    PubMed Central

    Moreno, Rodrigo; Brismar, Torkel B.; Pahr, Dieter H.; Smedby, Örjan

    2016-01-01

    Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2-values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research. PMID:27513664

  14. Hormonal Contraception, Pregnancy, Breastfeeding, and Risk of HIV Disease Progression Among Zambian Women

    PubMed Central

    Kilembe, William; Haddad, Lisa; Vwalika, Bellington; Lakhi, Shabir; Khu, Naw Htee; Brill, Ilene; Chomba, Elwyn; Mulenga, Joseph; Tichacek, Amanda; Allen, Susan

    2016-01-01

    Background: Some studies suggest that hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression. Methods: From 1994 to 2012, HIV discordant couples recruited at couples' voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and 2 outcomes among HIV-positive women: (1) time to death and (2) time to antiretroviral treatment (ART) initiation. Results: Among 1656 female seropositive, male seronegative couples followed for 3359 person-years (PY), 224 women died [6.7/100 PY; 95% confidence interval (CI): 5.8 to 7.6]. After 2003, 290 women initiated ART (14.5/100 PY; 95% CI: 12.9 to 16.2). In a multivariate model of time to death, hormonal implant [adjusted hazard ratio (aHR) = 0.30; 95% CI: 0.10 to 0.98] and injectable (aHR = 0.59; 95% CI: 0.36 to 0.97) were significantly protective relative to nonhormonal method use, whereas oral contraceptive pill (OCP) use was not (aHR = 1.08; 95% CI: 0.74 to 1.57) controlling for baseline HIV disease stage, time-varying pregnancy, time-varying breastfeeding, and year of enrollment. In a multivariate model of time-to-ART initiation, implant was significantly protective (aHR = 0.54; 95% CI: 0.31 to 0.95), whereas OCP (aHR = 0.70; 95% CI: 0.44 to 1.10) and injectable (aHR = 0.85; 95% CI: 0.55 to 1.32) were not relative to nonhormonal method use controlling for variables above, woman's age, and literacy. Pregnancy was not significantly associated with death (aHR = 1.07; 95% CI: 0.68 to 1.66) or ART initiation (aHR = 1.24; 95% CI: 0.83 to 1.86), whereas breastfeeding was protective for death (aHR = 0.34; 95% CI: 0.19 to 0.62) and ART initiation (aHR = 0.49; 95% CI: 0.29 to 0.85). Conclusions: Hormonal implants and injectables significantly predicted lower mortality; implants were protective for ART initiation. OCPs and pregnancy were not associated with

  15. A SEARCH FOR WIDE COMPANIONS TO THE EXTRASOLAR PLANETARY SYSTEM HR 8799

    SciTech Connect

    Close, Laird M.; Males, Jared R.

    2010-01-20

    The extrasolar planetary system around HR 8799 is the first multiplanet system ever imaged. It is also, by a wide margin, the highest mass system with >27 Jupiters of planetary mass past 25 AU. This is a remarkable system with no analog in any other known planetary system. In the first part of this paper, we investigated the nature of two faint objects imaged near the system. These objects are considerably fainter (H = 20.4 and 21.6 mag) and more distant (projected separations of 612 and 534 AU) than the three known planetary companions b, c, and d (68-24 AU). It is possible that these two objects could be lower mass planets (of mass approx5M{sub Jup} and approx3M{sub Jup}) that have been scattered to wider orbits. We make the first direct comparison of newly reduced archival Gemini adaptive optics images to archival Hubble Space Telescope/NICMOS images. With nearly a decade between these epochs, we can accurately assess the proper motion nature of each candidate companion. We find that both objects are unbound to HR 8799 and are background. We estimate that HR 8799 has no companions of H < 22 from approx5'' to 15''. Any scattered giant planets in the HR 8799 system are >600 AU or less than 3 M{sub Jup} in mass. In the second part of this paper, we search for any sign of a 'reverse parallax signature' in the astrometric residuals of HR 8799b. No such signal was found and we conclude, as expected, that HR 8799b has the same parallax as HR 8799A. In the third part of this paper, we carry out a search for wider common proper motion objects. We found one object within 1 deg{sup 2} in the Palomar Observatory Sky Survey-Digitized Sky Survey images with similar (<2sigma) proper motions to HR 8799 at a separation of 4.'0. We conclude that it is not likely a bound companion to HR 8799 based on available photometry.

  16. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes

    SciTech Connect

    Han, Sung Gu; Han, Seong-Su; Toborek, Michal; Hennig, Bernhard

    2012-06-01

    Tea flavonoids such as epigallocatechin gallate (EGCG) protect against vascular diseases such as atherosclerosis via their antioxidant and anti-inflammatory functions. Persistent and widespread environmental pollutants, including polychlorinated biphenyls (PCB), can induce oxidative stress and inflammation in vascular endothelial cells. Even though PCBs are no longer produced, they are still detected in human blood and tissues and thus considered a risk for vascular dysfunction. We hypothesized that EGCG can protect endothelial cells against PCB-induced cell damage via its antioxidant and anti-inflammatory properties. To test this hypothesis, primary vascular endothelial cells were pretreated with EGCG, followed by exposure to the coplanar PCB 126. Exposure to PCB 126 significantly increased cytochrome P450 1A1 (Cyp1A1) mRNA and protein expression and superoxide production, events which were significantly attenuated following pretreatment with EGCG. Similarly, EGCG also reduced DNA binding of NF-κB and downstream expression of inflammatory markers such as monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) after PCB exposure. Furthermore, EGCG decreased endogenous or base-line levels of Cyp1A1, MCP-1 and VCAM-1 in endothelial cells. Most of all, treatment of EGCG upregulated expression of NF-E2-related factor 2 (Nrf2)-controlled antioxidant genes, including glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in a dose-dependent manner. In contrast, silencing of Nrf2 increased Cyp1A1, MCP-1 and VCAM-1 and decreased GST and NQO1 expression, respectively. These data suggest that EGCG can inhibit AhR regulated genes and induce Nrf2-regulated antioxidant enzymes, thus providing protection against PCB-induced inflammatory responses in endothelial cells. -- Highlights: ► PCBs cause endothelial inflammation and subsequent atherosclerosis. ► Nutrition can modulate toxicity by environmental pollutants. ► We

  17. Association of self-reported race with AIDS death in continuous HAART users in a cohort of HIV-infected women in the United States

    PubMed Central

    Murphy, Kerry; Hoover, Donald R.; Shi, Qiuhu; Cohen, Mardge; Gandhi, Monica; Golub, Elizabeth T.; Gustafson, Deborah R.; Pearce, Celeste Leigh; Young, Mary; Anastos, Kathryn

    2013-01-01

    Objective: To assess the association of race with clinical outcomes in HIV-positive women on continuous HAART. Design: Prospective study that enrolled women from 1994 to 1995 and 2001 to 2002. Setting: Women's Interagency HIV Study, a community-based cohort in five US cities. Participants: One thousand, four hundred and seventy-one HIV-positive continuous HAART users. Main outcome measures: Times to AIDS and non-AIDS death and incident AIDS-defining illness (ADI) after HAART initiation. Results: In adjusted analyses, black vs. white women had higher rates of AIDS death [adjusted hazard ratio (aHR) 2.14, 95% confidence interval (CI) 1.30, 3.50; P = 0.003] and incident ADI (aHR 1.58, 95% CI 1.08, 2.32; P = 0.02), but not non-AIDS death (aHR 0.91, 95% CI 0.59, 1.39; P = 0.65). Cumulative AIDS death incidence at 10 years was 17.3 and 8.3% for black and white women, respectively. Other significant independent pre-HAART predictors of AIDS death included peak viral load (aHR 1.70 per log10, 95% CI 1.34, 2.16; P < 0.001), nadir CD4+ cell count (aHR 0.65 per 100 cells/μl, 95% CI 0.56, 0.76; P < 0.001), depressive symptoms by Center for Epidemiology Studies Depression score at least 16 (aHR 2.10, 95% CI 1.51, 2.92; P < 0.001), hepatitis C virus infection (aHR 1.57, 95% CI 1.02, 2.40; P = 0.04), and HIV acquisition via transfusion (aHR 2.33, 95% CI 1.21, 4.49; P = 0.01). In models with time-updated HAART adherence, association of race with AIDS death remained statistically significant (aHR 3.09, 95% CI 1.38, 6.93; P = 0.006). Conclusion: In continuous HAART-using women, black women more rapidly died from AIDS or experienced incident ADI than their white counterparts after adjusting for confounders. Future studies examining behavioral and biologic factors in these women may further the understanding of HAART prognosis. PMID:24037210

  18. Perceived autonomy and relatedness as moderating the impact of teacher-student mentoring relationships on student academic adjustment.

    PubMed

    Larose, Simon; Tarabulsy, George; Cyrenne, Diane

    2005-03-01

    This study examined the impact of a 10-hour teacher-student mentoring relationship on the academic adjustment of at-risk college students. A quasi-experimental design involving a comparison group (NM: students with No Mentor), a High Relatedness/Autonomy group (HR/HA: students who perceived high levels of relatedness and autonomy during the mentoring process) and a Low Relatedness/Autonomy group (LR/LA: students who perceived low levels of relatedness and autonomy during the mentoring process) was used for that purpose. Academic adjustment and performance were assessed before (Time 1) and five months after involvement in mentoring (Time 3) for all students. Perceived relatedness and autonomy were assessed after the last mentoring meeting (Time 2) for students involved in mentoring relationships only. Results indicated better social adjustment and institutional attachment in college for the HR students than for the LR and NM students, even after controlling for initial adjustment, performance and social network dispositions. In addition, the LR and LA students presented lower academic and emotional adjustment in college and lower academic performance than NM, HR, and HA students. The potential positive and negative impacts of mentoring relationships are discussed in light of autonomy and relatedness processes. Editors' Strategic Implications: Especially valuable is the articulation of why mentoring might be expected to affect social and academic adjustment outcomes via its effects on the development of autonomy and relatedness. Application of attachment theory and measurement to the study of mentoring is a strategy that shows promise.

  19. Individual and neighborhood predictors of mortality among HIV-positive Latinos with history of injection drug use, Florida, 2000–2011

    PubMed Central

    Sheehan, Diana M.; Trepka, Mary Jo; Fennie, Kristopher P.; Prado, Guillermo; Madhivanan, Purnima; Dillon, Frank R.; Maddox, Lorene

    2015-01-01

    Background The objectives are to examine disparities in all-cause mortality risk among HIV-positive Latinos with injection drug use (IDU) history, and to identify individual- and neighborhood-level predictors. Methods Florida surveillance data for persons diagnosed with HIV 2000–2008 were merged with 2007–2011 administrative data from the American Community Survey. Hazard ratios (HR) were calculated using multi-level weighted Cox regression adjusting for individual and neighborhood (ZCTA-level) factors. Results Of 10,989 HIV-positive Latinos, 10.3% had IDU history. Latinos with IDU history were at increased mortality risk compared with Latinos without IDU history after controlling for individual and neighborhood factors (adjusted HR [aHR] 1.61, 95% confidence interval [CI] 1.43–1.80). Factors associated with mortality for those with IDU history included: being 40–59 (aHR 6.48, 95% CI 1.41–121.05) and ≥60 years (aHR 18.75, 95% CI 3.83–356.45) compared with 13–19 years of age; being diagnosed with AIDS within 3 months of HIV (aHR 2.31, 95% CI 1.87–2.86); residing in an area with ≥50% Latinos compared with <25% Latinos (aHR 1.56, 95% CI 1.19–2.04); and residing in a rural compared with an urban area at the time of diagnosis (aHR 1.73, 95% CI 1.06–2.70). Race and neighborhood poverty were not predictors among those with IDU, but were among those without. Conclusion HIV-positive Latinos with IDU history are at increased mortality risk and have unique contributing factors. Tertiary prevention strategies should target those who are older, diagnosed at later stages, and those who live in predominantly Latino and rural areas. PMID:26208792

  20. Adjustable Induction-Heating Coil

    NASA Technical Reports Server (NTRS)

    Ellis, Rod; Bartolotta, Paul

    1990-01-01

    Improved design for induction-heating work coil facilitates optimization of heating in different metal specimens. Three segments adjusted independently to obtain desired distribution of temperature. Reduces time needed to achieve required temperature profiles.

  1. Heavy-element abundances in the classical barium star HR 774

    NASA Astrophysics Data System (ADS)

    Tomkin, J.; Lambert, D. L.

    1983-10-01

    Low-noise high-resolution Digicon and Reticon spectra of HR 774 are analyzed to determine abundances for all accessible heavy elements in the visual and near-infrared. The authors find evidence of departures from LTE as large as 0.5 dex affecting the low-excitation neutral lines of heavy elements in HR 774 and the standard star (β Gem). These severe effects cancel in a comparison of HR 774 with β Gem. Abundances of 19 heavy elements (Z ≥ 37) are determined and used to derive s-process overabundances. The predicted s-process abundances fit the derived s-process abundances remarkably well. The pattern of s-process abundances is consistent with the 13C(α, n)16O reaction as the neutron source and excludes the 22Ne(α, n)25Mg reaction.

  2. Qualitative risk assessment for the 100-HR-3 groundwater operable unit

    SciTech Connect

    Vukelich, S.E.

    1994-09-22

    This report provides the qualitative risk assessment for the 100-HR-3 operable unit on the Hanford Reservation. 100-HR-3 is a ground water unit. The purpose of the QRA at the 100-HR-3 operable unit is to focus on a predefined set of human and environmental exposure scenarios in order to provides sufficient information that will assist the Tri-Party signatories (Washington State Department of Ecology, EPA and US DOE) in making defensible decisions on the necessity of Interim Remedial Measures. Frequent- and occasional-use exposure scenarios are evaluated in the human health risk assessment to provide bounding estimates of risk. The ecological risk assessment consists of an evaluation of the risks to riparian and aquatic receptors which live in or near the Columbia River.

  3. Predictors of death among drug-resistant tuberculosis patients in Kuala Lumpur, Malaysia: A retrospective cohort study from 2009 to 2013.

    PubMed

    Mohd Shariff, Noorsuzana; Shah, Shamsul Azhar; Kamaludin, Fadzilah

    2016-09-01

    The emergence of drug-resistant tuberculosis (TB) is a major public health threat. However, little is known about the predictors of death in drug-resistant TB in Malaysia. This study aimed to determine the predictors of death in drug-resistant TB patients, including multidrug-resistant TB (MDR-TB), in Kuala Lumpur, Malaysia. This study adopted a retrospective cohort study design and involved laboratory-confirmed drug-resistant TB patients (n=426) from January 2009 to June 2013. A Cox regression model and Kaplan-Meier curves were used to model the outcome measure. Data were analysed by using SPSS v.20.0 for Windows. In this study, 15.3% (n=65) of the patients died. Among the study patients, 70.9% were monoresistant TB cases, 9.4% were poly-resistant TB and 19.7% were MDR-TB. MDR-TB [adjusted hazard ratio (aHR)=2.23, 95% confidence interval (CI) 1.26-3.95], ethnicity [Malay (aHR=5.95, 95% CI 2.30-15.41), Chinese (aHR=4.01, 95% CI 1.38-11.66) and Indian (aHR=3.76, 95% CI 1.19-11.85)], coronary heart disease (aHR=6.82, 95% CI 2.16-21.50), drug abuse (aHR=3.79, 95% CI 2.07-6.93) and treatment non-compliance (aHR=1.81, 95% CI 1.01-3.27) were independent predictors of poorer survival in the multivariate Cox regression analysis. This study suggests that MDR-TB, local ethnicity, coronary heart disease, history of drug abuse and treatment non-compliance are factors predicting poor survival in drug-resistant TB patients. More emphasis should be given to the management of drug-resistant TB patients with these characteristics to achieve better treatment outcomes.

  4. Effectiveness of Hormonal Contraception in HIV-Infected Women using Antiretroviral Therapy: A Prospective Study

    PubMed Central

    Pyra, Maria; Heffron, Renee; Mugo, Nelly R.; Nanda, Kavita; Thomas, Katherine K.; Celum, Connie; Kourtis, Athena P.; Were, Edwin; Rees, Helen; Bukusi, Elizabeth; Baeten, Jared M.

    2015-01-01

    Objective To assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods. Methods Using data from 5,153 HIV-infected women followed prospectively one to three years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral, or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHR) and test interactions between each method and ART use. Results During follow-up, 9% of women ever used implants, 40% used injectables, and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART (aHR 0.06, 95% CI 0.01-0.45) and not on ART (aHR 0.05, 95% CI 0.02-0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed non-statistically significant reduced effectiveness when concurrently using efavirenz. Conclusion Hormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use. PMID:26544706

  5. Use of a novel one-nostril mask-spacer device to evaluate airway hyperresponsiveness (AHR) in horses after chronic administration of albuterol.

    PubMed

    Mazan, Melissa R; Lascola, Kara; Bruns, Susan J; Hoffman, Andrew M

    2014-07-01

    Inflammatory airway disease (IAD) is very common in stabled horses. Short-acting beta agonist (SABA) drugs are often used to relieve clinical signs, although long-term exposure to these drugs may result in rebound bronchoconstriction. The purpose of this study was twofold: i) to describe the deposition of radiolabeled drugs using a novel one-nostril design mask-spacer combination with a breath-activated inhaler (BAI), and ii) to determine whether treatment for 10 d with inhaled albuterol using this device would impair the ability of albuterol to prevent bronchospasm during a histamine challenge test. The percentage of radio-aerosol deposited in the total lung was 12.39% ± 5.05%. All study horses demonstrated airway hyperresponsiveness (AHR) before enrollment in the study [mean provocative concentration eliciting 35% increase in delta flow (PC35) < 6 mg/mL histamine]. There was no significant difference in airway hyperresponsiveness to post-albuterol histamine challenge before or after treatment with albuterol. A 10-d treatment with placebo, however, caused a significant increase in airway hyperresponsiveness in all horses (P < 0.001). The results of this study show that the novel mask-spacer device was effective in delivering radiolabeled aerosolized drug to the lung and that delivery of a SABA for 10 d using this device did not result in increased airway hyperresponsiveness.

  6. Low-frequency GMRT observations of the magnetic Bp star HR Lup (HD 133880)

    NASA Astrophysics Data System (ADS)

    George, Samuel J.; Stevens, Ian R.

    2012-06-01

    We present radio observations of the magnetic chemically peculiar Bp star HR Lup (HD 133880) at 647 and 277 MHz with the GMRT. At both frequencies the source is not detected but we are able to determine upper limits to the emission. The 647 MHz limits are particularly useful, with a 5σ value of 0.45 mJy. Also, no large enhancements of the emission were seen. The non-detections, along with previously published higher frequency detections, provide evidence that an optically thick gyrosynchrotron model is the correct mechanism for the radio emission of HR Lup.

  7. Stability boundaries for massive stars in the sHR diagram

    NASA Astrophysics Data System (ADS)

    Saio, Hideyuki; Georgy, Cyril; Meynet, Georges

    2015-01-01

    Stability boundaries of radial pulsations in massive stars are compared with positions of variable and non-variable blue-supergiants in the spectroscopic HR (sHR) diagram (Langer & Kudritzki 2014), whose vertical axis is 4 log T eff - log g(= log L/M). Observational data indicate that variables tend to have higher L/M than non-variables in agreement with the theoretical prediction. However, many variable blue-supergiants are found to have values of L/M below the theoretical stability boundary; i.e., surface gravities seem to be too high by around 0.2-0.3 dex.

  8. Association of polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 genes with levels of DNA damage in peripheral blood lymphocytes among coke-oven workers

    SciTech Connect

    Yongwen Chen; Yun Bai; Jing Yuan; Weihong Chen; Jianya Sun; Hong Wang; Huashan Liang; Liang Guo; Xiaobo Yang; Hao Tan; Yougong Su; Qingyi Wei; Tangchun Wu

    2006-09-15

    Accumulating evidence has shown that both DNA damage caused by the metabolites of polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic genes contribute to individual susceptibility to PAH-induced carcinogenesis. However, the functional relevance of genetic polymorphisms in PAH-metabolic genes in exposed individuals is still unclear. In this study of 240 coke-oven workers (the exposed group) and 123 non-coke-oven workers (the control group), we genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR methods, and determined the levels of DNA damage in peripheral blood lymphocytes using the alkaline comet assay. It was found that the ln-transformed Olive tail moment (Olive TM) values in the exposed group were significantly higher than those in the control group. Furthermore, in the exposed group, the Olive TM values in subjects with the AhR Lys{sup 554} variant genotype were higher than those with the AhR Arg{sup 554}/Arg{sup 554} genotype. Similarly, the Olive TM values in the non-coke-oven workers with the CYP1A1 MspI CC + CT genotype were lower than the values of those with the CYP1A1 MspI TT genotype. However, these differences were not evident for GSTM1 and GSTT1. These results suggested that the polymorphism of AhR might modulate the effects of PAHs in the exposed group; however, the underlying molecular mechanisms by which this polymorphism may have affected the levels of PAH-induced DNA damage warrant further investigation.

  9. Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma.

    PubMed

    Yanik, Elizabeth L; Chinnakotla, Srinath; Gustafson, Sally K; Snyder, Jon J; Israni, Ajay K; Segev, Dorry L; Engels, Eric A

    2016-05-01

    For recipients of liver transplantations (LTs) for hepatocellular carcinoma (HCC), HCC recurrence after transplantation remains a major concern. Sirolimus (SRL), an immunosuppressant with anticarcinogenic properties, may reduce HCC recurrence and improve survival. In our study, the US Scientific Registry of Transplant Recipients was linked to pharmacy claims. For liver recipients transplanted for HCC, Cox regression was used to estimate associations of early SRL use with recurrence, cancer-specific mortality, and all-cause mortality, adjusting for recipient ethnicity, calendar year of transplant, total tumor volume, alpha-fetoprotein, transplant center size, use of interleukin 2 induction therapy, and allocated and calculated Model for End-Stage Liver Disease score. We performed stratified analyses among recipients who met Milan criteria, among those without renal failure, among those with deceased liver donors, by age at transplantation, and by tumor size. Among the 3936 included HCC LTs, 234 (6%) were SRL users. In total, there were 242 recurrences and 879 deaths, including 261 cancer-related deaths. All-cause mortality was similar in SRL users and nonusers (adjusted hazard ratio [aHR], 1.01; 95% CI, 0.73-1.39). HCC recurrence and cancer-specific mortality rates appeared lower in SRL users, but associations were not statistically significant (recurrence aHR, 0.86; 95% CI, 0.45-1.65; cancer-specific mortality aHR, 0.80; 95% CI, 0.43-1.50). Among recipients >55 years old, associations were suggestive of better outcomes for SRL users (all-cause mortality aHR, 0.62; 95% CI, 0.38-1.01; recurrence aHR, 0.52; 95% CI, 0.19-1.44; cancer-specific mortality aHR, 0.34; 95% CI, 0.11-1.09), whereas among recipients ≤55 years old, SRL users had worse outcomes (all-cause mortality aHR, 1.76; 95% CI, 1.12-2.75; recurrence aHR, 1.49; 95% CI, 0.62-3.61; cancer-specific mortality aHR, 1.54; 95% CI, 0.71-3.32). In conclusion, among HCC liver recipients overall, SRL did not appear

  10. Effect of Systemic Lupus Erythematosus on the Risk of Incident Respiratory Failure: A National Cohort Study

    PubMed Central

    Yeh, Jun-Jun; Wang, Yu-Chiao; Chen, Jiunn-Horng; Hsu, Wu-Huei

    2016-01-01

    Purpose We conducted a nationwide cohort study to investigate the relationship between systemic lupus erythematosus (SLE) and the risk of incident respiratory failure. Methods From the National Health Insurance Research Database, we identified 11 533 patients newly diagnosed with SLE and 46 132 controls without SLE who were randomly selected through frequency-matching according to age, sex, and index year. Both cohorts were followed until the end of 2011 to measure the incidence of incident respiratory failure, which was compared between the 2 cohorts through a Cox proportional hazards regression analysis. Results The adjusted hazard ratio (aHR) of incident respiratory failure was 5.80 (95% confidence interval [CI] = 5.15–6.52) for the SLE cohort after we adjusted for sex, age, and comorbidities. Both men (aHR = 3.44, 95% CI = 2.67–4.43) and women (aHR = 6.79, 95% CI = 5.93–7.77) had a significantly higher rate of incident respiratory failure in the SLE cohort than in the non-SLE cohort. Both men and women aged <35 years (aHR = 31.2, 95% CI = 21.6–45.2), 35–65 years; (aHR = 6.19, 95% CI = 5.09–7.54) and ≥65 years (aHR = 2.35, 95% CI = 1.92–2.87) had a higher risk of incident respiratory failure in the SLE cohort. Moreover, the risk of incident respiratory failure was higher in the SLE cohort than the non-SLE cohort, for subjects with (aHR = 2.65, 95% CI = 2.22–3.15) or without (aHR = 9.08, 95% CI = 7.72–10.7) pre-existing comorbidities. In the SLE cohort, subjects with >24 outpatient visits and hospitalizations per year had a higher incident respiratory failure risk (aHR = 21.7, 95% CI = 18.0–26.1) compared with the non-SLE cohort. Conclusion Patients with SLE are associated with an increased risk of incident respiratory failure, regardless of their age, sex, and pre-existing comorbidities; especially medical services with higher frequency. PMID:27654828

  11. Adjusting to Chronic Health Conditions.

    PubMed

    Helgeson, Vicki S; Zajdel, Melissa

    2017-01-03

    Research on adjustment to chronic disease is critical in today's world, in which people are living longer lives, but lives are increasingly likely to be characterized by one or more chronic illnesses. Chronic illnesses may deteriorate, enter remission, or fluctuate, but their defining characteristic is that they persist. In this review, we first examine the effects of chronic disease on one's sense of self. Then we review categories of factors that influence how one adjusts to chronic illness, with particular emphasis on the impact of these factors on functional status and psychosocial adjustment. We begin with contextual factors, including demographic variables such as sex and race, as well as illness dimensions such as stigma and illness identity. We then examine a set of dispositional factors that influence chronic illness adjustment, organizing these into resilience and vulnerability factors. Resilience factors include cognitive adaptation indicators, personality variables, and benefit-finding. Vulnerability factors include a pessimistic attributional style, negative gender-related traits, and rumination. We then turn to social environmental variables, including both supportive and unsupportive interactions. Finally, we review chronic illness adjustment within the context of dyadic coping. We conclude by examining potential interactions among these classes of variables and outlining a set of directions for future research.

  12. Rewarding and Developing Staff in Higher Education: Good Practice in Setting HR Strategies. Report.

    ERIC Educational Resources Information Center

    Higher Education Funding Council for England, Bristol.

    This guide aims to help universities and colleges in England think strategically about the contribution of human resources to their organization and then to turn this thinking into an agreed strategy document to manage their human resources (HR) effectively. In November 2000, the British government announced an additional 330 million pounds over 3…

  13. Searching for the HR 8799 Debris Disk with HST/STIS

    NASA Astrophysics Data System (ADS)

    Gerard, B.; Lawler, S.; Marois, C.; Tannock, M.; Matthews, B.; Venn, K.

    2016-06-01

    We present a new algorithm for space telescope high contrast imaging of close-to-face-on planetary disks called Optimized Spatially Filtered (OSFi) normalization. This algorithm is used on HR 8799 Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph (STIS) coronagraphic archival data, showing an over-luminosity after reference star point-spread function (PSF) subtraction that may be from the inner disk and/or planetesimal belt components of this system. The PSF-subtracted radial profiles in two separate epochs from 2011 and 2012 are consistent with one another, and self-subtraction shows no residual in both epochs. We explore a number of possible false-positive scenarios that could explain this residual flux, including telescope breathing, spectral differences between HR 8799 and the reference star, imaging of the known warm inner disk component, OSFi algorithm throughput and consistency with the standard spider normalization HST PSF subtraction technique, and coronagraph misalignment from pointing accuracy. In comparison to another similar STIS data set, we find that the over-luminosity is likely a result of telescope breathing and spectral difference between HR 8799 and the reference star. Thus, assuming a non-detection, we derive upper limits on the HR 8799 dust belt mass in small grains. In this scenario, we find that the flux of these micron-sized dust grains leaving the system due to radiation pressure is small enough to be consistent with measurements of other debris disk halos.

  14. Linking educational leadership styles to the HR architecture for new teachers in primary education.

    PubMed

    Vekeman, Eva; Devos, Geert; Valcke, Martin

    2016-01-01

    This study aims to gain insight in the relationship between principals' leadership styles and the configuration of different HR practices for new teachers in primary education. Besides the longstanding interest in educational leadership as a key element in teacher and student performance, there is a growing interest in strategic human resource management (SHRM) in the educational sector. However, few educational studies link educational leadership to SHRM. In particular, this study examines the relationship between principals' instructional and transformational leadership style and principals' strategic and HR orientation in configuring HR practices for new teachers. Data were gathered using a mixed methods approach, including interviews with 75 principals as well as an online survey of 1058 teachers in Flemish primary education. Qualitative interview data were transformed and analysed together with the quantitative survey data using logistic regression and ANOVA analyses. The results indicate that both instructional and transformational leadership is associated with the strategic orientation of principals. The HR orientation, on the other hand, is not reflected in the principals' leadership style. Recommendations for further research in this area are discussed.

  15. HR Technology Tools: Less Time on Paper and More on People

    ERIC Educational Resources Information Center

    Tillman, Tom

    2009-01-01

    Many human resource managers face a dilemma. They would like to spend more time improving the overall work environment for employees. They want to help their executives save on workforce-related expenses, find and hire better talent, and improve existing talent through training and development. Unfortunately, most days, HR managers are stuck doing…

  16. XAS and HR-TEM Analyses of the Nakhlite Hydrothermal Minerals

    NASA Astrophysics Data System (ADS)

    Hicks, L. J.; Bridges, J. C.; Gurman, S. J.

    2012-09-01

    We use Fe-K XANES and EXAFS, with HR-TEM observations, to show that the phyllosilicate minerals found in the Lafayette nakhlite are saponite and serpentine. An increase in ferric/ferrous ratio is identified as part of the hydrothermal activity.

  17. Homozygosity for the HR2 Haplotype: Is It a Risk Factor for Thrombosis?

    PubMed

    Ulu, Arzu; Yılmaz, Erkan; Akar, Ece; Akar, Nejat

    2003-12-05

    A4070G (His 1299 Arg) polymorphism in exon 13 of factor V gene can influence factor V levels and contribute to the activated protein C resistance. We are presenting our data concerning Turkish population and postulate that homozygosity for the HR2 haplotype may be an important risk factor for thrombosis.

  18. An infrared study of the remarkable dusty M star HR 3126

    NASA Technical Reports Server (NTRS)

    Chiar, J. E.; Whittet, D. C. B.; Aitken, D. K.; Roche, P. F.; Smith, C. H.; Walker, H. J.; Whitelock, P. A.; Wright, C.

