Science.gov

Sample records for adjusted hr ahr

  1. An essential role for UBE2A/HR6A in learning and memory and mGLUR-dependent long-term depression.

    PubMed

    Bruinsma, Caroline F; Savelberg, Sanne M C; Kool, Martijn J; Jolfaei, Mehrnoush Aghadavoud; Van Woerden, Geeske M; Baarends, Willy M; Elgersma, Ype

    2016-01-01

    UBE2A deficiency syndrome (also known as X-linked intellectual disability type Nascimento) is an intellectual disability syndrome characterized by prominent dysmorphic features, impaired speech and often epilepsy. The syndrome is caused by Xq24 deletions encompassing the UBE2A (HR6A) gene or by intragenic UBE2A mutations. UBE2A encodes an E2 ubiquitin-conjugating enzyme involved in DNA repair and female fertility. A recent study in Drosophila showed that dUBE2A binds to the E3 ligase Parkin, which is required for mitochondrial function and responsible for juvenile Parkinson's disease. In addition, these studies showed impairments in synaptic transmission in dUBE2A mutant flies. However, a causal role of UBE2A in of cognitive deficits has not yet been established. Here, we show that Ube2a knockout mice have a major deficit in spatial learning tasks, whereas other tested phenotypes, including epilepsy and motor coordination, were normal. Results from electrophysiological measurements in the hippocampus showed no deficits in synaptic transmission nor in the ability to induce long-term synaptic potentiation. However, a small but significant deficit was observed in mGLUR-dependent long-term depression, a pathway previously implied in several other mouse models for neurodevelopmental disorders. Our results indicate a causal role of UBE2A in learning and mGLUR-dependent long-term depression, and further indicate that the Ube2a knockout mouse is a good model to study the molecular mechanisms underlying UBE2A deficiency syndrome. PMID:26476408

  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. 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…

  4. 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.

  5. AhR signalling and dioxin toxicity.

    PubMed

    Sorg, Olivier

    2014-10-15

    Dioxins are a family of molecules associated to several industrial accidents such as Ludwigshafen in 1953 or Seveso in 1976, to the Agent Orange used during the war of Vietnam, and more recently to the poisoning of the former president of Ukraine, Victor Yushchenko. These persistent organic pollutants are by-products of industrial activity and bind to an intracellular receptor, AhR, with a high potency. In humans, exposure to dioxins, in particular 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a cutaneous syndrome known as chloracne, consisting in the development of many small skin lesions (hamartoma), lasting for 2-5 years. Although TCDD has been classified by the WHO as a human carcinogen, its carcinogenic potential to humans is not clearly demonstrated. It was first believed that AhR activation accounted for most, if not all, biological properties of dioxins. However, certain AhR agonists found in vegetables do not induce chloracne, and other chemicals, in particular certain therapeutic agents, may induce a chloracne-like syndrome without activating AhR. It is time to rethink the mechanism of dioxin toxicity and analyse in more details the biological events following exposure to these compounds and other AhR agonists, some of which have a very different chemical structure than TCDD. In particular various food-containing AhR agonists are non-toxic and may on the contrary have beneficial properties to human health. PMID:24239782

  6. In vitro and in silico evaluation of transactivation potencies of avian AHR1 and AHR2 by endogenous ligands: Implications for the physiological role of avian AHR2.

    PubMed

    Kim, In-Sung; Hwang, Ji-Hee; Hirano, Masashi; Iwata, Hisato; Kim, Eun-Young

    2016-09-01

    Aryl hydrocarbon receptor (AHR) is well conserved from invertebrates to vertebrates, and it mediates the toxic effects of exogenous ligands, including dioxins. Recent studies reported that AHRs activated by endogenous ligands play critical roles in mammalian physiological homeostasis. Avian species possess at least two AHR isoforms (AHR1 and AHR2), which exhibit species- and isoform-specific transactivation potencies to exogenous ligands, whereas mammals possess a single AHR. To delineate the profiles and roles of endogenous ligands for avian AHR isoforms, we investigated in vitro transactivation potencies of avian AHRs (AHR1 and AHR2 from the jungle crow, Corvus macrorhynchos; common cormorant, Phalacrocorax carbo; and black-footed albatross, Phoebastria nigripes) treated with the endogenous tryptophan metabolites 6-formylindolo [3,2-b] carbazole (FICZ), l-kynurenine (l-Kyn), kynurenic acid (KYNA), and indoxyl sulfate (IS). Furthermore, we analyzed the binding mode of these ligands to each avian AHR isoform by in silico docking simulations. The EC50 of FICZ (0.009-0.032nM) was similar regardless of the species or isoform of AHR. The estimated in silico binding mode of FICZ to AHRs was well conserved in both isoforms. The transactivation potencies of avian AHRs to other tryptophan metabolites were 10(5)-10(7) fold lower than those for FICZ, and EC50 values varied in a species- and isoform-specific manner. This was consistent with poor conservation of the binding mode of l-Kyn, KYNA, and IS predicted in in silico docking simulations. Our results suggest that in avian species, FICZ is the most potent endogenous AHR ligand, and that AHR1 and AHR2 are physiologically functional. PMID:27060260

  7. The aryl hydrocarbon receptor (AHR) transcription factor regulates megakaryocytic polyploidization

    PubMed Central

    Lindsey, Stephan; T. Papoutsakis, Eleftherios

    2012-01-01

    Summary We propose that the aryl hydrocarbon receptor (AHR) is a novel transcriptional regulator of megakaryopoietic polyploidization. Functional evidence was obtained that AHR impacts in vivo megakaryocytic differentiation and maturation; compared to wild-type mice, AHR-null mice had lower platelet counts, fewer numbers of newly synthesized platelets, increased bleeding times and lower-ploidy megakaryocytes (Mks). AHR mRNA increased 3·6-fold during ex vivo megakaryocytic differentiation, but reduced or remained constant during parallel isogenic granulocytic or erythroid differentiation. We interrogated the role of AHR in megakaryopoiesis using a validated Mk model of megakaryopoiesis, the human megakaryoblastic leukaemia CHRF cell line. Upon CHRF Mk differentiation, AHR mRNA and protein levels increased, AHR protein shifted from the cytoplasm to the nucleus and AHR binding to its consensus DNA binding sequence increased. Protein and mRNA levels of the AHR transcriptional target HES1 also increased. Mk differentiation of CHRF cells where AHR or HES1 was knocked-down using RNAi resulted in lower ploidy distributions and cells that were incapable of reaching ploidy classes ≥16n. AHR knockdown also resulted in increased DNA synthesis of lower ploidy cells, without impacting apoptosis. Together, these data support a role for AHR in Mk polyploidization and in vivo platelet function, and warrant further detailed investigations. PMID:21226706

  8. Immunological Relevance of the Coevolution of IDO1 and AHR

    PubMed Central

    Jaronen, Merja; Quintana, Francisco J.

    2014-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified because of its role in controlling the cellular response to environmental molecules. More recently, AHR has been shown to play a crucial role in controlling innate and adaptive immune responses through several mechanisms, one of which is the regulation of tryptophan metabolism. Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate-limiting enzymes in the tryptophan catabolism and play important roles in the regulation of the immunity. Moreover, AHR and IDO/TDO are closely interconnected: AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an AHR agonist. In this review, we propose to examine the relationship between AHR and IDO/TDO and its relevance for the regulation of the immune response in health and disease. PMID:25368620

  9. 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...

  10. AHR signaling in prostate growth, morphogenesis, and disease

    PubMed Central

    Vezina, Chad M.; Lin, Tien-Min; Peterson, Richard E.

    2010-01-01

    Most evidence of aryl hydrocarbon receptor (AHR) signaling in prostate growth, morphogenesis, and disease stems from research using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pharmacologically activate the AHR at various stages of development. This review discusses effects of TCDD on prostate morphogenesis and highlights interactions between AHR and other signaling pathways during normal and aberrant prostate growth. Although AHR signaling modulates estrogen and androgen signaling in other tissues, crosstalk between these steroid hormone receptors and AHR signaling cannot account for actions of TCDD on prostate morphogenesis. Instead, the AHR appears to act within a cooperative framework of developmental signals to regulate timing and patterning of prostate growth. Inappropriate activation of AHR signaling as a result of early life TCDD exposure disrupts the balance of these signals, impairs prostate morphogenesis, and has an imprinting effect on the developing prostate that predisposes to prostate disease in adulthood. Mechanisms of AHR signaling in prostate growth and disease are only beginning to be unraveled and recent studies have revealed its interactions with WNT5A, retinoic acid, fibroblast growth factor 10, and vascular endothelial growth factor signaling pathways. PMID:18977204

  11. 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.

  12. AhR sensing of bacterial pigments regulates antibacterial defence.

    PubMed

    Moura-Alves, Pedro; Faé, Kellen; Houthuys, Erica; Dorhoi, Anca; Kreuchwig, Annika; Furkert, Jens; Barison, Nicola; Diehl, Anne; Munder, Antje; Constant, Patricia; Skrahina, Tatsiana; Guhlich-Bornhof, Ute; Klemm, Marion; Koehler, Anne-Britta; Bandermann, Silke; Goosmann, Christian; Mollenkopf, Hans-Joachim; Hurwitz, Robert; Brinkmann, Volker; Fillatreau, Simon; Daffe, Mamadou; Tümmler, Burkhard; Kolbe, Michael; Oschkinat, Hartmut; Krause, Gerd; Kaufmann, Stefan H E

    2014-08-28

    The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production. The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns. PMID:25119038

  13. 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.

  14. 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

  15. Behavioral Rhythmicity of Mice Lacking AhR and Attenuation of Light-induced Phase Shift by 2,3,7,8-Tetracholordibenzo-p-dioxin

    PubMed Central

    Mukai, Motoko; Lin, Tien-Min; Peterson, Richard E.; Cooke, Paul S.; Tischkau, Shelley A.

    2008-01-01

    Transcription factors belonging to the Per/Arnt/Sim (PAS) domain family are highly conserved and many are involved in circadian rhythm regulation. One member of this family, aryl hydrocarbon receptor (AhR), is an orphan receptor whose physiological role is unknown. Recent findings have led to the hypothesis that AhR has a role in circadian rhythm, which is the focus of the present investigation. First, time-of-day dependent mRNA expression of AhR and its signaling target, cytochrome p4501A1 (Cyp1a1) was determined in C57BL/6J mice by quantitative RT-PCR. Circadian expression of AhR and Cyp1a1 was observed both in the suprachiasmatic nucleus (SCN) and liver. Next, the circadian phenotype of mice lacking AhR (AhRKO) was investigated using behavioral monitoring. Intact AhRKO mice had robust circadian rhythmicity with a similar tau under constant conditions compared to wild-type mice, but a significant difference in tau was observed between genotypes in ovariectomized female mice. Time to re-entrainment following 6-h advances or delays of the light/dark cycle was not significantly different between genotypes. However, mice exposed to the AhR agonist 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD, 1 μg/kg BW) displayed decreased phase shifts in response to light and had altered expression of Per1 and Bmal1. These results suggest that chronic activation of AhR may affect the ability of the circadian timekeeping system to adjust to alterations in environmental lighting by affecting canonical clock genes. Further studies are necessary to decipher the mechanism of how AhR agonists could disrupt light-induced phase shifts. If AhR does have a role in circadian rhythm, it may share redundant roles with other PAS domain proteins and/or the role of AhR may not be exhibited in the behavioral activity rhythm, but could be important elsewhere in the peripheral circadian system. PMID:18487412

  16. 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…

  17. Cardiac myocyte-specific AHR activation phenocopies TCDD-induced toxicity in zebrafish.

    PubMed

    Lanham, Kevin A; Plavicki, Jessica; Peterson, Richard E; Heideman, Warren

    2014-09-01

    Exposure of zebrafish embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the zebrafish aryl hydrocarbon receptor 2 (AHR) to produce developmental and cardiovascular toxicity. AHR is found in the heart; however, AHR activation by TCDD is not confined to the heart and occurs throughout the organism. In order to understand the cause of cardiotoxicity, we constructed a constitutively active AHR (caAHR) based on the zebrafish AHR2 and expressed it specifically in cardiomyocytes. We show that AHR activation within the cardiomyocytes can account for the heart failure induced by TCDD. Expression of the caAHR within the heart produced cardiac malformations, loss of circulation, and pericardial edema. The heart-specific activation of AHR reproduced several other well-characterized endpoints of TCDD toxicity outside of the cardiovascular system, including defects in swim bladder and craniofacial development. This work identifies a single cellular site of TCDD action, the myocardial cell, that can account for the severe cardiovascular collapse observed following early life stage exposure to TCDD, and contributes to other forms of toxicity. PMID:25037585

  18. Cardiac Myocyte-Specific AHR Activation Phenocopies TCDD-Induced Toxicity in Zebrafish

    PubMed Central

    Lanham, Kevin A.; Plavicki, Jessica; Peterson, Richard E.; Heideman, Warren

    2014-01-01

    Exposure of zebrafish embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the zebrafish aryl hydrocarbon receptor 2 (AHR) to produce developmental and cardiovascular toxicity. AHR is found in the heart; however, AHR activation by TCDD is not confined to the heart and occurs throughout the organism. In order to understand the cause of cardiotoxicity, we constructed a constitutively active AHR (caAHR) based on the zebrafish AHR2 and expressed it specifically in cardiomyocytes. We show that AHR activation within the cardiomyocytes can account for the heart failure induced by TCDD. Expression of the caAHR within the heart produced cardiac malformations, loss of circulation, and pericardial edema. The heart-specific activation of AHR reproduced several other well-characterized endpoints of TCDD toxicity outside of the cardiovascular system, including defects in swim bladder and craniofacial development. This work identifies a single cellular site of TCDD action, the myocardial cell, that can account for the severe cardiovascular collapse observed following early life stage exposure to TCDD, and contributes to other forms of toxicity. PMID:25037585

  19. 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.

  20. Molecular and functional characterization of a novel aryl hydrocarbon receptor isoform, AHR1β, in the chicken (Gallus gallus).

    PubMed

    Lee, Jin-Seon; Iwabuchi, Kohei; Nomaru, Koji; Nagahama, Nobumasa; Kim, Eun-Young; Iwata, Hisato

    2013-12-01

    Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause toxic effects through activation of the aryl hydrocarbon receptor (AHR)-mediated signaling pathway. Our previous studies have investigated the function of 2 AHR isoforms (AHR1 and AHR2) in avian species and identified a third AHR in the chicken (Gallus gallus) genome. Knowledge of multiple avian AHRs is indispensable to understand molecular mechanisms of AHR-mediated toxic effects and establish risk assessment framework for environmental AHR ligands in avian species. In this study, we successfully isolated a third novel AHR1-like cDNA from chicken and designated it as chicken AHR1 beta (ckAHR1β). The mRNA expression of ckAHR1β was primarily detected in the liver, and the hepatic protein expression was confirmed by Western blotting. Although mRNA expression of ckAHR1β was not altered by in ovo TCDD exposure, ckAHR1β exhibited specific binding to [(3)H]TCDD, TCDD-dependent nuclear translocation, and interaction with xenobiotic responsive elements (XREs) and AHR nuclear translocators (ARNTs). In vitro XRE-driven reporter gene assays revealed ckAHR1β-mediated transactivation of TCDD in a dose-dependent manner, showing a 10-fold reduced sensitivity (high EC50) compared with that mediated by ckAHR1. The mutation of Val(371) to Ser(371) in the ligand-binding domain of ckAHR1β shifted the TCDD-EC50 toward the value observed in ckAHR1, indicating the critical roles of the amino acid in sensitivity. Furthermore, ckAHR1β-mediated transactivation of TCDD was enhanced by 17β-estradiol (E2)-activated chicken estrogen receptor α (ckERα), suggesting a positive cross talk between ckERα and ckAHR1β signaling pathway. Both TCDD-induced and its enhanced activities by E2 were suppressed by the ckAHR repressor in a manner similar to ckAHR1. Collectively, our findings discover the role of ckAHR1β in dioxin toxicity and give an insight into the evolutionary history of the AHR signaling pathway. PMID:23997109

  1. HR Public meeting

    ScienceCinema

    None

    2011-10-06

    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.

  2. 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.

  3. 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.

  4. The aryl hydrocarbon receptor (AhR) mediates resistance to apoptosis induced in breast cancer cells.

    PubMed

    Bekki, Kanae; Vogel, Helena; Li, Wen; Ito, Tomohiro; Sweeney, Colleen; Haarmann-Stemmann, Thomas; Matsumura, Fumio; Vogel, Christoph F A

    2015-05-01

    The aryl hydrocarbon receptor (AhR) is well known as a ligand binding transcription factor regulating various biological effects. Previously we have shown that long-term exposure to estrogen in breast cancer cells caused not only down regulation of estrogen receptor (ER) but also overexpression of AhR. The AhR interacts with several cell signaling pathways associated with induction of tyrosine kinases, cytokines and growth factors which may support the survival roles of AhR escaping from apoptosis elicited by a variety of apoptosis inducing agents in breast cancer. In this study, we studied the anti-apoptotic role of AhR in different breast cancer cells when apoptosis was induced by exposure to UV light and chemotherapeutic agents. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in AhR overexpressing breast cancer cells effectively suppressed the apoptotic response induced by UV-irradiation, doxorubicin, lapatinib and paclitaxel. The anti-apoptotic response of TCDD was uniformly antagonized by the treatment with 3'methoxy-4'nitroflavone (MNF), a specific antagonist of AhR. TCDD's survival action of apoptosis was accompanied with the induction of well-known inflammatory genes, such as cyclooxygenase-2 (COX-2) and NF-κB subunit RelB. Moreover, TCDD increased the activity of the immunosuppressive enzyme indoleamine 2, 3-dioxygenase (IDO), which metabolizes tryptophan to kynurenine (Kyn) and mediates tumor immunity. Kyn also acts as an AhR ligand like TCDD, and kyn induced an anti-apoptotic response in breast cancer cells. Accordingly, our present study suggests that AhR plays a pivotal role in the development of breast cancer via the suppression of apoptosis, and provides an idea that the use of AhR antagonists with chemotherapeutic agents may effectively synergize the elimination of breast cancer cells. PMID:25987214

  5. TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway.

    PubMed

    Pombo, Mónica; Lamé, Michael W; Walker, Naomi J; Huynh, Danh H; Tablin, Fern

    2015-05-19

    The role of the aryl hydrocarbon receptor (AhR) in hemostasis has recently gained increased attention. Here, we demonstrate, by qRT-PCR and western blot, that human platelets express both AhR mRNA and AhR protein. AhR protein levels increase in a dose dependent manner when incubated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole. Treatment of platelets with puromycin blocks increased AhR protein synthesis in the presence of AhR activators. Additionally, treatment of platelets with either activator results in phosphorylation of p38MAPK and cPLA2, two key signaling molecules in platelet activation pathways. Using the AhR competitive inhibitors alpha naphthoflavone and CH-223191, we show that phosphorylation of p38MAPK is AhR dependent. Further, inhibition of p38MAPK blocks downstream cPLA2 phosphorylation induced by TCDD or omeprazole. Treatment with AhR activators results in platelet priming, as demonstrated by increased platelet aggregation, which is inhibited by AhR antagonists. Our data support a model of the platelet AhR non-genomic pathway in which treatment with AhR activators results in increased expression of the AhR, phosphorylation of p38MAPK and cPLA2, leading to platelet priming in response to agonist. PMID:25797602

  6. Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders.

    PubMed

    Busbee, Philip B; Rouse, Michael; Nagarkatti, Mitzi; Nagarkatti, Prakash S

    2013-06-01

    The aim of this review is to discuss research involving ligands for the aryl hydrocarbon receptor (AhR) and their role in immunomodulation. While activation of the AhR is well known for its ability to regulate the biochemical and toxic effects of environmental chemicals, more recently an exciting discovery has been made indicating that AhR ligation can also regulate T-cell differentiation, specifically through activation of Foxp3(+) regulatory T cells (Tregs) and downregulation of the proinflammatory Th17 cells. Such findings have opened new avenues of research on the possibility of targeting the AhR to treat inflammatory and autoimmune diseases. Specifically, this review will discuss the current research involving natural and dietary AhR ligands. In addition, evidence indicating the potential use of these ligands in regulating inflammation in various diseases will be highlighted. The importance of the AhR in immunological processes can be illustrated by expression of this receptor on a majority of immune cell types. In addition, AhR signaling pathways have been reported to influence a number of genes responsible for mediating inflammation and other immune responses. As interest in the AhR and its ligands increases, it seems prudent to consolidate current research on the contributions of these ligands to immune regulation during the course of inflammatory diseases. PMID:23731446

  7. Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders

    PubMed Central

    Busbee, Philip B; Rouse, Michael; Nagarkatti, Mitzi; Nagarkatti, Prakash S

    2014-01-01

    The aim of this review is to discuss research involving ligands for the aryl hydrocarbon receptor (AhR) and their role in immunomodulation. While activation of the AhR is well known for its ability to regulate the biochemical and toxic effects of environmental chemicals, more recently an exciting discovery has been made indicating that AhR ligation can also regulate T-cell differentiation, specifically through activation of Foxp3+ regulatory T cells (Tregs) and downregulation of the proinflammatory Th17 cells. Such findings have opened new avenues of research on the possibility of targeting the AhR to treat inflammatory and autoimmune diseases. Specifically, this review will discuss the current research involving natural and dietary AhR ligands. In addition, evidence indicating the potential use of these ligands in regulating inflammation in various diseases will be highlighted. The importance of the AhR in immunological processes can be illustrated by expression of this receptor on a majority of immune cell types. In addition, AhR signaling pathways have been reported to influence a number of genes responsible for mediating inflammation and other immune responses. As interest in the AhR and its ligands increases, it seems prudent to consolidate current research on the contributions of these ligands to immune regulation during the course of inflammatory diseases. PMID:23731446

  8. 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

    ... Federal Aviation Administration Eighth Meeting: RTCA Special Committee 219: Attitude and Heading Reference...). ACTION: Notice of RTCA Special Committee 219: Attitude and Heading Reference Systems (AHRS). SUMMARY: The...: Attitude and Heading Reference Systems (AHRS). DATES: The meeting will be held January 24-26, 2012, from...

  9. 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... Heading Reference System (AHRS). DATES: The meeting will be held September 14-16, 2010 from 9 a.m. to 5...

  10. Potential protective mechanisms of aryl hydrocarbon receptor (AHR) signaling in benign prostatic hyperplasia.

    PubMed

    Mehta, Vatsal; Vezina, Chad M

    2011-01-01

    The aryl hydrocarbon receptor (AHR) is an evolutionarily conserved ligand activated transcription factor best known for its role in mediating toxic responses to dioxin-like environmental contaminants. However, AHR signaling has also emerged as an active participant in processes of normal development and disease progression. Here, we review the role of AHR signaling in prostate development and disease processes, with a particular emphasis on benign prostatic hyperplasia (BPH). Inappropriate AHR activation has recently been associated with a decreased risk of symptomatic BPH in humans and has been shown to impair prostate development and disrupt endocrine signaling in rodents. We highlight known physiological responses to AHR activation in prostate and other tissues and discuss potential mechanisms by which it may act in adult human prostate to protect against symptomatic BPH. PMID:21684673

  11. Accurate Orientation Estimation Using AHRS under Conditions of Magnetic Distortion

    PubMed Central

    Yadav, Nagesh; Bleakley, Chris

    2014-01-01

    Low cost, compact attitude heading reference systems (AHRS) are now being used to track human body movements in indoor environments by estimation of the 3D orientation of body segments. In many of these systems, heading estimation is achieved by monitoring the strength of the Earth's magnetic field. However, the Earth's magnetic field can be locally distorted due to the proximity of ferrous and/or magnetic objects. Herein, we propose a novel method for accurate 3D orientation estimation using an AHRS, comprised of an accelerometer, gyroscope and magnetometer, under conditions of magnetic field distortion. The system performs online detection and compensation for magnetic disturbances, due to, for example, the presence of ferrous objects. The magnetic distortions are detected by exploiting variations in magnetic dip angle, relative to the gravity vector, and in magnetic strength. We investigate and show the advantages of using both magnetic strength and magnetic dip angle for detecting the presence of magnetic distortions. The correction method is based on a particle filter, which performs the correction using an adaptive cost function and by adapting the variance during particle resampling, so as to place more emphasis on the results of dead reckoning of the gyroscope measurements and less on the magnetometer readings. The proposed method was tested in an indoor environment in the presence of various magnetic distortions and under various accelerations (up to 3 g). In the experiments, the proposed algorithm achieves <2° static peak-to-peak error and <5° dynamic peak-to-peak error, significantly outperforming previous methods. PMID:25347584

  12. 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:…

  13. 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...

  14. 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

  15. Estrogenic and AhR activities in dissolved phase and suspended solids from wastewater treatment plants.

    PubMed

    Dagnino, Sonia; Gomez, Elena; Picot, Bernadette; Cavaillès, Vincent; Casellas, Claude; Balaguer, Patrick; Fenet, Hélène

    2010-05-15

    The distribution of estrogen receptor (ERalpha) and Aryl Hydrocarbon Receptor (AhR) activities between the dissolved phase and suspended solids were investigated during wastewater treatment. Three wastewater treatment plants with different treatment technologies (waste stabilization ponds (WSPs), trickling filters (TFs) and activated sludge supplemented with a biofilter system (ASB)) were sampled. Estrogenic and AhR activities were detected in both phases in influents and effluents. Estrogenic and AhR activities in wastewater influents ranged from 41.8 to 79 ng/L E(2) Eq. and from 37.9 to 115.5 ng/L TCDD Eq. in the dissolved phase and from 5.5 to 88.6 ng/g E(2) Eq. and from 15 to 700 ng/g TCDD Eq. in the suspended solids. For both activities, WSP showed greater or similar removal efficiency than ASB and both were much more efficient than TF which had the lowest removal efficiency. Moreover, our data indicate that the efficiency of removal of ER and AhR activities from the suspended solid phase was mainly due to removal of suspended solids. Indeed, ER and AhR activities were detected in the effluent suspended solid phase indicating that suspended solids, which are usually not considered in these types of studies, contribute to environmental contamination by endocrine disrupting compounds and should therefore be routinely assessed for a better estimation of the ER and AhR activities released in the environment. PMID:20303573

  16. 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. PMID:25721496

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

    PubMed Central

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

    2015-01-01

    Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in 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 assays in recombinant cell lines derived from four different species, although significant species differences in relative potency was 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. Malassezia furfur produces an expanded collection of extremely potent naturally occurring AhR agonists, which produce their biological effects in a species-specific manner.1 PMID:25721496

  18. 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.

  19. 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.

  20. 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. PMID:26392334

  1. Companions to peculiar red giants: HR 363 and HR 1105

    NASA Technical Reports Server (NTRS)

    Ake, Thomas B., III; Johnson, Hollis R.; Perry, Benjamin F., Jr.

    1988-01-01

    Recent IUE observations of two Tc-deficient S-type peculiar red giants that are also spectroscopic binaries, HR 363 and HR 1105 are reported. A 675 min SWP exposure of HR 363 shows emission lines of O I 1304 and Si II 1812 and a trace of continuum. Compared to the M giants, the far UV flux may be relatively larger, indicating a possible contribution from a white dwarf companion, but no high temperature emission lines are seen to indicate that this is an interacting system where mass-transfer recently occurred. However, HR 1105 appears to have a highly variable UV companion. In 1982, no UV flux was discerned for this system, but by 1986 C IV was strong, increasing by a factor of 3 in 1987 with prominent lines of Si III, C III, O III, Si IV, and N V. Using orbital parameters, these observations are consistent with high activity occuring when the side of the S-star primary illuminated by the companion faces the Earth, but since the IUE data were taken over 3 orbits, a secular change in the UV component cannot be excluded.

  2. The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells.

    PubMed

    Ibabao, Christopher N; Bunaciu, Rodica P; Schaefer, Deanna M W; Yen, Andrew

    2015-01-01

    In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14(+)CD11b(+) monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47(phox). Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr. PMID:25941627

  3. 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

  4. 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…

  5. 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. PMID:17828839

  6. 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

  7. VizieR Online Data Catalog: HR 5341, HD 142070, HR 6967 & HR 8434 uvby phot. (Adelman, 2001)

    NASA Astrophysics Data System (ADS)

    Adelman, S. J.