    1993-01-01

    HR 3126 is a unique M giant star embedded in the bipolar reflection nebula IC 2220. In this paper we present new photometric and spectroscopic observations of HR 3126 and combine them with existing data from the literature in an extensive reappraisal of the star's properties at infrared wavelengths. The spectral energy distribution is consistent with an optical classification of M0-3 II with infrared excess. The dust shell cannot be fitted by a single-temperature blackbody: at least three components are required, with temperatures in the range 35-1300 K. On the basis of spectroscopy at 1-4 and 7-25 microns, combined with an assessment of various color-color diagrams, we are able to reject the hypothesis that HR 3126 is carbon-rich. Weak silicate emission features are detected at 10 and 19 microns, and a previous report of silicon carbide emission at 11.2 microns is not substantiated. It seems likely that HR 2136 is in a phase of advanced and rapid postmain-sequence evolution, possibly beginning its ascent of the asymptotic giant branch.

  19. CHARACTERIZING THE ATMOSPHERES OF THE HR8799 PLANETS WITH HST/WFC3

    SciTech Connect

    Rajan, Abhijith; Patience, Jennifer; Barman, Travis; Soummer, Rémi; Hagan, J. Brendan; Pueyo, Laurent; Choquet, Élodie; Konopacky, Quinn; Macintosh, Bruce; Marois, Christian

    2015-08-20

    We present results from a Hubble Space Telescope (HST) program characterizing the atmospheres of the outer two planets in the HR8799 system. The images were taken over 15 orbits in three near-infrared (near-IR) medium-band filters—F098M, F127M, and F139M—using the Wide Field Camera 3. One of the three filters is sensitive to a water absorption band inaccessible from ground-based observations, providing a unique probe of the thermal emission from the atmospheres of these young giant planets. The observations were taken at 30 different spacecraft rolls to enable angular differential imaging (ADI), and the full data set was analyzed with the Karhunen–Loéve Image Projection routine, an advanced image processing algorithm adapted to work with HST data. To achieve the required high contrast at subarcsecond resolution, we utilized the pointing accuracy of HST in combination with an improved pipeline designed to combine the dithered ADI data with an algorithm designed to both improve the image resolution and accurately measure the photometry. The results include F127M (J) detections of the outer planets, HR8799b and c, and the first detection of HR8799b in the water-band (F139M) filter. The F127M photometry for HR8799c agrees well with fitted atmospheric models, resolving the longstanding difficulty in consistently modeling the near-IR flux of the planet.

  20. Getting People Involved: The Benefit of Intellectual Capital Management for Addressing HR Challenges

    ERIC Educational Resources Information Center

    Pook, Katja

    2011-01-01

    Purpose: This paper aims to explore the benefits of intellectual capital assessment for facing current challenges of human resources work and organizational development. Design/methodology/approach: The paper takes findings of studies on challenges in HR work and maps them with features of intellectual capital assessment methods. It is thus a…

  1. GFZ HR/LL GPS Ground station networks and their use

    NASA Astrophysics Data System (ADS)

    Reigber, C.; Galas, R.; Koehler, W.; Forberg, M.; Ramatschi, M.

    2003-12-01

    The contribution presents GFZ's global and local High-Rate and Low-Latency GPS networks. The global HR/LL network was established, in collaboration with JPL, to support the CHAMP and GRACE POD activities and the radio occultation experiment on both missions. The GFZ sub-network is composed of 13 continuously tracking stations, generating 15-min 1 Hz GPS data files and transmitting them to GFZ every 15 minutes. Eight stations contribute to the Galileo mission preparations. Since early 2003 eight HR sites are streaming GPS data in real time. Three of them take part in the IGS Real-Time Prototype Network. GPS HR/LL network for deformation monitoring is an example of local HR/LL GPS array. This 1 Hz network was installed on Popocapetel volcano end of 1999. For the calibration of satellite altimetry, an autonomous 10 Hz GPS-Buoy was developed by GFZ and is operating in the North Sea. The presentation describes shortly the three systems and discusses issues such as: data performance, real-time data aspects and quality monitoring. Application results from ultra-rapid CHAMP/GRACE orbit processing, radio-occultation routine processing, buoy monitoring and volcano monitoring in geodesy, geophysics and meteorology will be presented.

  2. MCCB warm adjustment testing concept

    NASA Astrophysics Data System (ADS)

    Erdei, Z.; Horgos, M.; Grib, A.; Preradović, D. M.; Rodic, V.

    2016-08-01

    This paper presents an experimental investigation in to operating of thermal protection device behavior from an MCCB (Molded Case Circuit Breaker). One of the main functions of the circuit breaker is to assure protection for the circuits where mounted in for possible overloads of the circuit. The tripping mechanism for the overload protection is based on a bimetal movement during a specific time frame. This movement needs to be controlled and as a solution to control this movement we choose the warm adjustment concept. This concept is meant to improve process capability control and final output. The warm adjustment device design will create a unique adjustment of the bimetal position for each individual breaker, determined when the testing current will flow thru a phase which needs to trip in a certain amount of time. This time is predetermined due to scientific calculation for all standard types of amperages and complies with the IEC 60497 standard requirements.

  3. Discovery of a Substellar Companion to the Nearby Debris Disk Host HR 2562

    NASA Astrophysics Data System (ADS)

    Konopacky, Quinn M.; Rameau, Julien; Duchêne, Gaspard; Filippazzo, Joseph C.; Giorla Godfrey, Paige A.; Marois, Christian; Nielsen, Eric L.; Pueyo, Laurent; Rafikov, Roman R.; Rice, Emily L.; Wang, Jason J.; Ammons, S. Mark; Bailey, Vanessa P.; Barman, Travis S.; Bulger, Joanna; Bruzzone, Sebastian; Chilcote, Jeffrey K.; Cotten, Tara; Dawson, Rebekah I.; De Rosa, Robert J.; Doyon, René; Esposito, Thomas M.; Fitzgerald, Michael P.; Follette, Katherine B.; Goodsell, Stephen; Graham, James R.; Greenbaum, Alexandra Z.; Hibon, Pascale; Hung, Li-Wei; Ingraham, Patrick; Kalas, Paul; Lafrenière, David; Larkin, James E.; Macintosh, Bruce A.; Maire, Jérôme; Marchis, Franck; Marley, Mark S.; Matthews, Brenda C.; Metchev, Stanimir; Millar-Blanchaer, Maxwell A.; Oppenheimer, Rebecca; Palmer, David W.; Patience, Jenny; Perrin, Marshall D.; Poyneer, Lisa A.; Rajan, Abhijith; Rantakyrö, Fredrik T.; Savransky, Dmitry; Schneider, Adam C.; Sivaramakrishnan, Anand; Song, Inseok; Soummer, Remi; Thomas, Sandrine; Wallace, J. Kent; Ward-Duong, Kimberly; Wiktorowicz, Sloane J.; Wolff, Schuyler G.

    2016-09-01

    We present the discovery of a brown dwarf companion to the debris disk host star HR 2562. This object, discovered with the Gemini Planet Imager (GPI), has a projected separation of 20.3 ± 0.3 au (0\\buildrel{\\prime\\prime}\\over{.} 618+/- 0\\buildrel{\\prime\\prime}\\over{.} 004) from the star. With the high astrometric precision afforded by GPI, we have confirmed, to more than 5σ, the common proper motion of HR 2562B with the star, with only a month-long time baseline between observations. Spectral data in the J-, H-, and K-bands show a morphological similarity to L/T transition objects. We assign a spectral type of L7 ± 3 to HR 2562B and derive a luminosity of log(L {}{bol}/{L}⊙ )=-4.62+/- 0.12, corresponding to a mass of 30 ± 15 {M}{Jup} from evolutionary models at an estimated age of the system of 300-900 Myr. Although the uncertainty in the age of the host star is significant, the spectra and photometry exhibit several indications of youth for HR 2562B. The source has a position angle that is consistent with an orbit in the same plane as the debris disk recently resolved with Herschel. Additionally, it appears to be interior to the debris disk. Though the extent of the inner hole is currently too uncertain to place limits on the mass of HR 2562B, future observations of the disk with higher spatial resolution may be able to provide mass constraints. This is the first brown-dwarf-mass object found to reside in the inner hole of a debris disk, offering the opportunity to search for evidence of formation above the deuterium burning limit in a circumstellar disk.

  4. Reconnaissance of the HR 8799 Exosolar System. II. Astrometry and Orbital Motion

    NASA Astrophysics Data System (ADS)

    Pueyo, L.; Soummer, R.; Hoffmann, J.; Oppenheimer, R.; Graham, J. R.; Zimmerman, N.; Zhai, C.; Wallace, J. K.; Vescelus, F.; Veicht, A.; Vasisht, G.; Truong, T.; Sivaramakrishnan, A.; Shao, M.; Roberts, L. C., Jr.; Roberts, J. E.; Rice, E.; Parry, I. R.; Nilsson, R.; Lockhart, T.; Ligon, E. R.; King, D.; Hinkley, S.; Hillenbrand, L.; Hale, D.; Dekany, R.; Crepp, J. R.; Cady, E.; Burruss, R.; Brenner, D.; Beichman, C.; Baranec, C.

    2015-04-01

    We present an analysis of the orbital motion of the four substellar objects orbiting HR 8799. Our study relies on the published astrometric history of this system augmented with an epoch obtained with the Project 1640 coronagraph with an integral field spectrograph (IFS) installed at the Palomar Hale telescope. We first focus on the intricacies associated with astrometric estimation using the combination of an extreme adaptive optics system (PALM-3000), a coronagraph, and an IFS. We introduce two new algorithms. The first one retrieves the stellar focal plane position when the star is occulted by a coronagraphic stop. The second one yields precise astrometric and spectrophotometric estimates of faint point sources even when they are initially buried in the speckle noise. The second part of our paper is devoted to studying orbital motion in this system. In order to complement the orbital architectures discussed in the literature, we determine an ensemble of likely Keplerian orbits for HR 8799bcde, using a Bayesian analysis with maximally vague priors regarding the overall configuration of the system. Although the astrometric history is currently too scarce to formally rule out coplanarity, HR 8799d appears to be misaligned with respect to the most likely planes of HR 8799bce orbits. This misalignment is sufficient to question the strictly coplanar assumption made by various authors when identifying a Laplace resonance as a potential architecture. Finally, we establish a high likelihood that HR 8799de have dynamical masses below 13 MJup, using a loose dynamical survival argument based on geometric close encounters. We illustrate how future dynamical analyses will further constrain dynamical masses in the entire system.

  5. UV spectral variability in the Herbig Ae star HR 5999. 11: The accretion interpretation

    NASA Technical Reports Server (NTRS)

    Perez, M. R.; Grady, C. A.; The, P. S.

    1993-01-01

    We report recent IUE high- and low-dispersion observations with the IUE long wavelength camera (LWP) and short wavelength camera (SWP) of the Herbig Ae star HR 5999. We have found a dramatic change in the structure of the Mg II h and k lines (2795.5, 2802.7 A) along with some continuum flux excesses especially at the short end of the SWP camera. LWP high dispersion observations of HR 5999 obtained between 1979 and 1990, at times of comparatively low UV continuum fluxes, exhibit P Cygni type m profiles in the Mg II resonance doublet. In contrast, observations made from September 1990 through March 16-18, 1992, with high W continuum fluxes, present Mg II lines with reverse P Cygni profiles indicative of some active episodic accretion. Accreting gas can also be detected in the additional red wings of the various Fe II and Mn II absorption lines, with velocities up to +300-350 km/s (September 1990). By September 10, 1992 the Mg II profile had returned to the type III P Cygni profile similar to those from earlier spectra. The correlation between the presence of large column densities of accreting gas and the continuum light variations supports suggestions by several authors that HR 5999 is surrounded by an optically thick, viscously heated accretion disk. Detection of accreting gas in the line of sight to HR 5999 permits us to place constraints on our viewing geometry for this system. A discussion is included comparing the spectral and physical similarities between HR 5999 and the more evolved proto-planetary candidate system, beta Pictoris.

  6. THE CHARA ARRAY ANGULAR DIAMETER OF HR 8799 FAVORS PLANETARY MASSES FOR ITS IMAGED COMPANIONS

    SciTech Connect

    Baines, Ellyn K.; White, Russel J.; Jones, Jeremy; Boyajian, Tabetha; McAlister, Harold A.; Ten Brummelaar, Theo A.; Turner, Nils H.; Sturmann, Judit; Sturmann, Laszlo; Goldfinger, P. J.; Farrington, Christopher D.; Riedel, Adric R.; Huber, Daniel; Ireland, Michael; Von Braun, Kaspar; Ridgway, Stephen T.

    2012-12-10

    HR 8799 is an hF0 mA5 {gamma} Doradus-, {lambda} Bootis-, Vega-type star best known for hosting four directly imaged candidate planetary companions. Using the CHARA Array interferometer, we measure HR 8799's limb-darkened angular diameter to be 0.342 {+-} 0.008 mas (an error of only 2%). By combining our measurement with the star's parallax and photometry from the literature, we greatly improve upon previous estimates of its fundamental parameters, including stellar radius (1.44 {+-} 0.06 R{sub Sun }), effective temperature (7193 {+-} 87 K, consistent with F0), luminosity (5.05 {+-} 0.29 L{sub Sun }), and the extent of the habitable zone (HZ; 1.62-3.32 AU). These improved stellar properties permit much more precise comparisons with stellar evolutionary models, from which a mass and age can be determined, once the metallicity of the star is known. Considering the observational properties of other {lambda} Bootis stars and the indirect evidence for youth of HR 8799, we argue that the internal abundance, and what we refer to as the effective abundance, is most likely near solar. Finally, using the Yonsei-Yale evolutionary models with uniformly scaled solar-like abundances, we estimate HR 8799's mass and age considering two possibilities: 1.516{sup +0.038}{sub -0.024} M{sub Sun} and 33{sup +7}{sub -13.2} Myr if the star is contracting toward the zero-age main sequence or 1.513{sup +0.023}{sub -0.024} M{sub Sun} and 90{sup +381}{sub -50} Myr if it is expanding from it. This improved estimate of HR 8799's age with realistic uncertainties provides the best constraints to date on the masses of its orbiting companions, and strongly suggests they are indeed planets. They nevertheless all appear to orbit well outside the HZ of this young star.

  7. Limited field investigation report for the 100-HR-3 operable unit

    SciTech Connect

    Not Available

    1994-09-01

    This limited field investigation (LFI) was conducted to assess the applicability of interim remedial measures (IRM) for reducing human health and environmental risks within the 100-HR-3 Groundwater Operable Unit. The 100-HR-3 Operable Unit is comprised of three subareas; the 100 D Area, the 100 H Area and those portions of the 600 Area between the two reactor areas. The operable unit is one of seven operable units associated with the 100 D and H Areas. Operable units 100-DR-1, 100-DR-2, 100-DR-3, 100-HR-1, 100-HR-2 and 100-IU-4 address contaminant sources while 100-HR-3 addresses contamination present in the underlying groundwater. The primary method of field investigation used during this LFI was the installation and sampling of monitoring wells. Samples were collected from the groundwater and soils, and submitted for laboratory analysis. Boreholes were surveyed for radiological contamination using downhole geophysical techniques to further delineate the locations and levels of contaminants. All samples were screened to ascertain the presence of volatile organic compounds and radionuclides. Analytical data were subjected to validation; all round one, two and three and a minimum of 10% of round four data associated with the LFI were validated. A screening method was used to identify contaminants of potential concern (COPC). This screening method eliminated from further consideration, constituents that were below background. Constituents which are considered non-toxic to humans were eliminated from the human health evaluation. Data consistency and blank contamination were also evaluated in the screening process. These COPC were then evaluated further in the qualitative risk assessment (QRA). A human health QRA was performed using conservative (maximum equilibrated contaminant levels from the LFI) analyses.

  8. Comparable-Worth Adjustments: Yes--Comparable-Worth Adjustments: No.

    ERIC Educational Resources Information Center

    Galloway, Sue; O'Neill, June

    1985-01-01

    Two essays address the issue of pay equity and present opinions favoring and opposing comparable-worth adjustments. Movement of women out of traditionally female jobs, the limits of "equal pay," fairness of comparable worth and market-based wages, implementation and efficiency of comparable worth system, and alternatives to comparable…

  9. Providing for consideration of the bill (H.R. 273) to eliminate the 2013 statutory pay adjustment for Federal employees, and for other purposes.

    THOMAS, 113th Congress

    Rep. Woodall, Rob [R-GA-7

    2013-02-13

    02/14/2013 On agreeing to the resolution Agreed to by the Yeas and Nays: 227 - 192 (Roll no. 42). (text: CR H516-517) (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  10. 75 FR 33379 - Railroad Cost Recovery Procedures-Productivity Adjustment; Quarterly Rail Cost Adjustment Factor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ... Surface Transportation Board Railroad Cost Recovery Procedures--Productivity Adjustment; Quarterly Rail... Railroads that the Board restate the previously published productivity adjustment for the 2003-2007 averaging period (2007 productivity adjustment) so that it tracks the 2007 productivity adjustment...

  11. Low systolic blood pressure and mortality from all-cause and vascular diseases among the rural elderly in Korea; Kangwha cohort study.

    PubMed

    Yi, Sang-Wook; Hong, Seri; Ohrr, Heechoul

    2015-01-01

    The association between low systolic blood pressure (SBP) and vascular diseases is unclear. The aim of this study was to prospectively examine the association between SBP, especially low SBP, and mortality from all causes and vascular diseases among the elderly in Korea. Six thousand two hundred ninety four residents in a rural community were followed-up for deaths from 1985 to 2008. The adjusted hazard ratios (aHR) and 95% confidence intervals were calculated by Cox proportional hazard model. A stratified analysis was conducted by age at enrollment. Among the elderly aged 65 and above, the lowest SBP (<100 mm Hg) group had an elevated aHR for mortality from vascular diseases (aHR = 2.1, 95% CI = 1.2-3.9) including stroke (aHR = 2.4, 95% CI = 0.9-6.3) and ischemic heart diseases (aHR = 5.1, 95% CI = 1.0-26.0) compared to those with SBP of 100-119 mm Hg, while higher SBP was associated with higher mortality. This J-curve association was generally maintained when analysis was restricted to those with fair or good self-rated health, or those with no known vascular diseases. In people below 65, increasing SBP nearly monotonically increased the mortality from all-cause and vascular diseases. Our results suggest that elderly persons with low SBP should be treated with caution, since low SBP may increase vascular mortality.

  12. Structural analysis of cortical porosity applied to HR-pQCT data

    PubMed Central

    Tjong, Willy; Nirody, Jasmine; Burghardt, Andrew J.; Carballido-Gamio, Julio; Kazakia, Galateia J.

    2014-01-01

    Purpose: The investigation of cortical porosity is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. With the emergence of HR-pQCT as a noninvasive tool suitable for clinical use, cortical porosity at appendicular sites can be directly visualized in vivo. The aim of this study was to introduce a novel topological analysis of the cortical pore network for HR-pQCT data and determine the influence of resolution on measures of cortical pore network microstructure and topology. Methods: Cadaveric radii were scanned using HR-pQCT at two different voxel sizes (41 and 82 μm) and also using μCT at a voxel size of 18 μm. HR-pQCT and μCT image sets were spatially coregistered. Segmentation and quantification of cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm) were achieved using an established extended cortical analysis technique. Topological classification of individual pores was performed using topology-preserving skeletonization and multicolor dilation algorithms. Based on the pore skeleton topological classification, the following parameters were quantified: total number of planar surface-skeleton canals (N.Slabs), tubular curve-skeleton canals (N.Tubes), and junction elements (N.Junctions), mean slab volume (Slab.Vol), mean tube volume (Tube.Vol), mean slab orientation (Slab.θ), mean tube orientation (Tube.θ), N.Slabs/N.Tubes, and integral (total) slab volume/integral tube volume (iSlab.Vol/iTube.Vol). An in vivo reproducibility study was also conducted to assess short-term precision of the topology parameters. Precision error was characterized using root mean square coefficient of variation (RMSCV%). Results: Correlations to μCT values for Ct.Po were significant for both the 41 and 82 μm HR-pQCT data (41: r2 = 0.82, p < 0.001, 82: r2 = 0.75, p < 0.001). For Ct.Po.Dm, only the 41 μm data were significantly predictive of μCT values (r2 = 0.72, p < 0.01) Data at both HR

  13. Resistance to teratogenesis by F1 and F2 embryos of PAH-adapted Fundulus heteroclitus is strongly inherited despite reduced recalcitrance of the AHR pathway.

    PubMed

    Clark, Bryan W; Bone, A J; Di Giulio, R T

    2014-12-01

    Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Superfund site on the Elizabeth River (Portsmouth, VA, USA) are exposed to a complex mixture of polycyclic aromatic hydrocarbons (PAHs) from former creosote operations, but are resistant to the acute toxicity and cardiac teratogenesis caused by PAHs. The resistance is associated with a dramatic recalcitrance to induction of cytochrome P450 (CYP1) metabolism enzymes following exposure to aryl hydrocarbon receptor (AHR) agonists, along with an elevated antioxidant response and increased expression of several other xenobiotic metabolism and excretion enzymes. However, the heritability of the resistance in the absence of chemical stressors has been inconsistently demonstrated. Understanding the heritability of this resistance will help clarify the nature of population-level responses to chronic exposure to PAH mixtures and aid in identifying the important mechanistic components of resistance to aryl hydrocarbons. We compared the response of Atlantic Wood F1 and F2 embryos to benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and a mixture of BkF and fluoranthene (Fl) to that of F1 embryos of reference site killifish. Resistance to cardiac teratogenesis and induction of CYP mRNA expression and CYP activity was determined. We found that both Atlantic Wood F1 and F2 embryos were highly resistance to cardiac teratogenesis. However, the resistance by Atlantic Wood F2 embryos to induction of CYP mRNA expression and enzyme activity was intermediate between that of Atlantic Wood F1 embryos and reference embryos. These results suggest that resistance to cardiac teratogenesis in Atlantic Wood fish is conferred by multiple factors, not all of which appear to be fully genetically heritable.

  14. Combining NMR spectral and structural data to form models of polychlorinated dibenzodioxins, dibenzofurans, and biphenyls binding to the AhR

    NASA Astrophysics Data System (ADS)

    Beger, Richard D.; Buzatu, Dan A.; Wilkes, Jon G.

    2002-10-01

    A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) modeling technique which uses NMR spectral and structural information that is combined in a 3D-connectivity matrix has been developed. A 3D-connectivity matrix was built by displaying all possible assigned carbon NMR chemical shifts, carbon-to-carbon connections, and distances between the carbons. Two-dimensional 13C-13C COSY and 2D slices from the distance dimension of the 3D-connectivity matrix were used to produce a relationship among the 2D spectral patterns for polychlorinated dibenzofurans, dibenzodioxins, and biphenyls (PCDFs, PCDDs, and PCBs respectively) binding to the aryl hydrocarbon receptor (AhR). We refer to this technique as comparative structural connectivity spectral analysis (CoSCoSA) modeling. All CoSCoSA models were developed using forward multiple linear regression analysis of the predicted 13C NMR structure-connectivity spectral bins. A CoSCoSA model for 26 PCDFs had an explained variance (r2) of 0.93 and an average leave-four-out cross-validated variance (q4 2) of 0.89. A CoSCoSA model for 14 PCDDs produced an r2 of 0.90 and an average leave-two-out cross-validated variance (q2 2) of 0.79. One CoSCoSA model for 12 PCBs gave an r2 of 0.91 and an average q2 2 of 0.80. Another CoSCoSA model for all 52 compounds had an r2 of 0.85 and an average q4 2 of 0.52. Major benefits of CoSCoSA modeling include ease of development since the technique does not use molecular docking routines.

  15. Resistance to teratogenesis by F1 and F2 embryos of PAH-adapted Fundulus heteroclitus is strongly inherited despite reduced recalcitrance of the AHR pathway

    PubMed Central

    Clark, B. W.; Bone, A. J.; Di Giulio, R. T.

    2014-01-01

    Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Superfund site on the Elizabeth River (Portsmouth, VA, USA) are exposed to a complex mixture of polycyclic aromatic hydrocarbons (PAHs) from former creosote operations, but are resistant to the acute toxicity and cardiac teratogenesis caused by PAHs. The resistance is associated with a dramatic recalcitrance to induction of cytochrome P450 (CYP1) metabolism enzymes following exposure to aryl hydrocarbon receptor (AHR) agonists, along with an elevated antioxidant response and increased expression of several other xenobiotic metabolism and excretion enzymes. However, the heritability of the resistance in the absence of chemical stressors has been inconsistently demonstrated. Understanding the heritability of this resistance will help clarify the nature of population-level responses to chronic exposure to PAH mixtures and aid in identifying the important mechanistic components of resistance to aryl hydrocarbons. We compared the response of Atlantic Wood F1 and F2 embryos to benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), 3,3’,4,4’,5-pentachlorobiphenyl (PCB-126), and a mixture of BkF and fluoranthene (Fl) to that of F1 embryos of reference site killifish. Resistance to cardiac teratogenesis and induction of CYP mRNA expression and CYP activity was determined. We found that both Atlantic Wood F1 and F2 embryos were highly resistance to cardiac teratogenesis. However, the resistance by Atlantic Wood F2 embryos to induction of CYP mRNA expression and enzyme activity was intermediate between that of Atlantic Wood F1 embryos and reference embryos. These results suggest that resistance to cardiac teratogenesis in Atlantic Wood fish is conferred by multiple factors, not all of which appear to be fully genetically heritable. PMID:24374617

  16. Adjustable Optical-Fiber Attenuator

    NASA Technical Reports Server (NTRS)

    Buzzetti, Mike F.

    1994-01-01

    Adjustable fiber-optic attenuator utilizes bending loss to reduce strength of light transmitted along it. Attenuator functions without introducing measurable back-reflection or insertion loss. Relatively insensitive to vibration and changes in temperature. Potential applications include cable television, telephone networks, other signal-distribution networks, and laboratory instrumentation.

  17. Dyadic Adjustment: An Ecosystemic Examination.

    ERIC Educational Resources Information Center

    Wilson, Stephan M.; Larson, Jeffry H.; McCulloch, B. Jan; Stone, Katherine L.

    1997-01-01

    Examines the relationship of background, individual, and family influences on dyadic adjustment, using an ecological perspective. Data from 102 married couples were used. Age at marriage for husbands, emotional health for wives, and number of marriage and family problems as well as family life satisfaction for both were related to dyadic…

  18. Problems of Adjustment to School.

    ERIC Educational Resources Information Center

    Bartolini, Leandro A.

    This paper, one of several written for a comprehensive policy study of early childhood education in Illinois, examines and summarizes the literature on the problems of young children in adjusting to starting school full-time and describes the nature and extent of their difficulties in relation to statewide educational policy. The review of studies…

  19. Economic Pressures and Family Adjustment.

    ERIC Educational Resources Information Center

    Haccoun, Dorothy Markiewicz; Ledingham, Jane E.

    The relationships between economic stress on the family and child and parental adjustment were examined for a sample of 199 girls and boys in grades one, four, and seven. These associations were examined separately for families in which both parents were present and in which mothers only were at home. Economic stress was associated with boys'…

  20. The LEECH Exoplanet Imaging Survey. Further constraints on the planet architecture of the HR 8799 system

    NASA Astrophysics Data System (ADS)

    Maire, A.-L.; Skemer, A. J.; Hinz, P. M.; Desidera, S.; Esposito, S.; Gratton, R.; Marzari, F.; Skrutskie, M. F.; Biller, B. A.; Defrère, D.; Bailey, V. P.; Leisenring, J. M.; Apai, D.; Bonnefoy, M.; Brandner, W.; Buenzli, E.; Claudi, R. U.; Close, L. M.; Crepp, J. R.; De Rosa, R. J.; Eisner, J. A.; Fortney, J. J.; Henning, T.; Hofmann, K.-H.; Kopytova, T. G.; Males, J. R.; Mesa, D.; Morzinski, K. M.; Oza, A.; Patience, J.; Pinna, E.; Rajan, A.; Schertl, D.; Schlieder, J. E.; Su, K. Y. L.; Vaz, A.; Ward-Duong, K.; Weigelt, G.; Woodward, C. E.

    2015-04-01

    Context. Astrometric monitoring of directly imaged exoplanets allows the study of their orbital parameters and system architectures. Because most directly imaged planets have long orbital periods (>20 AU), accurate astrometry is challenging when based on data acquired on timescales of a few years and usually with different instruments. The LMIRCam camera on the Large Binocular Telescope is being used for the LBT Exozodi Exoplanet Common Hunt (LEECH) survey to search for and characterize young and adolescent exoplanets in L' band (3.8 μm), including their system architectures. Aims: We first aim to provide a good astrometric calibration of LMIRCam. Then, we derive new astrometry, test the predictions of the orbital model of 8:4:2:1 mean motion resonance proposed for the system, and perform new orbital fitting of the HR 8799 bcde planets. We also present deep limits on a putative fifth planet inside the known planets. Methods: We use observations of HR 8799 and the Θ1 Ori C field obtained during the same run in October 2013. Results: We first characterize the distortion of LMIRCam. We determine a platescale and a true north orientation for the images of 10.707 ± 0.012 mas/pix and -0.430 ± 0.076°, respectively. The errors on the platescale and true north orientation translate into astrometric accuracies at a separation of 1'' of 1.1 mas and 1.3 mas, respectively. The measurements for all planets agree within 3σ with a predicted ephemeris. The orbital fitting based on the new astrometric measurements favors an architecture for the planetary system based on 8:4:2:1 mean motion resonance. The detection limits allow us to exclude a fifth planet slightly brighter or more massive than HR 8799 b at the location of the 2:1 resonance with HR 8799 e (~9.5 AU) and about twice as bright as HR 8799 cde at the location of the 3:1 resonance with HR 8799 e (~7.5 AU). The LBT is an international collaboration among institutions in the United States, Italy, and Germany. LBT

  1. A new molecular prognostic score for predicting the risk of distant metastasis in patients with HR+/HER2− early breast cancer

    PubMed Central

    Gong, Gyungyub; Kwon, Mi Jeong; Han, Jinil; Lee, Hee Jin; Lee, Se Kyung; Lee, Jeong Eon; Lee, Seon-Heui; Park, Sarah; Choi, Jong-Sun; Cho, Soo Youn; Ahn, Sei Hyun; Lee, Jong Won; Cho, Sang Rae; Moon, Youngho; Nam, Byung-Ho; Nam, Seok Jin; Choi, Yoon-La; Shin, Young Kee

    2017-01-01

    To make an optimal treatment decision for early stage breast cancer, it is important to identify risk of recurrence. Here, we developed and validated a new prognostic model for predicting the risk of distant metastasis in patients with pN0-N1, hormone receptor-positive, HER2-negative (HR+/HER2−) breast cancer treated with hormone therapy alone. RNA was extracted from formalin-fixed, paraffin-embedded tumor tissues and gene expression was measured by quantitative real-time reverse transcription-PCR. The relative expression of six novel prognostic genes was combined with two clinical variables (nodal status and tumor size) to calculate a risk score (BCT score). In the validation cohort treated with hormone therapy alone, the 10 year rate of distant metastasis in the high-risk group (26.3%) according to BCT score was significantly higher than that in the low-risk group (3.8%) (P < 0.001). Multivariate analysis adjusted for clinical variables revealed that BCT score is an independent predictor of distant metastasis. Moreover, the C-index estimate revealed that BCT score has a prognostic power superior to that of prognostic models based on clinicopathological parameters. The BCT score outperforms prognostic models based on traditional clinicopathological factors and predicts the risk of distant metastasis in patients with HR+/HER2− early breast cancer. PMID:28350001

  2. The Near Naked Hairless (HrN) Mutation Disrupts Hair Formation but is not Due to a Mutation in the Hairless Coding Region

    SciTech Connect

    Liu, Yutao; Das, Suchita; Olszewski, Robert Edward; Culiat, Cymbeline T; Carpenter, D A; Sundberg, John P; Soteropoulos, Patricia; Liu, Xiaochen; Doktycz, Mitchel John; Michaud III, Edward J; Voy, Brynn H

    2007-01-01

    Near naked hairless (HrN) is a semi-dominant mutation that arose spontaneously and was suggested by allelism testing to be an allele of mouse Hairless (Hr). HrN mice differ from other Hr mutants in that hair loss appears as the postnatal coat begins to emerge, as opposed to failure to initiate the first postnatal hair cycle, and that the mutation displays semi-dominant inheritance. We sequenced the Hr cDNA in HrN/HrN mice and characterized the pathological and molecular phenotypes to identify the basis for hair loss in this model. HrN/HrN mice exhibit dystrophic hairs that are unable to consistently emerge from the hair follicle, while HrN/+ mice display a sparse coat of hair and a milder degree of follicular dystrophy than their homozygous littermates. DNA microarray analysis of cutaneous gene expression demonstrates that numerous genes are downregulated in HrN/HrN mice, primarily genes important for hair structure. By contrast, Hr expression is significantly increased. Sequencing the Hr coding region, intron-exon boundaries, 5'- and 3'- UTR and immediate upstream region did not reveal the underlying mutation. Therefore HrN does not appear to be an allele of Hr but may result from a mutation in a closely linked gene or from a regulatory mutation in Hr.

  3. The near-naked hairless (Hr(N)) mutation disrupts hair formation but is not due to a mutation in the Hairless coding region.

    PubMed

    Liu, Yutao; Das, Suchita; Olszewski, Robert E; Carpenter, Donald A; Culiat, Cymbeline T; Sundberg, John P; Soteropoulos, Patricia; Liu, Xiaochen; Doktycz, Mitchel J; Michaud, Edward J; Voy, Brynn H

    2007-07-01

    Near-naked hairless (Hr(N)) is a semi-dominant, spontaneous mutation that was suggested by allelism testing to be allelic with mouse Hairless (Hr). Hr(N) mice differ from other Hr mutants in that hair loss appears as the postnatal coat begins to emerge, rather than as an inability to regrow hair after the first catagen and that the mutation displays semi-dominant inheritance. We sequenced the Hr cDNA in Hr(N)/Hr(N) mice and characterized the pathological and molecular phenotypes to identify the basis for hair loss in this model. Hr(N)/Hr(N) mice exhibit dystrophic hairs that are unable to emerge consistently from the hair follicle, whereas Hr(N)/+ mice display a sparse coat of hair and a milder degree of follicular dystrophy than their homozygous littermates. DNA microarray analysis of cutaneous gene expression demonstrates that numerous genes are downregulated in Hr(N)/Hr(N) mice, primarily genes important for hair structure. By contrast, Hr expression is significantly increased. Sequencing the Hr-coding region, intron-exon boundaries, 5'- and 3'-untranslated region, and immediate upstream region did not reveal the underlying mutation. Therefore, Hr(N) does not appear to be an allele of Hr but may result from a mutation in a closely linked gene or from a regulatory mutation in Hr.

  4. Long-Term Durability Analysis of a 100,000+ Hr Stirling Power Convertor Heater Head

    NASA Technical Reports Server (NTRS)

    Bartolotta, Paul A.; Bowman, Randy R.; Krause, David L.; Halford, Gary R.

    2000-01-01

    DOE and NASA have identified Stirling Radioisotope Power Systems (SRPS) as the power supply for deep space exploration missions the Europa Orbiter and Solar Probe. As a part of this effort, NASA has initiated a long-term durability project for critical hot section components of the Stirling power convertor to qualify flight hardware. This project will develop a life prediction methodology that utilizes short-term (t < 20,000 hr) test data to verify long-term (t > 100,000 hr) design life. The project consists of generating a materials database for the specific heat of alloy, evaluation of critical hermetic sealed joints, life model characterization, and model verification. This paper will describe the qualification methodology being developed and provide a status for this effort.

  5. Human performance and physiological function during a 24-hr exposure to 1 percent bromotrifluoromethane (Halon 1301)

    NASA Technical Reports Server (NTRS)

    Calkins, D. S.; Degioanni, J. J.; Tan, M. N.; Davis, J. R.; Pierson, D. L.

    1993-01-01

    Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1 percent (10,000 ppm) Halon 1301 (CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures, using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5 percent of baseline values. Physiological data obtained before, during, and after the exposures revealed significant changes during Halon inhalation for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1 percent Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

  6. Radio continuum observations of the Herbig Ae/Be stars HD 163296 and HR 5999

    NASA Technical Reports Server (NTRS)

    Brown, D. A.; Perez, M. R.; Yusef-Zadeh, F.

    1993-01-01

    Very Large Array (VLA) observations of the two bright Herbig Ae/Be stars HD 163296 and HR 5999 have been carried out at lambda 3.6 and 20 cm. We report the detection of a radio source at lambda 3.6 cm that may be associated with HD 163296. From the peak flux density of 0.39 mJy/beam area, we estimate a mass-loss rate of 1.8 x 10(exp -8) solar mass/yr if the flux is due to free-free emission in an ionized wind with spherical symmetry, assuming a terminal wind velocity of 200 km/s. HR 5999 was not detected at either wavelength. We discuss the results in terms of the stellar-driven and accretion-driven scenarios for line and wind formation in Herbig Ae/Be stars.

  7. Global well-posedness for Schrödinger equation with derivative in H(R)

    NASA Astrophysics Data System (ADS)

    Miao, Changxing; Wu, Yifei; Xu, Guixiang

    In this paper, we consider the Cauchy problem of the cubic nonlinear Schrödinger equation with derivative in H(R). This equation was known to be the local well-posedness for s⩾1/2 > (Takaoka, 1999 [27]), ill-posedness for s<1/2 > (Biagioni and Linares, 2001 [1], etc.) and global well-posedness for s>1/2 > (I-team, 2002 [10]). In this paper, we show that it is global well-posedness in the endpoint space H(R), which remained open previously. The main approach is the third generation I-method combined with a new resonant decomposition technique. The resonant decomposition is applied to control the singularity coming from the resonant interaction.

  8. Frequency analysis of the rapidly oscillating AP star HR 1217 (HD 24712)

    NASA Astrophysics Data System (ADS)

    Kurtz, D. W.; Seeman, J.

    1983-10-01

    High speed photometric observations of HR 1217 have been obtained during 119 hr on 18 nights in 1981. On five of those nights, contemporaneous observations were obtained at the South African Astronomical Observatory and Cerro Tololo Inter-American Observatory which greatly reduce the severe daily aliasing problem in the frequency analysis of this star. A frequency analysis of three nights of data at the phase of pulsation amplitude maximum reveals six nearly uniformly spaced frequencies which are thought to be associated with six consecutive overtones of pulsation. From the frequency ratios, the overtones of the pulsations are estimated at 76 to 81. Pulsation amplitude maximum coincides with magnetic maximum again for these data which, with previous data obtained in 1980 for this star, sets an upper limit of Ck, l at less than or equal to 0.002 at the 3-sigma level of confidence.

  9. Development of 1 L hr-1 scale hydrogen liquefier using Gifford-McMahon (GM) cryocooler

    NASA Astrophysics Data System (ADS)

    Baik, J. H.; Karng, S. W.; Garceau, N.; Jang, Y. H.; Lim, C. M.; Kim, S. Y.; Oh, I. H.

    2014-01-01

    Korea Institute of Science and Technology (KIST) and Florida Solar Energy Center (FSEC) have collaborated to develop a demonstration-scale hydrogen liquefier for future liquid hydrogen research in Korea. A 1 L hr-1 liquefaction rate, direct-cooling type hydrogen liquefier using a commercially available GM cryocooler has been designed, fabricated, and tested at KIST. The liquefier consists of a GM cryocooler, finned heat pipe, liquid nitrogen precooler, ortho-para hydrogen converter, and vacuum jacketed internal storage tank. The system successfully demonstrated more than 1 L hr-1 of hydrogen liquefaction rate from ambient temperature gas. A detailed design method, loss analysis, overview of component fabrication, and experimental results are discussed in this paper.

  10. Inspection results of advanced (sub-50nm design rule) reticles using the TeraScanHR

    NASA Astrophysics Data System (ADS)

    Sier, Jean-Paul; Broadbent, William; Yu, Paul

    2008-04-01

    Results from the recently available TeraScanHR reticle inspection system were published in early 2007. These results showed excellent inspection capability for 45nm logic and 5xnm half-pitch memory advanced production reticles, thus meeting the industry need for the mid-2007 start of production. The system has been in production use since that time. In early 2007, some evidence was shown of capability to inspect reticles for 32nm logic and sub-50nm half-pitch memory, but the results were incomplete due to the limited availability of such reticles. However, more of these advanced reticles have become available since that time. In this paper, inspection results of these advanced reticles from various leading-edge reticle manufacturers using the TeraScanHR are shown. These results indicate that the system has the capability to provide the needed inspection sensitivity for continued development work to support the industry roadmap.

  11. Trabecular bone class mapping across resolutions: translating methods from HR-pQCT to clinical CT

    NASA Astrophysics Data System (ADS)

    Valentinitsch, Alexander; Fischer, Lukas; Patsch, Janina M.; Bauer, Jan; Kainberger, Franz; Langs, Georg; DiFranco, Matthew

    2015-03-01

    Quantitative assessment of 3D bone microarchitecture in high-resolution peripheral quantitative computed tomography (HR-pQCT) has shown promise in fracture risk assessment and biomechanics, but is limited to the distal radius and tibia. Trabecular microarchitecture classes (TMACs), based on voxel-wise clustering texture and structure tensor features in HRpQCT, is extended in this paper to quantify trabecular bone classes in clinical multi-detector CT (MDCT) images. Our comparison of TMACs in 12 cadaver radii imaged using both HRpQCT and MDCT yields a mean Dice score of up to 0.717+/-0.40 and visually concordant bone quality maps. Further work to develop clinically viable bone quantitative imaging using HR-pQCT validation could have a significant impact on overall bone health assessment.

  12. Probing Covalency in the UO3 Polymorphs by U M4 edge HR- XANES

    NASA Astrophysics Data System (ADS)

    Podkovyrina, Y.; Pidchenko, I.; Prüßmann, T.; Bahl, S.; Göttlicher, J.; Soldatov, A.; Vitova, T.

    2016-05-01

    Local atomic and electronic structure investigations of uranium trioxide (UO3) crystalline phases performed by the U M4 edge HR-XANES technique is presented. The experimental U M4 edge HR-XANES spectra of α-UO3, β-UO3 and γ-UO3 polymorphic phases are compared with spectra of uranate (CaU2O7) and uranyl (UO3•1-2(H2O)) compounds. We describe a finger print approach valuable for characterization of variations of U-O axial bond lengths. Theoretical calculations of spectra using full-multiple-scattering theory (FEFF9.6 code) are performed. We have tested and selected input parameters, which provide best agreement between experimental and calculated spectra.

  13. HR 7920: a very bright new Delta Scuti star with possible Gamma Doradus variations

    NASA Astrophysics Data System (ADS)

    Koen, C.; van Wyk, F.; Laney, C. D.; Kilkenny, D.

    2017-04-01

    We present photometric and high-dispersion spectroscopic measurements that show HR 7920 is a periodic variable. The photometry reveals at least four frequencies higher that 10 d-1, two of which are also probably present in the radial velocity variations. The frequencies are in a range typical of δ Scuti star pulsations. A further low frequency of about 2.8 d-1 may be present in both radial velocities and photometry; if real, this points to γ Doradus variability, which would make HR 7920 a hybrid pulsator. An attempt is made to identify the modes of the δ Scuti pulsations, which include both radial and non-radial modes. A new rotational velocity of 75 km s-1 is derived from co-added spectra, contrasting with published values in the range 128-150 km s-1.

  14. Near-infrared Spectroscopy of the Extrasolar Planet HR 8799 b

    NASA Astrophysics Data System (ADS)

    Bowler, Brendan P.; Liu, Michael C.; Dupuy, Trent J.; Cushing, Michael C.

    2010-11-01

    We present 2.12-2.23 μm high contrast integral field spectroscopy of the extrasolar planet HR 8799 b. Our observations were obtained with OSIRIS on the Keck II telescope and sample the 2.2 μm CH4 feature, which is useful for spectral classification and as a temperature diagnostic for ultracool objects. The spectrum of HR 8799 b is relatively featureless, with little or no methane absorption, and does not exhibit the strong CH4 seen in T dwarfs of similar absolute magnitudes. The spectrum is consistent with field objects from early-L to T4 (3σ confidence level), with a best-fitting type of T2. A similar analysis of the published 1-4 μm photometry shows the infrared spectral energy distribution (SED) matches L5-L8 field dwarfs, especially the reddest known objects which are believed to be young and/or very dusty. Overall, we find that HR 8799 b has a spectral type consistent with L5-T2, although its SED is atypical compared to most field objects. We fit the 2.2 μm spectrum and the infrared SED using the Hubeny & Burrows, Burrows et al., and Ames-Dusty model atmosphere grids, which incorporate non-equilibrium chemistry, non-solar metallicities, and clear and cloudy variants. No models agree with all of the data, but those with intermediate clouds produce significantly better fits. The largest discrepancy occurs in the J band, which is highly suppressed in HR 8799 b. Models with high eddy diffusion coefficients and high metallicities are somewhat preferred over those with equilibrium chemistry and solar metallicity. The best-fitting effective temperatures range from 1300 to 1700 K with radii between ~0.3 and 0.5 R Jup. These values are inconsistent with evolutionary model-derived values of 800-900 K and 1.1-1.3 R Jup based on the luminosity of HR 8799 b and the age of HR 8799, a discrepancy that probably results from imperfect atmospheric models or the limited range of physical parameters covered by the models. The low temperature inferred from evolutionary models

  15. Impacts of Modeled Provisions of H.R. 6 EH: The Energy Policy Act of 2005

    EIA Publications

    2005-01-01

    This report responds to a May 2, 2005, request by Chairman Pete Domenici and Ranking Member Jeff Bingaman of the Senate Committee on Energy and Natural Resources for an assessment of the energy supply, consumption, import, price, and macroeconomic impacts of H.R. 6 EH, the Energy Policy Act of 2005, as passed by the U.S. House of Representatives on April 21, 2005.

  16. Sensitivity of mouse Skh:HR-2 to ultraviolet radiation: melanocyte inactivation

    SciTech Connect

    Warren, R.; Gardner, P.A.; Reed, J.C.

    1987-03-01

    The hairless mouse, Skh:HR-2, was exposed to doses of ultraviolet (UV) radiation known to induce skin pigmentation. Three parameters associated with perturbations in skin pigmentation were monitored following UV exposure. These include spectroscopy (skin darkness), histology (melanocyte density), and biochemistry (melanin). Within 90 min of UV exposure, the skin became lighter. This was associated with a reduction of quantifiable melanin and the inactivation of epidermal melanocytes.

  17. Hearing on National Youth Corps, H.R. 18 and H.R. 460. Hearing before the Subcommittee on Employment Opportunities of the Committee on Education and Labor. House of Representatives, One Hundredth Congress, Second Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    This document contains transcripts of oral and written testimony from witnesses at a hearing on H.R. 18 and H.R. 460, which would create a National Youth Corps. The National Youth Corps proposal links two other proposals, the Conservation Corps bill and the National Youth Service bill, into a comprehensive bill to provide alternatives for youth in…

  18. Redundant ecdysis regulatory functions of three nuclear receptor HR3 isoforms in the direct-developing insect Blattella germanica.

    PubMed

    Cruz, Josefa; Martín, David; Bellés, Xavier

    2007-03-01

    In hemimetabolous insects, the molecular basis of the 20-hydroxyecdysone (20E)-triggered genetic hierarchy is practically unknown. In the cockroach Blattella germanica, we had previously characterized one isoform of the ecdysone receptor, BgEcR-A, and two isoforms of its heterodimeric partner, BgRXR-S and BgRXR-L. One of the early-late genes of the 20E-triggered genetic hierarchy, is HR3. In the present paper, we report the discovery of three isoforms of HR3 in B. germanica, that were named BgHR3-A, BgHR3-B(1) and BgHR3-B(2). Expression studies in prothoracic gland, epidermis and fat body indicate that the expression of the three isoforms coincides with the peak of circulating ecdysteroids at each nymphal instar. Experiments in vitro with fat body tissue have shown that 20E induces the expression of BgHR3 isoforms, and that incubation with 20E and the protein inhibitor cycloheximide does not inhibit the induction, which indicates that the effect of 20E on BgHR3 activation is direct. This has been further confirmed by RNAi in vivo of BgEcR-A, which has shown that this nuclear receptor is required to fully activate the expression of BgHR3. RNAi has been also used to demonstrate the functions of BgHR3 in ecdysis. Nymphs with silenced BgHR3 completed the apolysis but were unable to ecdyse (they had duplicated and superimposed the mouth parts, the hypopharinge, the tracheal system and the cuticle layers). This indicates that BgHR3 is directly involved in ecdysis. Finally, RNAi of specific isoforms has showed that they are functionally redundant, at least regarding the ecdysis process.

  19. 12 CFR 19.240 - Inflation adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Inflation adjustments. 19.240 Section 19.240... PROCEDURE Civil Money Penalty Inflation Adjustments § 19.240 Inflation adjustments. (a) The maximum amount of each civil money penalty within the OCC's jurisdiction is adjusted in accordance with the...

  20. 12 CFR 19.240 - Inflation adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Inflation adjustments. 19.240 Section 19.240... PROCEDURE Civil Money Penalty Inflation Adjustments § 19.240 Inflation adjustments. (a) The maximum amount... Civil Penalties Inflation Adjustment Act of 1990 (28 U.S.C. 2461 note) as follows: ER10NO08.001 (b)...

  1. 12 CFR 19.240 - Inflation adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Inflation adjustments. 19.240 Section 19.240... PROCEDURE Civil Money Penalty Inflation Adjustments § 19.240 Inflation adjustments. (a) The maximum amount... Civil Penalties Inflation Adjustment Act of 1990 (28 U.S.C. 2461 note) as follows: ER10NO08.001 (b)...

  2. Adjusting to University: The Hong Kong Experience

    ERIC Educational Resources Information Center

    Yau, Hon Keung; Sun, Hongyi; Cheng, Alison Lai Fong

    2012-01-01

    Students' adjustment to the university environment is an important factor in predicting university outcomes and is crucial to their future achievements. University support to students' transition to university life can be divided into three dimensions: academic adjustment, social adjustment and psychological adjustment. However, these…

  3. A possible T Tauri companion to the long-term photometric variable HR 6000.

    NASA Astrophysics Data System (ADS)

    van den Ancker, M. E.; de Winter, D.; The, P. S.

    1996-09-01

    From Stroemgren uvby photometry, obtained during the last 14 years, we demonstrate that HR 6000 shows long-term photometric variations with a small (about 0.03mag in u, 0.02mag in v and 0.01mag in b) amplitude. Whereas previous authors classified HR 6000 spectroscopically as A0/3 IIIp and photometrically as B7, we conclude that the observed properties of this system may be explained by inferring that HR 6000 is in fact a binary system, consisting of a B6 V star and a T Tauri companion. The combined spectrum of these two components may easily have been mistaken for a chemically peculiar early A-type star. This scenario also explains the observed small amount of infrared excess and the observed ROSAT X-ray flux of this system as arising from a T Tauri companion. Other traces of this companion have not been detected in our studies. Detection of the T Tauri companion with near-IR spectroscopy may be possible due to the significant contribution of the companion to the total flux at these wavelengths.

  4. A search for circumstellar dust around HR 10, a proposed Beta Pictoris star

    NASA Technical Reports Server (NTRS)

    Cheng, Kwang-Ping; Grady, C. A.; Bruhweiler, Frederick C.

    1991-01-01

    Archival IRAS data and recent IUE observations of the A shell star HR 10 (HD 256) are presented. HR 10 is detected in the IRAS Faint Source Survey and ADDSCAN data at 12 and 25 microns and marginally detected at 60 microns. The IUE data indicate a spectral type of A2 with 0.1 mag of UV selective extinction following a galactic average extinction law. HR 10 shows an infrared excess, compared to normal A stars of the same spectral type, beginning at 12 microns and extending to longer wavelengths. The IR excess is consistent with free-free emission and a suggestion of CS dust. The IR colors for this star differ significantly from those of Beta Pic and are closer to those of Vega. The absence of circumstellar selective extinction shortward of 3200 A suggests that the circumstellar grain size distribution does not resemble that of the interstellar medium, but may be more like the grains around Vega and Beta Pic.

  5. P/2006 HR30 (Siding Spring): A Low-activity Comet in Near-Earth Space

    NASA Technical Reports Server (NTRS)

    Hicks, Michael D.; Bauer, James M.

    2007-01-01

    The low cometary activity of P/2006 HR30 (Siding Spring) allowed a unique opportunity to study the nucleus of a periodic comet while near perihelion. P/2006 HR30 was originally targeted as a potential extinct comet, and we measured spectral reflectance and dust production using long-slit CCD spectroscopy and wide-field imaging obtained at the Palomar Mountain 200 inch telescope on 2006 August 3 and 4. The dust production Afp = 19.7 +/- 0.4 cm and mass-loss rate Q(dust) 4.1 +/- 0.1 kg/sec of the comet were approximately 2 orders of magnitude dust less than 1P/Halley at similar heliocentric distance. The VRI colors derived from the spectral reflectance were compared to Kuiper Belt objects, Centaurs, and other cometary nuclei. We found that the spectrum of P/2006 HR30 was consistent with other comets. However, the outer solar system bodies have a color distribution statistically distinct from cometary nuclei. It is our conjecture that cometary activity, most likely the reaccretion of ejected cometary dust, tends to moderate and mute the visible colors of the surface of cometary nuclei.

  6. Coverage-adjusted entropy estimation.

    PubMed

    Vu, Vincent Q; Yu, Bin; Kass, Robert E

    2007-09-20

    Data on 'neural coding' have frequently been analyzed using information-theoretic measures. These formulations involve the fundamental and generally difficult statistical problem of estimating entropy. We review briefly several methods that have been advanced to estimate entropy and highlight a method, the coverage-adjusted entropy estimator (CAE), due to Chao and Shen that appeared recently in the environmental statistics literature. This method begins with the elementary Horvitz-Thompson estimator, developed for sampling from a finite population, and adjusts for the potential new species that have not yet been observed in the sample-these become the new patterns or 'words' in a spike train that have not yet been observed. The adjustment is due to I. J. Good, and is called the Good-Turing coverage estimate. We provide a new empirical regularization derivation of the coverage-adjusted probability estimator, which shrinks the maximum likelihood estimate. We prove that the CAE is consistent and first-order optimal, with rate O(P)(1/log n), in the class of distributions with finite entropy variance and that, within the class of distributions with finite qth moment of the log-likelihood, the Good-Turing coverage estimate and the total probability of unobserved words converge at rate O(P)(1/(log n)(q)). We then provide a simulation study of the estimator with standard distributions and examples from neuronal data, where observations are dependent. The results show that, with a minor modification, the CAE performs much better than the MLE and is better than the best upper bound estimator, due to Paninski, when the number of possible words m is unknown or infinite.

  7. Goddard High-Resolution Spectrograph Observations of Procyon and HR1099

    NASA Technical Reports Server (NTRS)

    Wood, Brian E.; Harper, Graham M.; Linsky, Jeffrey L.; Dempsey, Robert C.

    1996-01-01

    Goddard High Resolution Spectrograph (GHRS) observations have revealed the presence of broad wings in the transition-region lines of AU Mic and Capella. It has been proposed that these wings are signatures of microflares in the transition regions of these stars and that the solar analog for this phenomenon might be the 'transition region explosive events' discussed by Dere, Bartoe, & Brueckner. We have analyzed GHRS observations of Procyon (F5 IV-V) and HR 1099 (K1 IV + G5 IV) to search for broad wings in the UV emission lines of these stars. We find that the transition-region lines of HR 1099, which are emitted almost entirely by the K1 star, do indeed have broad wings that are even more prominent than those of AU Mic and Capella. This is consistent with the association of the broad wings with microflaring since HR 1099 is a very active binary system. In contrast, the transition-region lines of Procyon, a relatively inactive star, do not show evidence for broad wings, with the possible exception of N v lambda1239. However, Procyon's lines do appear to have excess emission in their blue wings. Linsky et al. found no evidence for broad wings in Capella's chromospheric lines, but we find that the Mg II resonance lines of HR 1099 do have broad wings. The striking resemblance between HR 1099's Mg II and C iv lines suggests that the Mg II line profiles may be regulated by turbulent processes similar to those that control the transition-region line profiles. If this is the case, microflaring may be occurring in the K1 star's chromosphere as well as in its transition region. However, radiative transfer calculations suggest that the broad wings of the Mg II lines can also result from normal chromospheric opacity effects rather than pure turbulence. The prominence of broad wings in the transition region and perhaps even chromospheric lines of active stars suggests that microflaring is very prevalent in the outer atmospheres of active stars.

  8. Multi-element abundance Doppler imaging of the rapidly oscillating Ap star HR 3831

    NASA Astrophysics Data System (ADS)

    Kochukhov, O.; Drake, N. A.; Piskunov, N.; de la Reza, R.

    2004-09-01

    We investigate magnetic field geometry and surface distribution of chemical elements in the rapidly oscillating Ap star HR 3831. Results of the model atmosphere analysis of the spectra of this star are combined with the Hipparcos parallax and evolutionary models to obtain new accurate estimates of the fundamental stellar parameters: Teffv{7650}, log L/L⊙=1.09, M/M⊙= 1.77 and an inclination angle i=68° of the stellar axis of rotation. We find that the variation of the longitudinal magnetic field of HR 3831 and the results of our analysis of the magnetic intensification of Fe I lines in the spectrum of this star are consistent with a dipolar magnetic topology with a magnetic obliquity β=87° and a polar strength Bp=2.5 kG. We apply a multi-element abundance Doppler imaging inversion code for the analysis of the spectrum variability of HR 3831, and recover surface distributions of 17 chemical elements, including Li, C, O, Na, Mg, Si, Ca, Ti, Cr, Mn, Fe, Co, Ba, Y, Pr, Nd, Eu. Our study represents the most thorough examination of the surface chemical structure in a magnetic Ap star and provides important observational constraints for modelling radiative diffusion in magnetic stars. The exceedingly high quality of some of our spectroscopic data allowed us to reconstruct unprecedented details of abundance distributions, demonstrating a high level of complexity in the surface structure down to the resolution limit of the Doppler maps. The Doppler imaging analysis of HR 3831 forms a basis for subsequent detailed observational investigations and theoretical modelling of non-radial oscillations in this star. We discuss the compound effect of the chemical nonuniformities and pulsational velocity field on the rapid line profile variations, and assess the possibility of identifying pulsation modes by using spatial filtering produced by an inhomogeneous abundance distribution. The results of our study of the surface chemical structure suggest that differences in

  9. Understanding the effectiveness of precursor reductions in lowering 8-hr ozone concentrations--Part II. The eastern United States.

    PubMed

    Reynolds, Steven D; Blanchard, Charles L; Ziman, Stephen D

    2004-11-01

    Analyses of ozone (O3) measurements in conjunction with photochemical modeling were used to assess the feasibility of attaining the federal 8-hr O3 standard in the eastern United States. Various combinations of volatile organic compound (VOC) and oxides of nitrogen (NOx) emission reductions were effective in lowering modeled peak 1-hr O3 concentrations. VOC emissions reductions alone had only a modest impact on modeled peak 8-hr O3 concentrations. Anthropogenic NOx emissions reductions of 46-86% of 1996 base case values were needed to reach the level of the 8-hr standard in some areas. As NOx emissions are reduced, O3 production efficiency increases, which accounts for the less than proportional response of calculated 8-hr O3 levels. Such increases in O3 production efficiency also were noted in previous modeling work for central California. O3 production in some urban core areas, such as New York City and Chicago, IL, was found to be VOC-limited. In these areas, moderate NOx emissions reductions may be accompanied by increases in peak 8-hr O3 levels. The findings help to explain differences in historical trends in 1- and 8-hr O3 levels and have serious implications for the feasibility of attaining the 8-hr O3 standard in several areas of the eastern United States.

  10. Molecular basis for hair loss in mice carrying a novel nonsense mutation (Hrrh-R ) in the hairless gene (Hr).

    PubMed

    Liu, Y; Sundberg, J P; Das, S; Carpenter, D; Cain, K T; Michaud, E J; Voy, B H

    2010-01-01

    Animal models carrying mutations in the hairless (Hr) gene provide a rich resource for study of hair follicle biology. A spontaneous mouse mutant with a phenotype strikingly similar to rhino mutants of Hr arose spontaneously in the mouse facility at Oak Ridge National Laboratory. Sequence analysis of Hr in these mutants uncovered a nonsense mutation in exon 12, designated as Hr(rh-R) (rhino, Oak Ridge). The mutation led to significant reduction in Hr mRNA levels, predicted to be due to nonsense-mediated decay. Histological analysis indicated dilated hair follicle infundibula at 14 days of age that rapidly became filled with cornified material. Microarray analyses revealed that expression levels of many genes involved in keratinocyte differentiation, epidermal regeneration, and wound healing were significantly upregulated before morphological detection of the phenotype, suggesting their role in onset of the Hr(rh-R) phenotype. Identification of this new Hr allele and the underlying molecular alterations allows further understanding of the role of Hr in hair follicle biology.

  11. The chlorinated AHR ligand 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) promotes reactive oxygen species (ROS) production during embryonic development in the killifish (Fundulus heteroclitus)

    USGS Publications Warehouse

    Arzuaga, Xabier; Wassenberg, Deena; Giulio, Richard D.; Elskus, Adria

    2006-01-01

    Exposure to dioxin-like chemicals that activate the aryl hydrocarbon receptor (AHR) can result in increased cellular and tissue production of reactive oxygen species (ROS). Little is known of these effects during early fish development. We used the fish model, Fundulus heteroclitus, to determine if the AHR ligand and pro-oxidant 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) can increase ROS production during killifish development, and to test a novel method for measuring ROS non-invasively in a living organism. The superoxide-sensitive fluorescent dye, dihydroethidium (DHE), was used to detect in ovo ROS production microscopically in developing killifish exposed to PCB126 or vehicle. Both in ovo CYP1A activity (ethoxyresorufin-o-deethylase, EROD) and in ovo ROS were induced by PCB126. In ovo CYP1A activity was inducible by PCB126 concentrations as low as 0.003 nM, with maximal induction occurring at 0.3 nM PCB126. These PCB126 concentrations also significantly increased in ovo ROS production in embryonic liver, ROS being detectable as early as 5 days post-fertilization. These data demonstrate that the pro-oxidant and CYP1A inducer, PCB126, increases both CYP1A activity and ROS production in developing killifish embryos. The superoxide detection assay (SoDA) described in this paper provides a semi-quantitative, easily measured, early indicator of altered ROS production that can be used in conjunction with simultaneous in ovo measurements of CYP1A activity and embryo development to explore functional relationships among biochemical, physiological and developmental responses to AHR ligands.