    2001-01-01

    Differential Stroemgren uvby observations from the Four College Automated Photoelectric Telescope (FCAPT) are presented for the mCP stars HD 142070, HR 6967, and HR 8434 and the CP star HR 5341. The latter star is found to be constant. Improved periods were derived for HD 142070, 3.37189d, HR 6967, 3.91227d, and HR 8434, 1.43237d. Further observations of HD 142070 are needed to phase the magnetic data with the photometry, of HR 6967 to settle minor discrepancies between y and scaled Geneva V photometry, and of HR 8434 to resolve small discrepancies between two uvby photometric data sets. (5 data files).

  8. The Evolving Role of the Aryl Hydrocarbon Receptor (AHR) in the Normophysiology of Hematopoiesis

    PubMed Central

    Lindsey, Stephan; Papoutsakis, Eleftherios T.

    2012-01-01

    In addition to its role as a toxicological signal mediator, the Aryl Hydrocarbon Receptor (AHR) is also a transcription factor known to regulate cellular responses to oxidative stress and inflammation through transcriptional regulation of molecules involved in the signaling of nucear factor-erythroid 2-related factor-2 (Nrf2), p53 (TRP53), retinoblastoma (RB1), and NFκB. Recent research suggests that AHR activation of these signaling pathways may provide the molecular basis for understanding AHR’s evolving role in endogenous developmental functions during hematopoietic stem-cell maintenance and differentiation. Recent developments into the hematopoietic roles for AHR are reviewed, aiming to reconcile divergent findings as to the endogenous function of AHR in hematopoiesis. Potential mechanistic explanations for AHR’s involvement in hematopoietic differentiation are discussed, focusing on its known role as a cell cycle mediator and its interactions with Hypoxia-inducible transcription factor-1 alpha (HIF1-α). Understanding the physiological mechanisms of AHR activation and signaling have far reaching implications ranging from explaining the action of various toxicological agents to providing novel ways to expand stem cell populations ex vivo for use in transplant therapies. PMID:22628113

  9. Tryptamine serves as a proligand of the AhR transcriptional pathway whose activation is dependent of monoamine oxidases.

    PubMed

    Vikström Bergander, Linda; Cai, Wen; Klocke, Bernward; Seifert, Martin; Pongratz, Ingemar

    2012-09-01

    The function of the aryl hydrocarbon receptor (AhR) in mediating the biological effect to environmental pollutants is well established. However, accumulated evidence indicates a wide range of physiological and pathological functions mediated by the AhR, suggesting the existence of endogenous AhR ligand(s). The nature of an AhR ligand remain elusive; however, it is known that the AhR is activated by several compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin or the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole. In this study, we show that physiological concentrations of tryptamine (TA) lead to induction of cytochrome P4501A1 transcription through an AhR-dependent mechanism. In addition, we show that activation of the AhR by TA requires a functional monoamino oxidase system, suggesting that TA acts as an AhR proligand possibly by converting to a high-affinity AhR ligand. Taken together, we show a possible mechanism, through which AhR signaling is activated by endogenous conversion of TA involving monoamine oxidases. PMID:22865928

  10. 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

  11. Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands

    PubMed Central

    2010-01-01

    Background Two year cancer bioassays conducted by the National Toxicology Program have shown chronic exposure to dioxin-like compounds (DLCs) to lead to the development of both neoplastic and non-neoplastic lesions in the hepatic tissue of female Sprague Dawley rats. Most, if not all, of the hepatotoxic effects induced by DLC's are believed to involve the binding and activation of the transcription factor, the aryl hydrocarbon receptor (AhR). Toxicogenomics was implemented to identify genomic responses that may be contributing to the development of hepatotoxicity in rats. Results Through comparative analysis of time-course microarray data, unique hepatic gene expression signatures were identified for the DLCs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (100 ng/kg/day) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) (1000 ng/kg/day) and the non-DLC 2,2',4,4',5,5',-hexachlorobiphenyl (PCB153) (1000 μg/kg/day). A common time independent signature of 41 AhR genomic biomarkers was identified which exhibited at least a 2-fold change in expression following subchronic (13-wk) and chronic (52-wk) p.o. exposure to TCDD and PCB126, but not the non DLC, PCB153. Real time qPCR analysis validated that 30 of these genes also exhibited at least a 2-fold change in hepatic expression at 24 hr following a single exposure to TCDD (5 μg/kg, po). Phenotypic anchoring was conducted which identified forty-six genes that were differently expressed both following chronic p.o. exposure to DLCs and in previously reported studies of cholangiocarcinoma or hepatocellular adenoma. Conclusions Together these analyses provide a comprehensive description of the genomic responses which occur in rat hepatic tissue with exposure to AhR ligands and will help to isolate those genomic responses which are contributing to the hepatotoxicity observed with exposure to DLCs. In addition, the time independent gene expression signature of the AhR ligands may assist in identifying other agents with the potential

  12. 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. PMID:23081860

  13. Regulation of zebrafish CYP3A65 transcription by AHR2.

    PubMed

    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. PMID:23624173

  14. Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).

    PubMed

    Oshida, Keiyu; Vasani, Naresh; Thomas, Russell S; Applegate, Dawn; Gonzalez, Frank J; Aleksunes, Lauren M; Klaassen, Curtis D; Corton, J Christopher

    2015-10-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dioxin-like compounds (DLC) as well as some drugs and endogenous tryptophan metabolites. Short-term activation of AhR can lead to hepatocellular steatosis, and chronic activation can lead to liver cancer in mice and rats. Analytical approaches were developed to identify biosets in a genomic database in which AhR activity was altered. A set of 63 genes was identified (the AhR gene expression biomarker) that was dependent on AhR for regulation after exposure to TCDD or benzo[a]pyrene and includes the known AhR targets Cyp1a1 and Cyp1b1. A fold-change rank-based test (Running Fisher's test; p-value ≤ 10(-4)) was used to evaluate the similarity between the AhR biomarker and a test set of 37 and 41 biosets positive or negative, respectively for AhR activation. The test resulted in a balanced accuracy of 95%. The rank-based test was used to identify factors that activate or suppress AhR in an annotated mouse liver/mouse primary hepatocyte gene expression database of ∼ 1850 comparisons. In addition to the expected activation of AhR by TCDD and DLC, AhR was activated by AP20189 and phenformin. AhR was suppressed by phenobarbital and 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) in a constitutive activated receptor (CAR)-dependent manner and pregnenolone-16α-carbonitrile in a pregnane X receptor (PXR)-dependent manner. Inactivation of individual genes in nullizygous models led to AhR activation (Pxr, Ghrhr, Taf10) or suppression (Ahr, Ilst6st, Hnf1a). This study describes a novel screening strategy for identifying factors in mouse liver that perturb AhR in a gene expression compendium. PMID:26215100

  15. Species-Specific Differential AhR Expression Protects Human Neural Progenitor Cells against Developmental Neurotoxicity of PAHs

    PubMed Central

    Gassmann, Kathrin; Abel, Josef; Bothe, Hanno; Haarmann-Stemmann, Thomas; Merk, Hans F.; Quasthoff, Kim N.; Rockel, Thomas Dino; Schreiber, Timm; Fritsche, Ellen

    2010-01-01

    Background Because of their lipophilicity, persistent organic pollutants (POPs) cross the human placenta, possibly affecting central nervous system development. Most POPs are known aryl hydrocarbon receptor (AhR) ligands and activators of AhR signaling. Therefore, AhR activation has been suggested to cause developmental neurotoxicity (DNT). Objective We studied the effects of AhR ligands on basic processes of brain development in two comparative in vitro systems to determine whether AhR-activation is the underlying mechanism for reported DNT of POPs in humans. Methods We employed neurosphere cultures based on human neural progenitor cells (hNPCs) and wild-type and AhR-deficient mouse NPCs (mNPCs) and studied the effects of different AhR agonists [3-methylcholanthrene (3-MC), benzo(a)pyrene [B(a)P], and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] and an antagonist [3′-methoxy-4′-nitroflavone (MNF)] on neurosphere development. Moreover, we analyzed expression of AhR and genes involved in AhR signaling. Results In contrast to wild-type mNPCs, hNPCs and AhR-deficient mNPCs were insensitive to AhR agonism or antagonism. Although AhR modulation attenuated wild-type mNPC proliferation and migration, hNPCs and AhR-deficient mNPCs remained unaffected. Results also suggest that species-specific differences resulted from nonfunctional AhR signaling in hNPCs. Conclusion Our findings suggest that in contrast to wild-type mNPCs, hNPCs were protected against polycyclic aromatic hydrocarbon–induced DNT because of an absence of AhR. This difference may contribute to species-specific differences in sensitivity to POPs. PMID:20570779

  16. Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in developing red seabream (Pagrus major) embryo: an association of morphological deformities with AHR1, AHR2 and CYP1A expressions.

    PubMed

    Yamauchi, Masanobu; Kim, Eun-Young; Iwata, Hisato; Shima, Yasuhiro; Tanabe, Shinsuke

    2006-11-16

    The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is mainly mediated by the aryl hydrocarbon receptor (AHR), which regulates the multiple target genes including cytochrome P4501A (CYP1A). In general, bony fishes, which possess at least two distinct AHRs are one of the most sensitive vertebrates to TCDD in early life stage. However, the physiological and toxicological roles of piscine multiple AHRs are not fully understood, especially in marine fish. To understand which AHR is responsible for TCDD toxicity in a marine fish species, we characterized the early life stage toxicity related to the expression of AHRs and CYP1A in red seabream (Pagrus major). The embryos at 10h post-fertilization (hpf) were treated with 0-100 microg/L TCDD for 80 min waterborne exposure. TCDD dose-dependently elicited developmental toxicities including mortality, yolk sac edema, retarded body growth, spinal deformity, reduced heart rate, shortened snout, underdeveloped fin, heart, and lower jaw. Intriguingly, hemorrhage and pericardium edema, typical TCDD developmental defects noticed in other fish species, were not found in red seabream until test termination. The EC(egg)50s for yolk sac edema, underdeveloped fin, and spinal deformity were 170, 240, and 340 pg/g, respectively. The LC(egg)50 was 360 pg/g embryo, indicating that this species is one of the most sensitive fishes to TCDD toxicity. The expression levels of rsAHR1, rsAHR2 and CYP1A mRNAs were also determined in different developmental stages. The rsAHR2 mRNA expression dose-dependently increased following TCDD exposure, while rsAHR1 mRNA level was not altered. Level of rsAHR2 mRNA measured by two-step real-time PCR was 30 times higher than rsAHR1 in embryos treated with the highest dose. Temporal patterns of rsAHR2 and CYP1A mRNAs were similar in TCDD-treated embryos, representing a significant positive correlation between rsAHR2 and CYP1A mRNA levels, but not between rsAHR1 and CYP1A. In comparison of

  17. Metabolic control of type 1 regulatory (Tr1) cell differentiation by AHR and HIF1-α

    PubMed Central

    Mascanfroni, Ivan D.; Takenaka, Maisa C.; Yeste, Ada; Patel, Bonny; Wu, Yan; Kenison, Jessica E.; Siddiqui, Shafiuddin; Basso, Alexandre S.; Otterbein, Leo E.; Pardoll, Drew M.; Pan, Fan; Priel, Avner; Clish, Clary B.; Robson, Simon C.; Quintana, Francisco J.

    2015-01-01

    Our understanding of the pathways that regulate lymphocyte metabolism, as well as the effects of metabolism and its products on the immune response, is still limited. We report that a metabolic program controlled by the transcription factors hypoxia inducible factor-1α (HIF1-α) and aryl hydrocarbon receptor (AHR) supports the differentiation of type 1 regulatory (Tr1) cells. HIF1-α controls the early metabolic reprograming of Tr1 cells. At later time points, AHR promotes HIF1-α degradation and takes control of Tr1 cell metabolism. Extracellular adenosine triphosphate (eATP) and hypoxia, linked to inflammation, trigger AHR inactivation by HIF1-α and inhibit Tr1 cell differentiation. Conversely, CD39 promotes Tr1 cell differentiation by depleting eATP. CD39 also contributes to Tr1 suppressive activity by generating adenosine in cooperation with CD73 expressed by responder T cells and antigen presenting cells. These results suggest that HIF1-α and AHR integrate immunological, metabolic and environmental signals to regulate the immune response. PMID:26005855

  18. 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...

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

    PubMed Central

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

    2010-01-01

    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 β-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. PMID:20605646

  20. 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. PMID:24777823

  1. Aryl Hydrocarbon Receptor (AhR) Regulates Silica-Induced Inflammation But Not Fibrosis

    PubMed Central

    Beamer, Celine A.; Seaver, Benjamin P.; Shepherd, David M.

    2012-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is responsible for mediating a variety of pharmacological and toxicological effects caused by halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, recent evidence has revealed that the AhR also has numerous physiological roles aside from xenobiotic metabolism, including regulation of immune and inflammatory signaling as well as normal development and homeostasis of several organs. To investigate the role of the AhR in crystalline silica (SiO2)–induced inflammation and fibrosis, C57Bl/6 and AhR−/− mice were exposed to SiO2 or vehicle. Similarly, C57Bl/6 mice were exposed to SiO2 and TCDD either simultaneously or sequentially to assess whether AhR activation alters inflammation and fibrosis. SiO2-induced acute lung inflammation was more severe in AhR−/− mice; however, the fibrotic response of AhR−/− mice was attenuated compared with C57Bl/6 mice. In a model of chronic SiO2 exposure, AhR activation by TCDD in C57Bl/6 mice resulted in reduced inflammation; however, the fibrotic response was not affected. Bone marrow–derived macrophages (BMM) from AhR−/− mice also produced higher levels of cytokines and chemokines in response to SiO2. Analysis of gene expression revealed that BMM derived from AhR−/− mice exhibit increased levels of pro-interleukin (IL)-1β, IL-6, and Bcl-2, yet decreased levels of signal transducers and activators of transcription (STAT)2, STAT5a, and serpin B2 (Pai-2) in response to SiO2. PMID:22273745

  2. 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…

  3. AhR modulates the IL-22-producing cell proliferation/recruitment in imiquimod-induced psoriasis mouse model.

    PubMed

    Cochez, Perrine M; Michiels, Camille; Hendrickx, Emilie; Van Belle, Astrid B; Lemaire, Muriel M; Dauguet, Nicolas; Warnier, Guy; de Heusch, Magali; Togbe, Dieudonnée; Ryffel, Bernhard; Coulie, Pierre G; Renauld, Jean-Christophe; Dumoutier, Laure

    2016-06-01

    IL-22 has a detrimental role in skin inflammatory processes, for example in psoriasis. As transcription factor, AhR controls the IL-22 production by several cell types (i.e. Th17 cells). Here, we analyzed the role of Ahr in IL-22 production by immune cells in the inflamed skin, using an imiquimod-induced psoriasis mouse model. Our results indicate that IL-22 is expressed in the ear of imiquimod-treated Ahr(-/-) mice but less than in wild-type mice. We then studied the role of AhR on three cell populations known to produce IL-22 in the skin: γδ T cells, Th17 cells, and ILC3, and a novel IL-22-producing cell type identified in this setting: CD4(-) CD8(-) TCRβ(+) T cells. We showed that AhR is required for IL-22 production by Th17, but not by the three other cell types, in the imiquimod-treated ears. Moreover, AhR has a role in the recruitment of γδ T cells, ILC3, and CD4(-) CD8(-) TCRβ(+) T cells into the inflamed skin or in their local proliferation. Taken together, AhR has a direct role in IL-22 production by Th17 cells in the mouse ear skin, but not by γδ T cells, CD4(-) CD8(-) TCRβ(+) T cells and ILCs. PMID:27000947

  4. Malformation of certain brain blood vessels caused by TCDD activation of Ahr2/Arnt1 signaling in developing zebrafish

    PubMed Central

    Teraoka, Hiroki; Ogawa, Akira; Kubota, Akira; Stegeman, John J.; Peterson, Richard E.; Hiraga, Takeo

    2011-01-01

    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). The AHR also plays important roles in normal development in mice, and AHR-/- mice show abnormal development of vascular structures in various blood vessels. Our previous studies revealed that Ahr type 2 (Ahr2) activation by TCDD and β-naphthoflavone (BNF) caused a significant decrease in blood flow in the dorsal midbrain of zebrafish embryos. Here we report effects of TCDD exposure on the morphology of some blood vessels in the head of developing zebrafish. TCDD caused concentration-dependent anatomical rearrangements in the shape of the prosencephalic artery in zebrafish larvae. In contrast, no major vascular defects were recognized in the trunk and tail regions following exposure to TCDD at least at the concentrations used. Essentially, the same observations were also confirmed in BNF-exposed larvae. Knock-down of either Ahr2 or Ahr nuclear translocator type 1 (Arnt1) by morpholino oligonucleotides (MOs) protected larvae against abnormal shape of the prosencephalic artery caused by TCDD and BNF. On the other hand, knock-down of Ahr2 or Arnt1 in vehicle-exposed zebrafish larvae had no clear effect on morphology of the prosencephalic artery or trunk vessels. Ascorbic acid, an antioxidant, protected against the TCDD-induced decrease in blood flow through the prosencephalic artery, but not the abnormal morphological changes in the shape of this artery. These results indicate that activation of Ahr2/Arnt1 pathway by TCDD and BNF affects the shape of certain blood vessels in the brain of developing zebrafish. PMID:20554057

  5. Réunion publique HR

    ScienceCinema

    None

    2011-10-06

    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

  6. 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

  7. 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

  8. ROLE OF THE ARYL HYDROCARBON RECEPTOR (AHR) IN LUNG INFLAMMATION1

    PubMed Central

    Beamer, Celine A.; Shepherd, David M.

    2013-01-01

    Millions of individuals worldwide are afflicted with acute and chronic respiratory diseases, causing temporary and permanent disabilities and even death. Oftentimes, these diseases occur as a result of altered immune responses. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, acts as a regulator of mucosal barrier function and may influence immune responsiveness in the lungs through changes in gene expression, cell-cell adhesion, mucin production, and cytokine expression. This review updates the basic immunobiology of the AhR signaling pathway with regards to inflammatory lung diseases such as asthma, chronic obstructive pulmonary disorder, and silicosis following data in rodent models and humans. Finally, we address the therapeutic potential of targeting the in regulating inflammation during acute and chronic respiratory diseases. PMID:23963493

  9. 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.

  10. Down regulation of hepatic PPARalpha function by AhR ligand.

    PubMed

    Shaban, Zein; El-Shazly, Samir; Abdelhady, Shawky; Fattouh, Ibrahim; Muzandu, Kaampwe; Ishizuka, Mayumi; Kimura, Kazuhiro; Kazusaka, Akio; Fujita, Shoichi

    2004-11-01

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) and related compounds. Peroxisome proliferator activated receptor alpha (PPARalpha) is a nuclear receptor involved in the maintenance of lipid and glucose homeostasis. In this study we hypothesized that one of the possible mechanisms for the effect of TCDD and its related chemicals on fat metabolism could be through down regulation of PPARalpha functions. We treated Wistar rats with an AhR ligand, Sudan III (S.III), and/or PPARalpha ligand, Clofibric Acid (CA), for 3 days. We analysed the expression of one of the PPARalpha-target gene products, CYP4A protein and its mRNA. We also tested HepG2 cells with the afore-mentioned treatments and evaluated their effects on PPARalpha and RXRalpha protein. Treatment of Wistar rats with S.III was found to down regulates CYP4A protein expression and reduced its induction with CA. It also decreased mRNA expressions of CYP4A1, CYP4A2, CYP4A3 and PPARalpha. In HepG2 cells, PPARalpha and RXRalpha protein expression was decreased by S.III treatment in a dose dependent manner. Our results suggest that AhR has an inhibitory effect on PPARalpha function and a new pathway by which AhR ligands could disturb lipid metabolism. PMID:15585952

  11. 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

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

    PubMed

    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

  13. 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

  14. 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

  15. 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.

  16. 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

    2016-01-01

    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

  17. The dust debris around HR 4796

    NASA Technical Reports Server (NTRS)

    Jura, M.

    1991-01-01

    The IRAS data strongly suggest that there is dust debris around the main-sequence A star HR 4796. The optical depth of the dust cloud around HR 4796 is probably twice that around Beta Pic, the main-sequence star in the Bright Star Catalog which was previously thought to have the most opaque dust debris cloud.

  18. 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

  19. HR 4453 - An anomalously bright UV source

    NASA Technical Reports Server (NTRS)

    Polidan, R. S.; Oegerle, W. R.; Margon, B.

    1980-01-01

    Crawford et al. (1979) reported that HR 4453 has an anomalously large UV flux in the 1350-1600 A band. This paper reports results of the UV spectrophotometry of HR 4453 obtained with the Copernicus satellite. Portions of the spectrum from 1120 to 2660 A were scanned, but no stellar signal was detected in any wavelength interval. This result is consistent with both components of the binary being normal A2A stars. UV variability or a source other than HR 4453 must be invoked to explain the observations of Crawford et al.

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

    PubMed

    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 3000μg/kg at 19h after TCDD exposure and time points ranging from 1.5 to 384h after exposure to 100μg/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 ED50 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. PMID:24355419

  1. Adjustment disorder

    MedlinePlus

    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va: American Psychiatric Publishing. 2013. Powell AD. Grief, bereavement, and adjustment disorders. In: Stern TA, Rosenbaum ...

  2. Arylhydrocarbon receptor (AhR) activation in airway epithelial cells induces MUC5AC via reactive oxygen species (ROS) production.

    PubMed

    Chiba, Takahito; Uchi, Hiroshi; Tsuji, Gaku; Gondo, Hisaki; Moroi, Yoichi; Furue, Masutaka

    2011-02-01

    The dioxins and dioxin-like compounds in cigarette smoke regulate various immunological responses via the arylhydrocarbon receptor (AhR). These environmental toxicants are known to cause bronchitis, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Recent studies have demonstrated that AhR activation upregulates the expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) in the airway epithelial cell line. However, the mechanism for the production of mucin has not been clarified. In this study, we investigated the role and pathway of AhR in airway epithelial cells by using selective agonists and antagonists. After stimulation with or without benzopyrene (B[a]P), an AhR agonist, MUC5AC expression was measured by real-time RT-PCR. The mechanism of AhR-induced MUC5AC expression in airway epithelial cells was studied in terms of the production of cytokine and reactive oxygen species (ROS). Treatment with B[a]P increased ROS generation in NCI-H₂₉₂ cells. Furthermore, B[a]P-induced MUC5AC upregulation and mucin production were inhibited by AhR siRNA or the use of an antioxidative agent. These results suggest that the AhR-induced increase of mucin production is partially mediated by ROS generation. An antioxidant therapy approach may help to cure AhR-induced mucus hypersecretory diseases. PMID:20709182

  3. The Q-rich/PST domain of the AHR regulates both ligand-induced nuclear transport and nucleocytoplasmic shuttling

    PubMed Central

    Tkachenko, Anna; Henkler, Frank; Brinkmann, Joep; Sowada, Juliane; Genkinger, Doris; Kern, Christian; Tralau, Tewes; Luch, Andreas

    2016-01-01

    The aryl hydrocarbon receptor (AHR) shuttles continuously between cytoplasm and nucleus, unless ligand-binding triggers association with the AHR nuclear translocator (ARNT) and subsequent binding to cognate DNA motifs. We have now identified Val 647 as mandatory residue for export from the nucleus and AHR-function. This residue prevents inactivation of the receptor as a consequence of nuclear sequestration via constitutive import. Concomitantly mutants lacking this residue are exclusively localised in the nucleus. Although ligands accelerate nuclear import transiently, stable nuclear transition depends on a motif adjacent to Val 647 that comprises residues 650–661. Together, this defined region within the Q-rich domain regulates intracellular trafficking of the AHR in context of both nucleocytoplasmic shuttling and receptor activation. Nuclear export therefore depends on the previously characterised N-terminal NES and the newly identified motif that includes V647. Nucleocytoplasmic distribution of full-length human AHR is further affected by a section of the PST domain that shows sequence similarities with nuclear export signals. In concert, these motifs maintain a predominant cytoplasmic compartmentalisation, receptive for ligand binding. PMID:27535013

  4. The Q-rich/PST domain of the AHR regulates both ligand-induced nuclear transport and nucleocytoplasmic shuttling.

    PubMed

    Tkachenko, Anna; Henkler, Frank; Brinkmann, Joep; Sowada, Juliane; Genkinger, Doris; Kern, Christian; Tralau, Tewes; Luch, Andreas

    2016-01-01

    The aryl hydrocarbon receptor (AHR) shuttles continuously between cytoplasm and nucleus, unless ligand-binding triggers association with the AHR nuclear translocator (ARNT) and subsequent binding to cognate DNA motifs. We have now identified Val 647 as mandatory residue for export from the nucleus and AHR-function. This residue prevents inactivation of the receptor as a consequence of nuclear sequestration via constitutive import. Concomitantly mutants lacking this residue are exclusively localised in the nucleus. Although ligands accelerate nuclear import transiently, stable nuclear transition depends on a motif adjacent to Val 647 that comprises residues 650-661. Together, this defined region within the Q-rich domain regulates intracellular trafficking of the AHR in context of both nucleocytoplasmic shuttling and receptor activation. Nuclear export therefore depends on the previously characterised N-terminal NES and the newly identified motif that includes V647. Nucleocytoplasmic distribution of full-length human AHR is further affected by a section of the PST domain that shows sequence similarities with nuclear export signals. In concert, these motifs maintain a predominant cytoplasmic compartmentalisation, receptive for ligand binding. PMID:27535013

  5. 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. PMID:27329138

  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 . PMID:27234499

  7. Adjustable microforceps.

    PubMed

    Bao, J Y

    1991-04-01

    The commonly used microforceps have a much greater opening distance and spring resistance than needed. A piece of plastic ring or rubber band can be used to adjust the opening distance and reduce most of the spring resistance, making the user feel more comfortable and less fatigued. PMID:2051437

  8. 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.

  9. Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.

    PubMed

    Rentas, Stefan; Holzapfel, Nicholas T; Belew, Muluken S; Pratt, Gabriel A; Voisin, Veronique; Wilhelm, Brian T; Bader, Gary D; Yeo, Gene W; Hope, Kristin J

    2016-04-28

    Umbilical cord blood-derived haematopoietic stem cells (HSCs) are essential for many life-saving regenerative therapies. However, despite their advantages for transplantation, their clinical use is restricted because HSCs in cord blood are found only in small numbers. Small molecules that enhance haematopoietic stem and progenitor cell (HSPC) expansion in culture have been identified, but 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 circuitry that underpins the self-renewal of human HSCs will facilitate the development of targeted strategies that expand HSCs for regenerative therapies. Whereas transcription factor networks have been shown to influence the self-renewal and lineage decisions of human HSCs, the post-transcriptional mechanisms that guide HSC fate have not been closely investigated. Here we show that overexpression of the RNA-binding protein 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 show that MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signalling through post-transcriptional downregulation of canonical AHR pathway components in cord blood HSPCs. Our study gives mechanistic insight into RNA networks controlled by RNA-binding proteins that underlie self-renewal and provides evidence that manipulating such networks ex vivo can enhance the regenerative potential of human HSCs. PMID:27121842

  10. 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.

  11. 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

  12. AhR ligand Aminoflavone inhibits α6-integrin expression and breast cancer sphere-initiating capacity.

    PubMed

    Brantley, Eileen; Callero, Mariana A; Berardi, Damian E; Campbell, Petreena; Rowland, Leah; Zylstra, Dain; Amis, Louisa; Yee, Michael; Simian, Marina; Todaro, Laura; Loaiza-Perez, Andrea I; Soto, Ubaldo

    2016-06-28

    Traditional chemotherapies debulk tumors but fail to produce long-term clinical remissions due to their inability to eradicate tumor-initiating cells (TICs). This necessitates therapy with activity against the TIC niche. Αlpha6-integrin (α6-integrin) promotes TIC growth. In contrast, aryl hydrocarbon receptor (AhR) signaling activation impedes the formation of mammospheres (clusters of cells enriched for TICs). We investigated the ability of AhR agonist Aminoflavone (AF) and AF pro-drug (AFP464) to disrupt mammospheres derived from breast cancer cells and a M05 mammary mouse model of breast cancer respectively. We further examined the capacity of AF and AFP464 to exhibit anticancer activity and modulate the expression of 'stemness' genes including α6-integrin using immunofluorescence, flow cytometry and qRT-PCR analysis. AF disrupted mammospheres and prevented secondary mammosphere formation. In contrast, AF did not disrupt mammospheres derived from AhR ligand-unresponsive MCF-7 cells. AFP464 treatment suppressed M05 tumor growth and disrupted corresponding mammospheres. AF and AFP464 reduced the expression and percentage of cells that stained for 'stemness' markers including α6-integrin in vitro and in vivo respectively. These data suggest AFP464 thwarts bulk breast tumor and TIC growth via AhR agonist-mediated α6-integrin inhibition. PMID:26996297

  13. Journeys on the H-R diagram

    SciTech Connect

    Kaler, J.B.

    1988-05-01

    The evolution of various types of stars along the H-R diagram is discussed. Star birth and youth is addressed, and the events that occur due to core contraction, shell burning, and double-shell burning are described. The evolutionary courses of planetary nebulae, white dwarfs, and supernovas are examined.

  14. National Survey in Regard to HR 5.

    ERIC Educational Resources Information Center

    Pennsylvania State Dept. of Education, Harrisburg.

    Local Education Agency (LEA) administrators (principals and superintendents) and State Chapter 1 coordinators representing all 50 states were surveyed regarding their reactions to House Omnibus bill (HR 5), which would significantly change Chapter 1 programs. Over 3,600 school districts responded. The respondents were asked to indicate their level…

  15. 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

  16. 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. PMID:22874369

  17. 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

  18. 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.

  19. 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

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

    PubMed

    Ghotbaddini, Maryam; Powell, Joann B

    2015-07-01

    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

  1. 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

  2. HR 1225 - New observations and period search

    NASA Astrophysics Data System (ADS)

    DuPuy, D. L.; Collins, G.; Swingler, D. N.

    1982-02-01

    Four nights of photoelectric observations of the delta Scuti star HR 1225 have been obtained. The light curve has a variable amplitude envelope indicating that more than one period is present. A search for periodicities using the Jurkevich method and Fourier analysis suggests periods of 0.156 d and 0.097 d. A least-squares solution yields a fair fit to the data with these two periods. The Fourier transform suggests that three periods are present.

  3. 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.

  4. 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.

  5. 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.

  6. 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. PMID:26361555

  7. 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

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

    PubMed

    Litzenburger, Ulrike M; Opitz, Christiane A; 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

    2014-02-28

    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

  9. Benzo[a]pyrene, 3-methylcholanthrene and beta-naphthoflavone induce oxidative stress in hepatoma hepa 1c1c7 Cells by an AHR-dependent pathway.

    PubMed

    Elbekai, Reem H; Korashy, Hesham M; Wills, Kelly; Gharavi, Negar; El-Kadi, Ayman O S

    2004-11-01

    Polycyclic aromatic hydrocarbons have been shown to cause oxidative stress in vitro and in vivo in various animal models but the mechanisms by which these compounds produce oxidative stress are unknown. In the current study we have investigated the role of the aryl hydrocarbon receptor (AHR) in the production of reactive oxygen species (ROS) by its cognate ligands and the consequent effect on cyp1a1 activity, mRNA and protein expressions. For this purpose, Hepa 1c1c7 cells wild-type (WT) and C12 mutant cells, which are AHR-deficient, were incubated with increasing concentrations of the AHR-ligands, benzo[a]pyrene (B[a]P, 0.25-25 microM), 3-methylcholanthrene (3MC, 0.1-10 microM) and beta-naphthoflavone (betaNF, 1-50 microM). The studied AHR-ligands dose-dependently increased lipid peroxidation in WT but not in C12 cells. However, only B[a]P and betaNF, at the highest concentrations tested, significantly increased H2O2 production in WT but not C12 cells. The increase in lipid peroxidation and H2O2 production by AHR-ligands were accompanied by a decrease in the cyp1a1 catalytic activity but not mRNA or protein expressions, which were significantly induced in a dose-dependent manner by all AHR-ligands, suggesting a post-translational mechanism is involved in the decrease of cyp1a1 activity. The AHR-ligand-mediated decrease in cyp1a1 activity was reversed by the antioxidant N-acetylcysteine. Our results show that the AHR-ligands induce oxidative stress by an AHR-dependent pathway. PMID:15621696

  10. TCDD promoted EMT of hFPECs via AhR, which involved the activation of EGFR/ERK signaling.

    PubMed

    Gao, Zhan; Bu, Yongjun; Liu, Xiaozhuan; Wang, Xugang; Zhang, Guofu; Wang, Erhui; Ding, Shibin; Liu, Yongfeng; Shi, Ruling; Li, Qiaoyun; Fu, Jianhong; Yu, Zengli

    2016-05-01

    One critical step of second palatal fusion is the newly formed medial epithelia seam (MES) disintegration, which involves apoptosis, epithelial to mesenchymal transition (EMT), and cell migration. Although the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate at high rates, little is known about the effects of TCDD exposure on the fate of palatal epithelial cells. By using primary epithelial cells isolated from human fetal palatal shelves (hFPECs), we show that TCDD increased cell proliferation and EMT, as demonstrated by increased the epithelial markers (E-cadherin and cytokeratin14) and enhanced the mesenchymal markers (vimentin and fibronectin), but had no effect on cell migration and apoptosis. TCDD exposure led to a dose-dependent increase in Slug protein expression. Coimmunoprecipitation revealed that TCDD promoted AhR to form a protein complex with Slug. ChIP assay confirmed that TCDD exposure recruited AhR to the xenobiotic responsive element of Slug promoter. Knockdown of AhR by siRNA remarkably weakened TCDD-induced binding of AhR to the XRE promoter of slug, thereby suppressed TCDD-induced vimentin. Further experiment showed that TCDD stimulated EGFR phosphorylation did not influence the TGFβ3/Smad signaling; whereas TCDD increased phosphorylation of ERK1/2 and p38 with no effect on activation of JNK. By using varieties of inhibitors, we confirmed that TCDD promoted proliferation and EMT of hFPECs via activation of EGFR/ERK pathway. These data make a novel contribution to the molecular mechanism of cleft palate by TCDD. PMID:26971374

  11. Role of endocrine disrupting chemicals in the occurrence of benign uterine leiomyomata: special emphasis on AhR tissue levels.

    PubMed

    Bidgoli, Sepideh Arbabi; Khorasani, Hoda; Keihan, Heideh; Sadeghipour, Alireza; Mehdizadeh, Abolfazl

    2012-01-01

    Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors. PMID:23317198

  12. Khellin and Visnagin Differentially Modulate AHR Signaling and Downstream CYP1A Activity in Human Liver Cells

    PubMed Central

    Proksch, Peter; Abel, Josef; Dvorak, Zdenek; Haarmann-Stemmann, Thomas

    2013-01-01

    Khellin and visnagin are two furanochromones that can be frequently found in ethnomedical formulations in Asia and the Middle East. Both compounds possess anti-inflammatory and analgesic properties, therefore modern medicine uses these compounds or structurally related derivatives for treatment of vitiligo, bronchial asthma and renal colics. Despite their frequent usage, the potential toxic properties of visnagin and khellin are not well characterized up-to-now. Many natural compounds modulate the expression and activity of cytochrome P450 1A1 (CYP1A1), which is well-known to bioactivate pro-carcinogens. The expression of this enzyme is controlled by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor and regulator of drug metabolism. Here, we investigated the influence of both furanochromones on AHR signaling in human HepG2 hepatocarcinoma cells and primary human hepatocytes. Both compounds transactivated xenobiotic response element (XRE)-driven reporter gene activity in a dose-dependent manner and induced CYP1A1 transcription in HepG2 cells and primary hepatocytes. The latter was abolished in presence of a specific AHR antagonist. CYP1A enzyme activity assays done in HepG2 cells and primary hepatocytes revealed an inhibition of enzyme activity by both furanochromones, which may become relevant regarding the metabolism of xenobiotics and co-administered therapeutic drugs. The observed induction of several other members of the AHR gene battery, whose gene products are involved in regulation of cell growth, differentiation and migration, indicates that a further toxicological characterization of visnagin and khelllin is urgently required in order to minimize potential drug-drug interactions and other toxic side-effects that may occur during therapeutic usage of these furanochromones. PMID:24069365

  13. 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

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

    PubMed

    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

  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. 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

  17. 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.

  18. Ultraviolet light converts propranolol, a nonselective β-blocker and potential lupus-inducing drug, into a proinflammatory AhR ligand.

    PubMed

    Dorgham, Karim; Amoura, Zahir; Parizot, Christophe; Arnaud, Laurent; Frances, Camille; Pionneau, Cédric; Devilliers, Hervé; Pinto, Sandra; Zoorob, Rima; Miyara, Makoto; Larsen, Martin; Yssel, Hans; Gorochov, Guy; Mathian, Alexis

    2015-11-01

    UV light and some medications are known to trigger lupus erythematosus (LE). A common mechanism underlying the immunopathologic effect, resulting from exposure to these two seemingly unrelated factors, remains unknown. The aryl hydrocarbon receptor (AhR) plays a key role in the regulation of IL-22 production in humans and can be activated by both xenobiotics and naturally occurring photoproducts. A significant expansion of Th17 and Th22 cells was observed in the peripheral blood of active systemic LE (SLE) patients, compared to inactive patients and controls. We also show that propranolol, a potential lupus-inducing drug, induced stronger AhR activation in PBMCs of SLE patients than in those of controls. AhR agonist activity of propranolol was enhanced by UV light exposure. MS analysis of irradiated propranolol revealed the generation of a proinflammatory photoproduct. This compound behaves like the prototypic AhR ligand 6-formylindolo[3,2-b]carbazole, a cutaneous UV light-induced tryptophan metabolite, both promoting IL-22, IL-8, and CCL2 secretion by T-cells and macrophages. Finally, LE patients exhibit signs of cutaneous AhR activation that correlate with lesional expression of the same proinflammatory cytokines, suggesting a role for photometabolites in the induction of skin inflammation. The AhR might therefore represent a target for therapeutic intervention in LE. PMID:26354876

  19. 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. PMID:25075865

  20. Hexachlorobenzene stimulates uroporphyria in low affinity AHR mice without increasing CYP1A2

    SciTech Connect

    Gorman, Nadia; Trask, Heidi S.; Robinson, Susan W.; Sinclair, Jacqueline F.; Smith, Andrew G.; Sinclair, Peter R. . E-mail: psinc@dartmouth.edu

    2007-06-01

    Hexachlorobenzene (HCB), a weak ligand of the aryl hydrocarbon receptor (AHR), causes hepatic uroporphyrin (URO) accumulation (uroporphyria) in humans and animals. CYP1A2 has been shown to be necessary in the development of uroporphyria in mice. Using mice expressing the low affinity form of the AH receptor (AHRd), we investigated whether the enhancement of uroporphyria by HCB involves an obligatory increase in CYP1A2 as measured by specific enzyme assays and immunoblotting. We compared the ability of HCB, in combination with iron dextran and the porphyrin precursor, 5-aminolevulinate (ALA), to cause uroporphyria in a strain of mice (C57BL/6) which expresses the high affinity form of the receptor (AHRb{sub 1}), with three strains of mice (SWR and two 129 sublines) expressing the low affinity AHRd. In C57BL/6 mice, HCB-enhanced uroporphyria was associated with a doubling of CYP1A2. HCB treatment produced uroporphyria in iron-loaded mice expressing AHRd, even though there was little or no increase in CYP1A2. Cyp1a2(-/-) mice in a 129 background were completely resistant to HCB-induced uroporphyria, and female Hfe(-/-) 129 mice, in which the levels of hepatic CYP1A2 were half of those of the male levels, responded poorly. The effect of exogenous iron, administered in the form of iron dextran, on HCB enhancement of uroporphryia could be replicated utilizing the endogenous hepatic iron accumulated in 129 Hfe(-/-) mice. In conclusion, some minimal basal expression of CYP1A2 is essential for HCB-mediated enhancement of uroporphyria, but increases in CYP1A2 above that level are not essential.

  1. UVBY Photometry of the Magnetic Chemically Peculiar Stars HR 1297, 36 Aurigae, and HR 2722 and the Nonmagnetic Chemically Peculiar Stars HR 1576 and alpha CANCRI

    NASA Astrophysics Data System (ADS)

    Adelman, Saul J.; Brunhouse, Eric F.

    1998-11-01

    Differential Strömgren uvby photometric observations from the Four College Automated Photoelectric Telescope are presented for the magnetic CP stars HR 1297, 36 Aur, and HR 2722 and the nonmagnetic CP stars HR 1576 and alpha Cnc. Both the moderately rotating HR 1576, a mercury-manganese star, and alpha Cnc, a metallic-line star, are nonvariable. For HR 1297 we refined Winzer's period to 1.06457 days. Our period of 14.366 days for 36 Aur is an alias of Winzer's period and is in keeping with the sharp-lined nature of this star. We found a more accurate period of 2.31523 days for the low-amplitude variable HR 2722.

  2. HR 5960 - New observations and period search

    NASA Astrophysics Data System (ADS)

    DuPuy, D. L.; Burgoyne, L. G.

    1983-01-01

    New photoelectric observations of the Delta Scuti star HR 5960 (CL Dra) obtained on nine closely spaced nights are discussed. It is noted that periodicities in the range of 0.06 d to 0.069 d have already been reported for this star. A Jurkevich periodogram analysis and nonlinear least-squares analysis give a primary period of 0.0676 d, with a secondary period of 0.0493 d. There is still some uncertainty whether the primary period is 0.0676 d or 0.0685 d. On the average, 55 observations of the variable were obtained each night, with an average interval of 5.5 minutes between observations. The air mass of the observations varied from 1.06 to 1.3. In all, 492 observations of the variable star were made.

  3. How HR Leaders Can Add Value to an Organization

    ERIC Educational Resources Information Center

    Smallwood, Norm; Ulrich, Dave

    2006-01-01

    Generally speaking, it is safe to say that human resource leaders whole-heartedly believe that the HR function should add value to an organization. However, many wonder where to start. In this article, the authors outline three ways in which the HR function, and the HR leader, can create sustained value for an organization and its stakeholders.

  4. 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

  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

    2012-03-01

    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. PMID:22296185

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

    PubMed

    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 200μg/kg of TCDD died within 20days, 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. PMID:24769090

  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. 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.

  9. Differential Proteomics Analysis Reveals a Role for E2F2 in the Regulation of the Ahr Pathway in T Lymphocytes§

    PubMed Central

    Azkargorta, Mikel; Fullaondo, Asier; Laresgoiti, Usua; Aloria, Kerman; Infante, Arantza; Arizmendi, Jesus M.; Zubiaga, Ana M.

    2010-01-01

    E2F transcription factors (E2F1-8) are best known for their role in cell proliferation, although it is clear that they regulate many other biological processes through the transcriptional modulation of distinct target genes. However, the specific set of genes regulated by each E2F remains to be characterized. To gain insight into the molecular pathways regulated by E2F2, we have analyzed the proteome of antigen receptor–activated T cells lacking E2F2. We report that loss of E2F2 results in a deregulated Aryl-hydrocarbon-receptor pathway. Proliferating E2F2−/− T lymphocytes expressed significantly higher levels of Aip, Ahr, and Arnt relative to wild-type (WT)1 controls. The mechanism for increased levels of Aip appears straightforward, involving direct regulation of the Aip gene promoter by E2F2. Although the Ahr and Arnt promoters also bind E2F2, their regulation appears to be more complex. Nevertheless, exposure to the environmental xenobiotic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a well-known exogenous ligand of the Ahr pathway, led to overexpression of the Ahr target gene Cyp1a1, and to increased sensitivity to TCDD-triggered apoptosis in E2F2−/− T cells compared with WT controls. These results suggest that E2F2 modulates cellular sensitivity to xenobiotic signals through the negative regulation of the Ahr pathway. PMID:20573986

  10. Structure of the C-terminal effector-binding domain of AhrC bound to its corepressor l-arginine

    SciTech Connect

    Garnett, James A.; Baumberg, Simon; Stockley, Peter G.; Phillips, Simon E. V.

    2007-11-01

    The crystal structure of the C-terminal domain hexameric core of AhrC, with bound corepressor (l-arginine), has been solved at 1.95 Å resolution. Binding of l-arginine results in a rotation between the two trimers of the hexamer, leading to the activation of the DNA-binding state. The arginine repressor/activator protein (AhrC) from Bacillus subtilis belongs to a large family of multifunctional transcription factors that are involved in the regulation of bacterial arginine metabolism. AhrC interacts with operator sites in the promoters of arginine biosynthetic and catabolic operons, acting as a transcriptional repressor at biosynthetic sites and an activator of transcription at catabolic sites. AhrC is a hexamer of identical subunits, each having two domains. The C-terminal domains form the core of the protein and are involved in oligomerization and l-arginine binding. The N-terminal domains lie on the outside of the compact core and play a role in binding to 18 bp DNA operators called ARG boxes. The C-terminal domain of AhrC has been expressed, purified and characterized, and also crystallized as a hexamer with the bound corepressor l-arginine. Here, the crystal structure refined to 1.95 Å is presented.

  11. Comparative in vitro transformation of the aromatic hydrocarbon receptor (AhR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (MC)

    SciTech Connect

    Riddick, D.S.; Harper, P.A.; Okey, A.B.; Riddick, D.S. )

    1992-02-26

    The induction of CYP1A1 by halogenated (e.g. TCDD) and nonhalogenated (e.g. MC) aromatic hydrocarbons is mediated by the AhR. In cytosol prepared from the mouse hepatoma cell line Hepa-1, AhR bound TCDD with 3 to 4-fold greater affinity than MC, whereas TCDD was 960-fold more potent than MC as an inducer of aryl hydrocarbon hydroxylase (AHH) activity in cultured Hepa-1 cells. The objective of this study was to compare the potency and efficacy of TCDD and MC with respect to transformation of the cytosolic AhR to its DNA-binding form. Following incubation of Hepa-1 cytosol with TCDD or MC at 30 C for 4 h, the extent of AhR transformation was assessed by measuring interaction of the AhR-ligand complex with a {sup 32}P-labeled 26-bp oligonucleotide containing a single dioxin-responsive element (DRE) consensus sequence in a gel retardation assay. Concentration-response studies indicated that TCDD and MC did not differ significantly in AhR transformation potency, but MC displayed only about 70% of the efficacy of TCDD. In vitro transformation efficacy appears to be a determinant of AHH induction efficacy, but the small difference between TCDD and MC in transformation potency does not seem adequate to explain quantitatively the large difference in AHH induction potency displayed by these ligands.

  12. The licorice flavonoid isoliquiritigenin reduces DNA-binding activity of AhR in MCF-7 cells.

    PubMed

    Wong, Tsz Yan; Lin, Shu-mei; Poon, Ching Ho; Leung, Lai K

    2014-09-25

    Licorice is derived from the rhizomes of Glycyrrhiza glabra. It has been used for confectioneries or culinary purposes. The rhizomes contain many flavonoidal compounds that have been shown to be biologically active. In the present study, effect of the licorice flavonoid isoliquiritigenin (ILN) on polycyclic aromatic hydrocarbon (PAH)-induced XRE transactivation and the downstream expression were investigated in MCF-7 cells. The environmental toxicant PAHs are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by cytochrome P450 (CYP) 1 enzymes. Reporter gene assay revealed that ILN reduced XRE transactivation triggered by 7,12-dimethylbenz[α]anthracene (DMBA) or 2,3,7,8-Tetrachlorodibenzodioxin (TCDD). Our EMSA results also demonstrated that the flavonoid diminished DMBA-induced XRE binding. The reduced transactivation could be the result of a decreased amount of AhR translocating from cytosol to nucleus as shown in Western analysis. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated that expressions of genes with XRE-containing promoters, including CYP1A1, 1A2, and 1B1, followed the same pattern of XRE transactivation. The present study illustrated that ILN might downregulate PAH-induced expressions through antagonizing AhR translocation. PMID:25110319

  13. Sequence variants at CYP1A1–CYP1A2 and AHR associate with coffee consumption

    PubMed Central

    Sulem, Patrick; Gudbjartsson, Daniel F.; Geller, Frank; Prokopenko, Inga; Feenstra, Bjarke; Aben, Katja K.H.; Franke, Barbara; den Heijer, Martin; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Yanek, Lisa R.; Becker, Lewis C.; Boyd, Heather A.; Stacey, Simon N.; Walters, G. Bragi; Jonasdottir, Adalbjorg; Thorleifsson, Gudmar; Holm, Hilma; Gudjonsson, Sigurjon A.; Rafnar, Thorunn; Björnsdottir, Gyda; Becker, Diane M.; Melbye, Mads; Kong, Augustine; Tönjes, Anke; Thorgeirsson, Thorgeir; Thorsteinsdottir, Unnur; Kiemeney, Lambertus A.; Stefansson, Kari

    2011-01-01

    Coffee is the most commonly used stimulant and caffeine is its main psychoactive ingredient. The heritability of coffee consumption has been estimated at around 50%. We performed a meta-analysis of four genome-wide association studies of coffee consumption among coffee drinkers from Iceland (n = 2680), the Netherlands (n = 2791), the Sorbs Slavonic population isolate in Germany (n = 771) and the USA (n = 369) using both directly genotyped and imputed single nucleotide polymorphisms (SNPs) (2.5 million SNPs). SNPs at the two most significant loci were also genotyped in a sample set from Iceland (n = 2430) and a Danish sample set consisting of pregnant women (n = 1620). Combining all data, two sequence variants significantly associated with increased coffee consumption: rs2472297-T located between CYP1A1 and CYP1A2 at 15q24 (P = 5.4 · 10−14) and rs6968865-T near aryl hydrocarbon receptor (AHR) at 7p21 (P = 2.3 · 10−11). An effect of ∼0.2 cups a day per allele was observed for both SNPs. CYP1A2 is the main caffeine metabolizing enzyme and is also involved in drug metabolism. AHR detects xenobiotics, such as polycyclic aryl hydrocarbons found in roasted coffee, and induces transcription of CYP1A1 and CYP1A2. The association of these SNPs with coffee consumption was present in both smokers and non-smokers. PMID:21357676

  14. Activation of Aryl Hydrocarbon Receptor (AhR) Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 Expression and Amelioration of Experimental Colitis

    PubMed Central

    Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2011-01-01

    Background Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3+ Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis. Methodology/Principal Findings Dextran sodium sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3+ T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight) was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR+/+ but not AhR -/- mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment. Conclusions/Significance These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation. PMID:21858153

  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. 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. PMID:26037956

  17. Aminoflavone, a ligand of the Aryl Hydrocarbon Receptor (AhR), inhibits HIF-1α expression in an AhR-independent fashion

    PubMed Central

    Terzuoli, Erika; Puppo, Maura; Rapisarda, Annamaria; Uranchimeg, Badarch; Cao, Liang; Burger, Angelika M.; Ziche, Marina; Melillo, Giovanni

    2010-01-01

    Aminoflavone (AF), the active component of a novel anticancer agent (AFP464) in phase I clinical trials, is a ligand of the aryl hydrocarbon receptor (AhR). AhR dimerizes with HIF-1β/ARNT, which is shared with HIF-1α, a transcription factor critical for the response of cells to oxygen deprivation. To address whether pharmacological activation of the AhR pathway might be a potential mechanism for inhibition of HIF-1, we tested the effects of AF on HIF-1 expression. AF inhibited HIF-1α transcriptional activity and protein accumulation in MCF-7 cells. However, inhibition of HIF-1α by AF was independent from a functional AhR pathway. Indeed, AF inhibited HIF-1α expression in AhR100 cells, in which the AhR pathway is functionally impaired, yet did not induce cytotoxicity, providing evidence that these effects are mediated by distinct signaling pathways. Moreover, AF was inactive in MDA-MB-231 cells, yet inhibited HIF-1α in MDA-MB-231 cells transfected with the SULT1A1 gene. AF inhibited HIF-1α mRNA expression by approximately 50%. Notably, actinomycin-D completely abrogated the ability of AF to down-regulate HIF-1α mRNA, indicating that active transcription was required for the inhibition of HIF-1α expression. Finally, AF inhibited HIF-1α protein accumulation and the expression of HIF-1-target genes in MCF-7 xenografts. These results demonstrate that AF inhibits HIF-1α in an AhR-independent fashion and they unveil additional activities of AF that may be relevant for its further clinical development. PMID:20736373

  18. 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.

  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. 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

  1. Professional Development of HR Practitioners--A Phenomenographic Study

    ERIC Educational Resources Information Center

    Bailey, Moira

    2015-01-01

    Purpose: The purpose of this paper is an investigation into the experiences of professional development of human resource (HR) practitioners in the North of Scotland, and the use of non-formal learning in that development. Design/methodology/approach: In-depth semi-structured interviews from a purposively selected sample of HR practitioners were…

  2. Implementing HR Strategies: A Guide to Good Practice.

    ERIC Educational Resources Information Center

    Higher Education Funding Council for England, Bristol.

    This guide aims to help institutions of higher education in England develop and implement their human resources (HR) strategies. It provides advice and examples of good practice in key areas, in response to requests from institutions. The report supplements earlier guidance on developing HR strategies (March 2002) and presents information for…

  3. 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…

  4. 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…

  5. The aryl hydrocarbon receptor-mediated disruption of vitellogenin synthesis in the fish liver: Cross-talk between AHR- and ERα-signalling pathways

    PubMed Central

    Bemanian, Vahid; Male, Rune; Goksøyr, Anders

    2004-01-01

    Background In the fish liver, the synthesis of egg yolk protein precursor vitellogenin (VTG) is under control of the estrogen receptor alpha (ERα). Environmental contaminants such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) are suspected to have antiestrogenic effects. The aryl hydrocarbon receptor (AHR) is the initial cellular target for TCDD and related compounds. The AHR is a ligand-activated transcription factor that stimulates the expression of the genes encoding xenobiotic metabolizing enzymes, such as cytochrome P450 1A (CYP1A). In this study, the effects of activation of AHR on the hepatic expression of VTG and ERα genes, in primary cultured salmon hepatocytes, have been investigated. Results The expression of the genes encoding VTG and ERα were strongly induced by 17β-estradiol (E2). However, the expression of VTG was disrupted by exposure of the cells to TCDD while CYP1A expression was enhanced. The effect of TCDD on VTG and CYP1A expression was annulled by the AHR-inhibitor α-naphthoflavone. Furthermore, exposure of the cells to TCDD abolished E2-induced accumulation of ERα mRNA. The AHR-mediated inhibitory effects on the expression of the VTG and ERα genes may occur at transcriptional and/or post-transcriptional levels. Nuclear run-off experiments revealed that simultaneous exposure of the cells to E2 and TCDD strongly inhibited the initiation of transcription of the VTG and ERα genes. In addition, inhibition of RNA synthesis by actinomycin D treatment showed that post-transcriptional levels of VTG and ERα mRNAs were not significantly altered upon treatment of the cells with TCDD. These results suggested that activation of AHR may inhibit the transactivation capacity of the ERα. Further, electrophoretic mobility shift assays using nuclear extracts prepared from cells treated for one or two hours with E2, alone or in mixture with TCDD, showed a strong reduction in the DNA binding activities upon TCDD treatment. These results also suggested

  6. A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer.

    PubMed

    D'Amato, Nicholas C; Rogers, Thomas J; Gordon, Michael A; Greene, Lisa I; Cochrane, Dawn R; Spoelstra, Nicole S; Nemkov, Travis G; D'Alessandro, Angelo; Hansen, Kirk C; Richer, Jennifer K

    2015-11-01

    The ability of a cancer cell to develop resistance to anoikis, a programmed cell death process triggered by substratum detachment, is a critical step in the metastatic cascade. Triple-negative breast cancers (TNBC) exhibit higher rates of metastasis after diagnosis, relative to estrogen-positive breast cancers, but while TNBC cells are relatively more resistant to anoikis, the mechanisms involved are unclear. Through gene expression and metabolomic profiling of TNBC cells in forced suspension culture, we identified a molecular pathway critical for anchorage-independent cell survival. TNBC cells in suspension upregulated multiple genes in the kynurenine pathway of tryptophan catabolism, including the enzyme tryptophan 2,3-dioxygenase (TDO2), in an NF-κB-dependent manner. Kynurenine production mediated by TDO2 in TNBC cells was sufficient to activate aryl hydrocarbon receptor (AhR), an endogenous kynurenine receptor. Notably, pharmacologic inhibition or genetic attenuation of TDO2 or AhR increased cellular sensitivity to anoikis, and also reduced proliferation, migration, and invasion of TNBC cells. In vivo, TDO2 inhibitor-treated TNBC cells inhibited colonization of the lung, suggesting that TDO2 enhanced metastatic capacity. In clinical specimens of TNBC, elevated expression of TDO2 was associated with increased disease grade, estrogen receptor-negative status, and shorter overall survival. Our results define an NF-κB-regulated signaling axis that promotes anoikis resistance, suggest functional connections with inflammatory modulation by the kynurenine pathway, and highlight TDO2 as an attractive target for treatment of this aggressive breast cancer subtype. PMID:26363006

  7. A high-resolution structure of the DNA-binding domain of AhrC, the arginine repressor/activator protein from Bacillus subtilis

    SciTech Connect

    Garnett, James A.; Baumberg, Simon; Stockley, Peter G.; Phillips, Simon E. V.