  12. Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene

    SciTech Connect

    Wakui, Shin . E-mail: wakui@azabu-u.ac.jp; Yokoo, Kiyofumi; Takahashi, Hiroyuki; Muto, Tomoko; Suzuki, Yoshihiko; Kanai, Yoshikatsu; Hano, Hiroshi; Furusato, Masakuni; Endou, Hitoshi

    2006-02-01

    We previously reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 {mu}g of PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 {mu}g group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunohistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.

  13. The combined effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and the phytoestrogen genistein on steroid hormone secretion, AhR and ERβ expression and the incidence of apoptosis in granulosa cells of medium porcine follicles

    PubMed Central

    PIASECKA-SRADER, Joanna; SADOWSKA, Agnieszka; NYNCA, Anna; ORLOWSKA, Karina; JABLONSKA, Monika; JABLONSKA, Olga; PETROFF, Brian K.; CIERESZKO, Renata E.

    2015-01-01

    Low doses of endocrine disrupting chemicals (EDCs) used in combination may act in a manner different from that of individual compounds. The objective of the study was to examine in vitro effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 100 pM) and genistein (500 nM) on: 1) progesterone (P4) and estradiol (E2) secretion (48 h); 2) dynamic changes in aryl hydrocarbon receptor (AhR) mRNA and protein expression (1, 3, 6, 24 and 48 h); 3) dynamic changes in estrogen receptor β (ERβ) mRNA and protein expression (1, 3, 6, 24 and 48 h); and 4) induction of apoptosis in porcine granulosa cells derived from medium follicles (3, 6 and 24 h). TCDD had no effect on P4 or E2 production, but potentiated the inhibitory effect of genistein on P4 production. In contrast to the individual treatments which did not produce any effects, TCDD and genistein administered together decreased ERβ and AhR protein expression in granulosa cells. Moreover, the inhibitory effect of TCDD on AhR mRNA expression was abolished by genistein. The treatments did not induce apoptosis in the cells. In summary, combined effects of low concentrations of TCDD and genistein on follicular function of pigs differed from that of individual compounds. The results presented in the current paper clearly indicate that effects exerted by low doses of EDCs applied in combination must be taken into consideration when studying potential risk effects of EDCs on biological processes. PMID:26568065

  14. Adjusting exposure limits for long and short exposure periods using a physiological pharmacokinetic model.

    PubMed

    Andersen, M E; MacNaughton, M G; Clewell, H J; Paustenbach, D J

    1987-04-01

    The rationale for adjusting occupational exposure limits for unusual work schedules is to assure, as much as possible, that persons on these schedules are placed at no greater risk of injury or discomfort than persons who work a standard 8 hr/day, 40 hr/week. For most systemic toxicants, the risk index upon which the adjustments are made will be either peak blood concentration or integrated tissue dose, depending on what chemical's presumed mechanism of toxicity. Over the past ten years, at least four different models have been proposed for adjusting exposure limits for unusually short and long work schedules. This paper advocates use of a physiologically-based pharmacokinetic (PB-PK) model for determining adjustment factors for unusual exposure schedules, an approach that should be more accurate than those proposed previously. The PB-PK model requires data on the blood:air and tissue:blood partition coefficients, the rate of metabolism of the chemical, organ volumes, organ blood flows and ventilation rates in humans. Laboratory data on two industrially important chemicals--styrene and methylene chloride--were used to illustrate the PB-PK approach. At inhaled concentrations near their respective 8-hr Threshold Limit Value-Time-weighted averages (TLV-TWAs), both of these chemicals are primarily eliminated from the body by metabolism. For these two chemicals, the appropriate risk indexing parameters are integrated tissue dose or total amount of parent chemical metabolized. Since methylene chloride is metabolized to carbon monoxide, the maximum blood carboxyhemoglobin concentrations also might be useful as an index of risk for this chemical.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Studies on the Role of The Ah Receptor (AhR) on the Etiology of Breast Cancer: A Novel Idea of Identifying this Receptor as a New Therapeutic Target

    DTIC Science & Technology

    2010-09-01

    and resistance to UV-irradiation induced apoptosis such as: luteolin curcumin, zerumbone and resveratrol . Second we tested the effectiveness of a...transplanted AHR overexpressing human breast cancer cells. Figures P20C P20E 0 25 50 75 100 125 150 Control Curcumin Luteolin Resveratrol ...treated with curcumin (10 µM), luteolin (5 µM), resveratrol (10 µM) or zerumbone (5 µM) for 48 h, respectively. CYP1A1 Co ntr ol TC DD Lu teo lin

  16. Inflation Adjustments for Defense Acquisition

    DTIC Science & Technology

    2014-10-01

    Harmon Daniel B. Levine Stanley A. Horowitz, Project Leader INSTITUTE FOR DEFENSE ANALYSES 4850 Mark Center Drive Alexandria, Virginia 22311-1882 Approved...T U T E F O R D E F E N S E A N A L Y S E S IDA Document D-5112 Inflation Adjustments for Defense Acquisition Bruce R. Harmon Daniel B. Levine...might do a better job? The focus of the study is on aircraft procurement. By way of terminology , “cost index,” “price index,” and “deflator” are used

  17. Adjustable extender for instrument module

    DOEpatents

    Sevec, J.B.; Stein, A.D.

    1975-11-01

    A blank extender module used to mount an instrument module in front of its console for repair or test purposes has been equipped with a rotatable mount and means for locking the mount at various angles of rotation for easy accessibility. The rotatable mount includes a horizontal conduit supported by bearings within the blank module. The conduit is spring-biased in a retracted position within the blank module and in this position a small gear mounted on the conduit periphery is locked by a fixed pawl. The conduit and instrument mount can be pulled into an extended position with the gear clearing the pawl to permit rotation and adjustment of the instrument.

  18. Atmospheric retrieval analysis of the directly imaged exoplanet HR 8799b

    SciTech Connect

    Lee, Jae-Min; Heng, Kevin; Irwin, Patrick G. J. E-mail: kevin.heng@csh.unibe.ch

    2013-12-01

    Directly imaged exoplanets are unexplored laboratories for the application of the spectral and temperature retrieval method, where the chemistry and composition of their atmospheres are inferred from inverse modeling of the available data. As a pilot study, we focus on the extrasolar gas giant HR 8799b, for which more than 50 data points are available. We upgrade our non-linear optimal estimation retrieval method to include a phenomenological model of clouds that requires the cloud optical depth and monodisperse particle size to be specified. Previous studies have focused on forward models with assumed values of the exoplanetary properties; there is no consensus on the best-fit values of the radius, mass, surface gravity, and effective temperature of HR 8799b. We show that cloud-free models produce reasonable fits to the data if the atmosphere is of super-solar metallicity and non-solar elemental abundances. Intermediate cloudy models with moderate values of the cloud optical depth and micron-sized particles provide an equally reasonable fit to the data and require a lower mean molecular weight. We report our best-fit values for the radius, mass, surface gravity, and effective temperature of HR 8799b. The mean molecular weight is about 3.8, while the carbon-to-oxygen ratio is about unity due to the prevalence of carbon monoxide. Our study emphasizes the need for robust claims about the nature of an exoplanetary atmosphere to be based on analyses involving both photometry and spectroscopy and inferred from beyond a few photometric data points, such as are typically reported for hot Jupiters.

  19. The luminous blue variable HR Carinae has a partner. Discovery of a companion with the VLTI

    NASA Astrophysics Data System (ADS)

    Boffin, Henri M. J.; Rivinius, Thomas; Mérand, Antoine; Mehner, Andrea; LeBouquin, Jean-Baptiste; Pourbaix, Dimitri; de Wit, Willem-Jan; Martayan, Christophe; Guieu, Sylvain

    2016-09-01

    Luminous blue variables (LBVs) are massive stars caught in a post-main sequence phase, during which they lose a significant amount of mass. Since, on one hand, it is thought that the majority of massive stars are close binaries that will interact during their lifetime, and on the other, the most dramatic example of an LBV, η Car, is a binary, it would be useful to find other binary LBVs. We present here interferometric observations of the LBV HR Car done with the AMBER and PIONIER instruments attached to ESO's Very Large Telescope Interferometer (VLTI). Our observations, spanning two years, clearly reveal that HR Car is a binary star. It is not yet possible to fully constrain the orbit, and the orbital period may lie between a few years and several hundred years. We derive a radius for the primary in the system and possibly also resolve the companion. The luminosity ratio in the H-band between the two components is changing with time, going from about 6 to 9. We also tentatively detect the presence of some background flux which remained at the 2% level until January 2016, but then increased to 6% in April 2016. Our AMBER results show that the emission line-forming region of Brγ is more extended than the continuum-emitting region as seen by PIONIER and may indicate some wind-wind interaction. Most importantly, we constrain the total masses of both components, with the most likely range being 33.6 M⊙ and 45 M⊙. Our results show that the LBV HR Car is possibly an η Car analog binary system with smaller masses, with variable components, and further monitoring of this object is definitively called for. Based on data obtained with ESO programmes 092.C-0243, 092.D-0289, 092.D-0296, 094.D-0069, and 596.D-0335.

  20. The Gemini NICI Planet-Finding Campaign: The Offset Ring of HR 4796 A

    NASA Technical Reports Server (NTRS)

    Wahhaj, Zahed; Liu, Michael C.; Biller, Beth A.; Nielsen, Eric L.; Hayward, Thomas L.; Kuchner, Marc J.; Close, Laird M.; Chun, Mark; Ftaclas, Christ; Toomey, Douglas W.

    2014-01-01

    We present J, H, CH4 short (1.578 micrometers), CH4 long (1.652 micrometers) and K(sub s)-band images of the dust ring around the 10 Myr old star HR 4796 A obtained using the Near Infrared Coronagraphic Imager (NICI) on the Gemini-South 8.1 m Telescope. Our images clearly show for the first time the position of the star relative to its circumstellar ring thanks to NICI's translucent focal plane occulting mask. We employ a Bayesian Markov chain Monte Carlo method to constrain the offset vector between the two. The resulting probability distribution shows that the ring center is offset from the star by 16.7 +/- 1.3 milliarcseconds along a position angle of 26 +/- 3deg, along the PA of the ring, 26.47 +/- 0.04deg. We find that the size of this offset is not large enough to explain the brightness asymmetry of the ring. The ring is measured to have mostly red reflectivity across the JHKs filters, which seems to indicate micron-sized grains. Just like Neptune's 3:2 and 2:1 mean-motion resonances delineate the inner and outer edges of the classical Kuiper belt, we find that the radial extent of the HR 4796 A and the Fomalhaut rings could correspond to the 3:2 and 2:1 mean-motion resonances of hypothetical planets at 54.7 AU and 97.7 AU in the two systems, respectively. A planet orbiting HR 4796 A at 54.7 AU would have to be less massive than 1.6 Jup mass so as not to widen the ring too much by stirring.

  1. Dufulin Activates HrBP1 to Produce Antiviral Responses in Tobacco

    PubMed Central

    Chen, Zhuo; Zeng, Mengjiao; Song, Baoan; Hou, Chengrui; Hu, Deyu; Li, Xiangyang; Wang, Zhenchao; Fan, Huitao; Bi, Liang; Liu, Jiaju; Yu, Dandan; Jin, Linhong; Yang, Song

    2012-01-01

    Background Dufulin is a new antiviral agent that is highly effective against plant viruses and acts by activating systemic acquired resistance (SAR) in plants. In recent years, it has been used widely to prevent and control tobacco and rice viral diseases in China. However, its targets and mechanism of action are still poorly understood. Methodology/Principal Findings Here, differential in-gel electrophoresis (DIGE) and classical two-dimensional electrophoresis (2-DE) techniques were combined with mass spectrometry (MS) to identify the target of Dufulin. More than 40 proteins were found to be differentially expressed (≥1.5 fold or ≤1.5 fold) upon Dufulin treatment in Nicotiana tabacum K326. Based on annotations in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, these proteins were found to be related to disease resistance. Directed acyclic graph (DAG) analysis of the various pathways demonstrated harpin binding protein-1 (HrBP1) as the target of action of Dufulin. Additionally, western blotting, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and real time PCR analyses were also conducted to identify the specific mechanism of action of Dufulin. Our results show that activation of HrBP1 triggers the salicylic acid (SA) signaling pathway and thereby produces antiviral responses in the plant host. A protective assay based on lesion counting further confirmed the antiviral activity of Dufulin. Conclusion This study identified HrBP1 as a target protein of Dufulin and that Dufulin can activate the SA signaling pathway to induce host plants to generate antiviral responses. PMID:22662252

  2. RECORD processing - A robust pathway to component-resolved HR-PGSE NMR diffusometry

    NASA Astrophysics Data System (ADS)

    Stilbs, Peter

    2010-12-01

    It is demonstrated that very robust spectral component separation can be achieved through global least-squares CORE data analysis of automatically or manually selected spectral regions in complex NMR spectra in a high-resolution situation. This procedure (acronym RECORD) only takes a few seconds and quite significantly improves the effective signal/noise of the experiment as compared to individual frequency channel fitting, like in the generic HR-DOSY approach or when using basic peak height or integral fitting. Results from RECORD processing can be further used as starting value estimates for subsequent CORE analysis of spectral data with higher degree of spectral overlap.

  3. COMPASS Final Report: Lunar Network Satellite-High Rate (LNS-HR)

    NASA Technical Reports Server (NTRS)

    oleson, Steven R.; McGuire, Melissa L.

    2012-01-01

    Two design options were explored to address the requirement to provide lunar piloted missions with continuous communications for outpost and sortie missions. Two unique orbits were assessed, along with the appropriate spacecraft (S/C) to address these requirements. Both constellations (with only two S/C each) provide full time coverage (24 hr/7 d) for a south polar base and also provide continuous 7 day coverage for sorties for specified sites and periodic windows. Thus a two-satellite system can provide full coverage for sorties for selected windows of opportunity without reconfiguring the constellation.

  4. Structural analysis of cortical porosity applied to HR-pQCT data

    SciTech Connect

    Tjong, Willy Nirody, Jasmine Burghardt, Andrew J. Carballido-Gamio, Julio Kazakia, Galateia J.

    2014-01-15

    Purpose: The investigation of cortical porosity is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. With the emergence of HR-pQCT as a noninvasive tool suitable for clinical use, cortical porosity at appendicular sites can be directly visualizedin vivo. The aim of this study was to introduce a novel topological analysis of the cortical pore network for HR-pQCT data and determine the influence of resolution on measures of cortical pore network microstructure and topology. Methods: Cadaveric radii were scanned using HR-pQCT at two different voxel sizes (41 and 82μm) and also using μCT at a voxel size of 18 μm. HR-pQCT and μCT image sets were spatially coregistered. Segmentation and quantification of cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm) were achieved using an established extended cortical analysis technique. Topological classification of individual pores was performed using topology-preserving skeletonization and multicolor dilation algorithms. Based on the pore skeleton topological classification, the following parameters were quantified: total number of planar surface-skeleton canals (N.Slabs), tubular curve-skeleton canals (N.Tubes), and junction elements (N.Junctions), mean slab volume (Slab.Vol), mean tube volume (Tube.Vol), mean slab orientation (Slab.θ), mean tube orientation (Tube.θ), N.Slabs/N.Tubes, and integral (total) slab volume/integral tube volume (iSlab.Vol/iTube.Vol). An in vivo reproducibility study was also conducted to assess short-term precision of the topology parameters. Precision error was characterized using root mean square coefficient of variation (RMSCV%). Results: Correlations toμCT values for Ct.Po were significant for both the 41 and 82 μm HR-pQCT data (41: r{sup 2} = 0.82, p < 0.001, 82: r{sup 2} = 0.75, p < 0.001). For Ct.Po.Dm, only the 41 μm data were significantly predictive of μCT values (r{sup 2} = 0.72, p < 0.01) Data at

  5. MULTI-CENTER PRECISION OF CORTICAL AND TRABECULAR BONE QUALITY MEASURES ASSESSED BY HR-PQCT

    PubMed Central

    Burghardt, Andrew J.; Pialat, Jean-Baptiste; Kazakia, Galateia J.; Boutroy, Stephanie; Engelke, Klaus; Patsch, Janina M.; Valentinitsch, Alexander; Liu, Danmei; Szabo, Eva; Bogado, Cesar E.; Zanchetta, Maria Belen; McKay, Heather A.; Shane, Elizabeth; Boyd, Steven K.; Bouxsein, Mary L.; Chapurlat, Roland; Khosla, Sundeep; Majumdar, Sharmila

    2012-01-01

    High-resolution peripheral quantitative computed tomography (HR-pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technique to address important skeletal health questions requires translation to standardized multi-center data pools. Our goal was to evaluate the feasibility of pooling data in multi-center HR-pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition-realistic phantoms constructed from cadaveric radii. Single-center precision was determined by repeat scanning over short (<72hrs), intermediate (3–5mo), and long-term intervals (28mo). Multi-center precision was determined by imaging the phantoms at nine different HR-pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single-center short-term RMSCVs were <1% for all parameters except Ct.Th (1.1%), Ct.Th.SD (2.6%), Tb.Sp.SD (1.8%), and porosity measures (6–8%). Intermediate-term RMSCVs were generally not statistically different from short-term values. Long-term variability was significantly greater for all density measures (0.7–2.0%; p < 0.05 vs. short-term) and several structure measures: Ct.Th (3.4%; p < 0.01 vs. short-term), Ct.Po (15.4%; p < 0.01 vs. short-term), and Tb.Th (2.2%; p < 0.01 vs. short-term). Multi-center RMSCVs were also significantly higher than short-term values: 2–4% for density and µFE measures (p < 0.0001), 2.6–5.3% for morphometric measures (p < 0.001), while Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multi-center precision errors for HR-pQCT parameters were generally less than 5%. Phantom-based multi-center precision was comparable to previously reported in vivo single-center precision errors, although this was approximately 2–5 times worse than ex vivo short

  6. C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins

    PubMed Central

    Zhang, Yong-Jie; Gendron, Tania F; Grima, Jonathan C; Sasaguri, Hiroki; Jansen-West, Karen; Xu, Ya-Fei; Katzman, Rebecca B; Gass, Jennifer; Murray, Melissa E; Shinohara, Mitsuru; Lin, Wen-Lang; Garrett, Aliesha; Stankowski, Jeannette N; Daughrity, Lillian; Tong, Jimei; Perkerson, Emilie A; Yue, Mei; Chew, Jeannie; Castanedes-Casey, Monica; Kurti, Aishe; Wang, Zizhao S; Liesinger, Amanda M; Baker, Jeremy D; Jiang, Jie; Lagier-Tourenne, Clotilde; Edbauer, Dieter; Cleveland, Don W; Rademakers, Rosa; Boylan, Kevin B; Bu, Guojun; Link, Christopher D; Dickey, Chad A; Rothstein, Jeffrey D; Dickson, Dennis W; Fryer, John D; Petrucelli, Leonard

    2016-01-01

    Neuronal inclusions of poly(GA), a protein unconventionally translated from G4C2 repeat expansions in C9ORF72, are abundant in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) caused by this mutation. To investigate poly(GA) toxicity, we generated mice that exhibit poly(GA) pathology, neurodegeneration and behavioral abnormalities reminiscent of FTD and ALS. These phenotypes occurred in the absence of TDP-43 pathology and required poly(GA) aggregation. HR23 proteins involved in proteasomal degradation and proteins involved in nucleocytoplasmic transport were sequestered by poly(GA) in these mice. HR23A and HR23B similarly colocalized to poly(GA) inclusions in C9ORF72 expansion carriers. Sequestration was accompanied by an accumulation of ubiquitinated proteins and decreased xeroderma pigmentosum C (XPC) levels in mice, indicative of HR23A and HR23B dysfunction. Restoring HR23B levels attenuated poly(GA) aggregation and rescued poly(GA)-induced toxicity in neuronal cultures. These data demonstrate that sequestration and impairment of nuclear HR23 and nucleocytoplasmic transport proteins is an outcome of, and a contributor to, poly(GA) pathology. PMID:26998601

  7. C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins.

    PubMed

    Zhang, Yong-Jie; Gendron, Tania F; Grima, Jonathan C; Sasaguri, Hiroki; Jansen-West, Karen; Xu, Ya-Fei; Katzman, Rebecca B; Gass, Jennifer; Murray, Melissa E; Shinohara, Mitsuru; Lin, Wen-Lang; Garrett, Aliesha; Stankowski, Jeannette N; Daughrity, Lillian; Tong, Jimei; Perkerson, Emilie A; Yue, Mei; Chew, Jeannie; Castanedes-Casey, Monica; Kurti, Aishe; Wang, Zizhao S; Liesinger, Amanda M; Baker, Jeremy D; Jiang, Jie; Lagier-Tourenne, Clotilde; Edbauer, Dieter; Cleveland, Don W; Rademakers, Rosa; Boylan, Kevin B; Bu, Guojun; Link, Christopher D; Dickey, Chad A; Rothstein, Jeffrey D; Dickson, Dennis W; Fryer, John D; Petrucelli, Leonard

    2016-05-01

    Neuronal inclusions of poly(GA), a protein unconventionally translated from G4C2 repeat expansions in C9ORF72, are abundant in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) caused by this mutation. To investigate poly(GA) toxicity, we generated mice that exhibit poly(GA) pathology, neurodegeneration and behavioral abnormalities reminiscent of FTD and ALS. These phenotypes occurred in the absence of TDP-43 pathology and required poly(GA) aggregation. HR23 proteins involved in proteasomal degradation and proteins involved in nucleocytoplasmic transport were sequestered by poly(GA) in these mice. HR23A and HR23B similarly colocalized to poly(GA) inclusions in C9ORF72 expansion carriers. Sequestration was accompanied by an accumulation of ubiquitinated proteins and decreased xeroderma pigmentosum C (XPC) levels in mice, indicative of HR23A and HR23B dysfunction. Restoring HR23B levels attenuated poly(GA) aggregation and rescued poly(GA)-induced toxicity in neuronal cultures. These data demonstrate that sequestration and impairment of nuclear HR23 and nucleocytoplasmic transport proteins is an outcome of, and a contributor to, poly(GA) pathology.

  8. Direct Detection and Orbit Analysis of the Exoplanets HR 8799 bcd from Archival 2005 Keck/NIRC2 Data

    NASA Technical Reports Server (NTRS)

    Currie, Thayne; Fukagawa, Misato; Thalmann, Christian; Matsumura, Soko; Plavchan, Peter

    2012-01-01

    We present previously unpublished July 2005 H-band coronagraphic data of the young, planet-hosting star HR 8799 from the newly-released Keck/NIRC2 archive. Despite poor observing conditions, we detect three of the planets (HR 8799 bcd), two of them (HR 8799 bc) without advanced image processing. Comparing these data with previously published 1998-2011 astrometry and that from re-reduced October 2010 Keck data constrains the orbits of the planets. Analyzing the planets' astrometry separately, HR 8799 d's orbit is likely inclined at least 25 deg from face-on and the others may be on in inclined orbits. For semimajor axis ratios consistent with a 4:2:1 mean-motion resonance our analysis yields precise values for HR 8799 bcd's orbital parameters and strictly constrains the planets' eccentricities to be less than 0.18-0.3. However, we find no acceptable orbital solutions with this resonance that place the planets in face-on orbits; HR 8799 d shows the largest deviation from such orbits. Moreover, few orbits make HR 8799 d coplanar with b and c, whereas dynamical stability analyses used to constrain the planets' masses typically assume coplanar and/or fare.on orbits. This paper illustrates the significant science gain enabled with the release of the NIRC2 archive.

  9. Spinal cord transection inhibits HR reduction in anesthetized rats immersed in an artificial CO2-hot spring bath

    NASA Astrophysics Data System (ADS)

    Yamamoto, Noriyuki; Hashimoto, Masaaki

    2007-01-01

    Like humans, the heart rate (HR) of anesthetized rats immersed in CO2-water is lower than that when immersed in tap water at the same temperature. To investigate the afferent signal pathway in the mechanism of HR reduction, Wistar rats were anesthetized with urethane and then the spinal cord was transected between T4 and T5. The animals were immersed up to the axilla in a bathtub of tap-water (CO2 contents: 10 20 mg·l-1) or of CO2-water (965 1,400 mg·l-1) at 35°C while recording HR, arterial blood pressure, and arterial blood gas parameters ( PaCO2, PaO2, pH). Arterial blood gas parameters did not change during immersion, irrespective of CO2 concentration of the bath water, whereas the HR was reduced in the CO2-water bath. The inhalation of CO2-mixed gas (5 % CO2, 20 % O2, 75 % N2) resulted in increased levels of blood gases and an increased HR during immersion in all types of water tested. The HR reduction observed in sham transected control animals immersed in CO2-water disappeared after subsequent spinal cord transection. These results show that the dominant afferent signal pathway to the brain, which is involved in inducing the reduced HR during immersion in CO2-water, is located in the neuronal route and not in the bloodstream.

  10. A bacterial hemerythrin-like protein MsmHr inhibits the SigF-dependent hydrogen peroxide response in mycobacteria

    PubMed Central

    Li, Xiaojing; Tao, Jun; Hu, Xinling; Chan, John; Xiao, Jing; Mi, Kaixia

    2015-01-01

    Hydrogen peroxide (H2O2) is one of a variety of reactive oxygen species (ROS) produced by aerobic organisms. Host production of toxic H2O2 in response to pathogen infection is an important classical innate defense mechanism against invading microbes. Understanding the mechanisms by which pathogens, in response to oxidative stress, mediate defense against toxic ROS, can reveal anti-microbial targets and shed light on pathogenic mechanisms. In this study, we provide evidence that a Mycobacterium smegmatis hemerythrin-like protein MSMEG_2415, designated MsmHr, is a H2O2-modulated repressor of the SigF-mediated response to H2O2. Circular dichroism and spectrophotometric analysis of MsmHr revealed properties characteristic of a typical hemerythrin-like protein. An msmHr knockout strain of M. smegmatis mc2155 (ΔmsmHr) was more resistant to H2O2 than its parental strain, and overexpression of MsmHr increased mycobacterial susceptibility to H2O2. Mutagenesis studies revealed that the hemerythrin domain of MsmHr is required for the regulation of the H2O2 response observed in the overexpression study. We show that MsmHr inhibits the expression of SigF (MSMEG_1804), an alternative sigma factor that plays an important role in bacterial oxidative stress responses, including those elicited by H2O2, thus providing a mechanistic link between ΔmsmHr and its enhanced resistance to H2O2. Together, these results strongly suggest that MsmHr is involved in the response of mycobacteria to H2O2 by negatively regulating a sigma factor, a function not previously described for hemerythrins. PMID:25642228

  11. Deep thermal infrared imaging of HR 8799 bcde: new atmospheric constraints and limits on a fifth planet

    SciTech Connect

    Currie, Thayne; Cloutier, Ryan; Jayawardhana, Ray; Burrows, Adam; Girard, Julien H.; Fukagawa, Misato; Sorahana, Satoko; Kuchner, Marc; Kenyon, Scott J.; Madhusudhan, Nikku; Itoh, Yoichi; Matsumura, Soko; Pyo, Tae-Soo

    2014-11-10

    We present new L' (3.8 μm) and Brα (4.05 μm) data and reprocessed archival L' data for the young, planet-hosting star HR 8799 obtained with Keck/NIRC2, VLT/NaCo, and Subaru/IRCS. We detect all four HR 8799 planets in each data set at a moderate to high signal-to-noise ratio (S/N ≳ 6-15). We fail to identify a fifth planet, 'HR 8799 f', at r < 15 AU at a 5σ confidence level: one suggestive, marginally significant residual at 0.''2 is most likely a point-spread function artifact. Assuming companion ages of 30 Myr and the Baraffe planet cooling models, we rule out an HR 8799 f with a mass of 5 M{sub J} (7 M{sub J} ), 7 M{sub J} (10 M{sub J} ), or 12 M{sub J} (13 M{sub J} ) at r {sub proj} ∼ 12 AU, 9 AU, and 5 AU, respectively. All four HR 8799 planets have red early T dwarf-like L' – [4.05] colors, suggesting that their spectral energy distributions peak in between the L' and M' broadband filters. We find no statistically significant difference in HR 8799 cde's color. Atmosphere models assuming thick, patchy clouds appear to better match HR 8799 bcde's photometry than models assuming a uniform cloud layer. While non-equilibrium carbon chemistry is required to explain HR 8799 b and c's photometry/spectra, evidence for it from HR 8799 d and e's photometry is weaker. Future, deep-IR spectroscopy/spectrophotometry with the Gemini Planet Imager, SCExAO/CHARIS, and other facilities may clarify whether the planets are chemically similar or heterogeneous.

  12. ST/HR hysteresis: exercise and recovery phase ST depression/heart rate analysis of the exercise ECG.

    PubMed

    Lehtinen, R

    1999-01-01

    ST segment depression/heart rate (ST/HR) hysteresis is a recently introduced novel computer method for integrating the exercise and recovery phase ST/HR analysis for improved detection of coronary artery disease (CAD). It is a continuous diagnostic variable that extracts the prevailing direction and average magnitude of the hysteresis in ST depression against HR during the first 3 consecutive minutes of postexercise recovery. This article reviews the development and evaluation of this new method in a clinical population of 347 patients referred for a routine bicycle exercise electrocardiographic (ECG) test at Tampere University Hospital, Finland. Of these patients, 127 had angiographically proven CAD, whereas 13 had no CAD according to angiography, 18 had no perfusion defect according to Tc-99m-sestamibi myocardial imaging and single photon emission computed tomography, and 189 were clinically normal with respect to cardiac diseases. For each patient, the values for ST/HR hysteresis, ST/HR index, end-exercise ST depression, and recovery ST depression were determined for each lead of the Mason-Likar modification of the standard 12-lead exercise ECG and maximum value from the lead system (aVL, aVR, and V1 excluded). The area under the receiver operating characteristics curve (ie, the discriminative capacity) of the ST/HR hysteresis was 89%, which was significantly larger than that of the end-exercise ST depression (76%, P < .0001), recovery ST depression (84%, P = .0063) or ST/HR index (83%, P = .0023), indicating the best diagnostic performance of the ST/HR hysteresis in detection of CAD regardless of the partition value selection. Furthermore, the superior diagnostic performance of the method was relatively insensitive to the ST segment measurement point or to the ECG lead selection. These results suggest that the ST/HR hysteresis improves the clinical utility of the exercise ECG test in detection of CAD.