    2007-11-01

    The structure of the winged helix–turn–helix DNA-binding domain of AhrC has been determined at 1.0 Å resolution. The largely hydrophobic β-wing shows high B factors and may mediate the dimer interface in operator complexes. In Bacillus subtilis the concentration of l-arginine is controlled by the transcriptional regulator AhrC, which interacts with 18 bp DNA operator sites called ARG boxes in the promoters of arginine biosynthetic and catabolic operons. AhrC is a 100 kDa homohexamer, with each subunit having two domains. The C-terminal domains form the core, mediating intersubunit interactions and binding of the co-repressor l-arginine, whilst the N-terminal domains contain a winged helix–turn–helix DNA-binding motif and are arranged around the periphery. The N-terminal domain of AhrC has been expressed, purified and characterized and it has been shown that the fragment still binds DNA operators as a recombinant monomer. The DNA-binding domain has also been crystallized and the crystal structure refined to 1.0 Å resolution is presented.

  8. Species-specific relative AHR1 binding affinities of 2,3,4,7,8-pentachlorodibenzofuran explain avian species differences in its relative potency.

    PubMed

    Farmahin, Reza; Jones, Stephanie P; Crump, Doug; Hahn, Mark E; Giesy, John P; Zwiernik, Matthew J; Bursian, Steven J; Kennedy, Sean W

    2014-04-01

    Results of recent studies showed that 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are equipotent in domestic chicken (Gallus gallus domesticus) while PeCDF is more potent than TCDD in ring-necked pheasant (Phasianus colchicus) and Japanese quail (Coturnix japonica). To elucidate the mechanism(s) underlying these differences in relative potency of PeCDF among avian species, we tested the hypothesis that this is due to species-specific differential binding affinity of PeCDF to the aryl hydrocarbon receptor 1 (AHR1). Here, we modified a cell-based binding assay that allowed us to measure the binding affinity of dioxin-like compounds (DLCs) to avian AHR1 expressed in COS-7 (fibroblast-like cells). The results of the binding assay show that PeCDF and TCDD bind with equal affinity to chicken AHR1, but PeCDF binds with greater affinity than TCDD to pheasant (3-fold) and Japanese quail (5-fold) AHR1. The current report introduces a COS-7 whole-cell binding assay and provides a mechanistic explanation for differential relative potencies of PeCDF among species of birds. PMID:24434118

  9. Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner.

    PubMed

    Wincent, Emma; Kubota, Akira; Timme-Laragy, Alicia; Jönsson, Maria E; Hahn, Mark E; Stegeman, John J

    2016-06-15

    6-Formylindolo[3,2-b]carbazole (FICZ) is a potent aryl hydrocarbon receptor (AHR) agonist that is efficiently metabolized by AHR-regulated cytochrome P4501 enzymes. FICZ is a proposed physiological AHR ligand that induces its own degradation as part of a regulatory negative feedback loop. In vitro studies in cells show that CYP1 inhibition in the presence of FICZ results in enhanced AHR activation, suggesting that FICZ accumulates in the cell when its metabolism is blocked. We used zebrafish (Danio rerio) embryos to investigate the in vivo effects of FICZ when CYP1A is knocked down or inhibited. Embryos were injected with morpholino antisense oligonucleotides targeting CYP1A (CYP1A-MO), Ahr2, or a combination of both. FICZ exposure of non-injected embryos or embryos injected with control morpholino had little effect. In CYP1A-MO-injected embryos, however, FICZ dramatically increased mortality, incidence and severity of pericardial edema and circulation failure, reduced hatching frequency, blocked swim bladder inflation, and strongly potentiated expression of Ahr2-regulated genes. These effects were substantially reduced in embryos with a combined knockdown of Ahr2 and CYP1A, indicating that the toxicity was mediated at least partly by Ahr2. Co-exposure to the CYP1 inhibitor alpha-naphthoflavone (αNF) and FICZ had similar effects as the combination of CYP1A-MO and FICZ. HPLC analysis of FICZ-exposed embryos showed increased levels of FICZ after concomitant CYP1A-MO injection or αNF co-exposure. Together, these results show that a functioning CYP1/AHR feedback loop is crucial for regulation of AHR signaling by a potential physiological ligand in vivo and further highlights the role of CYP1 enzymes in regulating biological effects of FICZ. PMID:27112072

  10. Hexachlorobenzene induces cell proliferation, and aryl hydrocarbon receptor expression (AhR) in rat liver preneoplastic foci, and in the human hepatoma cell line HepG2. AhR is a mediator of ERK1/2 signaling, and cell cycle regulation in HCB-treated HepG2 cells.

    PubMed

    de Tomaso Portaz, Ana Clara; Caimi, Giselle Romero; Sánchez, Marcela; Chiappini, Florencia; Randi, Andrea S; Kleiman de Pisarev, Diana L; Alvarez, Laura

    2015-10-01

    Hexachlorobenzene (HCB) is a widespread environmental pollutant, and a liver tumor promoter in rodents. Depending on the particular cell lines studied, exposure to these compounds may lead to cell proliferation, terminal differentiation, or apoptosis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is involved in drug and xenobiotic metabolism. AhR can also modulate a variety of cellular and physiological processes that can affect cell proliferation and cell fate determination. The mechanisms by which AhR ligands, both exogenous and endogenous, affect these processes involve multiple interactions between AhR and other signaling pathways. In the present study, we examined the effect of HCB on cell proliferation and AhR expression, using an initiation-promotion hepatocarcinogenesis protocol in rat liver and in the human-derived hepatoma cell line, HepG2. Female Wistar rats were initiated with a single dose of 100 mg/kg of diethylnitrosamine (DEN) at the start of the experiment. Two weeks later, daily dosing of 100 mg/kg HCB was maintained for 10 weeks. Partial hepatectomy was performed 3 weeks after initiation. The number and area of glutathione S-transferase-P (GST-P)-positive foci, in the rat liver were used as biomarkers of liver precancerous lesions. Immunohistochemical staining showed an increase in proliferating cell nuclear antigen (PCNA)-positive cells, along with enhanced AhR protein expression in hepatocytes within GST-P-positive foci of (DEN HCB) group, when compared to DEN. In a similar manner, Western blot analysis demonstrated that HCB induced PCNA and AhR protein expression in HepG2 cells. Flow cytometry assay indicated that the cells were accumulated at S and G2/M phases of the cell cycle. HCB increased cyclin D1 protein levels and ERK1/2 phosphorylation in a dose-dependent manner. Treatment of cells with a selective MEK1 inhibitor, prevented HCB-stimulatory effect on PCNA and cyclinD1, indicating that these effects

  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. AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio)

    SciTech Connect

    Van Tiem, Lindsey A.; Di Giulio, Richard T.

    2011-08-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants often present in aquatic systems as complex mixtures. Embryonic fish are sensitive to the developmental toxicity of some PAHs, but the exact mechanisms involved in this toxicity are still unknown. This study explored the role of the aryl hydrocarbon receptor (AHR) in the oxidative stress response of zebrafish to the embryotoxicity of select PAHs. Embryos were exposed to two PAHs, benzo[k]fluoranthene (BkF; a strong AHR agonist) and fluoranthene (FL; a cytochrome P4501A (CYP1A) inhibitor), alone and in combination. CYP1A, CYP1B1, CYP1C1, and redox-responsive genes glutathione s-transferase pi 2 (GSTp2), glutathione peroxidase 1 (GPx1), the glutamate-cysteine ligase catalytic subunit (GCLc), MnSOD and CuZnSOD mRNA expression was examined. CYP1 activity was measured via an in vivo ethoxyresorufin-O-deethlyase (EROD) activity assay, and the area of the pericardium was measured as an index of cardiotoxicity. BkF or FL alone caused no deformities whereas BkF + FL resulted in extreme pericardial effusion. BkF induced CYP activity above controls and co-exposure with FL inhibited this activity. BkF induced expression of all three CYPs, GSTp2, and GCLc. BkF + FL caused greater than additive induction of the three CYPs, GSTp2, GPx1, and GCLc but had no effect on MnSOD or CuZnSOD. AHR2 knockdown protected against the cardiac deformities caused by BkF + FL and significantly inhibited the induction of the CYPs, GSTp2, GPx1, and GCLc after BkF + FL compared to non-injected controls. These results further show the protective role of AHR2 knockdown against cardiotoxic PAHs and the role of AHR2 as a mediator of redox-responsive gene induction. - Research Highlights: > Co-exposure of the PAHs BkF and FL causes cardiotoxicity in zebrafish. > BkF and FL co-exposure upregulates certain XRE- and ARE-associated genes. > AHR2 knockdown prevents the deformities caused by BkF and FL co-exposure. > AHR2

  13. 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

  14. ADJUSTABLE DOUBLE PULSE GENERATOR

    DOEpatents

    Gratian, J.W.; Gratian, A.C.

    1961-08-01

    >A modulator pulse source having adjustable pulse width and adjustable pulse spacing is described. The generator consists of a cross coupled multivibrator having adjustable time constant circuitry in each leg, an adjustable differentiating circuit in the output of each leg, a mixing and rectifying circuit for combining the differentiated pulses and generating in its output a resultant sequence of negative pulses, and a final amplifying circuit for inverting and square-topping the pulses. (AEC)

  15. Adjustable sutures in children.

    PubMed

    Engel, J Mark; Guyton, David L; Hunter, David G

    2014-06-01

    Although adjustable sutures are considered a standard technique in adult strabismus surgery, most surgeons are hesitant to attempt the technique in children, who are believed to be unlikely to cooperate for postoperative assessment and adjustment. Interest in using adjustable sutures in pediatric patients has increased with the development of surgical techniques specific to infants and children. This workshop briefly reviews the literature supporting the use of adjustable sutures in children and presents the approaches currently used by three experienced strabismus surgeons. PMID:24924284

  16. AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio)

    PubMed Central

    Van Tiem, Lindsey A.; Di Giulio, Richard T.

    2011-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants often present in aquatic systems as complex mixtures. Embryonic fish are sensitive to the developmental toxicity of some PAHs, but the exact mechanisms involved in this toxicity are still unknown. This study explored the role of the aryl hydrocarbon receptor (AHR) in the oxidative stress response of zebrafish to the embryotoxicity of select PAHs. Embryos were exposed to two PAHs, benzo[k]fluoranthene (BkF; a strong AHR agonist) and fluoranthene (FL; a cytochrome P4501A (CYP1A) inhibitor), alone and in combination. CYP1A, CYP1B1, CYP1C1, and redox-responsive genes glutathione s-transferase pi 2 (GSTp2), glutathione peroxidase 1 (GPx1), the glutamate-cysteine ligase catalytic subunit (GCLc), MnSOD and CuZnSOD mRNA expression was examined. CYP1 activity was measured via an in vivo ethoxyresorufin-O-deethlyase (EROD) activity assay, and the area of the pericardium was measured as an index of cardiotoxicity. BkF or FL alone caused no deformities whereas BkF + FL resulted in extreme pericardial effusion. BkF induced CYP activity above controls and co-exposure with FL inhibited this activity. BkF induced expression of all three CYPs, GSTp2, and GCLc. BkF + FL caused greater than additive induction of the three CYPs, GSTp2, GPx1, and GCLc but had no effect on MnSOD or CuZnSOD. AHR2 knockdown protected against the cardiac deformities caused by BkF + FL and significantly inhibited the induction of the CYPs, GSTp2, GPx1 and GCLc after BkF + FL compared to non-injected controls. These results further show the protective role of AHR2 knockdown against cardiotoxic PAHs and the role of AHR2 as a mediator of redox-responsive gene induction. PMID:21600235

  17. 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

  18. 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

    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

  19. 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. PMID:27180721

  20. ASASSN-16hr Is a Type Ia SN Before Maximum

    NASA Astrophysics Data System (ADS)

    Bersier, D.

    2016-07-01

    We obtained a spectrum of the candidate supernova ASASSN-16hr/AT 2016eja (ATel #9270) with the SPRAT spectrograph mounted on the robotic 2m Liverpool Telescope at the Roque de los Muchachos observatory (La Palma).

  1. 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.

  2. Modelling the Inner Debris Disc of HR 8799

    NASA Astrophysics Data System (ADS)

    Contro, Bruna; Horner, Jonti; Wittenmyer, Rob; Marshall, Jonathan P.; Hinse, T. C.

    2016-08-01

    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 kms-1, the majority of collisions within HR 8799's inner belt occur with velocities of order 1.2 kms-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.

  3. High-resolution EEG (HR-EEG) and magnetoencephalography (MEG).

    PubMed

    Gavaret, M; Maillard, L; Jung, J

    2015-03-01

    High-resolution EEG (HR-EEG) and magnetoencephalography (MEG) allow the recording of spontaneous or evoked electromagnetic brain activity with excellent temporal resolution. Data must be recorded with high temporal resolution (sampling rate) and high spatial resolution (number of channels). Data analyses are based on several steps with selection of electromagnetic signals, elaboration of a head model and use of algorithms in order to solve the inverse problem. Due to considerable technical advances in spatial resolution, these tools now represent real methods of ElectroMagnetic Source Imaging. HR-EEG and MEG constitute non-invasive and complementary examinations, characterized by distinct sensitivities according to the location and orientation of intracerebral generators. In the presurgical assessment of drug-resistant partial epilepsies, HR-EEG and MEG can characterize and localize interictal activities and thus the irritative zone. HR-EEG and MEG often yield significant additional data that are complementary to other presurgical investigations and particularly relevant in MRI-negative cases. Currently, the determination of the epileptogenic zone and functional brain mapping remain rather less well-validated indications. In France, in 2014, HR-EEG is now part of standard clinical investigation of epilepsy, while MEG remains a research technique. PMID:25648821

  4. Effects of carcinogenic versus non-carcinogenic AHR-active PAHs and their mixtures: lessons from ecological relevance.

    PubMed

    Martins, Marta; Santos, José M; Diniz, Mário S; Ferreira, Ana M; Costa, Maria H; Costa, Pedro M

    2015-04-01

    Polycyclic aromatic hydrocarbons (PAHs) are priority environmental mutagens and carcinogens that occur in the aquatic environment as mixtures rather than the individual compounds for which guidelines are issued. The present work aimed at understanding the interaction effects between carcinogenic and non-carcinogenic PAHs in a model marine fish (Dicentrarchus labrax) in realistic scenarios. Laboratory assays under ecologically-relevant parameters were conducted for 28 days with sediments spiked with low-moderate concentrations (250-800ngg(-1)) of two model PAHs, phenanthrene (non-carcinogenic) and benzo[b]fluoranthene (carcinogenic to experimental animals). Both PAHs induced hepatic histopathological changes that indicate metabolic failure and inflammation, especially in animals exposed to mixtures. Phenanthrene elicited biochemical changes better related to oxidative stress (lipid peroxidation, glutathione and glutathione S-transferase activity) and CYP function, whereas B[b]F disrupted metabolic responses and defences to toxicological challenge. Conversely, mixed PAHs yielded lesions and responses that, altogether, are compatible with the AHR dependent pathway (the basis of PAH mutagenicity), potentially generating supra-additive effects. Nonetheless, the low, ecologically-relevant, concentrations of PAHs diluted dose and time-response relations. Overall, although seemingly predicting the risk of individual PAHs, environmental guidelines may not apply to mixtures by underestimating adverse effects, which calls for a redefinition of standards when determining the true risk of toxicants under realistic circumstances. PMID:25704830

  5. 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.

  6. 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.

  7. Data on AHR-dependent changes in the mitochondrial proteome in response to ,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Hwang, Hye Jin; Dornbos, Peter; LaPres, John J

    2016-09-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is the principal regulator of a cell׳s response to many polyaromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). To gain a better understanding of the impact of TCDD on the mitochondrial proteome, a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomic analysis was performed. We used two mouse hepatoma cell lines that differ in AHR expression levels, hepa1c1c7 (AHR-expressing) and hepac12 (AHR-deficient). The cell lines were exposed to TCDD (10 nM) for 72 h; each treatment was assayed in triplicate and were analyzed as separate runs on the mass-spectrometer. Mitochondria were then isolated and mitochondrial proteins were separated by SDS-PAGE and subject to mass spectrometry. The data presented were collected from four independent SILAC experiments. Within each experiment, three isotopes were employed to compare protein ratios via mass-spectrometry: (1) light l-arginine/l-lysine HCl (Arg0, Lys0), (2) medium (15)N4-l-arginin/(13)C6l-lysine HCl (Arg4, Lys6), and (3) heavy (13)C6 (15)N4l-arginine/(13)C6 (15)N2l-lysine HCl (Arg10, Lys8). The raw data includes approximately 2500 annotated proteins. The datasets provided by this study can be a reference to other toxicologists investigating TCDD-induced mitochondrial dysfunction. The data presented here are associated with the research article, "Mitochondrial-targeted Aryl Hydrocarbon Receptor and the Impact of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on Cellular Respiration and the Mitochondrial Proteome" (Hwang et al. (2016) [1]). PMID:27331086

  8. 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

  9. TCDD and a Putative Endogenous AhR Ligand, ITE, Elicit the Same Immediate Changes in Gene Expression in Mouse Lung Fibroblasts

    PubMed Central

    Henry, Ellen C.; Welle, Stephen L.; Gasiewicz, Thomas A.

    2010-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1′H-indolo-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5μM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible. PMID:19933214

  10. Impact of AhR, CYP1A1 and GSTM1 genetic polymorphisms on TP53 R273G mutations in individuals exposed to polycyclic aromatic hydrocarbons.

    PubMed

    Gao, Meili; Li, Yongfei; Xue, Xiaochang; Long, Jiangang; Chen, Lan; Shah, Walayat; Kong, Yu

    2014-01-01

    This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers. PMID:24761888

  11. Adjusting the Chain Gear

    NASA Astrophysics Data System (ADS)

    Koloc, Z.; Korf, J.; Kavan, P.

    The adjustment (modification) deals with gear chains intermediating (transmitting) motion transfer between the sprocket wheels on parallel shafts. The purpose of the adjustments of chain gear is to remove the unwanted effects by using the chain guide on the links (sliding guide rail) ensuring a smooth fit of the chain rollers into the wheel tooth gap.

  12. Adjustment to Recruit Training.

    ERIC Educational Resources Information Center

    Anderson, Betty S.

    The thesis examines problems of adjustment encountered by new recruits entering the military services. Factors affecting adjustment are discussed: the recruit training staff and environment, recruit background characteristics, the military's image, the changing values and motivations of today's youth, and the recruiting process. Sources of…

  13. The tertiary structures of porcine AhR and ARNT proteins and molecular interactions within the TCDD/AhR/ARNT complex.

    PubMed

    Orlowska, Karina; Molcan, Tomasz; Swigonska, Sylwia; Sadowska, Agnieszka; Jablonska, Monika; Nynca, Anna; Jastrzebski, Jan P; Ciereszko, Renata E

    2016-06-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by structurally diverse synthetic and natural chemicals, including toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the present study, homology models of the porcine AhR-ligand binding domain (LBD) and the porcine aryl hydrocarbon receptor nuclear translocator-ligand binding domain (ARNT-LBD) were created on the basis of structures of closely related respective proteins i.e., human Hif-2α and ARNT. Molecular docking of TCDD to the porcine AhR-LBD model revealed high binding affinity (-8.8kcal/mol) between TCDD and the receptor. Moreover, formation of the TCDD/AhR-LBD complex was confirmed experimentally with the use of electrophoretic mobility shift assay (EMSA). It was found that TCDD (10nM, 2h of incubation) not only bound to the AhR in the porcine granulosa cells but also activated the receptor. The current study provides a framework for examining the key events involved in the ligand-dependent activation of the AhR. PMID:27288759

  14. Multiple wavelength microwave observations of the RS Canum Venaticorum stars UX Arietis, HR 1099, HR 5110, and II Pegasi

    SciTech Connect

    Willson, R.F.; Lang, K.R.

    1987-01-01

    The variabilities, core size and magnetic field of the RS CVn star UX Arietis was measured with the VLA at pairs of frequencies near 1415 MHz and 4835 MHz on June 10, 1985. Data were also gathered on HR 1099, HR 5110 and II Peg. UX Arietis exhibited variability on time scales ranging from 30 sec to 1 hr at 4835 MHz, but no detectable variations at 1415 MHz. An upper limit of 900 billion cm was placed on the size of the core emitting region, which is estimated to have a magnetic field strength of 15 G. The 30 sec variations are attributed to absorption by thermal plasma between the G5 and K1 companions of the UX Arietis system. 37 references.

  15. Multiple wavelength microwave observations of the RS Canum Venaticorum stars UX Arietis, HR 1099, HR 5110, and II Pegasi

    NASA Technical Reports Server (NTRS)

    Willson, Robert F.; Lang, Kenneth R.

    1987-01-01

    The variabilities, core size and magnetic field of the RS CVn star UX Arietis was measured with the VLA at pairs of frequencies near 1415 MHz and 4835 MHz on June 10, 1985. Data were also gathered on HR 1099, HR 5110 and II Peg. UX Arietis exhibited variability on time scales ranging from 30 sec to 1 hr at 4835 MHz, but no detectable variations at 1415 MHz. An upper limit of 900 billion cm was placed on the size of the core emitting region, which is estimated to have a magnetic field strength of 15 G. The 30 sec variations are attributed to absorption by thermal plasma between the G5 and K1 companions of the UX Arietis system.

  16. Multiple wavelength microwave observations of the RS Canum Venaticorum stars UX Arietis, HR 1099, HR 5110, and II Pegasi

    NASA Astrophysics Data System (ADS)

    Willson, Robert F.; Lang, Kenneth R.

    1987-01-01

    The VLA was used to observe the RS CVn stars, UX Arietis, HR 1099, HR 5110, and II Pegasi with a time resolution of 6.6 s at two pairs of wavelengths near 4835 MHz and 1415 MHz. Variable emission was detected from UX Arietis at 4835 MHz on time scales ranging from 30 s to more than 1 hr. From the variations an upper limit to the source size of L ≤ 9×1011cm is derived. The authors also derive a magnetic field of H ≤ 15 G for the varying source and show that the time scale of the variations cannot be due to synchrotron radiation losses. Instead it is suggested that the variations may be due to absorption by a thermal plasma located between the stars of the binary system.

  17. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1.

    PubMed

    Moyer, Benjamin J; Rojas, Itzel Y; Kerley-Hamilton, Joanna S; Hazlett, Haley F; Nemani, Krishnamurthy V; Trask, Heidi W; West, Rachel J; Lupien, Leslie E; Collins, Alan J; Ringelberg, Carol S; Gimi, Barjor; Kinlaw, William B; Tomlinson, Craig R

    2016-06-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding specificity

  18. Atropine-resistant effects of the muscarinic agonists McN-A-343 and AHR 602 on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart

    PubMed Central

    Fozard, J.R.; Muscholl, E.

    1974-01-01

    1 The effects of 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) and N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602) on cardiac performance and noradrenaline release from terminal sympathetic fibres were measured in isolated perfused hearts of rabbits. 2 In the presence of sufficient atropine to block muscarinic receptors, high concentrations of McN-A-343 and AHR 602 caused no cardiac stimulation and there was no increase in the resting output of noradrenaline into the perfusates. 3 McN-A-343 and AHR 602 increased both the mechanical responses and the transmitter overflow evoked by electrical stimulation of the sympathetic nerves (SNS) but inhibited both parameters during perfusion with 1,1-dimethyl-4-phenylpiperazinium (DMPP). The effects were atropine-resistant and qualitatively similar to those seen with cocaine. Hexamethonium inhibited DMPP, but affected neither SNS per se nor the facilitatory effects of McN-A-343 and AHR 602 on SNS. 4 McN-A-343, cocaine and desipramine (but not AHR 602 or hexamethonium) blocked the net cardiac noradrenaline uptake and increased the positive chronotropic effect of noradrenaline. 5 Prior perfusion with concentrations of cocaine and desipramine sufficient to block uptake reduced or abolished the facilitatory effects of both McN-A-343 and AHR 602 on SNS. 6 Cocaine, McN-A-343 and AHR 602 displayed local anaesthetic properties on the guinea-pig wheal and frog nerve plexus tests, and their relative potencies in this respect were similar to those for inhibition of DMPP-evoked transmitter overflow. Hexamethonium did not produce local anaesthesia. 7 The results indicate that the facilitated release of noradrenaline after SNS and the inhibition of release after DMPP produced by McN-A-343 and AHR 602 are the result of their combined local anaesthetic action and inhibition of amine uptake. PMID:4447857

  19. 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…

  20. 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,…

  1. 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…

  2. Discovery of a Low-mass Companion Around HR 3549

    NASA Astrophysics Data System (ADS)

    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 MJ, 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.

  3. HR as Partner: Building Strategic Partnerships on Campus

    ERIC Educational Resources Information Center

    Connally, Sam; Neuman, Dawn

    2006-01-01

    Human resources is in an excellent position in many institutions to initiate collaboration and cooperation with other campus departments. In this article, the leaders of the departments of HR and academic resources at the University of Nevada, Las Vegas, share their insights on the importance of partnership-building on campus and describe how a…

  4. 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.…

  5. Are gaint planets forming around HR 4796A?

    NASA Technical Reports Server (NTRS)

    Chen, C. H.; Kamp, I.

    2004-01-01

    We have obtained Far Ultraviolet Spectroscopic Explorer and Hubble Space Telescope STIS spectra of HR 4796A, a nearby 8 Myr old main-sequence star that possesses a dusty circumstellar disk whose inclination has been constrained from high-resolution near-infrared observations to be 17 degrees from edge-on.

  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. Why doesn't this HR department get any respect?

    PubMed

    Galford, R

    1998-01-01

    Since becoming managing partner of human resources at Loft Securities more than a year ago, Luke Robinson has tried everything he can think of to change his department's reputation as an administrative backwater. But he's swimming against the tide. Ever since the retirement of a charismatic CEO in 1995, the firm has suffered a slow bleed of good people. The new CEO doesn't have a flair for attracting and retaining talented people, and the HR department hasn't been able to pick up the slack. Robinson has done his best to turn things around. He's met with just about everyone, from senior executives to administrative assistants to external contacts. And, when he found out that recruiting wasn't Loft's only problem, he took a variety of concrete steps. Among other things, he established internal service standards and performance guarantees for his department. He created "listening posts" and implemented and "HR ambassador" program. And he drafted plans for a program to help educate all the company's employees about the role of HR--specifically, how it can contribute to creating and upholding the firm's strategy for success. But Robinson has run over some major speed bumps. Just before he joined the company, HR sullied its reputation by mishandling the investigation of a discrimination charge. And while on Robinson's watch, HR botched the issuance of year-end bonus checks for the managing directors and vice presidents. The frustrations are piling up, leading Robinson to entertain thoughts of bailing out. Five commentators on this fictional case study explain why he should avoid quitting and how he can help his department earn new respect. PMID:10177864

  8. Multiple mean motion resonances in the HR 8799 planetary system

    NASA Astrophysics Data System (ADS)

    Goździewski, Krzysztof; Migaszewski, Cezary

    2014-06-01

    HR 8799 is a nearby star hosting at least four ˜10 mJup planets in wide orbits up to ˜70 au, detected through the direct, high-contrast infrared imaging. Large companions and debris discs reported interior to ˜10 au, and exterior to ˜100 au indicate massive protoplanetary disc in the past. The dynamical state of the HR 8799 system is not yet fully resolved, due to limited astrometric data covering tiny orbital arcs. We construct a new orbital model of the HR 8799 system, assuming rapid migration of the planets after their formation in wider orbits. We found that the HR 8799 planets are likely involved in double Laplace resonance, 1e:2d:4c:8b MMR. Quasi-circular planetary orbits are coplanar with the stellar equator and inclined by ˜25° to the sky plane. This best-fitting orbital configuration matches astrometry, debris disc models, and mass estimates from cooling models. The multiple mean motion resonance (MMR) is stable for the age of the star ˜160 Myr, for at least 1 Gyr unless significant perturbations to the N-body dynamics are present. We predict four configurations with the fifth hypothetical innermost planet HR 8799f in ˜9.7 au, or ˜7.5 au orbit, extending the MMR chain to triple Laplace resonance 1f:2e:4d:8c:16b MMR or to the 1f:3e:6d:12c:24b MMR, respectively. Our findings may establish strong boundary conditions for the system formation and its early history.

  9. SLIT ADJUSTMENT CLAMP

    DOEpatents

    McKenzie, K.R.

    1959-07-01

    An electrode support which permits accurate alignment and adjustment of the electrode in a plurality of planes and about a plurality of axes in a calutron is described. The support will align the slits in the electrode with the slits of an ionizing chamber so as to provide for the egress of ions. The support comprises an insulator, a leveling plate carried by the insulator and having diametrically opposed attaching screws screwed to the plate and the insulator and diametrically opposed adjusting screws for bearing against the insulator, and an electrode associated with the plate for adjustment therewith.

  10. CMS Frailty Adjustment Model

    PubMed Central

    Kautter, John; Pope, Gregory C.

    2004-01-01

    The authors document the development of the CMS frailty adjustment model, a Medicare payment approach that adjusts payments to a Medicare managed care organization (MCO) according to the functional impairment of its community-residing enrollees. Beginning in 2004, this approach is being applied to certain organizations, such as Program of All-Inclusive Care for the Elderly (PACE), that specialize in providing care to the community-residing frail elderly. In the future, frailty adjustment could be extended to more Medicare managed care organizations. PMID:25372243

  11. 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.

  12. 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.

  13. Black-White Latino Racial Disparities in HIV Survival, Florida, 2000-2011.

    PubMed

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

    2016-01-01

    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

  14. 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

  15. Possible functional co-operation of palindromes hr3 and hr4 in the genome of Cydia pomonella granulovirus affects viral replication capacity.

    PubMed

    Elmenofy, Wael H; Jehle, Johannes A

    2015-09-01

    After previous studies had shown that natural transposon insertion between the two homologous regions hr3 and hr4 of the genome of the Mexican (M) strain of Cydia pomonella granulovirus (CpGV-M) resulted in a loss of viral competitiveness, the function of these homologous regions was investigated. A CpGV-based bacmid (CpBAC) was constructed and mutants with deleted hr3 and hr4 palindromes (CpBAChr3/hr4KO) and a construct (CpBAChr3-kan-hr4) with physically separated hr3 and hr4 repeats were generated to investigate their involvement in in vivo replication. Based on median lethal concentration (LC50) and median survival time (ST50) of the mutant viruses vCpBAChr3/hr4KO and vCpBAChr3-kan-hr4 it was found that the infectivity of both mutants for codling moth Cydia pomonella L. (Lep.: Tortricidae) larvae was not influenced compared with the parental virus vCpBAC. Co-infection experiments with vCpBAChr3-kan-hr4 and vCpBAC using different virus ratios revealed that vCpBAChr3-kan-hr4 was efficiently out-competed by vCpBAC during in vivo replication. These findings suggested that the separation of hr3 and hr4 resulted in a replication disadvantage of the mutant similar to the observation made in previous co-infection experiments using the transposon-carrying mutant CpGV-MCp5 and WT CpGV-M. It was concluded that the palindromes hr3 and hr4 may play a non-essential but co-functional role in the replication of CpGV-M. PMID:26002301

  16. Ultraviolet, optical, infrared, and microwave observations of HR 5110

    NASA Technical Reports Server (NTRS)

    Little-Marenin, I. R.; Simon, T.; Ayres, T. R.; Cohen, N. L.; Feldman, P. A.

    1986-01-01

    Near-IR JHKLM photometric data and VLBI and IUE radio burst data collected on the short-period spectroscopic binary HR 5110 are analyzed to classify the object. The observed broadband colors were indicative of an F2 IV primary and a spotted K0 IV secondary. The system is being viewed pole-on, so is observable in the UV since the K companion has filled its Roche lobe. In comparisons of such features of Algol and RS VCn stars as the mass ratio, orbital inclination, presence or absence of evidence for mass streams, accretion disks, and active regions, spectral signatures, etc., sufficient similarities are found to classify HR 5110 as an Algol system.

  17. Pleiades-Hr Innovative Techniques for Radiometric Image Quality Commissioning

    NASA Astrophysics Data System (ADS)

    Blanchet, G.; Lebeque, L.; Fourest, S.; Latry, C.; Porez-Nadal, F.; Lacherade, S.; Thiebaut, C.

    2012-07-01

    The first Pleiades-HR satellite, part of a constellation of two, has been launched on December 17, 2011. This satellite produces high resolution optical images. In order to achieve good image quality, Pleiades-HR should first undergo an important 6 month commissioning phase period. This phase consists in calibrating and assessing the radiometric and geometric image quality to offer the best images to end users. This new satellite has benefited from technology improvements in various fields which make it stand out from other Earth observation satellites. In particular, its best-in-class agility performance enables new calibration and assessment techniques. This paper is dedicated to presenting these innovative techniques that have been tested for the first time for the Pleiades- HR radiometric commissioning. Radiometric activities concern compression, absolute calibration, detector normalization, and refocusing operations, MTF (Modulation Transfer Function) assessment, signal-to-noise ratio (SNR) estimation, and tuning of the ground processing parameters. The radiometric performances of each activity are summarized in this paper.

  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. PMID:25862330

  19. The dynamical structure of the HR8799 inner debris disk

    NASA Astrophysics Data System (ADS)

    Wittenmyer, Robert A.; Contro de Godoy, Bruna; Horner, Jonathan; Marshall, Jonathan P.

    2014-11-01

    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 exoplanet dynamics and debris disc-exoplanet interactions. Whilst the outer debris belt of HR 8799 has been well resolved by previous observations, the spatial extent of the inner disc remains unknown, leaving a 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 University of New South Wales's Katana supercomputing facility to follow the dynamical evolution of a model inner disc comprising 250,000 particles for a period of 100 million years. These simulations will (1) characterise the extent and structure of the inner disk in detail and (2) provide the first estimate of the small-body impact rate and water delivery prospects for possible (as-yet undetected) terrestrial planet(s) in the inner system.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Partial covariate adjusted regression

    PubMed Central

    Şentürk, Damla; Nguyen, Danh V.

    2008-01-01

    Covariate adjusted regression (CAR) is a recently proposed adjustment method for regression analysis where both the response and predictors are not directly observed (Şentürk and Müller, 2005). The available data has been distorted by unknown functions of an observable confounding covariate. CAR provides consistent estimators for the coefficients of the regression between the variables of interest, adjusted for the confounder. We develop a broader class of partial covariate adjusted regression (PCAR) models to accommodate both distorted and undistorted (adjusted/unadjusted) predictors. The PCAR model allows for unadjusted predictors, such as age, gender and demographic variables, which are common in the analysis of biomedical and epidemiological data. The available estimation and inference procedures for CAR are shown to be invalid for the proposed PCAR model. We propose new estimators and develop new inference tools for the more general PCAR setting. In particular, we establish the asymptotic normality of the proposed estimators and propose consistent estimators of their asymptotic variances. Finite sample properties of the proposed estimators are investigated using simulation studies and the method is also illustrated with a Pima Indians diabetes data set. PMID:20126296

  2. Medical Manuscript: Serum Total Testosterone as a Prognostic Indicator in Male Patients With Terminal Cancer.

    PubMed

    Kim, Se Won; Hwang, In Cheol; Ahn, Hee Kyung; Kyung, Sun Young; Ahn, Hong Yup

    2016-06-01

    The role of total serum testosterone in the prognosis of terminal cancer is unclear. We retrospectively investigated the total serum testosterone level in 69 male patients with terminal cancer in a palliative care unit. The association between the serum testosterone level and survival was assessed using Cox proportional hazard model. The median value of serum total testosterone was 44.5 ng/dL, far lower than previously reported in patients with advanced cancer. Multivariate analysis revealed thrombocytopenia (adjusted hazard ratio [aHR], 2.68), hypoalbuminemia (aHR, 2.02), azotemia (aHR, 2.67), and lower serum testosterone level (aHR, 2.03) were significantly negatively prognostic of survival. Lower serum testosterone level was an independent unfavorable prognostic factor for life expectancy in male patients with terminal cancer. PMID:25712105

  3. 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

  4. ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR.

    PubMed

    Wu, Yanming; Chen, Xiao; Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

    2014-01-01

    Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in

  5. ITE and TCDD Differentially Regulate the Vascular Remodeling of Rat Placenta via the Activation of AhR

    PubMed Central

    Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

    2014-01-01

    Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in

  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. Selective Aryl Hydrocarbon Receptor Modulator 3,3'-Diindolylmethane Impairs AhR and ARNT Signaling and Protects Mouse Neuronal Cells Against Hypoxia.

    PubMed

    Rzemieniec, J; Litwa, E; Wnuk, A; Lason, W; Krzeptowski, W; Kajta, M

    2016-10-01

    The neuroprotective potential of 3,3'-diindolylmethane (DIM), which is a selective aryl hydrocarbon receptor modulator, has recently been shown in cellular and animal models of Parkinson's disease and lipopolysaccharide-induced inflammation. However, there are no data concerning the protective capacity and mechanisms of DIM action in neuronal cells exposed to hypoxia. The aim of the present study was to investigate the neuroprotective potential of DIM against the hypoxia-induced damage in mouse hippocampal cells in primary cultures, with a particular focus on DIM interactions with the aryl hydrocarbon receptor (AhR), its nuclear translocator ARNT, and estrogen receptor β (ERβ). In the present study, 18 h of hypoxia induced apoptotic processes, in terms of the mitochondrial membrane potential, activation of caspase-3, and fragmentation of cell nuclei. These effects were accompanied by substantial lactate dehydrogenase release and neuronal cell death. The results of the present study demonstrated strong neuroprotective and anti-apoptotic actions of DIM in hippocampal cells exposed to hypoxia. In addition, DIM decreased the Ahr and Arnt mRNA expression and stimulated Erβ mRNA expression level. DIM-induced mRNA alterations were mirrored by changes in protein levels, except for ERβ, as detected by ELISA, Western blotting, and immunofluorescence labeling. We also demonstrated that DIM decreased the expression of AhR-regulated CYP1A1. Using specific siRNAs, we provided evidence that impairment of AhR and ARNT, but not ERβ plays a key role in the neuroprotective action of DIM against hypoxia-induced cell damage. This study may have implication for identifying new agents that could protect neurons against hypoxia by targeting AhR/ARNT signaling. PMID:26476840

  8. 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.

  9. 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.

  10. Rural to Urban Adjustment

    ERIC Educational Resources Information Center

    Abramson, Jane A.

    Personal interviews with 100 former farm operators living in Saskatoon, Saskatchewan, were conducted in an attempt to understand the nature of the adjustment process caused by migration from rural to urban surroundings. Requirements for inclusion in the study were that respondents had owned or operated a farm for at least 3 years, had left their…

  11. 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.

  12. 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.

  13. 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.

  14. COULD THE PLANETS AROUND HR 8799 BE BROWN DWARFS?

    SciTech Connect

    Moro-Martin, Amaya; Rieke, George H.; Su, Kate Y. L.

    2010-10-01

    We consider the limiting case for orbital stability of the companions to HR 8799. This case is only consistent with ages for the system of {approx}100 Myr, not with the 1 Gyr age proposed from asteroseismology. The discrepancy probably arises because the inclination of the star is smaller than assumed in analyzing the asteroseismology data. Given this young age, the best estimates of the companion masses place them by a small margin on the planet side of the division between planets and brown dwarfs.

  15. HR 1613, A Short-Period Spectroscopic Binary

    NASA Astrophysics Data System (ADS)

    Buggs, C.; Onouha, G.; Smith, B.; Burks, G. S.; Fekel, F. C.

    2004-12-01

    HR 1613, a barely naked-eye star in the constellation of Orion, is one of a number of bright, early-type stars that have few or no previous radial velocity measurements. Our observations show that it is a single-lined spectroscopic binary with a period of 8.11 days and a circular orbit. It has a spectral type of A9 V and is slowly rotating with v sin i = 12 km/s. The unseen secondary star is likely an M dwarf.

  16. The unusual interacting S star binary HR 1105

    NASA Technical Reports Server (NTRS)

    Ake, Thomas B., III; Johnson, Hollis R.; Bopp, Bernard W.

    1994-01-01

    IUE observations of HR 1105 over its 596-day orbit show strong orbital modulation of both continuum and emission lines. These are most intense just before both conjunctions and nearly disappear near quadratures, the most intense phase being just before the hot component passes in front of the S star. High dispersion observations exhibit a blue-shifted absorption feature in Mg II, representing an outflow of material of about 55 km/s. These observations are consistent with the UV source being an optically thin gas stream between the components of the system, which is partially eclipsed when the S star is in front.

  17. Detection of a magnetic region on HR 1099

    NASA Technical Reports Server (NTRS)

    Donati, J.-F.; Semel, M.; Rees, D. E.; Taylor, K.; Robinson, R. D.

    1990-01-01

    The paper reports results of a magnetic field measuring campaign on the active K component of the RS CVn system HR 1099, using Zeeman-Doppler imaging. A localized magnetic field is detected near quadrature (phase 0.85). Assuming this magnetic region has a circular shape, its longitude and latitude are, respectively, estimated to be 86 + or - 4 deg and 5 + or - 5 deg. This equatorial region is largely monopolar, has a mean field strength of 985 + or - 270 G, covers 18 + or - 3 percent of the total stellar surface and may be colocalized with a bright photospheric spot.

  18. Different AhR binding sites of diterpenoid ligands from Andrographis paniculata caused differential CYP1A1 induction in primary culture in mouse hepatocytes.

    PubMed

    Chatuphonprasert, Waranya; Remsungnen, Tawun; Nemoto, Nobuo; Jarukamjorn, Kanokwan

    2011-12-01

    Andrographis paniculata has been employed as a folklore remedy. Andrographolide (Andro), 14-deoxy-11,12-didehydroandrographolide (DHA), andrographiside (AS), and neoandrographolide (Neo), are major diterpenoids isolated from this plant. In the present study, influence of the four diterpenoids on CYP1A1 mRNA expression was investigated in primary cultured mouse hepatocytes. Additionally, binding of these compounds to aryl hydrocarbon receptor (AhR) was examined using molecular docking analysis to clarify mechanism of CYP1A1 induction. Andro and DHA induced CYP1A1 expression by itself, and co-treatment with a CYP1A1 inducer (BNF, beta-naphthoflavone) showed a synergistic increase of CYP1A1 expression. Andro demonstrated higher enhancing activity than DHA at every similar concentration. On the other hand, Neo suppressed BNF-induced CYP1A1 expression, but AS did not modify the induction. Results from molecular docking analysis of BNF and four diterpenoids on ligand binding domain of AhR were consistent with levels of CYP1A1 mRNA expressions. Furthermore, difference of binding sites of BNF in the presence of diterpenoids might affect the synergism or inhibition of CYP1A1 expression. These results suggest that use of A. paniculata as a health supplement should be concerned in term of herb-drugs interactions or risk of carcinogenesis, according to its ability to influence CYP1A1 expression. PMID:21963808

  19. Expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1) and CYP1 family monooxygenase mRNAs and their activity in chicken ovarian follicles following in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    PubMed

    Antos, Piotr A; Błachuta, Małgorzata; Hrabia, Anna; Grzegorzewska, Agnieszka K; Sechman, Andrzej

    2015-09-01

    The aim of this in vitro study was to determine the effect of TCDD and luteinizing hormone (LH) on mRNA expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1), and the CYP1 family monooxygenases (CYP1A4, CYP1A5, CYP1B1), and to assess the basal and TCDD-induced activity of these enzymes in chicken ovarian follicles. White (WF) and yellowish (YF) prehierarchical follicles and fragments of the theca (TL) and granulosa (GL) layers of the 3 largest preovulatory follicles (F3-F1) were exposed to TCDD (10nM), ovine LH (oLH; 10ng/mL) or a combination of TCDD (10nM) and oLH (10ng/mL), and increasing doses of TCDD (0.01-100nM). AHR1 and ARNT1 mRNA transcripts were found in all examined follicles. The effect of TCDD and oLH on AHR1 and ARNT1 mRNA expression depended on the maturational state of the follicle. CYP1A4 was predominantly expressed in the GL of the F3-F1 follicles; in comparison with the WF, a higher level of CYP1A5 mRNA was found both in the GL and TL of F3-F1 follicles. Alternatively, the highest level of CYP1B1 mRNA was noticed in the WF follicles. In different developmental stages of the follicle TCDD and oLH induced a different CYP1 isoform. TCDD increased EROD and MROD activities in all the investigated ovarian follicles. In conclusion, AHR1 and ARNT1 mRNA expression indicate that the chicken ovary is a target tissue for dioxin and dioxin-like compounds. The expression of CYP1-family genes and TCDD-inducible EROD and MROD activities in ovarian follicles suggest the possibility of xenobiotic detoxification in the chicken ovary. PMID:26043675

  20. 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.

  1. THERMAL INFRARED MMTAO OBSERVATIONS OF THE HR 8799 PLANETARY SYSTEM

    SciTech Connect

    Hinz, Philip M.; Rodigas, Timothy J.; Kenworthy, Matthew A.; Sivanandam, Suresh; Meyer, Michael R.; Heinze, Aren N.; Mamajek, Eric E.

    2010-06-10

    We present direct imaging observations at wavelengths of 3.3, 3.8 (L' band), and 4.8 (M band) {mu}m, for the planetary system surrounding HR 8799. All three planets are detected at L' . The c and d components are detected at 3.3 {mu}m, and upper limits are derived from the M-band observations. These observations provide useful constraints on warm giant planet atmospheres. We discuss the current age constraints on the HR 8799 system and show that several potential co-eval objects can be excluded from being co-moving with the star. Comparison of the photometry is made to models for giant planet atmospheres. Models that include non-equilibrium chemistry provide a reasonable match to the colors of c and d. From the observed colors in the thermal infrared, we estimate T {sub eff} < 960 K for b and T {sub eff} = 1300 and 1170 K for c and d, respectively. This provides an independent check on the effective temperatures and thus masses of the objects from the Marois et al. results.

  2. Thermal Infrared MMTAO Observations of the HR 8799 Planetary System

    NASA Astrophysics Data System (ADS)

    Hinz, Philip M.; Rodigas, Timothy J.; Kenworthy, Matthew A.; Sivanandam, Suresh; Heinze, Aren N.; Mamajek, Eric E.; Meyer, Michael R.

    2010-06-01

    We present direct imaging observations at wavelengths of 3.3, 3.8 (L' band), and 4.8 (M band) μm, for the planetary system surrounding HR 8799. All three planets are detected at L' . The c and d components are detected at 3.3 μm, and upper limits are derived from the M-band observations. These observations provide useful constraints on warm giant planet atmospheres. We discuss the current age constraints on the HR 8799 system and show that several potential co-eval objects can be excluded from being co-moving with the star. Comparison of the photometry is made to models for giant planet atmospheres. Models that include non-equilibrium chemistry provide a reasonable match to the colors of c and d. From the observed colors in the thermal infrared, we estimate T eff < 960 K for b and T eff = 1300 and 1170 K for c and d, respectively. This provides an independent check on the effective temperatures and thus masses of the objects from the Marois et al. results. Observations reported here were obtained at the MMT Observatory, a joint facility of the University of Arizona and the Smithsonian Institution.

  3. Restoration Technique for Pleiades-Hr Panchromatic Images

    NASA Astrophysics Data System (ADS)

    Latry, C.; Fourest, S.; Thiebaut, C.

    2012-07-01

    17th of December 2011 from Kourou Space Centre, French Guyana. Like others high resolution optical satellites, it acquires both panchromatic images, with 70cm spatial resolution, and lower resolution multispectral images with 2.8m spatial resolution. Pleiades-HR is an optimized system, which means that the Modulation Transfer Function has a low value at Nyquist frequency, in order to reduce both the telescope diameter and aliasing effects. Shannon sampling condition is thus met at first order, which also makes classical ground processing, such as image matching or resampling, more justified for a mathematical point of view. Raw images are thus blurry which implies a deconvolution stage that restores sharpness but also increases the noise level in the high frequency domain. A denoising step, based upon wavelet packet coefficients thresholding/shrinkage technique, allows controlling the final noise level. Each of these methods includes numerous parameters that have to be assessed during the inflight commissioning period: deconvolution filter that depends on MTF assessment, instrumental noise model, noise level target for denoised images, wavelet packet decomposition level. This paper aims to precisely describe the deconvolution/denoising algorithms and how their main parameters have been set up during the inflight commissioning stage. Special attention will be given to structured noise induced by Pleiades-HR on board wavelet-based compression algorithm

  4. 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.

  5. 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.

  6. 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

    Solaimani, Parrisa; Damoiseaux, Robert; Hankinson, Oliver

    2013-11-01

    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

  7. 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

  8. NEW PRECISION ORBITS OF BRIGHT DOUBLE-LINED SPECTROSCOPIC BINARIES. VIII. HR 1528, HR 6993, 2 SAGITTAE, AND 18 VULPECULAE

    SciTech Connect

    Fekel, Francis C.; Williamson, Michael H.; Tomkin, Jocelyn E-mail: michael.h.williamson@gmail.com

    2013-11-01

    Improved orbital elements for four A-star double-lined spectroscopic binaries have been determined with numerous new radial velocities. Three of the four systems, HR 1528, 2 Sge, and 18 Vul, have moderately short orbital periods of 7.05, 7.39, and 9.31 days, respectively, and also have circular or nearly circular orbits. Only HR 6993 with a period of 14.68 days has a significantly eccentric orbit. The close visual companion of 2 Sge has been detected spectroscopically, and its velocity measured. The 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) of the short-period binary components all have accuracies of 0.5% or better. We determine basic properties of the individual stars and compare them with solar-abundance evolutionary tracks to estimate their masses. Half of the eight components may be synchronously or pseudosynchronously rotating.

  9. Trabecular Bone Strength Predictions of HR-pQCT and Individual Trabeculae Segmentation (ITS)-Based Plate and Rod Finite Element Model Discriminate Postmenopausal Vertebral Fractures

    PubMed Central

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

    2013-01-01

    While 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 by 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 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 μCT voxel model of 19 trabecular sub-volumes from human cadaveric tibiae samples. Both 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 CPU time (>1,200-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 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 status in postmenopausal women. This accurate nonlinear μFE prediction of HR-pQCT PR model, which requires only seconds of

  10. Differential effects of mercury, lead and copper on the constitutive and inducible expression of aryl hydrocarbon receptor (AHR)-regulated genes in cultured hepatoma Hepa 1c1c7 cells.

    PubMed

    Korashy, Hesham M; El-Kadi, Ayman O S

    2004-09-01

    Both simultaneous and sequential exposure to heavy metals and aryl hydrocarbon receptor (AHR)-ligands potentially occur in human populations, yet there have been relatively few studies of combined effects of heavy metals and AHR-ligands on AHR-regulated genes. To investigate the effects of heavy metals on AHR-regulated genes; cytochrome P450 1a1 (cyp1a1), NAD(P)H:quinone oxidoreductase (QOR) and glutathione S-transferase Ya (GST Ya), murine hepatoma Hepa 1c1c7 cells were incubated with increasing concentrations of Hg2+ (2.5-10 microM), Pb2+ (10-100 microM), and Cu2+ (1-100 microM) alone or with the AHR-ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.1 nM), 3-methylcholanthrene (0.25 microM), beta-naphthoflavone (10 microM), or benzo[a]pyrene (1 microM). The results clearly showed that metals alone did not significantly alter the cyp1a1 activity and protein levels but increased its mRNA expression, whereas a significant reduction in AHR ligand-mediated induction of cyp1a1 activity was observed by all metals. The decrease in cyp1a1 activity was associated with an increase, no change, or decrease in cyp1a1 mRNA and protein levels by Hg2+, Pb2+ and Cu2+ respectively, suggesting pre- and post-transcription mechanisms are involved. With respect to QOR, the activity and mRNA levels were increased by all metals in the absence or presence of an AHR-ligand, with the exception of Cu2+ which significantly decreased the induction of QOR. Differently, GST Ya activity was significantly increased by Cu2+ and Pb2+ and inhibited by Hg2+, while its mRNA was increased by Hg2+ and Pb2+ and decreased by Cu2+. All metals significantly increased the expression of heme oxygenase-1, which coincided with the changes in the phase I and phase II enzyme activities. These results demonstrate that heavy metals differentially modulate the constitutive and the inducible expression of AHR-regulated genes. PMID:15297030

  11. Star-Based Methods for Pleiades HR Commissioning

    NASA Astrophysics Data System (ADS)

    Fourest, S.; Kubik, P.; Lebègue, L.; Déchoz, C.; Lacherade, S.; Blanchet, G.

    2012-07-01

    PLEIADES is the highest resolution civilian earth observing system ever developed in Europe. This imagery program is conducted by the French National Space Agency, CNES. It has been operating since 2012 a first satellite PLEIADES-HR launched on 2011 December 17th, a second one should be launched by the end of the year. Each satellite is designed to provide optical 70 cm resolution colored images to civilian and defense users. Thanks to the extreme agility of the satellite, new calibration methods have been tested, based on the observation of celestial bodies, and stars in particular. It has then been made possible to perform MTF measurement, re-focusing, geometrical bias and focal plane assessment, absolute calibration, ghost images localization, micro-vibrations measurement, etc… Starting from an overview of the star acquisition process, this paper will discuss the methods and present the results obtained during the first four months of the commissioning phase.

  12. 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.

  13. Ultraviolet and radio flares from UX Arietis and HR 1099

    NASA Technical Reports Server (NTRS)

    Lang, Kenneth R.; Willson, Robert F.

    1988-01-01

    Simultaneous observations of the RS CVn systems UX Ari and HR 1099 with the IUE satellite and the VLA are presented. Flaring activity is observed at ultraviolet wavelengths with the IUE when none is detected at radio wavelengths with the VLA. Radio flares with no detectable ultraviolet activity have also been observed. Thus, flares in the two spectral regions are either uncorrelated or weakly correlated. The flaring emission probably originates in different regions at the two wavelengths. Radio flares from RS CVn stars may originate in sources that are larger than, or comparable to, a star in size. This is in sharp contrast to compact, coherent radio flares from dwarf M stars. The ultraviolet flares from RS CVn stars probably originate in sources that are smaller than a component star.

  14. Photospheric imaging of the RS CVn system HR 1099

    NASA Technical Reports Server (NTRS)

    Donati, J.-F.; Brown, S. F.; Semel, M.; Rees, D. E.; Dempsey, R. C.; Matthews, J. M.; Henry, G. W.; Hall, D. S.

    1992-01-01

    Spectropolarimetric, spectroscopic, and photometric observations of the RS CVn binary system HR 1099 = V711 Tau (K1IV+G5V) were made from Oct. 1988 to Jan. 1991. From Doppler imaging of the unpolarized spectra and the corresponding data, two maximum entropy images of the temperature distribution of the active K1 subgiant at epochs 1988.9 and 1990.9 were derived. Zeeman-Doppler imaging of the circularly polarized spectra has led to the first magnetic maps of a star other than the sun. The fragmentary observations made at epoch 1989.6 suggest that the star's magnetic field lines were emerging radially and/or poloidally from an equatorial warm region at that time, quite likely one of these reconstructed in the 1988.9 temperature image.

  15. 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…

  16. MASSES, RADII, AND CLOUD PROPERTIES OF THE HR 8799 PLANETS

    SciTech Connect

    Marley, Mark S.; Saumon, Didier; Cushing, Michael; Ackerman, Andrew S.; Fortney, Jonathan J.; Freedman, Richard E-mail: dsaumon@lanl.gov E-mail: andrew.ackerman@nasa.gov E-mail: freedman@darkstar.arc.nasa.gov

    2012-08-01

    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 concluded that the atmospheres of planets b, c, and d are unusually cloudy or have unusual cloud properties. Some 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 observations of field L and T dwarfs, including the reddest L dwarfs. Unlike some previous studies, we require mutually consistent choices for effective temperature, gravity, cloud properties, and planetary radius. This procedure thus yields plausible 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 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 whether or not we include the H- and the K-band spectrum in our analysis. Solutions for planets c and d are consistent with the generally accepted constraints on the age of the primary star and orbital dynamics. We also confirm that, like in 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 an exploratory evolution calculation that accounts for this effect. Finally we recompute the bolometric luminosity of all three planets.

  17. [Evaluation of +Gz tolerance following simulation of 8-hr flight].