  13. Patient Characteristics and Outcomes by GN Subtype in ESRD

    PubMed Central

    Montez-Rath, Maria E.; Lafayette, Richard A.; Winkelmayer, Wolfgang C.

    2015-01-01

    Background and objectives Outcomes-based research rarely focuses on patients with ESRD caused by GN. The hypotheses were that the GN subtype would clinically discriminate patient groups and independently associate with survival after ESRD therapy initiation. Design, setting, participants, & measurements Data were extracted from the US Renal Data System for adult patients with incident (1996–2011) ESRD attributed to six GN subtypes: FSGS, IgA nephropathy (IgAN), membranous nephropathy, membranoproliferative glomeruonephritis, lupus nephritis (LN), and vasculitis. ESRD attributed to diabetes and autosomal dominant polycystic kidney disease served as non-GN comparators. Unadjusted and adjusted mortality hazard ratios (aHRs) with 95% confidence intervals (95% CIs) were estimated using Cox regression (reference, IgAN). Models sequentially adjusted for sociodemographic (model 2), comorbidity/laboratory (model 3), and ESRD treatment modality (model 4) variables. Results Among 84,301 patients with ESRD attributed to GN, the median age ranged from 39 (LN) to 66 (vasculitis) years, male sex ranged from 18% (LN) to 68% (IgAN), and black race ranged from 7% (IgAN) to 49% (LN). Patients with IgAN had the fewest comorbidities and lowest use of hemodialysis (70.1%). After a median follow-up of 2.5 (interquartile range, 1.0–4.9) years, crude mortality was lowest in IgAN (3.7 deaths/100 person years). Compared to IgAN, adjusted mortality was highest in LN (model 4 aHR=1.75; 95% CI, 1.68 to 1.83) and in diabetes (aHR=1.73; 95% CI, 1.67 to 1.79), and was also higher in all other GN subtypes (membranous nephropathy: aHR=1.23; 95% CI, 1.17 to 1.29; FSGS: aHR=1.37; 95% CI, 1.32 to 1.42; membranoproliferative GN: aHR=1.38; 95% CI, 1.31 to 1.45; vasculitis: aHR=1.51; 95% CI, 1.45 to 1.58) and in autosomal dominant polycystic kidney disease (aHR=1.22; 95% CI, 1.18 to 1.27). Conclusions This study exposes substantial heterogeneity across GN subtypes at ESRD therapy initiation and

  14. Adjusting the Contour of Reflector Panels

    NASA Technical Reports Server (NTRS)

    Palmer, W. B.; Giebler, M. M.

    1984-01-01

    Postfabrication adjustment of contour of panels for reflector, such as parabolic reflector for radio antennas, possible with simple mechanism consisting of threaded stud, two nuts, and flexure. Contours adjusted manually.

  15. 48 CFR 1450.103 - Contract adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract adjustments. 1450.103 Section 1450.103 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT... Contract adjustments....

  16. First Year Adjustment in the Secondary School.

    ERIC Educational Resources Information Center

    Loosemore, Jean Ann

    1978-01-01

    This study investigated the relationship between adjustment to secondary school and 17 cognitive and noncognitive variables, including intelligence (verbal and nonverbal reasoning), academic achievement, extraversion-introversion, stable/unstable, social adjustment, endeavor, age, sex, and school form. (CP)

  17. Dynamics of blood flow: modeling of the Fåhræus-Lindqvist effect.

    PubMed

    Chebbi, Rachid

    2015-06-01

    To model the Fåhræus-Lindqvist effect, Haynes' marginal zone theory is used, following previous works, i.e., a core layer of uniform red blood cells (RBCs) is assumed to be surrounded by an annular plasma layer in which no RBCs are present. A simplified trial-and-error solution procedure is provided to determine the size of the core region and the hematocrit level in that zone in addition to the apparent viscosity, given the (upstream) large vessel hematocrit level and the average hematocrit level in the (downstream) small vessel. To test the model, a set of experimental data is selected to provide not only apparent viscosity data but also the average hematocrit levels in small tubes of different diameters. The results are found to support Haynes' marginal theory, with no fitting parameters used in the computations. Viscous dissipation is determined. The use of the mechanical energy balance is found to lead to results that are consistent with those based on the momentum balance, while leaving the average hematocrit level undetermined and required by either experimental data or an additional equation based on further theoretical work. The present analysis is used to model bifurcation using published empirical correlations quantifying the Fåhræus effect and phase separation. The model equations are extended to microvascular networks with repeated bifurcations.

  18. Characterization of the Red Giant HR 2582 Using the CHARA Array

    NASA Astrophysics Data System (ADS)

    Baines, Ellyn K.; McAlister, Harold A.; ten Brummelaar, Theo A.; Turner, Nils H.; Sturmann, Judit; Sturmann, Laszlo; Farrington, Christopher D.; Vargas, Norm; van Belle, Gerard T.; Ridgway, Stephen T.

    2013-07-01

    We present the fundamental parameters of HR 2582, a high-mass red giant star whose evolutionary state is a mystery. We used the CHARA Array interferometer to directly measure the star's limb-darkened angular diameter (1.006 ± 0.020 mas) and combined our measurement with parallax and photometry from the literature to calculate its physical radius (35.76 ± 5.31 R ⊙), luminosity (517.8 ± 17.5 L ⊙), bolometric flux (14.8 ± 0.5 × 10-8 erg s-1 cm-2), and effective temperature (4577 ± 60 K). We then determined the star's mass (5.6 ± 1.7 M ⊙) using our new values with stellar oscillation results from Baudin et al. Finally, using the Yonsei-Yale evolutionary models, we estimated HR 2582's age to be 165^{+20}_{-15} Myr. While our measurements do not provide the precision required to definitively state where the star is in its evolution, it remains an excellent test case for evaluating stellar interior models.

  19. Operating characteristics of a 0.87 kW-hr flywheel energy storage module

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.; Parker, R. J.; Zaretsky, E. V.; Scibbe, H. W.

    1985-01-01

    Discussion is given of the design and loss characteristics of 0.87 kW-hr (peak) flywheel energy storage module suitable for aerospace and automotive applications. The maraging steel flywheel rotor, a 46-cm-(18-in-) diameter, 58-kg (128-lb) tapered disk, delivers 0.65 kW-hr of usable energy between operating speeds of 10,000 and 20,000 rpm. The rotor is supported by 20- and 25-mm bore diameter, deep-groove ball bearings, lubricated by a self-replenishing wick type lubrication system. To reduce aerodynamic losses, the rotor housing was evacuated to vacuum levels from 40 to 200 millitorr. Dynamic rotor instabilities uncovered during testing necessitated the use of an elastometric-bearing damper to limit shaft excursions. Spindown losses from bearing, seal, and aerodynamic drag at 50 millitorr typically ranged from 64 to 193 W at 10,000 and 20,000 rpm, respectively. Discharge efficiency of the flywheel system exceeded 96 percent at torque levels greater than 21 percent of rated torque.

  20. UVBY photometry of the magnetic CP stars HD 36668, 36 Lyncis, HD 86592, and HR 8861

    NASA Astrophysics Data System (ADS)

    Adelman, Saul J.

    2000-05-01

    Differential Strömgren uvby photometric observations from the Four College Automated Photoelectric Telescope (FCAPT) are presented for the magnetic CP stars HD 36668, 36 Lyn, HD 86592, and HR 8861. Using the FCAPT values, North's period for HD 36668 is refined to 2.11884 days. The 3.834 day period of Shore et al. for 36 Lyn, which was found from magnetic field measurements, is confirmed by photometry. The FCAPT observations also support the 2.8867 day period of Babel & North for HD 86592, demonstrate that this star is a large amplitude variable in v (0.13 mag.), and show that y varies crudely out of phase from u, v, and b which are in phase with one another. The variability of HR 8861 appears to be correlated with the meridional passages of regions of Si over- and underabundance as found by Piskunov et al. Tables~2, 3, 4 and 5 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/Abstract.html

  1. SPECTROSCOPIC AND PHOTOMETRIC VARIABILITY IN THE A0 SUPERGIANT HR 1040

    SciTech Connect

    Corliss, David J.; Morrison, Nancy D.; Adelman, Saul J.

    2015-12-15

    A time-series analysis of spectroscopic and photometric observables of the A0 Ia supergiant HR 1040 has been performed, including equivalent widths, radial velocities, and Strömgren photometric indices. The data, obtained from 1993 through 2007, include 152 spectroscopic observations from the Ritter Observatory 1 m telescope and 269 Strömgren photometric observations from the Four College Automated Photoelectric Telescope. Typical of late B- and early A-type supergiants, HR 1040 has a highly variable Hα profile. The star was found to have an intermittent active phase marked by correlation between the Hα absorption equivalent width and blue-edge radial velocity and by photospheric connections observed in correlations to equivalent width, second moment and radial velocity in Si ii λλ6347, 6371. High-velocity absorption (HVA) events were observed only during this active phase. HVA events in the wind were preceded by photospheric activity, including Si ii radial velocity oscillations 19–42 days prior to onset of an HVA event and correlated increases in Si ii W{sub λ} and second moment from 13 to 23 days before the start of the HVA event. While increases in various line equivalent widths in the wind prior to HVA events have been reported in the past in other stars, our finding of precursors in enhanced radial velocity variations in the wind and at the photosphere is a new result.

  2. UVBY photometry of the chemically peculiar stars HD 15980, HR 1094, 33 Gem, and HD 115708

    NASA Astrophysics Data System (ADS)

    Adelman, Saul J.

    1999-01-01

    Differential Strömgren uvby photometry obtained with the Four College Automated Photoelectric Telescope shows that the hot HgMn star 33 Gem is photometrically constant. The Si star HD 15980 is found to be a variable whose period is significantly greater than 2 years. The unusual magnetic chemically peculiar Co star HR 1094 is discovered to be a low amplitude photometric variable with the magnetic field period of Hill & Blake, 2.9761 days. The ephemeris for the magnetic chemically peculiar star HD 115708 of Wade et al. is confirmed with the error in its period of 5.07622 days being greatly reduced. The {u}, {v}, {b}, and {y} light curves for both HR 1094 and HD 115708 exhibit differences which indicate complex elemental photospheric abundance distributions. Tables 3-6 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/Abstract.html

  3. Human performance and physiological function during a 24-hr exposure to 1% bromotrifluoromethane (Halon 1301)

    NASA Technical Reports Server (NTRS)

    Calkins, D. S.; Degioanni, J. J.; Tan, M. N.; Davis, J. R.; Pierson, D. L.

    1993-01-01

    Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon 1301 (bromotrifluoromethane, CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5% of baseline values. Physiological data were obtained before, during, and after the exposures from clinical chemistry analyses of blood and urine samples, pulmonary function tests, and monitoring of vital signs. Significant change during Halon inhalation was observed for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1% Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

  4. CHARACTERIZATION OF THE RED GIANT HR 2582 USING THE CHARA ARRAY

    SciTech Connect

    Baines, Ellyn K.; McAlister, Harold A.; Ten Brummelaar, Theo A.; Turner, Nils H.; Sturmann, Judit; Sturmann, Laszlo; Farrington, Christopher D.; Vargas, Norm; Van Belle, Gerard T.; Ridgway, Stephen T.

    2013-07-20

    We present the fundamental parameters of HR 2582, a high-mass red giant star whose evolutionary state is a mystery. We used the CHARA Array interferometer to directly measure the star's limb-darkened angular diameter (1.006 {+-} 0.020 mas) and combined our measurement with parallax and photometry from the literature to calculate its physical radius (35.76 {+-} 5.31 R{sub Sun }), luminosity (517.8 {+-} 17.5 L{sub Sun }), bolometric flux (14.8 {+-} 0.5 Multiplication-Sign 10{sup -8} erg s{sup -1} cm{sup -2}), and effective temperature (4577 {+-} 60 K). We then determined the star's mass (5.6 {+-} 1.7 M{sub Sun }) using our new values with stellar oscillation results from Baudin et al. Finally, using the Yonsei-Yale evolutionary models, we estimated HR 2582's age to be 165{sup +20}{sub -15} Myr. While our measurements do not provide the precision required to definitively state where the star is in its evolution, it remains an excellent test case for evaluating stellar interior models.

  5. Astrometric Monitoring of the HR 8799 Planets: Orbit Constraints from Self-consistent Measurements

    NASA Astrophysics Data System (ADS)

    Konopacky, Q. M.; Marois, C.; Macintosh, B. A.; Galicher, R.; Barman, T. S.; Metchev, S. A.; Zuckerman, B.

    2016-08-01

    We present new astrometric measurements from our ongoing monitoring campaign of the HR 8799 directly imaged planetary system. These new data points were obtained with NIRC2 on the W.M. Keck II 10 m telescope between 2009 and 2014. In addition, we present updated astrometry from previously published observations in 2007 and 2008. All data were reduced using the SOSIE algorithm, which accounts for systematic biases present in previously published observations. This allows us to construct a self-consistent data set derived entirely from NIRC2 data alone. From this data set, we detect acceleration for two of the planets (HR 8799b and e) at >3σ. We also assess possible orbital parameters for each of the four planets independently. We find no statistically significant difference in the allowed inclinations of the planets. Fitting the astrometry while forcing coplanarity also returns χ 2 consistent to within 1σ of the best fit values, suggesting that if inclination offsets of ≲20° are present, they are not detectable with current data. Our orbital fits also favor low eccentricities, consistent with predictions from dynamical modeling. We also find period distributions consistent to within 1σ with a 1:2:4:8 resonance between all planets. This analysis demonstrates the importance of minimizing astrometric systematics when fitting for solutions to highly undersampled orbits.

  6. The 1991-2012 light curve of the old nova HR Lyrae

    SciTech Connect

    Honeycutt, R. K.; Shears, J.; Kafka, S.; Robertson, J. W.; Henden, A. A. E-mail: bunburyobservatory@hotmail.com E-mail: Jeff.Robertson@atu.edu

    2014-05-01

    The 22 yr light curve of HR Lyr, acquired with a typical cadence of 2-6 days, is examined for periodic and quasi-periodic variations. No persistent periodicities are revealed. Rather, the light curve variations often take the form of nearly linear rises and falls having typical e-folding times of about 100 days. Occasional ∼0.6 mag outbursts are also seen, with properties similar to those of small outbursts found in some nova-like cataclysmic variables. When the photometry is formed into yearly averages, a decline of 0.012 ± 0.005 mag yr{sup –1} is apparent, consistent with the fading of irradiation-induced M-dot following the nova. The equivalent width of Hα is tabulated at three epochs over the interval 1986-2008 in order to compare with a recent result for DK Lac in which Hα was found to be fading 50 yr after the nova. However, our results for such a fading in HR Lyr are inconclusive.

  7. Repeatability and reproducibility of the Tekscan HR-Walkway system in healthy children.

    PubMed

    Coda, Andrea; Carline, Tom; Santos, Derek

    2014-06-01

    This study investigated the repeatability and reproducibility of the HR Walkway system with regards to peak pressure values (PP) and pressure time integral (PTI) in healthy children, ranging between 5 and 18 years of age. Subjects recruited took part in two non-invasive clinical assessments, at baseline and 1 week later. Gait analysis was carried out using the PP box approach, and plantar foot recording was divided into 10 anatomical areas. The PP and PTI was investigated for the left, right and both feet accounted together. Interclass Correlation Coefficient (ICC) test was adopted for statistical analysis. Overall, 30 healthy patients were recruited and 60 appointments were completed, 53.3% (n=16) were female and 46.7% (n=14) were male. Mean age was 13.3 years (SD=4.5), with an age-range of 5-18.6 years old. Results indicated that for all variables tested the repeatability data were 'good' ICC for 73.8% (n=121) and 'moderate' ICC for 26.2% (n=43). For all variables tested, the reproducibility data showed that 'good' ICC for 70.7% (n=58) and 'moderate' ICC for 29.3% (n=24). In conclusion, the HR Walkway system is able to provide repeatable and reproducible data.

  8. Operating characteristics of a 0.87 kW-hr flywheel energy storage module

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.; Scibbe, H. W.; Parker, R. D.; Zaretsky, E. V.

    1985-01-01

    Discussion is given of the design and loss characteristics of 0.87 kW-hr (peak) flywheel energy storage module suitable for aerospace and automotive applications. The maraging steel flywheel rotor, a 46-cm- (18-in-) diameter, 58-kg (128-lb) tapered disk, delivers 0.65 kW-hr of usable energy between operating speeds of 10,000 and 20,000 rpm. The rotor is supported by 20- and 25-mm bore diameter, deep-groove ball bearings, lubricated by a self-replenishing wick type lubrication system. To reduce aerodynamic losses, the rotor housing was evacuated to vacuum levels from 40 to 200 millitorr. Dynamic rotor instabilities uncovered during testing necessitated the use of an elastometric-bearing damper to limit shaft excursions. Spindown losses from bearing, seal, and aerodynamic drag at 50 millitorr typically ranged from 64 to 193 W at 10,000 and 20,000 rpm, respectively. Discharge efficiency of the flywheel system exceeded 96 percent at torque levels greater than 21 percent of rated torque.

  9. [The thickness/radius ratio (h/r) of the left ventricle in pure mitral insufficiency].

    PubMed

    Guadalajara, J F; Alexánderson, E; Monobe, F; Nieto, S; Huerta, D

    1992-01-01

    We studied 11 patients with severe mitral regurgitation (MR). With 2-D echocardiogram we could obtain the septal and posterior wall thickness, left ventricular internal dimensions and ventricular function. With parasternal short axis view we calculate the h/r ratio (left ventricular thickness/radius). The results were compared with normal values: we found important left atrial and ventricle dilatation with significative difference from the normal values (P < 0.001), the diastolic and systolic h/r ratio was significative lower than the normal values (P < 0.005): the systolic wall stress was significative higher in relation to normal values (P < 0.001). We conclude that patients with severe (MR) initially have an important ventricular dilatation but no hypertrophy despite volume overload. The possible explanation is that in early stages of the disease, the afterload of the left ventricle is low and does not trigger the development of hypertrophy. The hypertrophy appears only when the systolic stress is high secondary to myocardial failure. The excessive dilatation of the left ventricle probably damages the myocardial fibers by excessive stretch. This mechanism probably explains the poor late surgical evolution of patients with mitral prosthesis. This we propose that the optimal surgical timing for such patients is when the systolic wall stress elevates over the normal limits, because this is an early sign of myocardial failure.

  10. Stroke and Risks of Development and Progression of Kidney Diseases and End-Stage Renal Disease: A Nationwide Population-Based Cohort Study

    PubMed Central

    Wu, Chia-Lin; Tsai, Chun-Chieh; Kor, Chew-Teng; Tarng, Der-Cherng; Lian, Ie-Bin; Yang, Tao-Hsiang; Chiu, Ping-Fang; Chang, Chia-Chu

    2016-01-01

    Background There is little information about the association between stroke and kidney diseases. We aimed to investigate the impact of stroke on long-term renal outcomes. Methods In this large population-based retrospective cohort study, we identified 100,353 subjects registered in the National Health Insurance Research Database of Taiwan from January 1, 2000, through December 31, 2012, including 33,451 stroke patients and 66,902 age-, sex- and Charlson’s comorbidity index score-matched controls. Results The incidence rate of chronic kidney disease (CKD) was higher in the stroke than in the control cohort (17.5 vs. 9.06 per 1000 person-years). After multivariate adjustment, the risk of developing CKD was significantly higher in patients with stroke (adjusted hazard ratio [aHR] 1.43, 95% confidence interval [CI] 1.36–1.50, P<0.001). Subgroup analysis showed that stroke patients <50 years (aHR 1.61, P<0.001) and those with concomitant diabetes mellitus (aHR 2.12, P<0.001), hyperlipidemia (aHR 1.53, P<0.001) or gout (aHR 1.84, P<0.001) were at higher risk of incident CKD. Additionally, the risks of progression to advanced CKD and end-stage renal disease (ESRD) were significantly higher for stroke patients (aHRs, 1.22 and 1.30; P = 0.04 and P = 0.008, respectively), independent of age, sex, comorbidities and long-term medications. Conclusions Stroke is associated with higher risks for incident CKD, decline in renal function and ESRD. Younger stroke patients, as well as those with concomitant diabetes mellitus, hyperlipidemia or gout are at greater risk for kidney diseases. PMID:27355475

  11. Generalized adjustment by least squares ( GALS).

    USGS Publications Warehouse

    Elassal, A.A.

    1983-01-01

    The least-squares principle is universally accepted as the basis for adjustment procedures in the allied fields of geodesy, photogrammetry and surveying. A prototype software package for Generalized Adjustment by Least Squares (GALS) is described. The package is designed to perform all least-squares-related functions in a typical adjustment program. GALS is capable of supporting development of adjustment programs of any size or degree of complexity. -Author

  12. 49 CFR 393.53 - Automatic brake adjusters and brake adjustment indicators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... brake adjustment indicators. (a) Automatic brake adjusters (hydraulic brake systems). Each commercial motor vehicle manufactured on or after October 20, 1993, and equipped with a hydraulic brake...

  13. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 11 2014-01-01 2014-01-01 false Budget adjustment. 1744.64 Section 1744.64... Disbursement of Funds § 1744.64 Budget adjustment. (a) If more funds are required than are available in a budget account, the borrower may request RUS's approval of a budget adjustment to use funds from...

  14. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 11 2012-01-01 2012-01-01 false Budget adjustment. 1744.64 Section 1744.64... Disbursement of Funds § 1744.64 Budget adjustment. (a) If more funds are required than are available in a budget account, the borrower may request RUS's approval of a budget adjustment to use funds from...

  15. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 11 2013-01-01 2013-01-01 false Budget adjustment. 1744.64 Section 1744.64... Disbursement of Funds § 1744.64 Budget adjustment. (a) If more funds are required than are available in a budget account, the borrower may request RUS's approval of a budget adjustment to use funds from...

  16. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 11 2011-01-01 2011-01-01 false Budget adjustment. 1744.64 Section 1744.64... Disbursement of Funds § 1744.64 Budget adjustment. (a) If more funds are required than are available in a budget account, the borrower may request RUS's approval of a budget adjustment to use funds from...

  17. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Budget adjustment. 1744.64 Section 1744.64... Disbursement of Funds § 1744.64 Budget adjustment. (a) If more funds are required than are available in a budget account, the borrower may request RUS's approval of a budget adjustment to use funds from...

  18. 24 CFR 5.611 - Adjusted income.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Adjusted income. 5.611 Section 5... Serving Persons with Disabilities: Family Income and Family Payment; Occupancy Requirements for Section 8 Project-Based Assistance Family Income § 5.611 Adjusted income. Adjusted income means annual income...

  19. 24 CFR 5.611 - Adjusted income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Adjusted income. 5.611 Section 5... Serving Persons with Disabilities: Family Income and Family Payment; Occupancy Requirements for Section 8 Project-Based Assistance Family Income § 5.611 Adjusted income. Adjusted income means annual income...

  20. 19 CFR 201.205 - Salary adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Salary adjustments. 201.205 Section 201.205 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Debt Collection § 201.205 Salary adjustments. Any negative adjustment to pay arising out of an employee's...

  1. 19 CFR 201.205 - Salary adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Salary adjustments. 201.205 Section 201.205 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Debt Collection § 201.205 Salary adjustments. Any negative adjustment to pay arising out of an employee's...

  2. 12 CFR 313.55 - Salary adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Salary adjustments. 313.55 Section 313.55 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE PROCEDURES FOR CORPORATE DEBT COLLECTION Salary Offset § 313.55 Salary adjustments. Any negative adjustment to pay...

  3. 12 CFR 313.55 - Salary adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Salary adjustments. 313.55 Section 313.55 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE PROCEDURES FOR CORPORATE DEBT COLLECTION Salary Offset § 313.55 Salary adjustments. Any negative adjustment to pay...

  4. 12 CFR 313.55 - Salary adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Salary adjustments. 313.55 Section 313.55 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE PROCEDURES FOR CORPORATE DEBT COLLECTION Salary Offset § 313.55 Salary adjustments. Any negative adjustment to pay...

  5. 12 CFR 313.55 - Salary adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Salary adjustments. 313.55 Section 313.55 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE PROCEDURES FOR CORPORATE DEBT COLLECTION Salary Offset § 313.55 Salary adjustments. Any negative adjustment to pay...

  6. 19 CFR 201.205 - Salary adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Salary adjustments. 201.205 Section 201.205 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Debt Collection § 201.205 Salary adjustments. Any negative adjustment to pay arising out of an employee's...

  7. 19 CFR 201.205 - Salary adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 3 2012-04-01 2012-04-01 false Salary adjustments. 201.205 Section 201.205 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Debt Collection § 201.205 Salary adjustments. Any negative adjustment to pay arising out of an employee's...

  8. 19 CFR 201.205 - Salary adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 false Salary adjustments. 201.205 Section 201.205 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Debt Collection § 201.205 Salary adjustments. Any negative adjustment to pay arising out of an employee's...

  9. 12 CFR 313.55 - Salary adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Salary adjustments. 313.55 Section 313.55 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE PROCEDURES FOR CORPORATE DEBT COLLECTION Salary Offset § 313.55 Salary adjustments. Any negative adjustment to pay...

  10. 12 CFR 1780.80 - Inflation adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Inflation adjustments. 1780.80 Section 1780.80... DEVELOPMENT RULES OF PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE Civil Money Penalty Inflation Adjustments § 1780.80 Inflation adjustments. The maximum amount of each civil money penalty within...

  11. 12 CFR 1780.80 - Inflation adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Inflation adjustments. 1780.80 Section 1780.80... DEVELOPMENT RULES OF PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE Civil Money Penalty Inflation Adjustments § 1780.80 Inflation adjustments. The maximum amount of each civil money penalty within...

  12. 34 CFR 36.2 - Penalty adjustment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Penalty adjustment. 36.2 Section 36.2 Education Office of the Secretary, Department of Education ADJUSTMENT OF CIVIL MONETARY PENALTIES FOR INFLATION § 36.2..., Section 36.2—Civil Monetary Penalty Inflation Adjustments Statute Description New maximum (and minimum,...

  13. 34 CFR 36.2 - Penalty adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Penalty adjustment. 36.2 Section 36.2 Education Office of the Secretary, Department of Education ADJUSTMENT OF CIVIL MONETARY PENALTIES FOR INFLATION § 36.2..., Section 36.2—Civil Monetary Penalty Inflation Adjustments Statute Description New maximum (and minimum,...

  14. Risk of dementia from proton pump inhibitor use in Asian population: A nationwide cohort study in Taiwan

    PubMed Central

    Tai, Shu-Yu; Chien, Chen-Yu; Wu, Deng-Chyang; Lin, Kun-Der; Ho, Bo-Lin; Chang, Yu-Han

    2017-01-01

    Introduction Concerns have been raised regarding the potential association between proton pump inhibitor (PPI) use and dementia. Objective This study aimed to examine this association in an Asian population. Methods Patients initiating PPI therapy between January 1, 2000 and December 31, 2003 without a prior history of dementia were identified from Taiwan’s National Health Insurance Research Database. The outcome of interest was all-cause dementia. Cox regression models were applied to estimate the hazard ratio (HR) of dementia. The cumulative PPI dosage stratified by quartiles of defined daily doses and adjusted for baseline disease risk score served as the primary variables compared against no PPI use. Results We analyzed the data of 15726 participants aged 40 years or older and free of dementia at baseline. PPI users (n = 7863; average follow-up 8.44 years) had a significantly increased risk of dementia over non—PPI users (n = 7863; average follow-up 9.55 years) (adjusted HR [aHR] 1.22; 95% confidence interval: 1.05–1.42). A significant association was observed between cumulative PPI use and risk of dementia (P for trend = .013). Subgroup analysis showed excess frequency of dementia in PPI users diagnosed with depression (aHR 2.73 [1.91–3.89]), hyperlipidemia (aHR 1.81 [1.38–2.38]), ischemic heart disease (aHR 1.55 [1.12–2.14]), and hypertension (aHR 1.54 [1.21–1.95]). Conclusions An increased risk for dementia was identified among the Asian PPI users. Cumulative PPI use was significantly associated with dementia. Further investigation into the possible biological mechanisms underlying the relationship between dementia and PPI use is warranted. PMID:28199356

  15. BK virus disease after allogeneic stem cell transplantation: a cohort analysis.

    PubMed

    Rorije, Nienke M G; Shea, Margaret M; Satyanarayana, Gowri; Hammond, Sarah P; Ho, Vincent T; Baden, Lindsey R; Antin, Joseph H; Soiffer, Robert J; Marty, Francisco M

    2014-04-01

    The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BKV disease after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials.

  16. Human trabecular bone microarchitecture can be assessed independently of density with second generation HR-pQCT.

    PubMed

    Manske, Sarah L; Zhu, Ying; Sandino, Clara; Boyd, Steven K

    2015-10-01

    The second generation HR-pQCT scanner (XtremeCTII, Scanco Medical) can assess human bone microarchitecture of peripheral limbs with a 61 μm nominal isotropic voxel size. This is a marked improvement from the first generation HR-pQCT that had a nominal isotropic voxel size of 82 μm, which is at the limit to accurately determine the thickness of individual human trabeculae. We sought to determine the accuracy of a direct morphometric approach to measure trabecular bone microarchitecture with three-dimensional morphological techniques using second generation HR-pQCT, and to compare this with the approach currently applied by the first generation HR-pQCT scanner based on derived indices using ex vivo scans of human cadaveric radii. We also compared images acquired and resampled to mimic the first generation HR-pQCT with those obtained directly from the first generation HR-pQCT. We evaluated 20 human cadaveric radii and a micro-CT performance phantom using the first (XtremeCT, Scanco Medical) and second generation HR-pQCT scanner (XtremeCTII) and compared a patient evaluation (XCTII, 61 μm) with a high resolution ex vivo protocol (HR, 30μm). We generated 82 μm scans of the same specimens to mimic a first-generation HR-pQCT evaluation (XCTIM, 82 μm) and compared these with a first-generation patient evaluation (XCTI, 82 μm). A standard structural extraction approach was applied to both XCTII and HR evaluations for assessment of bone volume fraction (BV/TV), and a distance transform was used to assess trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). For XCTI and XCTIM evaluations we followed the manufacturer's standard procedure and assessed bone mineral density (BMD), Tb.N with a distance transform, and then derived bone volume ratio (BV/TV(d)), trabecular thickness (Tb.Th(d)) and separation (Tb.Sp(d)). The spatial resolution (10% MTF) was 142.2 μm for XCTI, 108.9 μm for XCTIM, 95.2μm for XCTII, and 55.9 μm for HR. XCTI

  17. Make Win-Win a Reality: Delighting the Customer be Implementing Oracle HR - Integration Update to Fall 1997 Paper

    NASA Technical Reports Server (NTRS)

    Mills, J.; Shope, S.

    1998-01-01

    Implementing Oracle Human Resources Management System (HRMS) using a customer and integration approach provides the organization an enormous oppurtunity to create a win-win situation for customers, the HR department and the enterprise.