    PubMed

    Khomenko, M N; Bukhtiiarov, I V; Malashchuk, L S

    2005-01-01

    Tolerance of +Gz (head-pelvis) centrifugation of pilots was evaluated following simulation of a long flight on single-seat fighter. The experiment involved 5 test-subjects who were exposed to +Gz before and after simulated 8-hr flight with a growth gradient of 0.1 u/s without anti-g suits and muscles relaxed; in addition, limiting tolerance of intricate profile +Gz loads of 2.0 to 9.0 units with a growth gradient of 1.0 u/s of test-subjects in anti-g suits (AGS) with a change-over pressure valve in the peak mode using muscle straining and breathing maneuvers. To counteract the negative effects of extended flight, various seat configurations: with a back inclination at 30 degrees to the +Gz vector and changeable geometry with a back inclination at 55 degrees to the vector. The other counter-measures applied were cool air shower, suit ventilation, physical exercises, lower body massage with AGS, electrostimulation of the back and lumber region, profiling of the supporting and soft parts of the seat, and 30-s exposure to +5 Gz. Hemodynamic and respiration parameters as well as body temperature were measured in the course of 8 hrs of flight and during and shortly after centrifugation. According to the results of the investigation, seat inclination at 55 degrees to the +Gz vector and tested system of countermeasures prevent degradation of tolerance of large (9 u.) loads following 8-hr flight simulation with the use of the modern anti-g gear, PMID:16353624

  18. Acute hyperhydration reduces athlete biological passport OFF-hr score.

    PubMed

    Bejder, J; Hoffmann, M F; Ashenden, M; Nordsborg, N B; Karstoft, K; Mørkeberg, J

    2016-03-01

    Anecdotal evidence suggests that athletes hyperhydrate to mask prohibited substances in urine and potentially counteract suspicious fluctuations in blood parameters in the athlete biological passport (ABP). It is examined if acute hyperhydration changes parameters included in the ABP. Twenty subjects received recombinant human erythropoietin (rhEPO) for 3 weeks. After 10 days of rhEPO washout, 10 subjects ingested normal amount of water (∼ 270 mL), whereas the remaining 10 ingested a 1000 mL bolus of water. Blood variables were measured 20, 40, 60, and 80 min after ingestion. Three days later, the subjects were crossed-over with regard to water ingestion and the procedure was repeated. OFF-hr was reduced by ∼ 4%, ∼ 3%, and ∼ 2% at 40, 60, and 80 min, respectively, after drinking 1000 mL of water, compared with normal water ingestion (P < 0.05). Forty percent of the subjects were identified with atypical blood profiles (99% specificity level) before drinking 1000 mL of water, whereas 11% (n = 18), 10% and 11% (n = 18) were identified 40, 60, and 80 min, respectively, after ingestion. This was different (P < 0.05) compared with normal water intake, where 45% of the subjects were identified before ingestion, and 54% (n = 19), 45%, and 47% (n = 19) were identified 40, 60, and 80 min, respectively, after ingestion. In conclusion, acute hyperhydration reduces ABP OFF-hr and reduces ABP sensitivity. PMID:25773052

  19. Global Precipitation Analyses at Monthly to 3-HR Time Scales

    NASA Technical Reports Server (NTRS)

    Adler, Robert F.; Huffman, George; Curtis, Scott; Bolvin, David; Nelkin, Eric

    2002-01-01

    Global precipitation analysis covering the last few decades and the impact of the new TRMM precipitation observations are discussed. The 20+ year, monthly, globally complete precipitation analysis of the World Climate Research Program's (WCRP/GEWEX) Global Precipitation Climatology Project (GPCP) is used to explore global and regional variations and trends and is compared to the much shorter TRMM(Tropica1 Rainfall Measuring Mission) tropical data set. A trend pattern that is a combination of both El Nino and La Nina precipitation features is evident in the 20-year data set. This pattern is related to an increase with time in the number of combined months of El Nino and La Nina during the 20 year period. Monthly anomalies of precipitation are related to ENSO variations with clear signals extending into middle and high latitudes of both hemispheres. The GPCP daily, 1deg latitude-longitude analysis, which is available from January 1997 to the present is described and the evolution of precipitation patterns on this time scale related to El Nino and La Nina is described. Finally, a TRMM-based 3-hr analysis is described that uses TRMM to calibrate polar-orbit microwave observations from SSM/I and geosynchronous IR observations and merges the various calibrated observations into a final, 3-hr resolution map. This TRMM standard product will soon be available for the entire TRMM period (January 1998- present). A real-time version of this merged product is being produced and is available at 0.25deg latitude-longitude resolution over the latitude range from 50degN-50degS. Images from this data set can be seen at the U.S. TRMM web site (trmm.gsfc.nasa.gov). Examples will be shown, including its use in monitoring flood conditions and relating weather-scale events to climate variations.

  20. 77 FR 71637 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-03

    ...,989 Siemens Energy, Inc, Fort Madison, IA...... Renewables (Wind Power) Division. The investigation... Fremont, CA October 1, 2011. Design, Appsun, Delta General Corporation, etc. 82,043 Advantage.......... May 8, 2011. Advantage HR. Negative Determinations for Worker Adjustment Assistance In the...

  1. 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. PMID:24998545

  2. 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

  3. 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.

  4. Subsea adjustable choke valves

    SciTech Connect

    Cyvas, M.K. )

    1989-08-01

    With emphasis on deepwater wells and marginal offshore fields growing, the search for reliable subsea production systems has become a high priority. A reliable subsea adjustable choke is essential to the realization of such a system, and recent advances are producing the degree of reliability required. Technological developments have been primarily in (1) trim material (including polycrystalline diamond), (2) trim configuration, (3) computer programs for trim sizing, (4) component materials, and (5) diver/remote-operated-vehicle (ROV) interfaces. These five facets are overviewed and progress to date is reported. A 15- to 20-year service life for adjustable subsea chokes is now a reality. Another factor vital to efficient use of these technological developments is to involve the choke manufacturer and ROV/diver personnel in initial system conceptualization. In this manner, maximum benefit can be derived from the latest technology. Major areas of development still required and under way are listed, and the paper closes with a tabulation of successful subsea choke installations in recent years.

  5. 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. PMID:26183881

  6. 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.

  7. 77 FR 40387 - Price Adjustment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

    ... Price Adjustment AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently filed Postal Service request to adjust prices for several market dominant products... announcing its intent to adjust prices for several market dominant products within First-Class Mail...

  8. 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

  9. Aryl hydrocarbon receptor (AhR) activation during pregnancy, and in adult nulliparous mice, delays the subsequent development of DMBA-induced mammary tumors

    PubMed Central

    Wang, Tao; Gavin, Heather M.; Arlt, Volker M.; Lawrence, B. Paige; Fenton, Suzanne E.; Medina, Daniel; Vorderstrasse, Beth A.

    2010-01-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), the prototypic ligand for the aryl hydrocarbon receptor (AhR), promotes tumor formation in some model systems. However with regard to breast cancer, epidemiological and animal studies are inconclusive as to whether exposure increases tumor incidence or may instead be protective. We have previously reported that mice exposed to TCDD during pregnancy have impaired differentiation of mammary tissue, including decreased branching and poor development of lobuloalveolar structures. Because normal pregnancy-induced mammary differentiation may protect against subsequent neoplastic transformation, we hypothesized that TCDD-treated mice would be more susceptible to chemical carcinogenesis after parturition. To test this, mice were treated with TCDD or vehicle during pregnancy. Four weeks later, DMBA (7,12-dimethylbenz[a]anthracene) was administered to induce mammary tumor formation. Contrary to our hypothesis, TCDD-exposed parous mice showed a four-week delay in tumor formation relative to controls, and had a lower tumor incidence throughout the 27-week time course. The same results were obtained in nulliparous mice given TCDD and DMBA on the same schedule. We next addressed whether the delayed tumor incidence was a reflection of decreased tumor initiation, by testing the formation of DMBA-DNA adducts and preneoplastic lesions, induction of cytochrome P450s, and cell proliferation. None of these markers of tumor initiation differed between vehicle- and TCDD-treated animals. The expression of CXCL12 and CXCR4 was also measured to address their possible role in tumorigenesis. Taken together, our results suggest that AhR activation by TCDD slows the promotion of preneoplastic lesions to overt mammary tumors. PMID:20521247

  10. Amino acid sequence of the AhR1 ligand-binding domain predicts avian sensitivity to dioxin like compounds: in vivo verification in European starlings.

    PubMed

    Eng, Margaret L; Elliott, John E; Jones, Stephanie P; Williams, Tony D; Drouillard, Ken G; Kennedy, Sean W

    2014-12-01

    Research has demonstrated that the sensitivity of avian species to the embyrotoxic effects of dioxin-like compounds can be predicted by the amino acid identities at two key sites within the ligand-binding domain of the aryl hydrocarbon receptor 1 (AhR1). The domestic chicken (Gallus gallus domesticus) has been established as a highly sensitive species to the toxic effects of dioxin-like compounds. Results from genotyping and in vitro assays predict that the European starling (Sturnus vulgaris) is also highly sensitive to dioxin-like compound toxicity. The objective of the present study was to test that prediction in vivo. To do this, we used egg injections in field nesting starlings with 3,3',4,4',5-pentachlorobiphenyl (PCB-126), a dioxin-like polychlorinated biphenyl. Eggs were dosed with either the vehicle control or 1 of 5 doses (1.4, 7.1, 15.9, 32.1, and 52.9 ng PCB-126/g egg). A dose-dependent increase in embryo mortality occurred, and the median lethal dose (LD50; 95% confidence interval [CI]) was 5.61 (2.33-9.08) ng/g. Hepatic CYP1A4/5 messenger RNA (mRNA) expression in hatchlings also increased in a dose-dependent manner, with CYP1A4 being more induced than CYP1A5. No effect of dose on morphological measures was seen, and we did not observe any overt malformations. These results indicate that, other than the chicken, the European starling is the most sensitive species to the effects of PCB-126 on avian embryo mortality reported to date, which supports the prediction of relative sensitivity to dioxin-like compounds based on amino acid sequence of the AhR1. PMID:25209921

  11. AhR activation by 6-formylindolo[3,2-b]carbazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibit the development of mouse intestinal epithelial cells.

    PubMed

    Park, Joo-Hung; Choi, Ah-Jeong; Kim, Soo-Ji; Cheong, Seon-Woo; Jeong, So-Yeon

    2016-04-01

    The intestinal epithelium plays a central role in immune homeostasis in the intestine. AhR, a ligand-activated transcription factor, plays an important role in diverse physiological processes. The intestines are exposed to various exogenous and endogenous AhR ligands. Thus, AhR may regulate the intestinal homeostasis, directly acting on the development of intestinal epithelial cells (IEC). In this study, we demonstrated that 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibited the in vitro development of mouse intestinal organoids. The number of Paneth cells in the small intestine and the depth of crypts of the small and large intestines were reduced in mice administrated with FICZ. Immunohistochemical and flow cytometric assays revealed that AhR was highly expressed in Lgr5(+) stem cells. FICZ inhibited Wnt signaling lowering the level of β-catenin protein. Gene expression analyses demonstrated that FICZ increased expression of Lgr5, Math1, BMP4, and Indian Hedgehog while inhibiting that of Lgr4. PMID:26950395

  12. Differential Rotation of Close Binary Stars: Application to HR 1099

    NASA Astrophysics Data System (ADS)

    Petit, P.; Donati, J.-F.; Wade, G. A.; Landstreet, J. D.; Oliveira, J. M.; Shorlin, S. L. S.; Sigut, T. A. A.; Collier Cameron, A.

    We propose a new method for estimating differential rotation in binary stars, for which only moderate to poor phase coverage can be obtained (rotation period of order of a few days), preventing the use of conventional cross-correlation methods. Assuming a solar-like differential rotation law with two independent parameters (equatorial rotation rate φeq and rotational shear between pole and equator dφ), we reconstruct Doppler images for different values of the two parameters, and derive the optimal φeq, dφ and associated error bars from the corresponding 2 ° map. Simulations show that φeq and dφ can be recovered with good accuracy, even if the phase coverage per rotation cycle is poor, provided the total data set is long enough. From observations of the HR 1099 K1 subgiant secured in 1998, 1999 and 2000, we obtain that the equator rotates faster than the pole with a rotational shear about 3 times smaller than solar.

  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. Aquifer test plan for the 100-HR-3 Operable Unit

    SciTech Connect

    Swanson, L.C.; Hartman, M.J.

    1994-03-28

    This test plan directs hydrologic testing activities planned at three existing Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) wells in the 100-HR-3 Operable Unit of the Hanford Site. Three additional wells will be installed near these existing wells and used as additional testing arid observation points during the field activities. Figure 1 shows the locations of the three test sites. A primary objective of the testing program is to provide more detailed hydraulic characterization information for the unconfined aquifer and targeted test sites than provided by the initial reconnaissance-level slug testing of Vukelich. A second objective is to evaluate the applicability of slug interference and dipole flow tests for detailed hydraulic characterization in an unconfined aquifer. This aquifer testing program will also be useful for substantiating hydraulic conductivities reported from previous slug tests and evaluating the effects of filter pack volume/configuration on slug test data. Vukelich recommended additional testing to address the latter two issues.

  16. 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

    2016-03-01

    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 fit 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.

  17. Butterfly Diagram and Activity Cycles in HR 1099

    NASA Astrophysics Data System (ADS)

    Berdyugina, Svetlana V.; Henry, Gregory W.

    2007-04-01

    We analyze photometric data of the active RS CVn-type star HR 1099 for the years 1975-2006 with an inversion technique and reveal the nature of two activity cycles of 15-16 yr and 5.3+/-0.1 yr duration. The 16 yr cycle is related to variations of the total spot area and is coupled with the differential rotation, while the 5.3 yr cycle is caused by the symmetric redistribution of the spotted area between the opposite stellar hemispheres (flip-flop cycle). We recover long-lived active regions comprising two active longitudes that migrate in the orbital reference frame with a variable rate because of the differential rotation along with changes in the mean spot latitudes. The migration pattern is periodic with the 16 yr cycle. Combining the longitudinal migration of the active regions with a previously measured differential rotation law, we recover the first stellar butterfly diagram without an assumption about spot shapes. We find that mean latitudes of active regions at opposite longitudes change antisymmetrically in the course of the 16 yr cycle: while one active region migrates to the pole, the other approaches the equator. This suggests a precession of the global magnetic field with respect to the stellar rotational axis.

  18. 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. PMID:27262937

  19. Time-dependent transcriptomic and biochemical responses of 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are explained by AHR activation time.

    PubMed

    Farmahin, Reza; Crump, Doug; O'Brien, Jason M; Jones, Stephanie P; Kennedy, Sean W

    2016-09-01

    6-Formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are ligands of the aryl hydrocarbon receptor (AHR) and bind to the AHR with high affinity. Until recently, TCDD was considered to be the most potent AHR agonist, but several recent studies indicate that FICZ binds with greater affinity to the AHR than TCDD. To advance our understanding of the similarities and differences of the effects of FICZ and TCDD exposure in chicken embryo hepatocyte (CEH) cultures, we compared relative expression changes of 27 dioxin-responsive genes by the use of a chicken PCR array, porphyrin accumulation and ethoxyresorufin-O-deethylase (EROD) activity at different time points. In addition, an egg injection study was performed to assess the effects of FICZ on the developing chicken embryo. The results of the current study showed: (1) mean EROD-derived relative potency values for FICZ compared to TCDD changed as a function of time (i.e. 9, 0.004, 0.0008 and 0.00008 at 3, 8, 24, and 48h, respectively) in CEH cultures; (2) FICZ exposure did not result in porphyrin accumulation in CEH cultures; (3) concordance between gene expression profiles for FICZ and TCDD was time- and concentration-dependent, and (4) no mortality or morphological abnormalities were observed in chicken embryos injected with 0.87ng FICZ/g egg into the air cell. The results presented herein suggest that while FICZ and TCDD share similar molecular targets, transient versus sustained AHR activation by FICZ and TCDD result in differential transcriptomic responses. Moreover, rapid metabolism of FICZ in hepatocytes resulted in a significant decrease in the induction of EROD activity. PMID:27301797

  20. 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.

  1. Delay Adjusted Incidence Infographic

    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.

  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. Association Between Tuberculosis and Parkinson Disease

    PubMed Central

    Shen, Chih-Hao; Chou, Chung-Hsing; Liu, Feng-Cheng; Lin, Te-Yu; Huang, Wen-Yen; Wang, Yu-Chiao; Kao, Chia-Hung

    2016-01-01

    Abstract Few studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB. We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models. A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30–1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02–2.52), hypertension (aHR: 2.23, 95% CI: 2.04–2.44), head injury (aHR: 2.32, 95% CI: 1.95–2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49–2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66–2.05), depression (aHR: 4.66, 95% CI: 3.59–6.05), dementia (aHR: 3.70, 95% CI: 2.99–4.59), and stroke (aHR: 2.56, 95% CI: 2.28–2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58–2.00) and decreased with the follow-up period in the TB cohort. Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients. PMID:26937925

  4. Association Between Tuberculosis and Parkinson Disease: A Nationwide, Population-Based Cohort Study.

    PubMed

    Shen, Chih-Hao; Chou, Chung-Hsing; Liu, Feng-Cheng; Lin, Te-Yu; Huang, Wen-Yen; Wang, Yu-Chiao; Kao, Chia-Hung

    2016-02-01

    Few studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB.We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models.A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30-1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02-2.52), hypertension (aHR: 2.23, 95% CI: 2.04-2.44), head injury (aHR: 2.32, 95% CI: 1.95-2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49-2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66-2.05), depression (aHR: 4.66, 95% CI: 3.59-6.05), dementia (aHR: 3.70, 95% CI: 2.99-4.59), and stroke (aHR: 2.56, 95% CI: 2.28-2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58-2.00) and decreased with the follow-up period in the TB cohort.Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients. PMID:26937925

  5. Molecular evolution of HR, a gene that regulates the postnatal cycle of the hair follicle

    PubMed Central

    Abbasi, Amir Ali

    2011-01-01

    Hair is a unique mammalian trait that is absent in all other animal forms. Hairlessness is rare in mammals and humans are exceptional among primates in lacking dense layer of hair covering. HR was the first gene identified to be implicated in hair-cycle regulation. Point mutations in HR lead to congenital human hair loss, which results in the complete loss of body and scalp hairs. HR functions are indispensable for initiation of postnatal hair follicular cycling. This study investigates the phylogenetic history and analyzes the protein evolutionary rate to provide useful insight into the molecular evolution of HR. The data demonstrates an acceleration of HR sequence evolution in human branch and suggests that the ability of HR protein to mediate postnatal hair-cycling has been altered in the course of human evolution. In particular those residues were pinpointed which should be regarded as target of positive Darwinian selection during human evolution. PMID:22355551

  6. Clinical Outcomes with First-line Endocrine Therapy or Chemotherapy in Postmenopausal HR+/HER2− Metastatic Breast Cancer

    PubMed Central

    Song, Yan; Hao, Yanni; Macalalad, Alexander R.; Lin, Peggy L.; Signorovitch, James E.; Wu, Eric Q.

    2015-01-01

    OBJECTIVE To describe patient profiles and clinical outcomes associated with first-line endocrine monotherapy (ET) and chemotherapy (CT) for postmenopausal HR+/HER2− metastatic breast cancer (mBC) patients. METHODS This is a retrospective chart review of 139 postmenopausal HR+/HER2− mBC patients initiating first-line ET monotherapy or CT. Overall survival (OS) was described using Kaplan–Meier curves. Exploratory comparative proportional hazards regression was conducted. RESULTS Patients on first-line CT had significantly more frequent liver metastases than patients on first-line ET monotherapy at baseline. The median OS was 35.5 months [95% confidence interval (CI), 22.7–41.2 months] for patients on first-line ET monotherapy and 22.2 months (95% CI, 13.6–25.9 months) for those on first-line CT (P = 0.021). Adjusting for baseline characteristics, the OS between first-line ET monotherapy and CT was not significantly different. CONCLUSIONS Patients who were prescribed CT as first-line treatment had evidence of more advanced disease at baseline and shorter OS than those who received ET monotherapy as first-line treatment, suggesting a need for additional safe and effective treatment options for these patients. PMID:26380551

  7. Coordinated Regulation of Hepatic Phase I and II Drug-Metabolizing Genes and Transporters using AhR-, CAR-, PXR-, PPARα-, and Nrf2-Null Mice

    PubMed Central

    Aleksunes, Lauren M.

    2012-01-01

    The transcription factors aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor α (PPARα), and nuclear factor erythroid 2-related factor 2 (Nrf2) regulate genes encoding drug-metabolizing enzymes and transporters in livers of mice after chemical activation. However, the specificity of their transcriptional regulation has not been determined systematically in vivo. The purpose of this study was to identify genes encoding drug-metabolizing enzymes and transporters altered by chemical activators in a transcription factor-dependent manner using wild-type and transcription factor-null mice. Chemical activators were administered intraperitoneally to mice once daily for 4 days. Livers were collected 24 h after the final dose, and total RNA was isolated for mRNA quantification of cytochromes P450, NAD(P)H quinone oxidoreductase 1 (Nqo1), aldehyde dehydrogenases (Aldhs), glutathione transferases (Gsts), sulfotransferases (Sults), UDP-glucuronosyltransferases (Ugts), organic anion-transporting polypeptides (Oatps), and multidrug resistance-associated proteins (Mrps). Pharmacological activation of each transcription factor leads to mRNA induction of drug metabolic and transport genes in livers of male and female wild-type mice, but no change in null mice: AhR (Cyp1a2, Nqo1, Aldh7a1, Ugt1a1, Ugt1a6, Ugt1a9, Ugt2b35, Sult5a1, Gstm3, and Mrp4), CAR (Cyp2b10, Aldh1a1, Aldh1a7, Ugt1a1, Ugt2b34, Sult1e1, Sult3a1, Sult5a1, Papps2, Gstt1, Gsta1, Gsta4, Gstm1–4, and Mrp2–4), PXR (Cyp3a11, Ugt1a1, Ugt1a5, Ugt1a9, Gsta1, Gstm1–m3, Oatp1a4, and Mrp3), PPARα (Cyp4a14, Aldh1a1, mGst3, Gstm4, and Mrp4), and Nrf2 (Nqo1, Aldh1a1, Gsta1, Gsta4, Gstm1–m4, mGst3, and Mrp3–4). Taken together, these data reveal transcription factor specificity and overlap in regulating hepatic drug disposition genes by chemical activators. Coordinated regulation of phase I, phase II, and transport genes by

  8. 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

  9. 78 FR 62712 - Rate Adjustment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... Rate Adjustment AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing seeking postal rate adjustments based on exigent circumstances... On September 26, 2013, the Postal Service filed an exigent rate request with the Commission...

  10. Adjustable holder for transducer mounting

    NASA Technical Reports Server (NTRS)

    Deotsch, R. C.

    1980-01-01

    Positioning of acoustic sensor, strain gage, or similar transducer is facilitated by adjustable holder. Developed for installation on Space Shuttle, it includes springs for maintaining uniform load on transducer with adjustable threaded cap for precisely controlling position of sensor with respect to surrounding structure.

  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. Mood Adjustment via Mass Communication.

    ERIC Educational Resources Information Center

    Knobloch, Silvia

    2003-01-01

    Proposes and experimentally tests mood adjustment approach, complementing mood management theory. Discusses how results regarding self-exposure across time show that patterns of popular music listening among a group of undergraduate students differ with initial mood and anticipation, lending support to mood adjustment hypotheses. Describes how…

  13. 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. PMID:26924718

  14. 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…

  15. 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…

  16. 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

  17. The Neighborhood Schools Improvement Act, H.R. 3320: Summary and Analysis. CRS Report for Congress.

    ERIC Educational Resources Information Center

    Riddle, Wayne; Stedman, James B.

    The Neighborhood Schools Improvement Act (H.R. 3320) was ordered to be reported by the House Committee on Education and Labor on October 17, 1991. This report provides an introduction to the "systemic statewide reform" concept, on which H.R. 3320 is largely based, plus a summary of the bill, and a discussion of selected issues related to this…

  18. 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…

  19. Elemental abundances of the mercury-manganese stars HR 4817 and Chi Lupi

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

    Fine analyses of limited spectral regions of the mercury-manganese stars HR 4817 and Chi Lup confirm that these stars have abundances of typical class members. The best determined values of HR 4817 are similar to those of 53 Tau which is an anomalous class member.

  20. 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.

  1. 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.

  2. Subtotal Gastrectomy With Billroth II Anastomosis Is Associated With a Low Risk of Ischemic Stroke in Peptic Ulcer Disease Patients: A Nationwide Population-Based Study.

    PubMed

    Chen, Chien-Hua; Lin, Cheng-Li; Kao, Chia-Hung

    2016-04-01

    Duodenal diversion can ameliorate lipid and glucose metabolism. We assessed the risk of stroke after subtotal gastrectomy with Billroth II anastomosis (SGBIIA) in peptic ulcer disease (PUD).We identified 6425 patients who received SGBIIA for PUD between 1998 and 2010 from the Taiwan National Health Insurance Research Database as the study cohort; we frequency-matched them with 25,602 randomly selected controls from the PUD population who did not receive SGBIIA according to age, sex, index year, and comorbidities including hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease (COPD), and obesity. All patients were followed until the end of 2011 to determine the incidence of stroke.The incidence of stroke was lower in patients in the SGBIIA cohort than in those in the non-SGBIIA cohort (18.9 vs 22.9 per 1000 person-years, adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.72-0.89, P < 0.001). The risk of ischemic stroke (aHR 0.77, 95% CI 0.69-0.86, P < 0.001), rather than hemorrhagic stroke (aHR 1.00, 95% CI 0.78-1.28), was lower for the SGBIIA cohort than for the non-SGBIIA cohort according to the multivariable Cox proportional hazard regression analysis. The relative risk of ischemic stroke after SGBIIA was lower in men (aHR 0.77, 95% CI 0.69-0.86) than in women (aHR 0.80, 95% CI 0.65-0.99) and in patients aged ≥65 years (aHR 0.72, 95% CI 0.63-0.81) than in those of other age groups (≤49 years, aHR 0.82, 95% CI 0.48-1.39; 50-64 years, aHR 1.01, 95% CI 0.79-1.28). The relative risk of ischemic stroke after SGBIIA was also reduced in patients with comorbidities (aHR 0.84, 5% CI 0.75-0.95) rather than in those without comorbidities (aHR 0.81, 95% CI 0.59-1.12).SGBIIA is associated with a low risk of ischemic stroke for PUD patients, and its protective effect is prominent in men, patients aged ≥65 years, and those with comorbidities

  3. Subtotal Gastrectomy With Billroth II Anastomosis Is Associated With a Low Risk of Ischemic Stroke in Peptic Ulcer Disease Patients

    PubMed Central

    Chen, Chien-Hua; Lin, Cheng-Li; Kao, Chia-Hung

    2016-01-01

    Abstract Duodenal diversion can ameliorate lipid and glucose metabolism. We assessed the risk of stroke after subtotal gastrectomy with Billroth II anastomosis (SGBIIA) in peptic ulcer disease (PUD). We identified 6425 patients who received SGBIIA for PUD between 1998 and 2010 from the Taiwan National Health Insurance Research Database as the study cohort; we frequency-matched them with 25,602 randomly selected controls from the PUD population who did not receive SGBIIA according to age, sex, index year, and comorbidities including hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease (COPD), and obesity. All patients were followed until the end of 2011 to determine the incidence of stroke. The incidence of stroke was lower in patients in the SGBIIA cohort than in those in the non-SGBIIA cohort (18.9 vs 22.9 per 1000 person-years, adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.72–0.89, P < 0.001). The risk of ischemic stroke (aHR 0.77, 95% CI 0.69–0.86, P < 0.001), rather than hemorrhagic stroke (aHR 1.00, 95% CI 0.78–1.28), was lower for the SGBIIA cohort than for the non-SGBIIA cohort according to the multivariable Cox proportional hazard regression analysis. The relative risk of ischemic stroke after SGBIIA was lower in men (aHR 0.77, 95% CI 0.69–0.86) than in women (aHR 0.80, 95% CI 0.65–0.99) and in patients aged ≥65 years (aHR 0.72, 95% CI 0.63–0.81) than in those of other age groups (≤49 years, aHR 0.82, 95% CI 0.48–1.39; 50–64 years, aHR 1.01, 95% CI 0.79–1.28). The relative risk of ischemic stroke after SGBIIA was also reduced in patients with comorbidities (aHR 0.84, 5% CI 0.75–0.95) rather than in those without comorbidities (aHR 0.81, 95% CI 0.59–1.12). SGBIIA is associated with a low risk of ischemic stroke for PUD patients, and its protective effect is prominent in men, patients aged ≥65

  4. 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

  5. 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.

  6. 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.

  7. Inhibition of UVR-induced tanning and immunosuppression by topical applications of vitamins C and E to the skin of hairless (hr/hr) mice.

    PubMed

    Quevedo, W C; Holstein, T J; Dyckman, J; McDonald, C J; Isaacson, E L

    2000-04-01

    Exposure of C3HBYB/Wq hairless (hr/hr) mice to ultra-violet radiation (UVR) for 15 days induced intense tanning of their dorsal skin. Small, dark freckles appeared first, gradually enlarging and coalescing as treatment progressed yielding a uniform tan. Histologically, the gross changes in skin color were matched initially by the appearance of scattered epidermal melanocytes that subsequently proliferated to form discrete, progressively expanding and abutting populations resulting in a uniform melanocyte network throughout the basal layer of the interfollicular epidermis. In contrast, when applied topically before each daily exposure to UVR, a cream or lotion vehicle containing both vitamins C and E (Vits C/E) inhibited UVR-induced erythema and tanning. Application of Vits C/E, both before and after irradiation, was no more effective in providing photoprotection than pre-treatment only. At the tissue level, UVR-induced proliferation and melanogenesis of melanocytes were reduced compared with irradiated controls. The density of individual melanocyte populations was reduced, as was the number of melanocyte populations achieving merger (confluence) with others. Confluence grades and cell counts, estimating the maximum density of melanocyte populations in UVR-Vits C/E-treated mice, were approximately two thirds those of UVR-vehicle-treated controls. However, tanning was only one fifth that of UVR-vehicle-treated controls, suggesting that melanogenesis was also inhibited. In addition to its inhibitory actions on irradiated melanocytes, Vits C/E also inhibited UVR-induced suppression of contact hypersensitivity (CHS) in haired (Hr/hr) and hr/hr mice of the C3HBYB/Wq strain. The common denominators for most, if not all, of the influences of topically-applied Vits C/E in muting the responses of the melanocyte and immune systems to UVR may stem from the vitamins' combined ability to suppress UVR-stimulated inflammation and its associated cascade of mediators. PMID:10841030

  8. 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. PMID:27530850

  9. 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.

  10. 7 CFR 251.7 - Formula adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Formula adjustments. 251.7 Section 251.7 Agriculture... GENERAL REGULATIONS AND POLICIES-FOOD DISTRIBUTION THE EMERGENCY FOOD ASSISTANCE PROGRAM § 251.7 Formula adjustments. Formula adjustments. (a) Commodity adjustments. The Department will make annual adjustments...

  11. 12 CFR 1209.80 - Inflation adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Inflation adjustments. 1209.80 Section 1209.80... PROCEDURE Civil Money Penalty Inflation Adjustments § 1209.80 Inflation adjustments. The maximum amount of... thereafter adjusted in accordance with the Inflation Adjustment Act, on a recurring four-year cycle, is...

  12. 12 CFR 1209.80 - Inflation adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 9 2012-01-01 2012-01-01 false Inflation adjustments. 1209.80 Section 1209.80... PROCEDURE Civil Money Penalty Inflation Adjustments § 1209.80 Inflation adjustments. The maximum amount of... thereafter adjusted in accordance with the Inflation Adjustment Act, on a recurring four-year cycle, is...

  13. 12 CFR 1209.80 - Inflation adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 9 2013-01-01 2013-01-01 false Inflation adjustments. 1209.80 Section 1209.80... PROCEDURE Civil Money Penalty Inflation Adjustments § 1209.80 Inflation adjustments. The maximum amount of... thereafter adjusted in accordance with the Inflation Adjustment Act, on a recurring four-year cycle, is...

  14. 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

  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

    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. PMID:24374617

  16. 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

  17. 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.

  18. An Age Estimate for the beta Pictoris Analog HR 4796A

    NASA Astrophysics Data System (ADS)

    Stauffer, John R.; Hartmann, Lee W.; Barrado y Navascues, David

    1995-12-01

    We have obtained a high-resolution, moderate signal-to-noise spectrum for the M dwarf companion to HR 4796A, an AO star with a β Pictoris-type IR excess. The spectrum of the M star shows an extraordinarily strong lithium 6708 Å absorption line with an equivalent width of 550 mÅ. Age estimates derived from the lithium strength and from pre-main-sequence isochrone fitting indicate an age of about 8 ± 2 Myr for HR 4796B. Assuming this age is also applicable to HR 4796A, we conclude that HR 4796A is a relatively normal A star seen at an unusual time (i.e., when it is very young) rather than an A star of "average" age which has somehow managed to retain or acquire a dense, circumstellar disk, in rough agreement with conclusions reached previously by Jura et al.

  19. Citron and lemon under the lens of HR-MAS NMR spectroscopy.

    PubMed

    Mucci, Adele; Parenti, Francesca; Righi, Valeria; Schenetti, Luisa

    2013-12-01

    High Resolution Magic Angle Spinning (HR-MAS) is an NMR technique that can be applied to semi-solid samples. Flavedo, albedo, pulp, seeds, and oil gland content of lemon and citron were studied through HR-MAS NMR spectroscopy, which was used directly on intact tissue specimens without any physicochemical manipulation. HR-MAS NMR proved to be a very suitable technique for detecting terpenes, sugars, organic acids, aminoacids and osmolites. It is valuable in observing changes in sugars, principal organic acids (mainly citric and malic) and ethanol contents of pulp specimens and this strongly point to its use to follow fruit ripening, or commercial assessment of fruit maturity. HR-MAS NMR was also used to derive the molar percentage of fatty acid components of lipids in seeds, which can change depending on the Citrus species and varieties. Finally, this technique was employed to elucidate the metabolic profile of mold flavedo. PMID:23871074

  20. 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.

  1. Initiating Improvements: The HR Department as the Architect of Quality-of-Life Initiatives.

    ERIC Educational Resources Information Center

    Reis, Frank William

    2002-01-01

    Describes how a wellness program, campus safety and security program, and institutional knowledge management program are succeeding at Cuyahoga Community College after the human resources (HR) department won administrative support for their implementation. (EV)

  2. Chromospheric and transition region structure of the Herbig emission stars HR 5999 and BN Ori

    NASA Technical Reports Server (NTRS)

    Brown, A.; Tjinadjie, H. R. E.; The, P. S.

    1986-01-01

    The IUE spectra of HR 5999 and BN Ori were analyzed, showing strong emission lines of C II, C IV, O I, and Si IV (also Mg II in HR 5999), indicating the presence of chromospheres and transition regions around these high mass premain sequence (PMS) stars. Infrared, optical, and ultraviolet observations show that BN Ori has a spectral type of FO-2 IIIe, a bolometric luminosity of 36 L, age 1.5 million yr, and mass 2 to 2.5 solar mass. As HR 5999 fades, the ratio of total to selective absorption increases indicating the appearance of larger grains or changes in grain alignment. Emission measure distributions are used to investigate the atmospheric structure of the stars. As HR 5999 fades the emission measure distribution rises systematically and the inferred transition region pressures increase. The transition region and chromospheric radiative losses are large and imply input mechanical energy fluxes similar to those of lower mass PMS stars.

  3. 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. PMID:25311296

  4. 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

  5. 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.

  6. 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.

  7. A 10,000-hr life test of an engineering model resistojet

    NASA Technical Reports Server (NTRS)

    Slutz, Rodger J.

    1990-01-01

    One of the major issues associated with using resistojet thrusters on Space Station Freedom is the long life required. An engineering model resistojet was life-tested to determine if it was capable of meeting that requirement. This thruster, which was designed for 10,000 hr of operation at 2552.4 F (1400 C) or less under cyclical thermal conditions, successfully operated for 10,036 hr at 1836 F (1002 C) while undergoing 141 thermal cycles.

  8. Final RQ adjustments rule issued

    SciTech Connect

    Bergeson, L.L.

    1995-08-01

    On June 12, 1995, the US Environmental Protection Agency (EPA) issued its long awaited final rule adjusting certain reportable quantities (RQs) for hazardous substances under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). The rule: revises the table of hazardous substances to add 47 individual Clean Air Act (CAA) hazardous air pollutants (HAPs); adjustments their statutory one-pound RQs; adds five other CAA HAPs that are categories of substances and assigns no RQ to the categories; and adjusts RQs for 11 Resource Conservation and Recovery Act (RCRA) listed hazardous wastes. EPA made conforming changes to the Clean Water Act table of hazardous substances and the Emergency Planning and Community Right-to-Know Act (EPCRA) table of extremely hazardous substances. The rule became effective July 12, 1995.

  9. 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.

  10. Adjustable spacer with rotational lock

    SciTech Connect

    Bowyer, M.L.

    1984-02-28

    A spacing apparatus for tubing conduit in a subterranean well, normally for use with an electric component with a longitudinally extending external electrical cable, permits irrotational adjustment of the length of the tubing conduit. The spacing apparatus comprises telescoping members which are keyed to prevent rotation therebetween. A threaded member, longitudinally fixed relative to one longitudinal member, normally engages threads extending substantially along the entire length of the other telescoping member. Movement of a retaining sleeve permits disengagement of the threaded segments which ratchet along the threads during telescoping movement. The length of the conduit can thus be irrotationally adjusted to remove slack from the electrical cable.

  11. Convective adjustment in baroclinic atmospheres

    NASA Technical Reports Server (NTRS)

    Emanuel, Kerry A.

    1986-01-01

    Local convection in planetary atmospheres is generally considered to result from the action of gravity on small regions of anomalous density. That in rotating baroclinic fluids the total potential energy for small scale convection contains a centrifugal as well as a gravitational contribution is shown. Convective adjustment in such an atmosphere results in the establishment of near adiabatic lapse rates of temperature along suitably defined surfaces of constant angular momentum, rather than in the vertical. This leads in general to sub-adiabatic vertical lapse rates. That such an adjustment actually occurs in the earth's atmosphere is shown by example and the magnitude of the effect for several other planetary atmospheres is estimated.

  12. 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

  13. 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...

  14. Visual adjustments to temporal blur

    NASA Astrophysics Data System (ADS)

    Bilson, Aaron C.; Mizokami, Yoko; Webster, Michael A.

    2005-10-01

    After observers have adapted to an edge that is spatially blurred or sharpened, a focused edge appears too sharp or blurred, respectively. These adjustments to blur may play an important role in calibrating spatial sensitivity. We examined whether similar adjustments influence the perception of temporal edges, by measuring the appearance of a step change in the luminance of a uniform field after adapting to blurred or sharpened transitions. Stimuli were square-wave alternations (at 1 to 8 Hz) filtered by changing the slope of the amplitude spectrum. A two-alternative-forced-choice task was used to adjust the slope until it appeared as a step change, or until it matched the perceived transitions in a reference stimulus. Observers could accurately set the waveform to a square wave, but only at the slower alternation rates. However, these settings were strongly biased by prior adaptation to filtered stimuli, or when the stimuli were viewed within temporally filtered surrounds. Control experiments suggest that the latter induction effects result directly from the temporal blur and are not simply a consequence of brightness induction in the fields. These results suggest that adaptation and induction adjust visual coding so that images are focused not only in space but also in time.

  15. Self-Adjusting Fluency Therapy.

    ERIC Educational Resources Information Center

    Schneider, Phillip

    1998-01-01

    Presents a rationale and methodology for a self-adjusting "fluency sensitive" approach to working with children who exhibit overt speech-fluency interruptions and a minimal amount of avoidance behavior. The approach emphasizes repeated experiences of volitional increases and decreases in loudness and pauses. Case examples demonstrate how several…

  16. Adjustable Walker for the Handicapped

    NASA Technical Reports Server (NTRS)

    Kitts, R. G.

    1984-01-01

    Front legs adjust at touch of lever for use on stairs or ramps. Spring loaded legs extend when lever is depressed by user. Legs lock in position when lever is released. Lever mounted on either side of walker or on both sides, so legs operated independently.

  17. 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.

  18. Adjustable-Angle Drill Block

    NASA Technical Reports Server (NTRS)

    Gallimore, F. H.

    1986-01-01

    Adjustable angular drill block accurately transfers hole patterns from mating surfaces not normal to each other. Block applicable to transfer of nonperpendicular holes in mating contoured assemblies in aircraft industry. Also useful in general manufacturing to transfer mating installation holes to irregular and angular surfaces.

  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. Hearing on Computer Education. Hearing before the Subcommittee on Elementary, Secondary, and Vocational Education of the Committee on Education and Labor, House of Representatives, Ninety-Eighth Congress, Second Session, on H.R. 3750, H.R. 1134, and H.R. 4628.

    ERIC Educational Resources Information Center

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

    This hearing report covers three bills: (1) H.R. 3750, which would authorize grants to local educational agencies to purchase computer equipment; (2) H.R. 1134, which would provide funds to establish and operate model centers for computers in education; and (3) H.R. 4628, which would establish a government corporation to promote the development…

  1. 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)...

  2. 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)...

  3. 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... Civil Penalties Inflation Adjustment Act of 1990 (28 U.S.C. 2461 note) as follows: ER10NO08.001 (b)...

  4. Cultural Adjustment and the Puerto Rican.

    ERIC Educational Resources Information Center

    Prewitt-Diaz, Joseph O.

    This review of the literature on cultural adjustment is divided into four sections: the nature of cultural adjustment; acculturation as a model of cultural adjustment; psychological responses to acculturation; and a model of cultural adjustment developed by the author as a result of his immigration from Puerto Rico to the United States mainland.…

  5. 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…

  6. 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.

  7. 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.

  8. 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

    Piasecka-Srader, Joanna; Sadowska, Agnieszka; Nynca, Anna; Orlowska, Karina; Jablonska, Monika; Jablonska, Olga; Petroff, Brian K; Ciereszko, Renata E

    2016-02-20

    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

  9. 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.

  10. Semi-parametric time-domain quantification of HR-MAS data from prostate tissue

    PubMed Central

    Ratiney, Helene; Albers, Mark J.; Rabeson, Herald; Kurhanewicz, John

    2011-01-01

    High Resolution – Magic Angle Spinning (HR-MAS) spectroscopy provides rich biochemical profiles that require accurate quantification to permit biomarker identification and to understand the underlying pathological mechanisms. Meanwhile, quantification of HR-MAS data from prostate tissue samples is challenging due to significant overlap between the resonant peaks, the presence of short T2∗ metabolites such as citrate or polyamines (T2 from 25 to 100 msec) and macromolecules, and variations in chemical shifts and T2∗s within a metabolite’s spin systems. Since existing methods do not address these challenges completely, a new quantification method was developed and optimized for HR-MAS data acquired with an ultra short TE and over 30,000 data points. The proposed method, named HR-QUEST (High Resolution – QUEST), iteratively employs the QUEST time-domain semi-parametric strategy with a new model function that incorporates prior knowledge from whole and subdivided metabolite signals. With these features, HR-QUEST is able to independently fit the chemical shifts and T2∗s of a metabolite’s spin systems, a necessity for HR-MAS data. By using the iterative fitting approach, it is able to account for significant contributions from macromolecules and to handle shorter T2 metabolites, such as citrate and polyamines. After subdividing the necessary metabolite basis signals, the root mean square (RMS) of the residual was reduced by 52% for measured HR-MAS data from prostate tissue. Monte Carlo studies on simulated spectra with varied macromolecular contributions showed that the iterative fitting approach (6 iterations) coupled with inclusion of long T2 macromolecule components in the basis set improve the quality of the fit, as assessed by the reduction of the RMS of the residual and of the RMS error of the metabolite signal estimate, by 27% and 71% respectively. With this optimized configuration, HR-QUEST was applied to measured HR-MAS prostate data and reliably

  11. Incidence Density and Risk Factors of Diabetic Retinopathy Within Type 2 Diabetes: A Five-Year Cohort Study in China (Report 1)

    PubMed Central

    Liu, Lei; Wu, Jingyang; Yue, Song; Geng, Jin; Lian, Jie; Teng, Weiping; Huang, Desheng; Chen, Lei

    2015-01-01

    A prospective study was carried out from August 2010 to August 2014 in the community of Fengyutan (China). Six hundred and twenty two T2D subjects were collected. The incidence density of diabetic retinopathy (DR) was 1.81% person-year (95% confidence interval, CI: 1.21–2.43% person-year). After a Cox regression model analysis and adjusted confounding factors, independent predictors related to the incidence of DR including male gender (adjusted hazard ratios, aHR: 1.47, 95% CI: 1.21–1.62), with hypertension (aHR: 1.49, 95%: 1.12–1.73), duration of diabetes > 10 years (aHR: 2.28, 95%: 2.05–2.42), uncontrolled diabetes (aHR: 1.76, 95%: 1.41–2.01), total cholesterol ≥ 200 mg/dL (aHR: 1.54, 95%: 1.34–1.72) and HbA1c ≥ 7% (mmol/mol) (aHR: 2.12, 95%: 1.87–2.32). Duration of T2D revealed the significantly dose-response relationship to the onset of DR. The incidence density of DR in the Chinese community was relatively low in comparison with other studies. More attention should be paid to the T2D patients, especially of male gender, with hypertension, longer duration of diabetes, uncontrolled diabetes, total cholesterol ≥ 200mg/dL and HbA1c ≥ 7% (mmol/mol). PMID:26184262

  12. Mining machine with adjustable jib

    SciTech Connect

    Hart, D.

    1987-05-26

    A mining machine is described having a pair of crawler tracks, a means for individually driving each of the crawler tracks, a frame mounted on the crawler tracks, an elongated jib carrying a sprocket at each end, an endless cutting chain supported on the sprockets, cutters and loading flights mounted on the endless cutting chain, and means on the frame supporting the elongated jib. The means support the elongated jib consisting of a bridge on the frame, at least one scissors linkage pivotally mounted on the bridge, and arm having a first end attached to the scissors linkage, a front plate mounted on the second end of the arm and means adjustably mounting the elongated jib on the front plate. The means adjustably mount the elongated jib on the front plate including a first means for rotating the elongated jib between a vertical position and a horizontal position.

  13. Developmental defects and male sterility in mice lacking the ubiquitin-like DNA repair gene mHR23B.

    PubMed

    Ng, Jessica M Y; Vrieling, Harry; Sugasawa, Kaoru; Ooms, Marja P; Grootegoed, J Anton; Vreeburg, Jan T M; Visser, Pim; Beems, Rudolph B; Gorgels, Theo G M F; Hanaoka, Fumio; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J

    2002-02-01

    mHR23B encodes one of the two mammalian homologs of Saccharomyces cerevisiae RAD23, a ubiquitin-like fusion protein involved in nucleotide excision repair (NER). Part of mHR23B is complexed with the XPC protein, and this heterodimer functions as the main damage detector and initiator of global genome NER. While XPC defects exist in humans and mice, mutations for mHR23A and mHR23B are not known. Here, we present a mouse model for mHR23B. Unlike XPC-deficient cells, mHR23B(-/-) mouse embryonic fibroblasts are not UV sensitive and retain the repair characteristics of wild-type cells. In agreement with the results of in vitro repair studies, this indicates that mHR23A can functionally replace mHR23B in NER. Unexpectedly, mHR23B(-/-) mice show impaired embryonic development and a high rate (90%) of intrauterine or neonatal death. Surviving animals display a variety of abnormalities, including retarded growth, facial dysmorphology, and male sterility. Such abnormalities are not observed in XPC and other NER-deficient mouse mutants and point to a separate function of mHR23B in development. This function may involve regulation of protein stability via the ubiquitin/proteasome pathway and is not or only in part compensated for by mHR23A. PMID:11809813

  14. 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. PMID:17567838

  15. IUE observations of HR 6902 - Effect of luminosity on supergiant chromospheres

    NASA Technical Reports Server (NTRS)

    Ahmad, Imad A.

    1990-01-01

    IUE observations of the most recently discovered Zeta Aurigae system, HR 6902, are reported to reveal profound differences in the spectrum of the chromosphere of the cool primary from those of all other Zeta Aurigae systems. Unlike its sister systems, HR 6902 shows evidence of neither strong wind nor an extended chromosphere for the cool primary. Instead, the spectrum is like that of a single blue dwarf. The most likely reason for this contrast to all other Zeta Aur systems observed with IUE is the lower luminosity of the HR 6902 primary: a type-II 'bright giant' as opposed to the type I (or Ib-II in the case of 22 Vul) 'supergiants' in the other Zeta Aur systems.

  16. 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.

  17. Attachment and social adjustment: relationships to suicide attempt and major depressive episode in a prospective study

    PubMed Central

    Grunebaum, Michael F.; Galfalvy, Hanga C.; Mortenson, Lindsey Y.; Burke, Ainsley K.; Oquendo, Maria A.; Mann, J. John

    2009-01-01

    Objective To study two aspects of interpersonal function - attachment security and social adjustment – in relation to suicide attempt and major depressive episode (MDE) during naturalistic follow-up of up to one year after presentation with MDE. Method 136 adults who presented with a DSM-IV MDE completed the Adult Attachment Scale and the Social Adjustment Scale-Self Report at study entry. Based on follow-up interviews at three months and one year, we used survival analysis to investigate the relationship of scores on these measures with time to a suicide attempt and time to recurrent MDE. Results Less secure/more avoidant attachment predicted increased risk of suicide attempt during the 1-year follow-up (Wald χ2=9.14, df=1, p=.003, HR=1.16, 95% CI=1.05 to 1.27). Poorer social adjustment predicted increased risk of recurrent MDE (Wald χ2=6.95, df=1, p=.008, HR=2.36, 95% CI=1.25 to 4.46), and that in turn increased the risk of a suicide attempt (z=4.19, df=1, p<.001, HR=17.3, 95% CI=4.6 to 65.5). Conclusions Avoidant attachment in the setting of major depressive disorder is a potential therapeutic target to prevent suicidal behavior. Enhancing social adjustment may reduce relapse in major depressive disorder and thereby reduce risk of a suicide attempt. Study limitations include small sample size and use of a self-report attachment scale. PMID:19819021

  18. 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.

  19. The long-period K + Be binary HR 2577 (MWC 827)

    NASA Technical Reports Server (NTRS)

    Dempsey, Robert C.; Bopp, Bernard W.; Parsons, Sidney B.

    1988-01-01

    New spectroscopic observations near H-alpha and Na I D, along with ultraviolet IUE scans, have been obtained for the K + Be composite system HR 2577. High-precision radial-velocity measures do not support the suggested 58-year orbit of Hendry (1982). The H-alpha emission from the Be component undergoes considerable variations typical of its class. The presence of a Li I 6707 A feature as well as the IUE observations support the idea that little or no interaction between the binary components of HR 2577 is taking place.

  20. NEAR-INFRARED SPECTROSCOPY OF THE EXTRASOLAR PLANET HR 8799 b

    SciTech Connect

    Bowler, Brendan P.; Liu, Michael C.; Dupuy, Trent J.; Cushing, Michael C.

    2010-11-01

    We present 2.12-2.23 {mu}m 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 {mu}m CH{sub 4} 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 CH{sub 4} seen in T dwarfs of similar absolute magnitudes. The spectrum is consistent with field objects from early-L to T4 (3{sigma} confidence level), with a best-fitting type of T2. A similar analysis of the published 1-4 {mu}m 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 {mu}m spectrum and the infrared SED using the Hubeny and 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 {approx}0.3 and 0.5 R{sub Jup}. These values are inconsistent with evolutionary model-derived values of 800-900 K and 1.1-1.3 R{sub 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

  1. Adjustable link for kinematic mounting systems

    DOEpatents

    Hale, L.C.

    1997-07-01

    An adjustable link for kinematic mounting systems is disclosed. The adjustable link is a low-cost, passive device that provides backlash-free adjustment along its single constraint direction and flexural freedom in all other directions. The adjustable link comprises two spheres, two sockets in which the spheres are adjustable retain, and a connection link threadly connected at each end to the spheres, to provide a single direction of restraint and to adjust the length or distance between the sockets. Six such adjustable links provide for six degrees of freedom for mounting an instrument on a support. The adjustable link has applications in any machine or instrument requiring precision adjustment in six degrees of freedom, isolation from deformations of the supporting platform, and/or additional structural damping. The damping is accomplished by using a hollow connection link that contains an inner rod and a viscoelastic separation layer between the two. 3 figs.

  2. Adjustable link for kinematic mounting systems

    DOEpatents

    Hale, Layton C.

    1997-01-01

    An adjustable link for kinematic mounting systems. The adjustable link is a low-cost, passive device that provides backlash-free adjustment along its single constraint direction and flexural freedom in all other directions. The adjustable link comprises two spheres, two sockets in which the spheres are adjustable retain, and a connection link threadly connected at each end to the spheres, to provide a single direction of restraint and to adjust the length or distance between the sockets. Six such adjustable links provide for six degrees of freedom for mounting an instrument on a support. The adjustable link has applications in any machine or instrument requiring precision adjustment in six degrees of freedom, isolation from deformations of the supporting platform, and/or additional structural damping. The damping is accomplished by using a hollow connection link that contains an inner rod and a viscoelastic separation layer between the two.

  3. The HR97 (NR1L) group of nuclear receptors: a new group of nuclear receptors discovered in Daphnia species.

    PubMed

    Li, Yangchun; Ginjupalli, Gautam K; Baldwin, William S

    2014-09-15

    The recently sequenced Daphnia pulex genome revealed the NR1L nuclear receptor group consisting of three novel receptors. Phylogenetic studies show that this group is related to the NR1I group (CAR/PXR/VDR) and the NR1J group (HR96), and were subsequently named HR97a/b/g. Each of the HR97 paralogs from Daphnia magna, a commonly used crustacean in toxicity testing, was cloned, sequenced, and partially characterized. Phylogenetic analysis indicates that the HR97 receptors are present in primitive arthropods such as the chelicerates but lost in insects. qPCR and immunohistochemistry demonstrate that each of the receptors is expressed near or at reproductive maturity, and that HR97g, the most ancient of the HR97 receptors, is primarily expressed in the gastrointestinal tract, mandibular region, and ovaries, consistent with a role in reproduction. Transactivation assays using an HR97a/b/g-GAL4 chimera indicate that unlike Daphnia HR96 that is promiscuous with respect to ligand recognition, the HR97 receptors do not respond to many of the ligands that activate CAR/PXR/HR96 nuclear receptors. Only three putative ligands of HR97 receptors were identified in this study: pyriproxyfen, methyl farnesoate, and arachidonic acid. Only arachidonic acid, which acts as an inverse agonist, alters HR97g activity at concentrations that would be considered within physiologically relevant ranges. Overall, this study demonstrates that, although closely related to the promiscuous receptors in the NR1I and NR1J groups, the HR97 receptors are mostly likely not multi-xenobiotic sensors, but rather may perform physiological functions, potentially in reproduction, unique to crustaceans and other non-insect arthropod groups. PMID:25092536

  4. Correlates of household seismic hazard adjustment adoption.

    PubMed

    Lindell, M K; Whitney, D J

    2000-02-01

    This study examined the relationships of self-reported adoption of 12 seismic hazard adjustments (pre-impact actions to reduce danger to persons and property) with respondents' demographic characteristics, perceived risk, perceived hazard knowledge, perceived protection responsibility, and perceived attributes of the hazard adjustments. Consistent with theoretical predictions, perceived attributes of the hazard adjustments differentiated among the adjustments and had stronger correlations with adoption than any of the other predictors. These results identify the adjustments and attributes that emergency managers should address to have the greatest impact on improving household adjustment to earthquake hazard. PMID:10795335

  5. 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.

  6. 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:

  7. 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.

  8. The Leader's Leader: Examining the HR Executive's Role as Performance Coach at the Management Level

    ERIC Educational Resources Information Center

    Strodel, Neil; Novak, Christopher

    2005-01-01

    Higher education human resource professionals know the importance of performance management and coaching for university employees. However, the standards of performance often are not enforced to those in high-level positions. Neil Strodel and Christopher Novak examine how HR leaders are in a unique position to extend performance coaching to those…

  9. 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…

  10. H.R.3729 — 113th Congress (2013-2014) Korean Immigration Commemorative Coin Act

    THOMAS, 113th Congress

    Rep. Andrews, Robert E. [D-NJ-1

    2013-12-12

    02/27/2014 Ms. Meng asked unanimous consent that she be considered the first sponsor of H.R. 3729, a bill originally introduced by Representative Andrews of New Jersey, for the purposes of adding cosponsors and requesting reprintings pursuant to clause 7 or rule XII. (All Actions)

  11. 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…

  12. 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.