  18. Physical Activity, Sedentary Time, and Bone Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR-pQCT study.

    PubMed

    Gabel, Leigh; Macdonald, Heather M; Nettlefold, Lindsay; McKay, Heather A

    2017-03-22

    Bone strength is influenced by bone geometry, density, and bone microarchitecture, which adapt to increased mechanical loads during growth. Physical activity (PA) is essential for optimal bone strength accrual; however, less is known about how sedentary time influences bone strength and its determinants. Thus, our aim was to investigate the prospective associations between PA, sedentary time, and bone strength and its determinants during adolescence. We used HR-pQCT at distal tibia (8% site) and radius (7% site) in 173 girls and 136 boys (aged 9 to 20 years at baseline). We conducted a maximum of four annual measurements at the tibia (n = 785 observations) and radius (n = 582 observations). We assessed moderate-to-vigorous PA (MVPA) and sedentary time with accelerometers (ActiGraph GT1M). We aligned participants on maturity (years from age at peak height velocity) and fit a mixed-effects model adjusting for maturity, sex, ethnicity, leg muscle power, lean mass, limb length, dietary calcium, and MVPA in sedentary time models. MVPA was a positive independent predictor of bone strength (failure load [F.Load]) and bone volume fraction (BV/TV) at the tibia and radius, total area (Tt.Ar) and cortical porosity (Ct.Po) at the tibia, and negative predictor of load-to-strength ratio at the radius. Sedentary time was a negative independent predictor of Tt.Ar at both sites and Ct.Po at the tibia and a positive predictor of cortical thickness (Ct.Th), trabecular thickness (Tb.Th), and cortical bone mineral density (Ct.BMD) at the tibia. Bone parameters demonstrated maturity-specific associations with MVPA and sedentary time, whereby associations were strongest during early and mid-puberty. Our findings support the importance of PA for bone strength accrual and its determinants across adolescent growth and provide new evidence of a detrimental association of sedentary time with bone geometry but positive associations with microarchitecture. This study highlights maturity

  19. The Gemini NICI planet-finding campaign: The offset ring of HR 4796 A

    NASA Astrophysics Data System (ADS)

    Wahhaj, Zahed; Liu, Michael C.; Biller, Beth A.; Nielsen, Eric L.; Hayward, Thomas L.; Kuchner, Marc; Close, Laird M.; Chun, Mark; Ftaclas, Christ; Toomey, Douglas W.

    2014-07-01

    We present J,H, CH4 short (1.578 μm), CH4 long (1.652 μm) and Ks-band images of the dust ring around the 10 Myr old star HR 4796 A obtained using the Near Infrared Coronagraphic Imager (NICI) on the Gemini-South 8.1 m Telescope. Our images clearly show for the first time the position of the star relative to its circumstellar ring thanks to NICI's translucent focal plane occulting mask. We employ a Bayesian Markov chain Monte Carlo method to constrain the offset vector between the two. The resulting probability distribution shows that the ring center is offset from the star by 16.7 ± 1.3 milliarcseconds along a position angle of 26 ± 3°, along the PA of the ring, 26.47 ± 0.04°. We find that the size of this offset is not large enough to explain the brightness asymmetry of the ring. The ring is measured to have mostly red reflectivity across the JHKs filters, which seems to indicate micron-sized grains. Just like Neptune's 3:2 and 2:1 mean-motion resonances delineate the inner and outer edges of the classical Kuiper belt, we find that the radial extent of the HR 4796 A and the Fomalhaut rings could correspond to the 3:2 and 2:1 mean-motion resonances of hypothetical planets at 54.7 AU and 97.7 AU in the two systems, respectively. A planet orbiting HR 4796 A at 54.7 AU would have to be less massive than 1.6 MJup so as not to widen the ring too much by stirring. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the Science and Technology Facilities Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência e Tecnologia (Brazil) and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina).Tables 5 and 6 are available in electronic form at

  20. Children-Adult Comparisons of VO2 and HR Kinetics during Submaximum Exercise.

    ERIC Educational Resources Information Center

    Sady, Stanley P.; And Others

    1983-01-01

    Oxygen uptake and heart rate kinetics for submaximum exercise (bicycle riding) were compared in prepubescent boys and adult men. Resulting data suggest that children and adults do not differ significantly in cardiorespiratory adjustments during low-intensity exercise. (Authors/PP)

  1. The WHO construct of health-related functioning (HrF) and its implications for health policy

    PubMed Central

    2011-01-01

    Background The International Classification of Functioning (ICF) has acquired a central role in the WHO Family of International Classifications and it has been extensively adopted as the reference framework for health-related functioning (HrF). This review aims to provide a description of the ICF/HrF to contextualise ICF/HrF in relation to other approaches to health functioning and to describe its application in policy and legislation with a special focus on Spain. Methods Narrative review based on the scientific literature and prior expert knowledge. Results ICF is both a coding system and a conceptual framework of HrF, which is framed as a unidimensional, bipolar and asymmetric construct with a negative pole (disability) and a positive pole (good functioning) with higher complexity. Other models of HrF include health promotion, quality of life and activities of daily living (ADL). The curtailed taxonomy of ICF and its unclear distinction from other approaches have had significant implications for research, policy and legislation, as illustrated by the case of the legislation and services for functional dependency in Spain and other examples. Conclusions The ICF model of functioning is more comprehensive and usable than previous alternatives, but a full taxonomy of the HrF construct is needed to avoid further confusions in this field. This should also comprise harmonisation with other classifications of the WHO Family of International Classifications and other models of health functioning. PMID:21624195

  2. A NORMETEX MODEL 15 M3/HR WATER VAPOR PUMPING TEST

    SciTech Connect

    Klein, J.; Fowley, M.; Steeper, T.

    2010-12-20

    Tests were performed using a Model 15 m{sup 3}/hr Normetex vacuum pump to determine if pump performance degraded after pumping a humid gas stream. An air feed stream containing 30% water vapor was introduced into the pump for 365 hours with the outlet pressure of the pump near the condensation conditions of the water. Performance of the pump was tested before and after the water vapor pumping test and indicated no loss in performance of the pump. The pump also appeared to tolerate small amounts of condensed water of short duration without increased noise, vibration, or other adverse indications. The Normetex pump was backed by a dual-head diaphragm pump which was affected by the condensation of water and produced some drift in operating conditions during the test.

  3. Observations of the gas stream in the mass transfer binary HR 2142 prime 1

    NASA Technical Reports Server (NTRS)

    Peters, G. J.

    1981-01-01

    The mass transfer binary system HR 2142 was observed at selected phases with the high resolution spectrograph on IUE. The observations were scheduled throughout the interval 0.91 phi 0.00 in order to allow viewing of the light of the primary star through the gas stream as it presents different orientations to the line of sight. Numerous UV lines formed in the gas stream were identified. The strengths and velocity variations displayed by these lines are compared with those observed in the ground based spectral region. As part of a preliminary analysis of the IUE data, column densities and velocities from Si III (4), Si IV (1), and Ti III (1) are used to deduce electron densities in the gas stream as well as its thickness. Possible evidence for stratification in the gas stream is presented.

  4. Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by 1H HR-MAS NMR Metabolomics

    PubMed Central

    Tavel, Laurette; Fontana, Francesca; Garcia Manteiga, Josè Manuel; Mari, Silvia; Mariani, Elisabetta; Caneva, Enrico; Sitia, Roberto; Camnasio, Francesco; Marcatti, Magda; Cenci, Simone; Musco, Giovanna

    2016-01-01

    Multiple myeloma (MM) is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased 1H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusterization of samples in accordance with a posteriori histological findings. We investigated the relationship between morphological and NMR features by merging morphological data and metabolite profiling into a single correlation matrix. Data-merging addressed tissue heterogeneity, and greatly facilitated the mapping of lesions and nearby healthy tissues. Our proof-of-principle study reveals integrated metabolomics and histomorphology as a promising approach for the targeted study of osteolytic lesions. PMID:27809247

  5. VizieR Online Data Catalog: HR 7355 differential BV light curves (Mikulasek+, 2010)

    NASA Astrophysics Data System (ADS)

    Mikulasek, Z.; Krticka, J.; Henry, G. W.; de Villiers, S. N.; Paunzen, E.; Zejda, M.

    2010-02-01

    Differential BV photometry of the He strong CP star HR 5153=HD 182180 versus the comparison star HD 179520. Most of data was acquired by G.W.Henry (GWH) with the T3 0.4-m automatic photoelectric telescope (APT) at Fairborn Observatory in southern Arizona during 2008 May and June. The T3 APT uses a temperature-stabilised EMI 9924B photomultiplier tube to measure photon count rates sequentially through B and V filters. We acquired there 43 B and 38 V measurements. We also obtained 7 continuous hours of BV photometry with a photoelectric photometer attached to a 0.28-m reflector on the night of 2009 July 26 UT at the private observatory of S.N. de Villiers (SNV) in Cape Town, South Africa. We acquired 16 and 17 measurements in B and V. (1 data file).

  6. HR 7578 - A K dwarf double-lined spectroscopic binary with peculiar abundances

    NASA Technical Reports Server (NTRS)

    Fekel, F. C., Jr.; Beavers, W. I.

    1983-01-01

    The number of double-lined K and M dwarf binaries which is currently known is quite small, only a dozen or less of each type. The HR 7578 system was classified as dK5 on the Mount Wilson system and as K2 V on the MK ystem. A summary of radial-velocity measurements including the observatory and weight of each observation is given in a table. The star with the stronger lines has been called component A. The final orbital element solution with all observations appropriately weighted was computed with a differential corrections computer program described by Barker et al. (1967). The program had been modified for the double-lined case. Of particular interest are the very large eccentricity of the system and the large minimum masses for each component. These large minimum masses suggest that eclipses may be detectable despite the relatively long period and small radii of the stars.

  7. Gemini Planet Imager Spectroscopy of the HR 8799 Planets c and d

    DOE PAGES

    Ingraham, Patrick; Marley, Mark S.; Saumon, Didier; ...

    2014-09-30

    During the first-light run of the Gemini Planet Imager we obtained K-band spectra of exoplanets HR 8799 c and d. Analysis of the spectra indicates that planet d may be warmer than planet c. Comparisons to recent patchy cloud models and previously obtained observations over multiple wavelengths confirm that thick clouds combined with horizontal variation in the cloud cover generally reproduce the planets’ spectral energy distributions.When combined with the 3 to 4μm photometric data points, the observations provide strong constraints on the atmospheric methane content for both planets. Lastly, the data also provide further evidence that future modeling efforts mustmore » include cloud opacity, possibly including cloud holes, disequilibrium chemistry, and super-solar metallicity.« less

  8. Gemini Planet Imager Spectroscopy of the HR 8799 Planets c and d

    NASA Astrophysics Data System (ADS)

    Ingraham, Patrick; Marley, Mark S.; Saumon, Didier; Marois, Christian; Macintosh, Bruce; Barman, Travis; Bauman, Brian; Burrows, Adam; Chilcote, Jeffrey K.; De Rosa, Robert J.; Dillon, Daren; Doyon, René; Dunn, Jennifer; Erikson, Darren; Fitzgerald, Michael P.; Gavel, Donald; Goodsell, Stephen J.; Graham, James R.; Hartung, Markus; Hibon, Pascale; Kalas, Paul G.; Konopacky, Quinn; Larkin, James A.; Maire, Jérôme; Marchis, Franck; McBride, James; Millar-Blanchaer, Max; Morzinski, Katie M.; Norton, Andrew; Oppenheimer, Rebecca; Palmer, Dave W.; Patience, Jenny; Perrin, Marshall D.; Poyneer, Lisa A.; Pueyo, Laurent; Rantakyrö, Fredrik; Sadakuni, Naru; Saddlemyer, Leslie; Savransky, Dmitry; Soummer, Rémi; Sivaramakrishnan, Anand; Song, Inseok; Thomas, Sandrine; Wallace, J. Kent; Wiktorowicz, Sloane J.; Wolff, Schuyler G.

    2014-10-01

    During the first-light run of the Gemini Planet Imager we obtained K-band spectra of exoplanets HR 8799 c and d. Analysis of the spectra indicates that planet d may be warmer than planet c. Comparisons to recent patchy cloud models and previously obtained observations over multiple wavelengths confirm that thick clouds combined with horizontal variation in the cloud cover generally reproduce the planets' spectral energy distributions. When combined with the 3 to 4 μm photometric data points, the observations provide strong constraints on the atmospheric methane content for both planets. The data also provide further evidence that future modeling efforts must include cloud opacity, possibly including cloud holes, disequilibrium chemistry, and super-solar metallicity.

  9. Gemini Planet Imager Spectroscopy of the HR 8799 Planets c and d

    SciTech Connect

    Ingraham, Patrick; Marley, Mark S.; Saumon, Didier; Marois, Christian; Macintosh, Bruce; Barman, Travis; Bauman, Brian; Burrows, Adam; Chilcote, Jeffrey K.; De Rosa, Robert J.; Dillon, Daren; Doyon, René; Dunn, Jennifer; Erikson, Darren; Fitzgerald, Michael P.; Gavel, Donald; Goodsell, Stephen J.; Graham, James R.; Hartung, Markus; Hibon, Pascale; Kalas, Paul G.; Konopacky, Quinn; Larkin, James A.; Marchis, Franck; McBride, James; Millar-Blanchaer, Max; Morzinski, Katie M.; Norton, Andrew; Oppenheimer, Rebecca; Palmer, Dave W.; Patience, Jenny; Perrin, Marshall D.; Poyneer, Lisa A.; Pueyo, Laurent; Rantakyrö, Fredrik; Sadakuni, Naru; Saddlemyer, Leslie; Savransky, Dmitry; Soummer, Rémi; Sivaramakrishnan, Anand; Song, Inseok; Thomas, Sandrine; Kent Wallace, J.; Wiktorowicz, Sloane J.; Wolff, Schuyler G.

    2014-09-30

    During the first-light run of the Gemini Planet Imager we obtained K-band spectra of exoplanets HR 8799 c and d. Analysis of the spectra indicates that planet d may be warmer than planet c. Comparisons to recent patchy cloud models and previously obtained observations over multiple wavelengths confirm that thick clouds combined with horizontal variation in the cloud cover generally reproduce the planets’ spectral energy distributions.When combined with the 3 to 4μm photometric data points, the observations provide strong constraints on the atmospheric methane content for both planets. Lastly, the data also provide further evidence that future modeling efforts must include cloud opacity, possibly including cloud holes, disequilibrium chemistry, and super-solar metallicity.

  10. GEMINI PLANET IMAGER SPECTROSCOPY OF THE HR 8799 PLANETS c AND d

    SciTech Connect

    Ingraham, Patrick; Macintosh, Bruce; Marley, Mark S.; Saumon, Didier; Marois, Christian; Dunn, Jennifer; Erikson, Darren; Barman, Travis; Bauman, Brian; Burrows, Adam; Chilcote, Jeffrey K.; Fitzgerald, Michael P.; De Rosa, Robert J.; Dillon, Daren; Gavel, Donald; Doyon, René; Goodsell, Stephen J.; Hartung, Markus; Hibon, Pascale; Graham, James R.; and others

    2014-10-10

    During the first-light run of the Gemini Planet Imager we obtained K-band spectra of exoplanets HR 8799 c and d. Analysis of the spectra indicates that planet d may be warmer than planet c. Comparisons to recent patchy cloud models and previously obtained observations over multiple wavelengths confirm that thick clouds combined with horizontal variation in the cloud cover generally reproduce the planets' spectral energy distributions. When combined with the 3 to 4 μm photometric data points, the observations provide strong constraints on the atmospheric methane content for both planets. The data also provide further evidence that future modeling efforts must include cloud opacity, possibly including cloud holes, disequilibrium chemistry, and super-solar metallicity.

  11. HR-HSBC: Measuring heteronuclear one-bond couplings with enhanced resolution.

    PubMed

    Görling, Benjamin; Bräse, Stefan; Luy, Burkhard

    2012-12-01

    Heteronuclear one-bond couplings have a variety of applications, and their accurate determination is the basis for obtaining specific structural information of mostly small organic compounds. In this context, it is of utmost importance to reduce signal overlap to a minimum, and a number of techniques has been introduced during the last decades. Here, we introduce a modified version of the HR-HMBC (Magn. Reson. Chem. 2010, 48, 179-183) for heteronuclear one-bond coupling measurements with improved resolution because of the J-resolved-like tilt of corresponding multiplet patterns. The pulse sequence is introduced, and its performance is compared with a standard ω(2)-coupled HSQC experiment. Example spectra on glucose and maltose demonstrate that signals can be resolved that overlap otherwise. The approach is discussed in detail.

  12. Molecular degradation of ancient documents revealed by 1H HR-MAS NMR spectroscopy

    PubMed Central

    Corsaro, Carmelo; Mallamace, Domenico; Łojewska, Joanna; Mallamace, Francesco; Pietronero, Luciano; Missori, Mauro

    2013-01-01

    For centuries mankind has stored its knowledge on paper, a remarkable biomaterial made of natural cellulose fibers. However, spontaneous cellulose degradation phenomena weaken and discolorate paper over time. The detailed knowledge of products arising from cellulose degradation is essential in understanding deterioration pathways and in improving durability of cultural heritage. In this study, for the first time, products of cellulose degradation were individually detected in solid paper samples by means of an extremely powerful proton HR-MAS NMR set-up, in combination to a wise use of both ancient and, as reference, artificially aged paper samples. Carboxylic acids, in addition to more complex dicarboxylic and hydroxy-carboxylic acids, were found in all samples studied. Since these products can catalyze further degradation, their knowledge is fundamental to improve conservation strategies of historical documents. Furthermore, the identification of compounds used in ancient production techniques, also suggests for artifacts dating, authentication and provenance. PMID:24104201

  13. Complete genome sequence of Desulfohalobium retbaense type strain (HR100T)

    PubMed Central

    Spring, Stefan; Nolan, Matt; Lapidus, Alla; Glavina Del Rio, Tijana; Copeland, Alex; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Land, Miriam; Chen, Feng; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Ivanova, Natalia; Mavromatis, Konstantinos; Mikhailova, Natalia; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Hauser, Loren; Chang, Yun-Juan; Jeffries, Cynthia D.; Munk, Christine; Kiss, Hajnalka; Chain, Patrick; Han, Cliff; Brettin, Thomas; Detter, John C.; Schüler, Esther; Göker, Markus; Rohde, Manfred; Bristow, Jim; Eisen, Jonathan A.; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C.; Klenk, Hans-Peter

    2010-01-01

    Desulfohalobium retbaense (Ollivier et al. 1991) is the type species of the polyphyletic genus Desulfohalobium, which comprises, at the time of writing, two species and represents the family Desulfohalobiaceae within the Deltaproteobacteria. D. retbaense is a moderately halophilic sulfate-reducing bacterium, which can utilize H2 and a limited range of organic substrates, which are incompletely oxidized to acetate and CO2, for growth. The type strain HR100T was isolated from sediments of the hypersaline Retba Lake in Senegal. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the family Desulfohalobiaceae. The 2,909,567 bp genome (one chromosome and a 45,263 bp plasmid) with its 2,552 protein-coding and 57 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID:21304676

  14. The RS Canum Venaticorum phenomena. I - H-alpha emission in HR 1099

    NASA Astrophysics Data System (ADS)

    Fraquelli, D. A.

    1984-01-01

    Photographic H-alpha spectrophotometry of the active chromosphere star HR 1099 is presented. The data were obtained during both radio-quiescent periods and radio flares during the years 1976-1979. This paper presents the data and data reduction techniques. In particular, the method used to correct the observed H-alpha profiles for the distortion introduced by the irregular 'continuum,' due to the underlying absorption lines, is presented and discussed. The techniques for measuring the equivalent widths and estimating the errors are presented. In addition to the major results presented earlier, it is found that the line widths of the H-alpha emission are broader than can be accounted for by rotation and orbital motion.

  15. Studies on the fracture of HR-2 steel and LY12 aluminum cylinders under explosive imploding

    SciTech Connect

    Tang Tiegang; Hu Haibo; Li Qingzhong; Sun Xueling; Wang Desheng

    2007-12-12

    Experimental studies were conducted on the fracture phenomena of HR-2 steel and LY12 aluminum alloy cylinder under explosive imploding. Optical and flash X-ray photography showed that thermo-plastic instability in the form of shear fracture occurs during the imploding process. Shear initiation and propagation processes on the inner wall was directly observed by high-speed photography. The two kinds of experimental records and examination of recovered fragments showed that shear cracks initiate from the inner surface of the cylinder at a very early stage and propagate along the maximum shear stress paths radically outward and longitudinal along the detonation direction to form shear fracture surfaces. Under imploding conditions there is a strong tendency to form self-organized shear fractures in comparison to exploding fracture of identical cylinder material and loading intensity.

  16. Complete genome sequence of Desulfohalobium retbaense type strain (HR100T)

    SciTech Connect

    Spring, Stefan; Nolan, Matt; Lapidus, Alla L.; Glavina Del Rio, Tijana; Copeland, A; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Land, Miriam L; Chen, Feng; Bruce, David; Goodwin, Lynne A.; Pitluck, Sam; Ivanova, N; Mavromatis, K; Mikhailova, Natalia; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Hauser, Loren John; Chang, Yun-Juan; Jeffries, Cynthia; Munk, Christine; Kiss, Hajnalka; Chain, Patrick S. G.; Han, Cliff; Brettin, Thomas S; Detter, J. Chris; Schuler, Esther; Goker, Markus; Rohde, Manfred; Bristow, James; Eisen, Jonathan; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter

    2010-01-01

    Desulfohalobium retbaense (Ollivier et al. 1991) is the type species of the polyphyletic genus Desulfohalobium, which comprises, at the time of writing, two species and represents the family Desulfohalobiaceae within the Deltaproteobacteria. D. retbaense is a moderately halophilic sulfate-reducing bacterium, which can utilize H2 and a limited range of organic substrates, which are incompletely oxidized to acetate and CO2, for growth. The type strain HR100T was isolated from sediments of the hypersaline Retba Lake in Senegal. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the family Desulfohalobiaceae. The 2,909,567 bp genome (one chromosome and a 45,263 bp plasmid) with its 2,552 protein-coding and 57 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

  17. Limited field investigation report for the 100-HR-1 Operable Unit

    SciTech Connect

    Not Available

    1994-08-01

    This limited field investigation (LFI) report summarizes the data collection and analysis activities conducted during the 100-HR-1 Source Operable Unit LFI and the associated qualitative risk assessment (QRA) (WHC 1993a), and makes recommendations on the continued candidacy of high-priority sites for interim remedial measures (IRM). The results and recommendations presented in this report are generally independent of future land use scenarios. A LFI Report is required, in accordance with the HPPS, when waste sites are to be considered for IRMs. The LFI is an integral part of the remedial investigation/feasibility study (RI/FS) or Resource Conservation and Recovery Act (RCRA) facility investigation/corrective measures study (RFI/CMS) and process and functions as a focused RI or RFI for selection of IRMs. The purpose of the report is to identify those sites that are recommended to remain as candidates for IRMs, provide a preliminary summary of site characterization studies, refine the conceptual model as needed, identify contaminant- and location-specific applicable or relevant and appropriate requirements (ARA), and provide a qualitative assessment of the risks associated with the sites. This assessment includes consideration of whether contaminant concentrations pose an unacceptable risk that warrants action through IRMs. The 100-HR-1 unit encompasses approximately 100 acres adjacent to the Columbia River shoreline. It contains waste units associated with the original plant facilities constructed to support the H Reactor. The area also contains evaporation basins which received liquid process wastes and nonroutine deposits of chemical wastes from the 300 Area, where fuel elements for the N Reactor were produced.

  18. Pilot-scale treatability test plan for the 100-HR-3 operable unit

    SciTech Connect

    Not Available

    1994-08-01

    This document presents the treatability test plan for pilot-scale pump-and-treat testing at the 100-HR-3 Operable Unit. The test will be conducted in fulfillment of interim Milestone M-15-06E to begin pilot-scale pump-and-treat operations by August 1994. The scope of the test was determined based on the results of lab/bench-scale tests (WHC 1993a) conducted in fulfillment of Milestone M-15-06B. These milestones were established per agreement between the U.S. Department of Energy (DOE), the Washington State Department of Ecology and the U.S. Environmental Protection Agency (EPA), and documented on Hanford Federal of Ecology Facility Agreement and Consent Order Change Control Form M-15-93-02. This test plan discusses a pilot-scale pump-and-treat test for the chromium plume associated with the D Reactor portion of the 100-HR-3 Operable Unit. Data will be collected during the pilot test to assess the effectiveness, operating parameters, and resource needs of the ion exchange (IX) pump-and-treat system. The test will provide information to assess the ability to remove contaminants by extracting groundwater from wells and treating extracted groundwater using IX. Bench-scale tests were conducted previously in which chromium VI was identified as the primary contaminant of concern in the 100-D reactor plume. The DOWEX 21K{trademark} resin was recommended for pilot-scale testing of an IX pump-and-treat system. The bench-scale test demonstrated that the system could remove chromium VI from groundwater to concentrations less than 50 ppb. The test also identified process parameters to monitor during pilot-scale testing. Water will be re-injected into the plume using wells outside the zone of influence and upgradient of the extraction well.

  19. The Hot Companion and Circumbinary Disk of the Be Star HR 2142

    NASA Astrophysics Data System (ADS)

    Peters, Geraldine J.; Wang, Luqian; Gies, Douglas R.; Grundstrom, Erika D.

    2016-09-01

    We present a spectroscopic investigation of the Be+sdO binary system HR 2142 that is based upon large sets of ultraviolet observations from the International Ultraviolet Explorer (IUE) and ground-based Hα observations. We measured radial velocities for the Be star component from these spectra and computed a revised orbit. In order to search for the spectral signature of the hot subdwarf, we cross-correlated the short wavelength end of each IUE spectrum with a model hot star spectrum, and then we used the predicted Doppler shifts of the subdwarf to shift-and-add all the cross-correlation functions to the frame of the subdwarf. This merged function shows the weak signal from the spectral lines of the hot star, and a best fit is obtained with a mass ratio {M}2/{M}1=0.07+/- 0.02, companion temperature {T}{{eff}}≥slant 43+/- 5 kK, projected rotational velocity V\\sin i\\lt 30 km s-1, and a monochromatic flux ratio near 1170 Å of {f}2/{f}1\\gt 0.009+/- 0.001. This hot subdwarf creates a one-armed spiral, tidal wake in the disk of the Be star, and we present a circumbinary disk model that can explain the occurrence of shell absorption lines by gas enhancements that occur where gas crossing the gap created by the subdwarf strikes the disk boundaries. The faint companion of HR 2142 may be representative of a significant fraction of Be stars with undetected former mass donor companion stars.

  20. Generalized interpretation scheme for arbitrary HR InSAR image pairs

    NASA Astrophysics Data System (ADS)

    Boldt, Markus; Thiele, Antje; Schulz, Karsten

    2013-10-01

    Land cover classification of remote sensing imagery is an important topic of research. For example, different applications require precise and fast information about the land cover of the imaged scenery (e.g., disaster management and change detection). Focusing on high resolution (HR) spaceborne remote sensing imagery, the user has the choice between passive and active sensor systems. Passive systems, such as multispectral sensors, have the disadvantage of being dependent from weather influences (fog, dust, clouds, etc.) and time of day, since they work in the visible part of the electromagnetic spectrum. Here, active systems like Synthetic Aperture Radar (SAR) provide improved capabilities. As an interactive method analyzing HR InSAR image pairs, the CovAmCohTM method was introduced in former studies. CovAmCoh represents the joint analysis of locality (coefficient of variation - Cov), backscatter (amplitude - Am) and temporal stability (coherence - Coh). It delivers information on physical backscatter characteristics of imaged scene objects or structures and provides the opportunity to detect different classes of land cover (e.g., urban, rural, infrastructure and activity areas). As example, railway tracks are easily distinguishable from other infrastructure due to their characteristic bluish coloring caused by the gravel between the sleepers. In consequence, imaged objects or structures have a characteristic appearance in CovAmCoh images which allows the development of classification rules. In this paper, a generalized interpretation scheme for arbitrary InSAR image pairs using the CovAmCoh method is proposed. This scheme bases on analyzing the information content of typical CovAmCoh imagery using the semisupervised k-means clustering. It is shown that eight classes model the main local information content of CovAmCoh images sufficiently and can be used as basis for a classification scheme.

  1. On the Morphology and Chemical Composition of the HR 4796A Debris Disk

    NASA Astrophysics Data System (ADS)

    Rodigas, Timothy J.; Stark, Christopher C.; Weinberger, Alycia; Debes, John H.; Hinz, Philip M.; Close, Laird; Chen, Christine; Smith, Paul S.; Males, Jared R.; Skemer, Andrew J.; Puglisi, Alfio; Follette, Katherine B.; Morzinski, Katie; Wu, Ya-Lin; Briguglio, Runa; Esposito, Simone; Pinna, Enrico; Riccardi, Armando; Schneider, Glenn; Xompero, Marco

    2015-01-01

    We present resolved images of the HR 4796A debris disk using the Magellan adaptive optics system paired with Clio-2 and VisAO. We detect the disk at 0.77 μm, 0.91 μm, 0.99 μm, 2.15 μm, 3.1 μm, 3.3 μm, and 3.8 μm. We find that the deprojected center of the ring is offset from the star by 4.76 ± 1.6 AU and that the deprojected eccentricity is 0.06 ± 0.02, in general agreement with previous studies. We find that the average width of the ring is 14+3-2% (11.1+2.4-1.6 AU), also comparable to previous measurements. Combining our new scattered light data with archival Hubble Space Telescope images at ~0.5-2 μm, along with previously unpublished Spitzer/MIPS thermal emission data and all other literature thermal data, we set out to constrain the chemical composition of the dust grains. After testing 19 individual root compositions and more than 8400 unique mixtures of these compositions, we find that good fits to the scattered light alone and thermal emission alone are discrepant, suggesting that caution should be exercised if fitting to only one or the other. When we fit to both data sets simultaneously, we find that silicates and organics are generally the most favored, while large abundances of water ice are usually not favored. These results suggest the HR 4796A dust grains are similar to interstellar dust and solar system comets, though improved modeling is necessary to place better constraints on the exact chemical composition of the dust. This paper includes data obtained at the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

  2. Evaluation of the management of Hr-HPV+/PapTest- women: results at 1-year recall.

    PubMed

    Chiappetta, Caterina; Puggioni, Chiara; Lendaro, Eugenio; Cacciotti, Jessica; Zaralli, Roberto; Migliore, Giovanna; Bellardini, Paola; Petrozza, Vincenzo; Della Rocca, Carlo; Di Cristofano, Claudio

    2015-01-01

    With cervical cancer screening the choice of 1-year as a period of follow-up in positive high-risk HPV women without cytological lesions is still under discussion. We evaluated the management of these women and the role of HPV genotyping test. We did a cervical cancer screening study of women aged 35-64 with primary high-risk HPV test. Women positive for high-risk HPV with negative cytology were followed-up after 1 year. In this study we selected women with high-risk HPV+/PapTest- resulted high-risk HPV+ at recall and performed the PapTest and HPV genotyping test. The detection rate of squamous high grade (CIN2+) relative to the total screened cohort was 2.1‰, and it was 0.2‰ at the 1-year recall. The colposcopy performed in women referred at the 1-year recall accounted for 48.8% of the total (baseline + 1-year recall), and 84.3% of these women had no cytological lesions. The most frequent hr-HPV genotype detected was HPV16 and 66.7% of co-infections were due to HPV16 and HPV18. 54.5% of women presented a persistent infection at 1-year recall with the same HPV subtype, 50% of persistent infections was due to HPV16 and 16.7% of these were determined to be CIN2+ histological lesions. Our data show that it may be useful to extend the period of follow-up for women hr-HPV+/PapTest- so as to reduce the number of unnecessary colposcopies due to the transitory infections and that the genotyping test could help to identify the persistent infections in which HPV16 is involved.

  3. Assessment of volume fraction and fabric in the distal radius using HR-pQCT.

    PubMed

    Varga, P; Zysset, P K

    2009-11-01

    The aim of this study was to investigate the capabilities of the state of the art HR-pQCT technique to predict mineral content, volume fraction and fabric of trabecular bone structure compared to the gold standard microCT. Four cadaveric human forearms were scanned with HR-pQCT and the dissected radius epiphyses with microCT. After registering the images, bone mineral density (BMD), volume fraction (BV/TV) and fabric were computed on corresponding cubical regions of interest for both image sources. In particular, the effect of the segmentation procedure on BV/TV was analyzed. Assessment of fabric was performed with three different methods comparing their efficiency and robustness against resolution change. The results showed that in order to achieve optimal results at the lower image resolution, different filtering and thresholding approaches needed to be selected for different tasks. Therefore, to preserve BV/TV, the BMD-based volume fraction provided best match with the reference values of microCT, while in case of Mean Intercept Length (MIL) fabric a Gaussian filter and a histogram-based threshold were optimal. Using the latter, MIL was found to be more robust against resolution change than the other approaches. Additionally, we proposed a linear model for describing the mathematical transformation that the second order fabric tensor undergoes when the resolution of the input images changes. As a conclusion, we found that the investigated properties of trabecular bone structure can be adequately predicted from the lower resolution technique that is available in vivo for peripheral bones, when proper image processing and corrections are applied.

  4. DEBRIS DISTRIBUTION IN HD 95086—A YOUNG ANALOG OF HR 8799

    SciTech Connect

    Su, Kate Y. L.; Smith, Paul S.; Rieke, George H.; Morrison, Sarah; Malhotra, Renu; Balog, Zoltan

    2015-02-01

    HD 95086 is a young early-type star that hosts (1) a 5 M{sub J} planet at the projected distance of 56 AU revealed by direct imaging, and (2) a prominent debris disk. Here we report the detection of 69 μm crystalline olivine feature from the disk using the Spitzer/MIPS-SED data covering 55-95 μm. Due to the low resolution of the MIPS-SED mode, this feature is not spectrally resolved, but is consistent with the emission from crystalline forsterite contributing ∼5% of the total dust mass. We also present detailed analysis of the disk spectral energy distribution and re-analysis of resolved images obtained by Herschel. Our results suggest that the debris structure around HD 95086 consists of a warm (∼175 K) belt, a cold (∼55 K) disk, and an extended disk halo (up to ∼800 AU), and is very similar to that of HR 8799. We compare the properties of the three debris components, and suggest that HD 95086 is a young analog of HR 8799. We further investigate and constrain single-planet, two-planet, three-planet, and four-planet architectures that can account for the observed debris structure and are compatible with dynamical stability constraints. We find that equal-mass four-planet configurations of geometrically spaced orbits, with each planet of mass ∼ 5 M{sub J} , could maintain the gap between the warm and cold debris belts, and also be just marginally stable for timescales comparable to the age of the system.

  5. SIMULTANEOUS DETECTION OF WATER, METHANE, AND CARBON MONOXIDE IN THE ATMOSPHERE OF EXOPLANET HR 8799 b

    SciTech Connect

    Barman, Travis S.; Konopacky, Quinn M.; Macintosh, Bruce; Marois, Christian

    2015-05-01

    Absorption lines from water, methane, and carbon monoxide are detected in the atmosphere of exoplanet HR 8799 b. A medium-resolution spectrum presented here shows well-resolved and easily identified spectral features from all three molecules across the K band. The majority of the lines are produced by CO and H{sub 2}O, but several lines clearly belong to CH{sub 4}. Comparisons between these data and atmosphere models covering a range of temperatures and gravities yield log mole fractions of H{sub 2}O between −3.09 and −3.91, CO between −3.30 and −3.72, and CH{sub 4} between −5.06 and −5.85. More precise mole fractions are obtained for each temperature and gravity studied. A reanalysis of H-band data, previously obtained at a similar spectral resolution, results in a nearly identical water abundance as determined from the K-band spectrum. The methane abundance is shown to be sensitive to vertical mixing and indicates an eddy diffusion coefficient in the range of 10{sup 6}–10{sup 8} cm{sup 2} s{sup −1}, comparable to mixing in the deep troposphere of Jupiter. The model comparisons also indicate a carbon-to-oxygen ratio (C/O) between ∼0.58 and 0.7, encompassing previous estimates for a second planet in the same system, HR 8799 c. Super-stellar C/O could indicate planet formation by core-accretion; however, the range of possible C/O for these planets (and the star) is currently too large to comment strongly on planet formation. More precise values of the bulk properties (e.g., effective temperature and surface gravity) are needed for improved abundance estimates.

  6. Exploration adjustment by ant colonies

    PubMed Central

    2016-01-01

    How do animals in groups organize their work? Division of labour, i.e. the process by which individuals within a group choose which tasks to perform, has been extensively studied in social insects. Variability among individuals within a colony seems to underpin both the decision over which tasks to perform and the amount of effort to invest in a task. Studies have focused mainly on discrete tasks, i.e. tasks with a recognizable end. Here, we study the distribution of effort in nest seeking, in the absence of new nest sites. Hence, this task is open-ended and individuals have to decide when to stop searching, even though the task has not been completed. We show that collective search effort declines when colonies inhabit better homes, as a consequence of a reduction in the number of bouts (exploratory events). Furthermore, we show an increase in bout exploration time and a decrease in bout instantaneous speed for colonies inhabiting better homes. The effect of treatment on bout effort is very small; however, we suggest that the organization of work performed within nest searching is achieved both by a process of self-selection of the most hard-working ants and individual effort adjustment. PMID:26909180

  7. Plant polyphenols differentially modulate inflammatory responses of human keratinocytes by interfering with activation of transcription factors NF{kappa}B and AhR and EGFR-ERK pathway

    SciTech Connect

    Potapovich, Alla I.; Lulli, Daniela; Fidanza, Paolo; Kostyuk, Vladimir A.; De Luca, Chiara; Pastore, Saveria; Korkina, Liudmila G.

    2011-09-01

    Molecular mechanisms underlying modulation of inflammatory responses in primary human keratinocytes by plant polyphenols (PPs), namely the glycosylated phenylpropanoid verbascoside, the stilbenoid resveratrol and its glycoside polydatin, and the flavonoid quercetin and its glycoside rutin were evaluated. As non-lethal stimuli, the prototypic ligand for epidermal growth factor receptor (EGFR) transforming growth factor alpha (TGFalpha), the combination of tumor necrosis factor (TNFalpha) and interferon (IFNgamma) (T/I), UVA + UVB irradiation, and bacterial lipopolysaccharide (LPS) were used. We demonstrated differential modulation of inflammatory responses in keratinocytes at signal transduction, gene transcription, and protein synthesis levels as a function of PP chemical structure, the pro-inflammatory trigger used, and PP interaction with intracellular detoxifying systems. The PPs remarkably inhibited constitutive, LPS- and T/I-induced but not TGFalpha-induced ERK phosphorylation. They also suppressed NFkappaB activation by LPS and T/I. Verbascoside and quercetin invariably impaired EGFR phosphorylation and UV-associated aryl hydrocarbon receptor (AhR)-mediated signaling, while rutin, polydatin and resveratrol did not affect EGFR phosphorylation and further activated AhR machinery in UV-exposed keratinocytes. In general, PPs down-regulated gene expression of pro-inflammatory cytokines/enzymes, except significant up-regulation of IL-8 observed under stimulation with TGFalpha. Both spontaneous and T/I-induced release of IL-8 and IP-10 was suppressed, although 50 {mu}M resveratrol and polydatin up-regulated IL-8. At this concentration, resveratrol activated both gene expression and de novo synthesis of IL-8 and AhR-mediated mechanisms were involved. We conclude that PPs differentially modulate the inflammatory response of human keratinocytes through distinct signal transduction pathways, including AhR and EGFR. - Graphical abstract: Display Omitted Highlights

  8. Alterations of bone density, microstructure, and strength of the distal radius in male patients with rheumatoid arthritis: a case-control study with HR-pQCT.

    PubMed

    Zhu, Tracy Y; Griffith, James F; Qin, Ling; Hung, Vivian W; Fong, Tsz-Ning; Au, Sze-Ki; Li, Martin; Lam, Yvonne Yi-On; Wong, Chun-Kwok; Kwok, Anthony W; Leung, Ping-Chung; Li, Edmund K; Tam, Lai-Shan

    2014-09-01

    In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, -3.9% to -23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, -8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in

  9. A zero-augmented generalized gamma regression calibration to adjust for covariate measurement error: A case of an episodically consumed dietary intake.

    PubMed

    Agogo, George O

    2017-01-01

    Measurement error in exposure variables is a serious impediment in epidemiological studies that relate exposures to health outcomes. In nutritional studies, interest could be in the association between long-term dietary intake and disease occurrence. Long-term intake is usually assessed with food frequency questionnaire (FFQ), which is prone to recall bias. Measurement error in FFQ-reported intakes leads to bias in parameter estimate that quantifies the association. To adjust for bias in the association, a calibration study is required to obtain unbiased intake measurements using a short-term instrument such as 24-hour recall (24HR). The 24HR intakes are used as response in regression calibration to adjust for bias in the association. For foods not consumed daily, 24HR-reported intakes are usually characterized by excess zeroes, right skewness, and heteroscedasticity posing serious challenge in regression calibration modeling. We proposed a zero-augmented calibration model to adjust for measurement error in reported intake, while handling excess zeroes, skewness, and heteroscedasticity simultaneously without transforming 24HR intake values. We compared the proposed calibration method with the standard method and with methods that ignore measurement error by estimating long-term intake with 24HR and FFQ-reported intakes. The comparison was done in real and simulated datasets. With the 24HR, the mean increase in mercury level per ounce fish intake was about 0.4; with the FFQ intake, the increase was about 1.2. With both calibration methods, the mean increase was about 2.0. Similar trend was observed in the simulation study. In conclusion, the proposed calibration method performs at least as good as the standard method.

  10. Trade Adjustment Assistance Extension Act of 2010

    THOMAS, 111th Congress

    Sen. Brown, Sherrod [D-OH

    2010-12-22

    12/22/2010 Read twice and referred to the Committee on Finance. (All Actions) Notes: For further action, see H.R.6517, which became Public Law 111-344 on 12/29/2010. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  11. Ergonomic evaluation of the Apple Adjustable Keyboard

    SciTech Connect

    Tittiranonda, P.; Burastero, S.; Shih, M.; Rempel, D.

    1994-05-01

    This study presents an evaluation of the Apple Adjustable Keyboard based on subjective preference and observed joint angles during typing. Thirty five keyboard users were asked to use the Apple adjustable keyboard for 7--14 days and rate the various characteristics of the keyboard. Our findings suggest that the most preferred opening angles range from 11--20{degree}. The mean ulnar deviation on the Apple Adjustable keyboard is 11{degree}, compared to 16{degree} on the standard keyboard. The mean extension was decreased from 24{degree} to 16{degree} when using the adjustable keyboard. When asked to subjectively rate the adjustable keyboard in comparison to the standard, the average subject felt that the Apple Adjustable Keyboard was more comfortable and easier to use than the standard flat keyboard.

  12. Efficient Adjustable Reflectivity Smart Window

    SciTech Connect

    D. Morgan Tench

    2005-12-01

    This project addressed the key technical issues for development of an efficient smart window based on reversible electrochemical transfer of silver between a mirror electrode and a localized counter electrode. Effort to provide uniform switching over large areas focused on use of a resistive transparent electrode innerlayer to increase the interelectrode resistance. An effective edge seal was developed in collaboration with adhesive suppliers and an electrochromic device manufacturer. Work to provide a manufacturable counter electrode focused on fabricating a dot matrix electrode without photolithography by electrodeposition of Pt nuclei on inherent active sites on a transparent oxide conductor. An alternative counter electrode based on a conducting polymer and an ionic liquid electrolyte was also investigated. Work in all of these areas was successful. Sputtered large-bandgap oxide innerlayers sandwiched between conductive indium tin oxide (ITO) layers were shown to provide sufficient cross-layer resistance (>300 ohm/cm{sup 2}) without significantly affecting the electrochemical properties of the ITO overlayer. Two edge seal epoxies, one procured from an epoxy manufacturer and one provided by an electrochromic device manufacturer in finished seals, were shown to be effective barriers against oxygen intrusion up to 80 C. The optimum density of nuclei for the dot matrix counter electrode was attained without use of photolithography by electrodeposition from a commercial alkaline platinum plating bath. Silver loss issues for cells with dot matrix electrodes were successfully addressed by purifying the electrolyte and adjusting the cell cycling parameters. More than 30K cycles were demonstrated for a REM cell (30-cm square) with a dot matrix counter electrode. Larger cells (30-cm square) were successfully fabricated but could not be cycled since the nucleation layers (provided by an outside supplier) were defective so that mirror deposits could not be produced.

  13. Smoking and survival of colorectal cancer patients: population-based study from Germany.

    PubMed

    Walter, Viola; Jansen, Lina; Hoffmeister, Michael; Ulrich, Alexis; Chang-Claude, Jenny; Brenner, Hermann

    2015-09-15

    Current evidence on the association between smoking and colorectal cancer (CRC) prognosis after diagnosis is heterogeneous and few have investigated dose-response effects or outcomes other than overall survival. Therefore, the association of smoking status and intensity with several prognostic outcomes was evaluated in a large population-based cohort of CRC patients; 3,130 patients with incident CRC, diagnosed between 2003 and 2010, were interviewed on sociodemographic factors, smoking behavior, medication and comorbidities. Tumor characteristics were collected from medical records. Vital status, recurrence and cause of death were documented for a median follow-up time of 4.9 years. Using Cox proportional hazards regression, associations between smoking characteristics and overall, CRC-specific, non-CRC related, recurrence-free and disease-free survival were evaluated. Among stage I-III patients, being a smoker at diagnosis and smoking ≥15 cigarettes/day were associated with lower recurrence-free (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93-1.79 and aHR: 1.31; 95%-CI: 0.92-1.87) and disease-free survival (aHR: 1.26; 95%-CI: 0.95-1.67 and aHR: 1.29; 95%-CI: 0.94-1.77). Smoking was associated with decreased survival in stage I-III smokers with pack years ≥20 (Overall survival: aHR: 1.40; 95%-CI: 1.01-1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%-CI: 1.05-2.17) and men (Recurrence-free survival: aHR: 1.51; 95%-CI: 1.09-2.10; disease-free survival: aHR: 1.49; 95%-CI: 1.12-1.97), whereas no associations were seen among women, stage IV or rectal cancer patients. The observed patterns support the existence of adverse effects of smoking on CRC prognosis among nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by promotion of smoking cessation, embedded in tertiary prevention programs warrants careful evaluation in future investigations.

  14. Factors associated with the time to the first wheezing episode in infants: a cross-sectional study from the International Study of Wheezing in Infants (EISL).

    PubMed

    Pacheco-Gonzalez, Rosa M; Mallol, Javier; Solé, Dirceu; Brand, Paul L P; Perez-Fernandez, Virginia; Sanchez-Solis, Manuel; Garcia-Marcos, Luis

    2016-01-21

    Male gender, asthmatic heredity, perinatal tobacco smoke exposure and respiratory infections have been associated with wheeze in the first years of life, among other risk factors. However, information about what factors modify the time to the first episode of wheeze in infants is lacking. The present study analyses which factors are associated with shorter time to the first episode of wheeze in infants. Parents of 11- to 24-month-old children were surveyed when attending their health-care centres for a control visit. They answered a questionnaire including the age in months when a first wheeze episode (if any) had occurred (outcome variable). The study was performed in 14 centres in Latin America (LA) and in 8 centres in Europe (EU) (at least 1,000 infants per centre). Factors known to be associated with wheezing in the cohort were included in a survival analysis (Cox proportional hazards model). Summary hazard ratios adjusted for all risk factors (aHR) were calculated using the meta-analysis approach with random effects. A total of 15,067 infants had experienced wheezing at least once, out of 35,049 surveyed. Male gender in LA (aHR 1.05, 95% confidence interval (CI) 1.00-1.10, P=0.047), parental asthma in LA and EU (aHR 1.05, 95% CI 1.00-1.11, P=0.037), infant eczema in EU (aHR 1.25, 95% CI 1.12-1.39, P<0.001) and having a cold during the first 3 months in LA and EU (aHR 1.97, 95% CI 1.90-2.04, P<0.001), in LA (aHR 1.98, 95% CI 1.90-2.06, P<0.001) and in EU (aHR 1.91, 95% CI 1.75-2.09, P<0.001) were associated with a shorter period of time to the first episode. Breast feeding for at least 3 months was associated with a longer period, only in LA (aHR 0.91, 95% CI 0.86-0.96, P<0.001). Cold symptoms during the first 3 months is the most consistent factor shortening the time to the first episode of wheezing; breast feeding for ⩾3 months delays it only in LA, whereas eczema shortens it only in EU. Avoiding a common cold in the first months of life could be a good

  15. Three-dimensional adjustment of trilateration data

    NASA Technical Reports Server (NTRS)

    Sung, L.-Y.; Jackson, D. D.

    1985-01-01

    The three-dimensional locations of the monuments in the USGS Hollister trilateration network were adjusted to fit line length observations observed in 1977, using a Bayesian approach, and incorporating prior elevation estimates as data in the adjustment procedure. No significant discrepancies in the measured line lengths were found, but significant elevation adjustments (up to 1.85 m) were needed to fit the length data.

  16. Multi-adjustable headband. [for headsets

    NASA Technical Reports Server (NTRS)

    Toole, Pierce C. (Inventor); Chalson, Howard E. (Inventor); Bussey, Walter S. (Inventor)

    1988-01-01

    This invention relates to a headband for a headset having separate coarse and fine adjustment features. The adjustments may be to the axial distance between at least one earpiece element and a side support. Such adjustment to the axial distance varies the pressure exerted on the head of the user. The present fine adjustment feature may be used while the headset is being worn, thereby permitting a user to optimize the amount of pressure between the contending criteria of comfort and keeping the headset in place on the user's head.

  17. Standardization of age-adjusted mortality rates

    SciTech Connect

    Selvin, S.; Sacks, S.T.; Merrill, D.W.

    1980-02-01

    Because age is a significant variable in the occurrence and frequency of human disease, any comparison of disease or mortality rates, to be useful, must be age-specific or age-adjusted. Age-specific comparisons are not always appropriate or possible, however. A common method of eliminating the influence of age in comparing mortality rates from one community to another is to employ statistical methods of age-adjustment. While a variety of methods will accomplish this task, most are weighted averages of the age-specific rates. Two widely used adjustment procedures are direct and indirect age-adjustment.

  18. Recombinant protein of heptad-repeat HR212, a stable fusion inhibitor with potent anti-HIV action in vitro

    SciTech Connect

    Pang, Wei; Wang Ruirui; Yang Liumeng; Liu Changmei; Tien Po Zheng Yongtang

    2008-07-20

    HR212, a recombinant protein expressed in Escherichia coli, has been previously reported to inhibit HIV-1 membrane fusion at low nanomolar level. Here we report that HR212 is effective in blocking laboratory strain HIV-1{sub IIIB} entry and replication with EC{sub 50} values of 3.92 {+-} 0.62 and 6.59 {+-} 1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1{sub KM018} with EC{sub 50} values of 44.44 {+-} 10.20 nM, as well as suppressing HIV-1-induced cytopathic effect with an EC{sub 50} value of 3.04 {+-} 1.20 nM. It also inhibited HIV-2{sub ROD} and HIV-2{sub CBL-20} entry and replication in the {mu}M range. Notably, HR212 was highly effective against T20-resistant strains with EC{sub 50} values ranging from 5.09 to 7.75 nM. Unlike T20, HR212 showed stability sufficient to inhibit syncytia formation in a time-of-addition assay, and was insensitive to proteinase K digestion. These results suggest that HR212 has great potential to be further developed as novel HIV-1 fusion inhibitor for treatment of HIV/AIDS patients, particularly for those infected by T20-resistant variants.

  19. The Nuclear Receptor Genes HR3 and E75 Are Required for the Circadian Rhythm in a Primitive Insect

    PubMed Central

    Kamae, Yuichi; Uryu, Outa; Miki, Taiki; Tomioka, Kenji

    2014-01-01

    Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim) and period (per). Although the transcriptional regulation of Clock (Clk) has been profoundly studied, little is known about the regulation of cycle (cyc). Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Rorα and Rev-erbα, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes. PMID:25502221

  20. THE 5 hr PULSE PERIOD AND BROADBAND SPECTRUM OF THE SYMBIOTIC X-RAY BINARY 3A 1954+319

    SciTech Connect

    Marcu, Diana M.; Pottschmidt, Katja; Fuerst, Felix; Grinberg, Victoria; Mueller, Sebastian; Wilms, Joern; Postnov, Konstantin A.; Corbet, Robin H. D.; Markwardt, Craig B.; Cadolle Bel, Marion

    2011-11-20

    We present an analysis of the highly variable accreting X-ray pulsar 3A 1954+319 using 2005-2009 monitoring data obtained with INTEGRAL and Swift. This considerably extends the pulse period history and covers flaring episodes in 2005 and 2008. In 2006 the source was identified as one of only a few known symbiotic X-ray binaries (SyXBs), i.e., systems composed of a neutron star accreting from the inhomogeneous medium around an M-giant star. The extremely long pulse period of {approx}5.3 hr is directly visible in the 2008 INTEGRAL-ISGRI outburst light curve. The pulse profile is double peaked and generally not significantly energy dependent although there is an indication of possible softening during the main pulse. During the outburst a strong spin-up of -1.8 Multiplication-Sign 10{sup -4} hr hr{sup -1} occurred. Between 2005 and 2008 a long-term spin-down trend of 2.1 Multiplication-Sign 10{sup -5} hr hr{sup -1} was observed for the first time for this source. The 3-80 keV pulse peak spectrum of 3A 1954+319 during the 2008 flare could be well described by a thermal Comptonization model. We interpret the results within the framework of a recently developed quasi-spherical accretion model for SyXBs.

  1. The nuclear receptor genes HR3 and E75 are required for the circadian rhythm in a primitive insect.

    PubMed

    Kamae, Yuichi; Uryu, Outa; Miki, Taiki; Tomioka, Kenji

    2014-01-01

    Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim) and period (per). Although the transcriptional regulation of Clock (Clk) has been profoundly studied, little is known about the regulation of cycle (cyc). Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Rorα and Rev-erbα, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes.

  2. Estimation of vitamin B1 excretion in 24-hr urine by assay of first-morning urine.

    PubMed

    Ihara, Hiroshi; Matsumoto, Takayuki; Kakinoki, Takashi; Shino, Yoshio; Hashimoto, Reiko; Hashizume, Naotaka

    2008-01-01

    Urinary B1 (vitamin B1) excretion is commonly determined in 24-hr urine specimens to obtain an estimate of nutritional status. The aim of our study was to investigate whether B1 in random urine specimens, corrected for the urine creatinine (Cr), can be substituted for B1 in 24-hr urines. Collection of such hour urines is often fraught with errors; an alternative method is described here. All urine specimens voided over 24 hr were collected from 32 healthy adults as were the first-morning urines from 30 healthy Japanese women. The B1 excretion was expressed as the ratio of B1 to Cr. Although the B1 excretion was expressed as the B1/Cr ratio, the B1 excretion varied with the urine volume and the time of urine collection. The B1/Cr ratio in random urine specimens not collected at a fixed time may mislead the evaluation of the nutritional status. We found that the B1/Cr ratio in the first-morning urine correlated significantly with the ratio in 24-hr urines (r=0.970, P<0.001) and also with the concentration of total B1 (B1 plus its phosphate esters) in whole blood (r=0.733, P<0.001). We conclude that the B1/Cr ratio in 24-hr urines could be estimated by measuring the ratio in the first-morning urine.

  3. E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair

    PubMed Central

    Singh, Randeep K.; Dagnino, Lina

    2016-01-01

    Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis. PMID:27028861

  4. Congenital cerebral palsy and prenatal exposure to self-reported maternal infections, fever, or smoking

    PubMed Central

    Streja, Elani; Miller, Jessica E.; Bech, Bodil H.; Greene, Naomi; Pedersen, Lars Henning; Yeargin-Allsopp, Marshalyn; Van Naarden Braun, Kim; Schendel, Diana E.; Christensen, Deborah; Uldall, Peter; Olsen, Jørn

    2015-01-01

    OBJECTIVE The objective of the study was to investigate the association between maternal self-reported infections, fever, and smoking in the prenatal period and the subsequent risk for congenital cerebral palsy (CP). STUDY DESIGN We included the 81,066 mothers of singletons born between 1996 and 2003 who participated in the Danish National Birth Cohort. Children were followed up through December 2008. Information on maternal infections, fever, smoking, and other demographic and lifestyle factors during pregnancy were reported by mothers in computer-assisted telephone interviews in early and midgestation. We identified 139 CP cases including 121 cases of spastic CP (sCP) as confirmed by the Danish National Cerebral Palsy Register. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS Self-reported vaginal infections were associated with an increased risk of CP and sCP (aHR, 1.52; 95% CI, 1.04–2.24; and aHR, 1.73; 95% CI, 1.16–2.60, respectively) and particularly untreated vaginal infections were associated with an increased risk of sCP (aHR, 1.95; 95% CI, 1.16–3.26). Fever was associated with the risk of CP (aHR, 1.53; 95% CI, 1.06–2.21). Smoking 10 or more cigarettes per day during pregnancy was also associated with sCP (aHR, 1.80; 95% CI, 1.10–2.94). There was a modest excess in risk for children exposed to both heavy smoking and vaginal infections. No other self-reported infections were significantly associated with CP. CONCLUSION Self-reported vaginal infections, fever, and smoking 10 or more cigarettes per day during pregnancy were associated with a higher risk of overall CP and/or sCP. PMID:23791566

  5. Differences in the action of lower and higher chlorinated polychlorinated naphthalene (PCN) congeners on estrogen dependent breast cancer cell line viability and apoptosis, and its correlation with Ahr and CYP1A1 expression.

    PubMed

    Gregoraszczuk, Ewa L; Barć, Justyna; Falandysz, Jerzy

    2016-07-29

    There are data showing that exposition to PCNs mixture increased incidence of gastrointestinal and respiratory neoplasms, but data regarding incidence of hormone-dependent cancer so far not shown. The objective was to determine if exposure to single lower and higher chlorinated PCN congeners is associated with altered proliferation and apoptosis of estrogen dependent breast cancer cells, and whether such effects are related to induction of AhR and CYP1A1 protein expression. MCF-7 cells were exposed to PCN 34, 39, 42, 46, 48, 52, 53, 54, 66, 67, 70, 71, 73 and 74 at concentrations of 100-10,000pg/ml. We evaluated the action of these PCN congeners on cell proliferation, DNA fragmentation and caspase-8,-9 activity. AhR and CYP1A1 protein expression and CYP1A1 activity was evaluated at a concentration of 1000pg/ml. An opposite action of tri- to tetraCNs than of penta-to heptaCNs on cell proliferation and apoptosis was evident. Tetra PCNs increased cell proliferation, but had no effect on DNA fragmentation nor caspase activity. Fast induction of CYP1A1 protein expression under the influence of lower chlorinated PCNs suggests faster metabolism and a possible stimulatory action of locally formed metabolites on cell proliferation. None of the higher chlorinated PCNs affected cell proliferation but all higher chlorinated PCNs increased caspase-8 activity, and hexa PCNs also increased caspase-9 activity. The rapid activation of the Ah receptor and CYP1A1 protein expression by higher chlorinated PCNs point to their toxicity; however, it is not sufficient for potential carcinogenicity. Action of lower chlorinated naphthalenes metabolites should be explored.

  6. Dose- and time-dependent expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) in PCB-, B[a]P-, and TBT-exposed intertidal copepod Tigriopus japonicus.

    PubMed

    Kim, Bo-Mi; Rhee, Jae-Sung; Hwang, Un-Ki; Seo, Jung Soo; Shin, Kyung-Hoon; Lee, Jae-Seong

    2015-02-01

    The aryl hydrocarbon receptor (AhR) and aryl hydrocarbon nuclear translocator (ARNT) genes from the copepod Tigriopus japonicus (Tj) were cloned to examine their potential functions in the invertebrate putative AhR-CYP signaling pathway. The amino acid sequences encoded by the Tj-AhR and Tj-ARNT genes showed high similarity to homologs of Daphnia and Drosophila, ranging from 68% and 70% similarity for the AhR genes to 56% for the ARNT genes. To determine whether Tj-AhR and Tj-ARNT are modulated by environmental pollutants, transcriptional expression of Tj-AhR and Tj-ARNT was analyzed in response to exposure to five concentrations of polychlorinated biphenyl (PCB 126) (control, 10, 50, 100, 500 μg L(-1)), benzo[a]pyrene (B[a]P) (control, 5, 10, 50, 100 μg L(-1)), and tributyltin (TBT) (control, 1, 5, 10, 20 μg L(-1)) 24h after exposure. A time-course experiment (0, 3, 6, 12, 24h) was performed to analyze mRNA expression patterns after exposure to PCB, B[a]P, and TBT. T. japonicus exhibited dose-dependent and time-dependent upregulation of Tj-AhR and Tj-ARNT in response to pollutant exposure, and the degree of expression was dependent on the pollutant, suggesting that pollutants such as PCB, B[a]P, and TBT modulate expression of Tj-AhR and Tj-ARNT genes in the putative AhR-CYP signaling pathway.

  7. Precision Adjustable Liquid Regulator (ALR)

    NASA Astrophysics Data System (ADS)

    Meinhold, R.; Parker, M.

    2004-10-01

    A passive mechanical regulator has been developed for the control of fuel or oxidizer flow to a 450N class bipropellant engine for use on commercial and interplanetary spacecraft. There are several potential benefits to the propulsion system, depending on mission requirements and spacecraft design. This system design enables more precise control of main engine mixture ratio and inlet pressure, and simplifies the pressurization system by transferring the function of main engine flow rate control from the pressurization/propellant tank assemblies, to a single component, the ALR. This design can also reduce the thermal control requirements on the propellant tanks, avoid costly Qualification testing of biprop engines for missions with more stringent requirements, and reduce the overall propulsion system mass and power usage. In order to realize these benefits, the ALR must meet stringent design requirements. The main advantage of this regulator over other units available in the market is that it can regulate about its nominal set point to within +/-0.85%, and change its regulation set point in flight +/-4% about that nominal point. The set point change is handled actively via a stepper motor driven actuator, which converts rotary into linear motion to affect the spring preload acting on the regulator. Once adjusted to a particular set point, the actuator remains in its final position unpowered, and the regulator passively maintains outlet pressure. The very precise outlet regulation pressure is possible due to new technology developed by Moog, Inc. which reduces typical regulator mechanical hysteresis to near zero. The ALR requirements specified an outlet pressure set point range from 225 to 255 psi, and equivalent water flow rates required were in the 0.17 lb/sec range. The regulation output pressure is maintained at +/-2 psi about the set point from a P (delta or differential pressure) of 20 to over 100 psid. Maximum upstream system pressure was specified at 320 psi

  8. Diurnal temperature fluctuation effects on potatoes grown with 12 hr photoperiods

    NASA Technical Reports Server (NTRS)

    Bennett, S. M.; Tibbitts, T. W.; Cao, W.

    1991-01-01

    This study was designed to characterize the growth responses of potato (Solanum tuberosum L.) to diurnal temperature fluctuations. Potato plants of two cultivars, Norland and Denali, were grown for 90 days under 12 hr photoperiod in walk-in growth rooms at the University of Wisconsin Biotron. The alternating temperature was 22 C light/14 C dark and compared to a constant 18 C as control. At all temperature regimes vapor pressure deficit was maintained at 0.62 kPa (70% relative humidity [correction of humdidity] at 18 C). Plant height, plant dry weight, tuber dry weight, and harvest index were overall greater under the warm light/cool dark alternating temperatures than under the constant temperature. The differences between temperature treatments were greater for Denali than for Norland. Alternating temperatures increased Denali tuber weights by 25%, but no significant increase was found with Norland. Also the total plant weight was increased over 20% with Denali, but increased with Norland in only one of the two replications of the experiment. This study documents that alternating temperatures are a benefit to some cultivars but may not be of benefit to all cultivars.

  9. A ∼ 3.8 hr PERIODICITY FROM AN ULTRASOFT ACTIVE GALACTIC NUCLEUS CANDIDATE

    SciTech Connect

    Lin, Dacheng; Irwin, Jimmy A.; Godet, Olivier; Webb, Natalie A.; Barret, Didier

    2013-10-10

    Very few galactic nuclei are found to show significant X-ray quasi-periodic oscillations (QPOs). After carefully modeling the noise continuum, we find that the ∼3.8 hr QPO in the ultrasoft active galactic nucleus candidate 2XMM J123103.2+110648 was significantly detected (∼5σ) in two XMM-Newton observations in 2005, but not in the one in 2003. The QPO root mean square (rms) is very high and increases from ∼25% in 0.2-0.5 keV to ∼50% in 1-2 keV. The QPO probably corresponds to the low-frequency type in Galactic black hole X-ray binaries, considering its large rms and the probably low mass (∼10{sup 5} M {sub ☉}) of the black hole in the nucleus. We also fit the soft X-ray spectra from the three XMM-Newton observations and find that they can be described with either pure thermal disk emission or optically thick low-temperature Comptonization. We see no clear X-ray emission from the two Swift observations in 2013, indicating lower source fluxes than those in XMM-Newton observations.

  10. VizieR Online Data Catalog: HR8752 evolving through the void (Nieuwenhuijzen+ 2012)

    NASA Astrophysics Data System (ADS)

    Nieuwenhuijzen, H.; de Jager, C.; Kolka, I.; Israelian, G.; Lobel, A.; Zsoldos, E.; Maeder, A.; Meynet, G.

    2012-06-01

    The main paper on the hypergiant HR8752 evolving through the void combines observational data from various sources: new spectral data, new and already published (B-V), V data. it also describes a new three-dimensional chebychev interpolating code, and gives information on the temperature calibration for hypergiants, and adds some extra Tables on colour excess and historical context (cf. below). The electronic appendix contains a number of tables, too large for publishing in the paper. In the text and in the appendix, they are referred to as Table Axx, resp. Cxx. We note, however, that tables A1.1 to A1.6 in Section 2 of the main paper are here referred to as tables appena11 to appena16. The observational tables appena11 to appena16, appena2, appena3, appena4 all refer to Section 2 in the main paper, while tables appena5, appena6, appena7, appena8 are used in Section 3 of the main paper. The technical table appenc1 describes the three-dimensional chebychev interpolation method used in Section 2 of the main paper. The second technical table appenc2 describes the (hypergiant) temperature calibration and transformation codes between Mk, Teff, and (B-V) data, used in Section 3 of the main paper. Table appena9 discusses some measured colour excesses (Section 3.3 of the main paper). Table appena10 discusses the possibility of historical context (Section 5.11 of the main paper). (20 data files).

  11. Exploring the multifaceted circumstellar environment of the luminous blue variable HR Carinae

    NASA Astrophysics Data System (ADS)

    Buemi, C. S.; Trigilio, C.; Leto, P.; Umana, G.; Ingallinera, A.; Cavallaro, F.; Cerrigone, L.; Agliozzo, C.; Bufano, F.; Riggi, S.; Molinari, S.; Schillirò, F.

    2017-03-01

    We present a multiwavelength study of the Galactic luminous blue variable HR Carinae, based on new high-resolution mid-infrared (IR) and radio images obtained with the Very Large Telescope (VLT) and the Australia Telescope Compact Array (ATCA), which have been complemented by far-infrared Herschel-Photodetector Array Camera and Spectrometer (PACS) observations and ATCA archive data. The Herschel images reveal the large-scale distribution of the dusty emitting nebula, which extends mainly to the north-east direction, up to 70 arcsec from the central star, and is oriented along the direction of the space motion of the star. In the mid-infrared images, the brightness distribution is characterized by two arc-shaped structures, tracing an inner envelope surrounding the central star more closely. At radio wavelengths, the ionized gas emission lies on the opposite side of the cold dust with respect to the position of the star, as if the ionized front were confined by the surrounding medium in the north-south direction. Comparison with previous data indicates significant changes in the radio nebula morphology and in the mass-loss rate from the central star, which has increased from 6.1 × 10-6 M⊙ yr-1 in 1994-1995 to 1.17 × 10-5 M⊙ yr-1 in 2014. We investigate possible scenarios that could have generated the complex circumstellar environment revealed by our multiwavelength data.

  12. Urban Area Extent Extraction in Spaceborne HR and VHR Data Using Multi-Resolution Features

    PubMed Central

    Iannelli, Gianni Cristian; Lisini, Gianni; Dell'Acqua, Fabio; Feitosa, Raul Queiroz; da Costa, Gilson Alexandre Ostwald Pedro; Gamba, Paolo

    2014-01-01

    Detection of urban area extents by means of remotely sensed data is a difficult task, especially because of the multiple, diverse definitions of what an “urban area” is. The models of urban areas listed in technical literature are based on the combination of spectral information with spatial patterns, possibly at different spatial resolutions. Starting from the same data set, “urban area” extraction may thus lead to multiple outputs. If this is done in a well-structured framework, however, this may be considered as an advantage rather than an issue. This paper proposes a novel framework for urban area extent extraction from multispectral Earth Observation (EO) data. The key is to compute and combine spectral and multi-scale spatial features. By selecting the most adequate features, and combining them with proper logical rules, the approach allows matching multiple urban area models. Experimental results for different locations in Brazil and Kenya using High-Resolution (HR) data prove the usefulness and flexibility of the framework. PMID:25271564

  13. 1H HR-MAS NMR of carotenoids in aqueous samples and raw vegetables.

    PubMed

    Miglietta, M L; Lamanna, R

    2006-07-01

    Carotenoids are linear C40 tetraterpenoid hydrocarbons and represent a wide category of natural pigments. They are components of the pigment system of chloroplasts and are involved in the primary light absorption and the photon canalization of photosynthesis. Moreover, they also behave as quenchers of singlet oxygen, protecting cells and organisms against lipid peroxidation. Carotenoids have a strong lipophilic character and are usually analyzed in organic solvents. However, because of their biological activity, the characterization of these compounds in an aqueous environment or in the natural matrix is very important. One of the most important dietary carotenoids is beta-carotene, which has been extensively studied both in vivo and in model systems, but because of the low concentration and strong interaction with the biological matrix, beta-carotene has never been observed by NMR in solid aqueous samples.In the present work, a model system has been developed for the detection and identification of beta-carotene in solid aqueous samples by 1H HR-MAS NMR. The efficiency of the model has led to the identification of beta-carotene in a raw vegetable matrix.

  14. PDK1 and HR46 Gene Homologs Tie Social Behavior to Ovary Signals

    PubMed Central

    Wang, Ying; Amdam, Gro V.; Rueppell, Olav; Wallrichs, Megan A.; Fondrk, M. Kim; Kaftanoglu, Osman; Page, Robert E.

    2009-01-01

    The genetic basis of division of labor in social insects is a central question in evolutionary and behavioral biology. The honey bee is a model for studying evolutionary behavioral genetics because of its well characterized age-correlated division of labor. After an initial period of within-nest tasks, 2–3 week-old worker bees begin foraging outside the nest. Individuals often specialize by biasing their foraging efforts toward collecting pollen or nectar. Efforts to explain the origins of foraging specialization suggest that division of labor between nectar and pollen foraging specialists is influenced by genes with effects on reproductive physiology. Quantitative trait loci (QTL) mapping of foraging behavior also reveals candidate genes for reproductive traits. Here, we address the linkage of reproductive anatomy to behavior, using backcross QTL analysis, behavioral and anatomical phenotyping, candidate gene expression studies, and backcross confirmation of gene-to-anatomical trait associations. Our data show for the first time that the activity of two positional candidate genes for behavior, PDK1 and HR46, have direct genetic relationships to ovary size, a central reproductive trait that correlates with the nectar and pollen foraging bias of workers. These findings implicate two genes that were not known previously to influence complex social behavior. Also, they outline how selection may have acted on gene networks that affect reproductive resource allocation and behavior to facilitate the evolution of social foraging in honey bees. PMID:19340296

  15. Ascertaining serum levels of trace elements in melanoma patients using PIXE and HR-ICPMS

    NASA Astrophysics Data System (ADS)

    Bernardes, S.; Tabacniks, M. H.; Santos, I. D. A. O.; Oliveira, A. F.; Shie, J. N.; Sarkis, J. E. S.; Oliveira, T.

    2014-01-01

    Melanoma is a serious and deadly form of skin cancer. However, patients' chances of survival and recovery are considerably increased when it is diagnosed and treated in its early stages. In this study, trace element concentrations in serum samples from patients with melanoma were measured using PIXE (Proton Induced X-ray Emission) and HR-ICPMS (High-Resolution Inductively Coupled Plasma Mass Spectrometry), with the purpose of correlating these concentrations with the disease. Blood samples from 30 melanoma patients and 116 healthy donors were collected at São Paulo Hospital (protocol CEP 1036/08 UNIFESP). Relevant clinical information on the patients has also been included in the statistical analysis. Analysis of the control group showed different P and Mg concentrations in individuals above and below 40 years of age. P, S, Ca, Cu and Zn concentrations in healthy individuals differed according to gender, highlighting the necessity to include age and gender variables in the case-control analysis. There were also differences in K, S, Ca and Se concentrations between the control and melanoma groups.

  16. TRMM Science Highlights and 3-hr Quasi-global Precipitation Estimates

    NASA Technical Reports Server (NTRS)

    Adler, Robert F.; Einaudi, Franco (Technical Monitor)

    2002-01-01

    The Tropical Rainfall Measuring Mission (TRMM) has completed more than four years in orbit. A summary of research highlights will be presented focusing on application of TRMM data to topics ranging over climate analysis, improving forecasts, precipitation processes and non-precipitation applications. One focus of the talk will be the quasi-global TRMM real-time merged rainfall analysis with 3-hr resolution, which uses TRMM to calibrate estimates from other polar-orbit and geosynchronous satellites. These rainfall estimates provide useful information for applications for assimilation into numerical models and for hydrological studies. The status of precipitation estimates from different TRMM instruments and algorithms will be described. Monthly surface rainfall estimates over the ocean based on different instruments on TRMM currently differ by 20% in overall mean. In addition, time changes in global ocean rainfall between El Nino and La Nina conditions show differences between the active and passive microwave products. Improved versions of algorithms will shortly resolve most of these differences. The TRMM rainfall estimates are intercompared among themselves and with other estimates, including those of the standard, monthly Global Precipitation Climatology Project (GPCP) analysis. A four-year TRMM rainfall climatology is presented, including anomaly fields related to the changing ENSO situation during the mission. The evolution of precipitation analysis incorporating Advanced Microwave Scanning Radiometer (AMSR) data on AQUA and ADEOS II and eventually data from the Global Precipitation Mission (GPM) will also be described.

  17. Conceptual Design of a Vertical Takeoff and Landing Unmanned Aerial Vehicle with 24-HR Endurance

    NASA Technical Reports Server (NTRS)

    Fredericks, William J.

    2010-01-01

    This paper describes a conceptual design study for a vertical takeoff and landing (VTOL) unmanned aerial vehicle (UAV) that is able to carry a 25-lb science payload for 24 hr and is able to land and take off at elevations as high as 15,000 ft without human intervention. In addition to the science payload, this vehicle must be able to carry a satellite communication system, and the vehicle must be able to be transported in a standard full-size pickup truck and assembled by only two operators. This project started with a brainstorming phase to devise possible vehicle configurations that might satisfy the requirements. A down select was performed to select a near-term solution and two advanced vehicle concepts that are better suited to the intent of the mission. Sensitivity analyses were also performed on the requirements and the technology levels to obtain a better understanding of the design space. This study found that within the study assumptions the mission is feasible; the selected concepts are recommended for further development.

  18. Laser damage of HR, AR-coatings, monolayers and bare surfaces at 1064 nm

    NASA Technical Reports Server (NTRS)

    Garnov, S. V.; Klimentov, S. M.; Said, A. A.; Soileau, M. J.

    1993-01-01

    Laser induced damage thresholds and morphologies were investigated in a variety of uncoated and coated surfaces, including monolayers and multi-layers of different chemical compositions. Both antireflective (AR) and highly reflective (HR) were tested. Testing was done at 1064 nm with 25 picosecond and 8 nanosecond YAG/Nd laser single pulses. Spot diameter in the experiments varied from 0.09 to 0.22 mm. The laser damage measurement procedure consisted of 1-on-1 (single laser pulse in the selected site) and N-on-1 experiments including repeated irradiation by pulses of the same fluence and subsequently raised from pulse to pulse fluence until damage occurred. The highest picosecond damage thresholds of commercially available coatings averaged 12 - 14 J/sq cm, 50 percent less than thresholds obtained in bare fused silica. Some coatings and bare surfaces revealed a palpable preconditioning effect (an increase in threshold of 1.2 to 1.8 times). Picosecond and nanosecond data were compared to draw conclusions about pulse width dependence. An attempt was made to classify damage morphologies according to the type of coating, class of irradiating, and damage level.

  19. The variable Herbig Ae Star HR 5999. X - Its photometric 'pulse-shaped' variability

    NASA Technical Reports Server (NTRS)

    Perez, M. R.; Webb, J. R.; The, P. S.

    1992-01-01

    We present additional photometric observations (Stromgren y filter) of the Herbig Ae Star HR 5999. This new set of data, composed of 282 data points covering April 1983 to August 1989, was used in conjunction with the 362 data points compiled by Baade and Stahl (1989). Our aim was to detect single or multiple periods in the integrated set of data spanning nearly 20 yr. Through the use of series analysis techniques, and by removing any linear component present in the raw data, we were able to detect weak peaks in the power spectra (in the order of intensity the strongest peaks are at 301 and 113 d) which were not self-evident in the phase diagrams. The overall picture of the data shows a small linear component, which is more noticeable in the new set of data, indicating that the recent maxima appear brighter. By a detailed analysis of the full light curve we were able to detect the presence of well-defined 'pulses' or bursts. Further Gaussian fits of these bursts indicated that the pulses are relatively rapid, of the order of 10 d, with some of them being closely spaced. No periodicity was found for the pulses. A possible explanation of these aperiodic outbursts is that they detect a flow of matter accompanied by magnetic field disturbances originated from the interior of the star, unlike those originating externally such as binary perturbations, which tend to be periodic.

  20. TRANSITS AND OCCULTATIONS OF AN EARTH-SIZED PLANET IN AN 8.5 hr ORBIT

    SciTech Connect

    Sanchis-Ojeda, Roberto; Rappaport, Saul; Winn, Joshua N.; Levine, Alan; Kotson, Michael C.; Latham, David W.; Buchhave, Lars A. E-mail: sar@mit.edu E-mail: aml@space.mit.edu

    2013-09-01

    We report the discovery of an Earth-sized planet (1.16 {+-} 0.19 R{sub Circled-Plus }) in an 8.5 hr orbit around a late G-type star (KIC 8435766, Kepler-xx). The object was identified in a search for short-period planets in the Kepler database and confirmed to be a transiting planet (as opposed to an eclipsing stellar system) through the absence of ellipsoidal light variations or substantial radial-velocity variations. The unusually short orbital period and the relative brightness of the host star (m{sub Kep} = 11.5) enable robust detections of the changing illumination of the visible hemisphere of the planet, as well as the occultations of the planet by the star. We interpret these signals as representing a combination of reflected and reprocessed light, with the highest planet dayside temperature in the range of 2300 K-3100 K. Follow-up spectroscopy combined with finer sampling photometric observations will further pin down the system parameters and may even yield the mass of the planet.

  1. Images of the Extended Outer Regions of the Debris Ring around HR 4796 A

    NASA Astrophysics Data System (ADS)

    Thalmann, C.; Janson, M.; Buenzli, E.; Brandt, T. D.; Wisniewski, J. P.; Moro-Martín, A.; Usuda, T.; Schneider, G.; Carson, J.; McElwain, M. W.; Grady, C. A.; Goto, M.; Abe, L.; Brandner, W.; Dominik, C.; Egner, S.; Feldt, M.; Fukue, T.; Golota, T.; Guyon, O.; Hashimoto, J.; Hayano, Y.; Hayashi, M.; Hayashi, S.; Henning, T.; Hodapp, K. W.; Ishii, M.; Iye, M.; Kandori, R.; Knapp, G. R.; Kudo, T.; Kusakabe, N.; Kuzuhara, M.; Matsuo, T.; Miyama, S.; Morino, J.-I.; Nishimura, T.; Pyo, T.-S.; Serabyn, E.; Suto, H.; Suzuki, R.; Takahashi, Y. H.; Takami, M.; Takato, N.; Terada, H.; Tomono, D.; Turner, E. L.; Watanabe, M.; Yamada, T.; Takami, H.; Tamura, M.

    2011-12-01

    We present high-contrast images of HR 4796 A taken with Subaru/HiCIAO in the H band, resolving the debris disk in scattered light. The application of specialized angular differential imaging methods allows us to trace the inner edge of the disk with high precision and reveals a pair of "streamers" extending radially outward from the ansae. Using a simple disk model with a power-law surface brightness profile, we demonstrate that the observed streamers can be understood as part of the smoothly tapered outer boundary of the debris disk, which is most visible at the ansae. Our observations are consistent with the expected result of a narrow planetesimal ring being ground up in a collisional cascade, yielding dust with a wide range of grain sizes. Radiation forces leave large grains in the ring and push smaller grains onto elliptical or even hyperbolic trajectories. We measure and characterize the disk's surface brightness profile, and confirm the previously suspected offset of the disk's center from the star's position along the ring's major axis. Furthermore, we present first evidence for an offset along the minor axis. Such offsets are commonly viewed as signposts for the presence of unseen planets within a disk's cavity. Our images also offer new constraints on the presence of companions down to the planetary mass regime (~9 M Jup at 0farcs5, ~3 M Jup at 1''). Based on data collected at the Subaru Telescope, which is operated by the National Astronomical Observatory of Japan.

  2. Images of the Extended Outer Regions of the Debris Ring around HR 4796 A

    NASA Technical Reports Server (NTRS)

    Thalmann, C.; Janson, M.; Buenzli, E.; Brandt, T. D.; Wisniewski, J. P.; Moro-Martin, A.; Usuda, T.; Schneider, G.; Carson, J.; McElwain, M. W.; Grady, C. A.; Goto, M.; Abe, L.; Brandner, W.; Dominik, C.; Egner, S.; Feldt, M.; Fukue, T.; Golota, T.; Guyon, O.; Hashimoto, J.; Hayano, Y.; Hayashi, M.; Hayashi, S.; Serabyn, E.

    2012-01-01

    We present high-contrast images of HR 4796 A taken with Subaru/HiCIAO in H-band, resolving the debris disk in scattered light. The application of specialized angular differential imaging methods (ADI) allows us to trace the inner edge of the disk with high precision, and reveals a pair of "streamers" extending radially outwards from the ansae. Using a simple disk model with a power-law surface brightness profile, we demonstrate that the observed streamers can be understood as part of the smoothly tapered outer boundary of the debris disk, which is most visible at the ansae. Our observations are consistent with the expected result of a narrow planetesimal ring being ground up in a collisional cascade, yielding dust with a wide range of grain sizes. Radiation forces leave large grains in the ring and push smaller grains onto elliptical, or even hyperbolic trajectories. We measure and characterize the disk's surface brightness profile, and confirm the previously suspected offset of the disk's center from the star's position along the ring's major axis. Furthermore, we present first evidence for an offset along the minor axis. Such offsets are commonly viewed as signposts for the presence of unseen planets within a disk's cavity. Our images also offer new constraints on the presence of companions down to the planetary mass regime (approx 9 M(sub Jup) at 0".5, approx 3 M(sub Jup) at 1").

  3. Investigation of HV/HR-CMOS technology for the ATLAS Phase-II Strip Tracker Upgrade

    NASA Astrophysics Data System (ADS)

    Fadeyev, V.; Galloway, Z.; Grabas, H.; Grillo, A. A.; Liang, Z.; Martinez-Mckinney, F.; Seiden, A.; Volk, J.; Affolder, A.; Buckland, M.; Meng, L.; Arndt, K.; Bortoletto, D.; Huffman, T.; John, J.; McMahon, S.; Nickerson, R.; Phillips, P.; Plackett, R.; Shipsey, I.; Vigani, L.; Bates, R.; Blue, A.; Buttar, C.; Kanisauskas, K.; Maneuski, D.; Benoit, M.; Di Bello, F.; Caragiulo, P.; Dragone, A.; Grenier, P.; Kenney, C.; Rubbo, F.; Segal, J.; Su, D.; Tamma, C.; Das, D.; Dopke, J.; Turchetta, R.; Wilson, F.; Worm, S.; Ehrler, F.; Peric, I.; Gregor, I. M.; Stanitzki, M.; Hoeferkamp, M.; Seidel, S.; Hommels, L. B. A.; Kramberger, G.; Mandić, I.; Mikuž, M.; Muenstermann, D.; Wang, R.; Zhang, J.; Warren, M.; Song, W.; Xiu, Q.; Zhu, H.

    2016-09-01

    ATLAS has formed strip CMOS project to study the use of CMOS MAPS devices as silicon strip sensors for the Phase-II Strip Tracker Upgrade. This choice of sensors promises several advantages over the conventional baseline design, such as better resolution, less material in the tracking volume, and faster construction speed. At the same time, many design features of the sensors are driven by the requirement of minimizing the impact on the rest of the detector. Hence the target devices feature long pixels which are grouped to form a virtual strip with binary-encoded z position. The key performance aspects are radiation hardness compatibility with HL-LHC environment, as well as extraction of the full hit position with full-reticle readout architecture. To date, several test chips have been submitted using two different CMOS technologies. The AMS 350 nm is a high voltage CMOS process (HV-CMOS), that features the sensor bias of up to 120 V. The TowerJazz 180 nm high resistivity CMOS process (HR-CMOS) uses a high resistivity epitaxial layer to provide the depletion region on top of the substrate. We have evaluated passive pixel performance, and charge collection projections. The results strongly support the radiation tolerance of these devices to radiation dose of the HL-LHC in the strip tracker region. We also describe design features for the next chip submission that are motivated by our technology evaluation.

  4. Evidence for cross-linking in tomato cutin using HR-MAS NMR spectroscopy.

    PubMed

    Deshmukh, Ashish P; Simpson, André J; Hatcher, Patrick G

    2003-11-01

    Cutin is a polyester biopolymer component of plant leaf and fruit cuticles, most often associated with waxes and cuticular polysaccharides, and sometimes with another aliphatic biopolymer called cutan. Insolubility of these cuticular biopolymers has made it difficult to apply traditional analytical techniques for structure determination, because most techniques providing molecular level details require solubility. By using the relatively new technique of one and two-dimensional high-resolution magic angle spinning (HR-MAS) NMR spectroscopy, with added information from solid-state 13C NMR spectroscopy, detailed through-bond connectivities and assignments are made for cutin from Lycopersicon esculentum (tomato) fruit. Based on the data obtained, tomato cutin is found to be predominantly an aliphatic polyester with some olefinic and aromatic moieties, consistent with previous studies that employed various degradative approaches. Aside from esters, there are free primary and secondary alcohol groups, as well as free fatty acids. A significant finding is the presence of alpha-branched fatty acids/esters. Mid-chain hydroxyls appear to be generally unesterified, but esters of mid-chain hydroxyls have been identified. The alpha-branched fatty acids/esters and esters of mid-chain hydroxyls could point towards cross-linking.

  5. A wearable ECG-HR detector and its application to automatic assist-mode selection of an electrically assisted bicycle.

    PubMed

    Ueno, Akinori; Miyashita, Osamu; Yoshida, Toshiya; Yamamoto, Junichi; Lataire, Philippe

    2011-01-01

    Recently, an electrically assisted bicycle has been widely used in daily life and becomes very popular. The user selects the stepwise assist-mode to determine the assistive torque for pleasurable running. From the viewpoint of improvement of health by exercise, the electrically assisted bicycle can be an exercise machine like a treadmill. The heart rate (HR) is regarded as an indication of exercise load. This paper presents an automatic assist-mode selection system based on the HR of the bicycle user. The HR is obtained from the R-waves measured by the proposed wearable electrocardiograph on the user. The mode-selection system is simply implemented by a personal computer, USB-connected interface, and some electronic switching circuits. The running experiments confirm that the proposed assist-mode selection method has practicability.

  6. miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

    SciTech Connect

    Liu, Shikai; Song, Lili Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

    2015-04-17

    Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1.

  7. Family Adjustment Measure: Scale Construction and Validation

    ERIC Educational Resources Information Center

    Daire, Andrew P.; Dominguez, Vanessa N.; Carlson, Ryan G.; Case-Pease, Jenene

    2014-01-01

    We administered the Family Adjustment Measure to 368 parents of children with special needs to identify positive adjustment. We randomly split the sample to conduct exploratory factor analysis ("n" = 194) and confirmatory factor analysis ("n" = 174). Results indicated four possible subscales and that explain 51% of the variance.

  8. 49 CFR 630.11 - Data adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Data adjustments. 630.11 Section 630.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.11 Data adjustments. Errors in the data used...

  9. 49 CFR 630.11 - Data adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Data adjustments. 630.11 Section 630.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.11 Data adjustments. Errors in the data used...

  10. 49 CFR 630.11 - Data adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Data adjustments. 630.11 Section 630.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.11 Data adjustments. Errors in the data used...

  11. 49 CFR 630.11 - Data adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Data adjustments. 630.11 Section 630.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.11 Data adjustments. Errors in the data used...

  12. 49 CFR 630.11 - Data adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Data adjustments. 630.11 Section 630.11 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.11 Data adjustments. Errors in the data used...

  13. Parenting Styles and Adjustment in Gifted Children

    ERIC Educational Resources Information Center

    Pilarinos, Vassiliki; Solomon, C. R.

    2017-01-01

    The present study examined the relationship between parenting styles and the psychosocial adjustment of 48 children aged 7 to 11 years, each of whom had been identified as gifted on the basis of a score of 130 or above on the Wechsler Intelligence Scale for Children--Fourth Edition. Parenting styles and child psychosocial adjustment were measured…

  14. Ergonomically Adjustable School Furniture for Male Students

    ERIC Educational Resources Information Center

    Al-Saleh, Khalid S.; Ramadan, Mohamed Z.; Al-Ashaikh, Riyad A.

    2013-01-01

    The need for adjustability in school furniture, in order to accommodate the variation in anthropometric measures of different genders, cultures and ages is becoming increasingly important. Four chair-table combinations, different in dimensions, with adjustable chair seating heights and table heights were designed, manufactured and distributed to…

  15. Adjustable, Audible Continuity Tester For Delicate Circuits

    NASA Technical Reports Server (NTRS)

    Mcalister, William B.

    1988-01-01

    Unit adjustable to resistances up to 35 ohms. Adjustable, audible electrical-continuity tester gives audible indication. Used safely on circuit boards in which semiconductor components installed, and on complementary metal oxide/semiconductor integrated circuits. Tester compact and circuit simple. Built from inexpensive standard components.

  16. Adjustably Preloaded Quick-Release Pin

    NASA Technical Reports Server (NTRS)

    Reimers, Harold W.

    1992-01-01

    Modified adjustable-grip-length quick-release pin holds two bodies together. Threaded shaft of pin threaded in floating nut to pretension fastener. Pin connects and disconnects rapidly and adjusted to accommodate small differences between thicknesses of nominally identical sets of parts to be attached to each other.

  17. 78 FR 70080 - Market Dominant Price Adjustment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-22

    ... Market Dominant Price Adjustment AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The... market dominant products. The adjustments are scheduled to take effect January 26, 2014. This notice.... Ordering Paragraphs I. Overview A. Index-Based Price Changes for Market Dominant Classes of Mail...

  18. College Student Adjustment and Health Behaviors

    ERIC Educational Resources Information Center

    Hall, Lisa Anne

    2010-01-01

    This study explored the relationship between student adjustment theory and college student health behaviors. Specifically, this research examined first-year freshmen college student physical activity and nutrition behaviors and impact on adjustment to college (N = 37,564). The design for this study was a non-experimental "ex post facto"…

  19. 34 CFR 36.2 - Penalty adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Title IV of the HEA, which authorizes the Federal Family Education Loan Program $35,000. 20 U.S.C. 1094... 34 Education 1 2014-07-01 2014-07-01 false Penalty adjustment. 36.2 Section 36.2 Education Office of the Secretary, Department of Education ADJUSTMENT OF CIVIL MONETARY PENALTIES FOR INFLATION §...

  20. 28 CFR 11.7 - Salary adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Salary adjustments. 11.7 Section 11.7 Judicial Administration DEPARTMENT OF JUSTICE DEBT COLLECTION Administration of Debt Collection § 11.7 Salary adjustments. The following debts shall not be subject to the salary offset procedures of §...