  13. EVALUATION OF THE UNION CARBIDE PURASIV (TRADE NAME) HR VAPOR RECOVER SYSTEM

    EPA Science Inventory

    The goal of this study was to perform an engineering evaluation of a new fluidized-bed adsorption technology that was developed in Japan. This technology has been licensed by Union Carbide and is now being marketed in the United States, under the name PURASIV HR Vapor Recovery Sy...

  14. The composite nature of the peculiar star HR 6560 (HD 159870)

    NASA Technical Reports Server (NTRS)

    Wegner, Gary; Cowley, Charles R.

    1992-01-01

    Ground-based high-dispersion photographic spectra and ultraviolet spectra obtained with the IUE satellite are described and employed to determine the nature of the peculiar star HR 6560 (HD 159870). Previously this object had been described as both a composite system and as a strong Fm star. The UBVRI, Stromgren, and ultraviolet colors of HR 6560 are compared with objects classified composite from the Bright Star Catalogue and normal dwarfs and giants. The colors of HR 6560 are not unusual for a composite and are consistent with a late-A dwarf, combined with a late-G or early-K giant. The ultraviolet satellite clearly shows the presence of an A component, but its precise spectral type is difficult to assign. The IUE and TD-1 data suggest that the ultraviolet is dominated by light from an A5 V secondary and the visual from a GO III primary. This does not agree well with the most plausible model that fits the visual photometry. The peculiar nature of HR 6560's spectrum is most likely due to its composite nature.

  15. The Corona of the Remarkable Hertzsprung-Gap Giant HR 9024

    NASA Technical Reports Server (NTRS)

    Ayres, Thomas R.

    1998-01-01

    The final report is a study on an ASCA program to record the X-ray spectrum and lightcurve of the bright X-ray source HR 9024 (HD 223460: G1 III), an approximately 2.7 solar mass giant at the red edge of the Hertzsprung gap, a critical juncture in the evolution of magnetically-inspired stellar coronae.

  16. Gas and oil fired package boilers 20,000 - 50,000 lb/hr

    SciTech Connect

    Day, L.K.

    1996-11-01

    Gas and oil fired package boilers rated at 20,000-50,000 lb/hr are discussed. The fleet consists of approximately 75 units, divided into two basic groups: (1) mobile boiler rooms - these consist of van mounted firetube boilers from 100-350 hp, complete with feedwater systems and water treatment equipment; and (2) trailer-mounted boilers - these consist of {open_quotes}O{close_quotes} type watertube boilers from 24,000 - 120,000 lb/hr, specially designed and mounted on highway legal lowboy trailers for mobility. Other products include new and reconditioned skid-mounted package boilers up to 150,000 lb/hr, turnkey {open_quotes}fast track{close_quotes} steam plants, and custom designed mobile or transportable steam plants for sale or lease. One of the earlier introductions into low NOx technology was a new equipment sale to Union Oil in Arroyo Grande, CA in 1983. A 100,000 lb/hr custom designed boiler with side wall NOx ports and low excess air burner to meet 80 ppm on natural gas was supplied. With the enactment of 40ppm low NOx mandates in Southern California in 2987, it was necessary to quickly retrofit the rental fleet and to work closely with boiler and burner manufacturers to meet the new standards.

  17. Long-term stability of the HR 8799 planetary system without resonant lock

    NASA Astrophysics Data System (ADS)

    Götberg, Ylva; Davies, Melvyn B.; Mustill, Alexander J.; Johansen, Anders; Church, Ross P.

    2016-08-01

    HR 8799 is a star accompanied by four massive planets on wide orbits. The observed planetary configuration has been shown to be unstable on a timescale much shorter than the estimated age of the system (~30 Myr) unless the planets are locked into mean motion resonances. This condition is characterised by small-amplitude libration of one or more resonant angles that stabilise the system by preventing close encounters. We simulate planetary systems similar to the HR 8799 planetary system, exploring the parameter space in separation between the orbits, planetary masses and distance from the Sun to the star. We find systems that look like HR 8799 and remain stable for longer than the estimated age of HR 8799. None of our systems are forced into resonances. We find, with nominal masses (Mb = 5 MJup and Mc,d,e = 7 MJup) and in a narrow range of orbit separations, that 5 of 100 systems match the observations and lifetime. Considering a broad range of orbit separations, we find 12 of 900 similar systems. The systems survive significantly longer because of their slightly increased initial orbit separations compared to assuming circular orbits from the observed positions. A small increase in separation leads to a significant increase in survival time. The low eccentricity the orbits develop from gravitational interaction is enough for the planets to match the observations. With lower masses, but still comfortably within the estimated planet mass uncertainty, we find 18 of 100 matching and long-lived systems in a narrow orbital separation range. In the broad separation range, we find 82 of 900 matching systems. Our results imply that the planets in the HR 8799 system do not have to be in strong mean motion resonances. We also investigate the future of wide-orbit planetary systems using our HR 8799 analogues. We find that 80% of the systems have two planets left after strong planet-planet scattering and these are on eccentric orbits with semi-major axes of a1 ~ 10 AU and a2

  18. 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.

  19. 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.

  20. The CHARA Array Angular Diameter of HR 8799 Favors Planetary Masses for its Imaged Companions

    NASA Astrophysics Data System (ADS)

    Baines, Ellyn K.; White, Russel J.; Huber, Daniel; 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.; Ireland, Michael; von Braun, Kaspar; Ridgway, Stephen T.

    2012-12-01

    HR 8799 is an hF0 mA5 γ Doradus-, λ 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 ⊙), effective temperature (7193 ± 87 K, consistent with F0), luminosity (5.05 ± 0.29 L ⊙), 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 λ 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+0.038 -0.024 M ⊙ and 33+7 -13.2 Myr if the star is contracting toward the zero-age main sequence or 1.513+0.023 -0.024 M ⊙ and 90+381 -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.

  1. 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.

  2. DomHR: Accurately Identifying Domain Boundaries in Proteins Using a Hinge Region Strategy

    PubMed Central

    Zhang, Xiao-yan; Lu, Long-jian; Song, Qi; Yang, Qian-qian; Li, Da-peng; Sun, Jiang-ming; Li, Tong-hua; Cong, Pei-sheng

    2013-01-01

    Motivation The precise prediction of protein domains, which are the structural, functional and evolutionary units of proteins, has been a research focus in recent years. Although many methods have been presented for predicting protein domains and boundaries, the accuracy of predictions could be improved. Results In this study we present a novel approach, DomHR, which is an accurate predictor of protein domain boundaries based on a creative hinge region strategy. A hinge region was defined as a segment of amino acids that covers part of a domain region and a boundary region. We developed a strategy to construct profiles of domain-hinge-boundary (DHB) features generated by sequence-domain/hinge/boundary alignment against a database of known domain structures. The DHB features had three elements: normalized domain, hinge, and boundary probabilities. The DHB features were used as input to identify domain boundaries in a sequence. DomHR used a nonredundant dataset as the training set, the DHB and predicted shape string as features, and a conditional random field as the classification algorithm. In predicted hinge regions, a residue was determined to be a domain or a boundary according to a decision threshold. After decision thresholds were optimized, DomHR was evaluated by cross-validation, large-scale prediction, independent test and CASP (Critical Assessment of Techniques for Protein Structure Prediction) tests. All results confirmed that DomHR outperformed other well-established, publicly available domain boundary predictors for prediction accuracy. Availability The DomHR is available at http://cal.tongji.edu.cn/domain/. PMID:23593247

  3. 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.

  4. 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.

  5. 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....

  6. Effects of Parity and Serum Prolactin Levels on the Incidence and Regression of DMBA-Induced Tumors in OFA hr/hr Rats

    PubMed Central

    López-Fontana, Constanza M.; Ezquer, Marcelo E.; Jahn, Graciela A.

    2014-01-01

    Prolactin (PRL) is a key player in the development of mammary cancer. We studied the effects of parity or hyperprolactinemia on mammary carcinogenesis in OFA hr/hr treated with 7,12-dimethylbenzanthracene. They were divided into three groups: nulliparous (Null), primiparous (PL, after pregnancy and lactation), and hyperprolactinemic rats (I, implanted in the arcuate nucleus with 17β-estradiol). The tumor incidence was similar in the three groups. However, a higher percentage of regressing tumors was evident in the PL group. Serum PRL, mammary development, and mammary β-casein content were higher in I rats compared to Null. The expression of hormone receptors was similar in the different groups. However, mammary tissue from PL rats bearing tumors had increased expression of PRL and estrogen alpha receptors compared to rats free of tumors. Our results suggest that serum PRL levels do not have relevance on the incidence of tumors, probably because the low levels of PRL in OFA rats are not further decreased by PL like in other strains. However, supraphysiological levels of PRL affect carcinogenesis. PL induces regression of the tumors due to the differentiation produced on the mammary cells. Alterations in the expression of hormonal receptors may be involved in progression and regression of tumors. PMID:25136563

  7. Retention and risk factors for attrition among adults in antiretroviral treatment programmes in Tanzania, Uganda and Zambia

    PubMed Central

    Koole, Olivier; Tsui, Sharon; Wabwire-Mangen, Fred; Kwesigabo, Gideon; Menten, Joris; Mulenga, Modest; Auld, Andrew; Agolory, Simon; Mukadi, Ya Diul; Colebunders, Robert; Bangsberg, David R.; van Praag, Eric; Torpey, Kwasi; Williams, Seymour; Kaplan, Jonathan; Zee, Aaron; Denison, Julie

    2016-01-01

    OBJECTIVES We assessed retention and predictors of attrition (recorded death or loss to follow-up) in antiretroviral treatment (ART) clinics in Tanzania, Uganda and Zambia. METHODS We conducted a retrospective cohort study among adults (≥18 years) starting ART during 2003–2010. We purposefully selected six health facilities per country and randomly selected 250 patients from each facility. Patients who visited clinics at least once during the 90 days before data abstraction were defined as retained. Data on individual and programme level risk factors for attrition were obtained through chart review and clinic manager interviews. Kaplan–Meier curves for retention across sites were created. Predictors of attrition were assessed using a multivariable Cox-proportional hazards model, adjusted for site-level clustering. RESULTS From 17 facilities, 4147 patients were included. Retention ranged from 52.0% to 96.2% at 1 year to 25.8%–90.4% at 4 years. Multivariable analysis of ART initiation characteristics found the following independent risk factors for attrition: younger age [adjusted hazard ratio (aHR) and 95% confidence interval (95%CI) = 1.30 (1.14–1.47)], WHO stage 4 ([aHR (95% CI): 1.56 (1.29–1.88)], >10% bodyweight loss [aHR (95%CI) = 1.17 (1.00–1.38)], poor functional status [ambulatory aHR (95%CI) = 1.29 (1.09–1.54); bedridden aHR1.54 (1.15–2.07)], and increasing years of clinic operation prior to ART initiation in government facilities [aHR (95%CI) = 1.17 (1.10–1.23)]. Patients with higher CD4 cell count were less likely to experience attrition [aHR (95%CI) = 0.88 (0.78–1.00)] for every log (tenfold) increase. Sites offering community ART dispensing [aHR (95% CI) = 0.55 (0.30–1.01) for women; 0.40 (0.21–0.75) for men] had significantly less attrition. CONCLUSIONS Patient retention to an individual programme worsened over time especially among males, younger persons and those with poor clinical indicators. Community ART drug dispensing

  8. Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy.

    PubMed

    Latimer, Nicholas R; Bell, Helen; Abrams, Keith R; Amonkar, Mayur M; Casey, Michelle

    2016-05-01

    Trametinib, a selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, significantly improves progression-free survival compared with chemotherapy in patients with BRAF V600E/K mutation-positive advanced or metastatic melanoma (MM). However, the pivotal clinical trial permitted randomized chemotherapy control group patients to switch to trametinib after disease progression, which confounded estimates of the overall survival (OS) advantage of trametinib. Our purpose was to estimate the switching-adjusted treatment effect of trametinib for OS and assess the suitability of each adjustment method in the primary efficacy population. Of the patients randomized to chemotherapy, 67.4% switched to trametinib. We applied the rank-preserving structural failure time model, inverse probability of censoring weights, and a two-stage accelerated failure time model to obtain estimates of the relative treatment effect adjusted for switching. The intent-to-treat (ITT) analysis estimated a 28% reduction in the hazard of death with trametinib treatment (hazard ratio [HR], 0.72; 95% CI, 0.52-0.98) for patients in the primary efficacy population (data cut May 20, 2013). Adjustment analyses deemed plausible provided OS HR point estimates ranging from 0.48 to 0.53. Similar reductions in the HR were estimated for the first-line metastatic subgroup. Treatment with trametinib, compared with chemotherapy, significantly reduced the risk of death and risk of disease progression in patients with BRAF V600E/K mutation-positive advanced melanoma or MM. Adjusting for switching resulted in lower HRs than those obtained from standard ITT analyses. However, CI are wide and results are sensitive to the assumptions associated with each adjustment method. PMID:27172483

  9. 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

  10. 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.

  11. 76 FR 4395 - Postal Service Price Adjustment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... Postal Service Price Adjustment AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to establish price adjustments for all market... with the Commission announcing price adjustments, effective April 17, 2011, affecting all...

  12. 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...

  13. 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,...

  14. 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...

  15. 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...

  16. 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,...

  17. 34 CFR 36.2 - Penalty adjustment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 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,...

  18. 34 CFR 36.2 - Penalty adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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 § 36.2..., Section 36.2—Civil Monetary Penalty Inflation Adjustments Statute Description New maximum (and minimum,...

  19. 34 CFR 36.2 - Penalty adjustment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 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,...

  20. 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...

  1. Adjustment to College in Students with ADHD

    ERIC Educational Resources Information Center

    Rabiner, David L.; Anastopoulos, Arthur D.; Costello, Jane; Hoyle, Rick H.; Swartzwelder, H. Scott

    2008-01-01

    Objective: To examine college adjustment in students reporting an ADHD diagnosis and the effect of medication treatment on students' adjustment. Method: 1,648 first-semester freshmen attending a public and a private university completed a Web-based survey to examine their adjustment to college. Results: Compared with 200 randomly selected control…

  2. Dimensions of Adjustment among College Women.

    ERIC Educational Resources Information Center

    Tomlinson-Clarke, Saundra

    1998-01-01

    Examines academic, social, and personal-emotional adjustment, as well as institutional attachment for women (N=198) attending a predominantly white coeducational research university. Significant main effects were found on academic achievement for year in college. Students differed on personal-emotional adjustment by race. Academic adjustment and…

  3. 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

  4. COOPERATION MAINTAINED BY FITNESS ADJUSTMENT

    PubMed Central

    TAYLOR, CHRISTINE; CHEN, JANET; IWASA, YOH

    2008-01-01

    Questions Whether or not cooperation can be enhanced if players with a performance higher than the mean are forced to pay an additional cost in each generation? Mathematical Methods Analysis of replicator dynamics with mutation. The ESS distribution of cooperation level is obtained. Key Assumptions Players engage in cooperative dilemma game, and at the end of each generation, those with higher performance than the mean are forced to pay additional cost. Conclusions Without mutation, the entire population eventually conforms to a single cooperation level determined by the initial composition of the population. With mutation, there is an equilibrium distribution of cooperation level, which has a peak at an intermediate level of cooperation. Whether it is institutionalized such as tax or just a social custom, fitness adjustment based ultimately on people’s emtion of “envy” is able to maintain cooperation. PMID:19079742

  5. 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. PMID:24462984

  6. Carboplatin–paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer

    PubMed Central

    Lee, C K; Gurney, H; Brown, C; Sorio, R; Donadello, N; Tulunay, G; Meier, W; Bacon, M; Maenpaa, J; Petru, E; Reed, N; Gebski, V; Pujade-Lauraine, E; Lord, S; Simes, R J; Friedlander, M

    2011-01-01

    Background: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin–paclitaxel (CP) or carboplatin–liposomal doxorubicin (CPLD). Methods: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 109 per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. Results: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin–liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008). Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin–liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). Conclusion: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity. PMID:21750553

  7. 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

  8. 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

  9. Worker Retraining. Hearing before the Subcommittee on Employment Opportunities of the Committee on Education and Labor, House of Representatives, Ninety-Ninth Congress, First Session on H.R. 26 and H.R. 1219.

    ERIC Educational Resources Information Center

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

    This Congressional report contains the testimony presented at a hearing focusing on two bills dealing with worker retraining. The two bills, H.R. 26 and H.R. 1219, are intended to establish a system of individual training accounts in the Unemployment Trust Fund, amend the Internal Revenue Code of 1954 to provide that certain contributions to such…

  10. Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif.

    PubMed

    Flynn, P; Mellor, H; Palmer, R; Panayotou, G; Parker, P J

    1998-01-30

    PRK1 (PKN) is a serine/threonine kinase that has been shown to be activated by RhoA (Amano, M., Mukai, H., Ono, Y., Chihara, K., Matsui, T., Hamajima, Y., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) Science 271, 648-650). Detailed analysis of the PRK1 region involved in RhoA binding has revealed that two homologous sequences within the HR1 domain (HR1a and HR1b) both bind to RhoA; the third repeat within this domain, HR1cPRK1, does not bind RhoA. The related HR1 motif is also found to confer RhoA binding activity to the only other fully cloned member of this kinase family, PRK2. Furthermore, the predictive value of this motif is established for an HR1a sequence derived from a Caenorhabditis elegans open reading frame encoding a protein kinase of unknown function. Interestingly, the HR1aPRK1 and HR1bPRK1 subdomains are shown to display a distinctive nucleotide dependence for RhoA binding. HRIaPRK1 is entirely GTP-dependent, while HR1bPRK1 binds both GTP- and GDP-bound forms of RhoA. This distinction indicates that there are two sites of contact between RhoA and PRK1, one contact through a region that is conformationally dependent upon the nucleotide-bound state of RhoA and one that is not. Analysis of binding to Rho/Rac chimera provides evidence for a HR1aPRK1 but not HR1bPRK1 interaction in the central third of Rho. Additionally, it is observed that the V14RhoA mutant binds HR1a but does not bind HR1b. This distinct binding behavior corroborates the conclusion that there are independent contacts on RhoA for the HR1aPRK1 and HR1bPRK1 motifs. PMID:9446575

  11. VizieR Online Data Catalog: Elemental abundance analysis of HR 8216 (Caliskan, 2005)

    NASA Astrophysics Data System (ADS)

    Caliskan, H.

    2003-09-01

    We have performed the abundance analysis of the cool magnetic CP star HR 8216 (=HD 204411) using 2.4{AA}/mm Dominion Astrophysical Observatory Reticon exposures covering ll 3830-4770{AA} with a typical signal-to-noise ratio of 200. The spectrograms were measured interactively with the graphics computer program REDUCE. We performed a fine analysis with an ATLAS9 metal-rich model atmosphere whose predictions best matched the optical region fluxes and the Hg profile. HR 8216's anomalies are primarily an enhancement of many iron peak elements with the rare earths elements much less enhanced than for many similar cool magnetic CP stars .Using the results of the fine analysis we synthetized the spectrum. Comparison with the observed spectrum showed that agreement is better. (1 data file).

  12. 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.

  13. 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.

  14. 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.

  15. IUE observations of cool stars - Alpha Aurigae, HR1099, Lambda Andromedae, and Epsilon Eridani

    NASA Technical Reports Server (NTRS)

    Linsky, J. L.; Ayres, T. R.; Basri, G. S.; Morrison, N. D.; Boggess, A.; Schiffer, F. H., III; Holm, A.; Cassatella, A.; Heck, A.; Macchetto, F.

    1978-01-01

    Initial IUE observations of four cool stars are reported. Observed fluxes and surface fluxes are given for several UV emission lines in the spectral range 1175-2000 A, obtained at low and high dispersion with the short-wavelength spectrograph and camera. These lines are formed in the outer atmospheres of these stars, in regions presumably analogous to the solar chromosphere and transition region. The surface fluxes in the lines increase along the sequence: quiet sun, Epsilon Eri, Lambda And, Alpha Aur, and HR1099. The 2.8-d RS CVn-type binary HR1099, observed on 1 March 1978 near the end of a major flaring episode, has line surface fluxes roughly 100 times that of the quiet sun, similar to those seen in solar flares. Line profiles and flux ratios in multiplets for Capella are presented, and comments given on the opacity of the lines and on a tendency of line width to increase with temperature of formation.

  16. Imaging Discovery of a Low-Mass Companion Around HR 3549

    NASA Astrophysics Data System (ADS)

    Stapelfeldt, Karl; Mawet, Dimitri; David, Trevor; Bottom, Michael; Hinkley, Sasha; Padgett, Deborah; Mennesson, Bertrand; Serabyn, Eugene; Morales, Farisa Y.; Kuhn, Jonas

    2015-12-01

    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. We imaged the companion at the Very Large Telescope with NAOS-CONICA in the L-band in January 2013 and January 2015. The companion is at a projected separation of 80 AU and position angle of 157° . Our age estimate for this object corresponds to a mass in the range 15-80 M 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.

  17. 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.

  18. 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

  19. Detection of a sub-milliarcsecond radio component in the RS CVn system HR 1099

    NASA Technical Reports Server (NTRS)

    Mutel, R. L.; Phillips, R. B.; Webber, J. C.; Niell, A. E.; Preston, R. A.; Lestrade, J.-F.

    1984-01-01

    The RS CVn system HR 1099 was observed with a five station VLBI array at a frequency of 8.4 GHz during a strong radio outburst of approximately 400 mJy. The data are consistent with a circular Gaussian source of 0.8 + or - 0.12 milli-arcsec (FWHM), corresponding to a linear size of 4 + or - 0.6 x 10 to the 11th cm. This is comparable to the distance between the surfaces of the two stars, or to 75 percent of the diameter of the chromospherically active K star. Extrapolation of published photometric data shows that the starspot formation of HR 1099 was facing toward the observers at the times of observations. The high equivalent brightness temperature, approximately 10 billion K, is consistent with gyrosynchrotron emission from a power-law energy distribution of electrons in a magnetic field of strength about 30 gauss.

  20. 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.

  1. The November 1987 eclipse of the zeta-Aur system HR 2554

    NASA Technical Reports Server (NTRS)

    Ake, Thomas B., III; Parsons, Sidney B.

    1988-01-01

    It is confirmed that HR 2554 (G6 II + A0 V) is an atmospheric eclipsing system of the zeta-Aur type. The IUE observations of the Nov. 1987 eclipse indicate that the eclipse of the A star lasts 4 days and is not total. Absorption lines due to the extended atmosphere of the primary can be seen a day before and after the eclipse and are missing 2 days from first and 4th contact. Thus the outer envelope of the primary extends to less than 1 stellar radius beyond the photosphere. Compared to 22 Vul (G3 Ib-II + B9 V), where the absorption can be traced to a few stellar radii, HR 2554 is a more moderate case of mass outflow, which implies there is reduced interaction of the secondary within the wind from the primary as is seen in the other zeta-Aur systems.

  2. Mg II chromospheric-emission dating of HR 1614 moving-group stars

    NASA Technical Reports Server (NTRS)

    Hufnagel, Beth; Smith, Graeme H.

    1994-01-01

    A 2800 A Mg II line index I(Mg II) that is sensitive to chromospheric activity has been measured from International Ultraviolet Explorer spectra of a sample of eight HR 1614 moving-group dwarfs. All of these dwarfs have values of I(Mg II) indicative of ages greater than or equal to 3 Gyr. The relatively old ages of these dwarfs, together with their similar and peculiar kinematics and high metal abundance, is consistent with, although not conclusive proof of, coeval formation in close physical proximity to each other. The age, chemical abundance, and kinematics of the HR 1614 moving group -- with the notable exception of height above the Galactic plane -- are similar to the properties of the old open cluster NGC 6791.

  3. 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.

  4. 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.

  5. Data validation report for the 100-HR-3 Operable Unit, fifth round groundwater samples

    SciTech Connect

    Vukelich, S.E.

    1994-01-20

    The data from the chemical analysis of 68 samples from the 100-HR-3 Operable Unit Third Quarter 1993 Groundwater Sampling Investigation and their related quality assurance samples were reviewed and validated to verify that reported sample results were of sufficient quality to support decisions regarding remedial actions performed at the site. Sample analysis included inorganics and general chemical parameters. Fifty three samples were validated for radiochemical parameters.

  6. 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.

  7. 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.

  8. Measuring apparent trabecular structure with pQCT: a comparison with HR-pQCT.

    PubMed

    Lala, Deena; Cheung, Angela M; Lynch, Cheryl L; Inglis, Dean; Gordon, Chris; Tomlinson, George; Giangregorio, Lora

    2014-01-01

    We evaluated how comparable peripheral quantitative computed tomography (pQCT) measurements of cortical thickness, density, and apparent trabecular structure at the ultradistal tibia were with those measured with high-resolution pQCT (HR-pQCT). We also examined whether the accuracy of the pQCT-based trabecular and cortical measurements improved with reductions in slice thickness from the standard 2.2mm to 1.1 and 0.6mm. We immersed 15 dry tibia specimens in saline in a sealed cylinder and scanned 22.5mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT underestimated cortical thickness by Stratec (CThStratec) and trabecular spacing (Tb.Sp) by 21.4% and 72.9%, whereas bone volume to total volume (BV/TV) and cortical density (CDen) were overestimated by 265.8% and 13.1%, respectively. Measurements of trabecular volumetric bone mineral density, trabecular area, total area, cortical thickness by custom software were comparable, but for CThStratec, Tb.Sp, BV/TV, and CDen, the differences between imaging devices varied with magnitude of the estimate. We recommend that researchers or clinicians interested in using pQCT to measure apparent trabecular structure or cortical thickness at the epiphyses, or in comparing findings from different devices, be aware of the differences between HR-pQCT and pQCT. PMID:23567093

  9. 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.

  10. Performance of radiation-hard HV/HR CMOS sensors for the ATLAS inner detector upgrades

    NASA Astrophysics Data System (ADS)

    Liu, J.; Barbero, M.; Bilbao De Mendizabal, J.; Breugnon, P.; Godiot-Basolo, S.; Pangaud, P.; Rozanov, A.

    2016-03-01

    A major upgrade (Phase II Upgrade) to the Large Hadron Collider (LHC), scheduled for 2022, will be brought to the machine so as to extend its discovery potential. The upgraded LHC, called High-Luminosity LHC (HL-LHC), will run with a nominal leveled instantaneous luminosity of 5×1034 cm-2s-1, more than twice the expected luminosity. This unprecedented luminosity will result in higher occupancy and background radiations, which will request the design of a new Inner Tracker (ITk) which should have higher granularity, reduced material budget and improved radiation tolerance. A new pixel sensor concept based on High Voltage and High Resistivity CMOS (HV/HR CMOS) technology targeting the ATLAS inner detector upgrade is under exploration. With respect to the traditional hybrid pixel detector, the HV/HR CMOS sensor can potentially offer lower material budget, reduced pixel pitch and lower cost. Several prototypes have been designed and characterized within the ATLAS upgrade R&D effort, to investigate the detection and radiation hardness performance of various commercial technologies. An overview of the HV/HR CMOS sensor operation principle is described in this paper. The characterizations of three prototypes with X-ray, proton and neutron irradiation are also given.

  11. Hepatitis C treatment failure is associated with increased risk of hepatocellular carcinoma.

    PubMed

    Lu, Mei; Li, Jia; Rupp, Loralee B; Holmberg, Scott D; Moorman, Anne C; Spradling, Philip R; Teshale, Eyasu H; Zhou, Yueren; Boscarino, Joseph A; Schmidt, Mark A; Lamerato, Lois E; Trinacty, Connie; Trudeau, Sheri; Gordon, Stuart C

    2016-09-01

    Sustained virological response (SVR) to antiviral therapy for hepatitis C (HCV) reduces risk of hepatocellular carcinoma (HCC), but there is little information regarding how treatment failure (TF) compares to lack of treatment. We evaluated the impact of treatment status on risk of HCC using data from the Chronic Hepatitis Cohort Study (CHeCS-an observational study based in four large US health systems, with up to 7 years of follow-up on patients). Multivariable analyses were used to adjust for bias in treatment selection, as well as other covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681 (36%) received treatment, 2099 (57%) experienced treatment failure (TF), and 1582 (43%) of these achieved sustained virological response (SVR). TF patients demonstrated almost twice the risk of HCC than untreated patients [adjusted hazard ratio (aHR) = 1.95, 95% confidence interval (CI) 1.50-2.53]; this risk persisted across all stages of fibrosis. Several sensitivity analyses validated these results. Although African Americans were at increased risk of treatment failure, they were at lower risk for HCC and all-cause mortality compared to White patients. SVR patients had lower risk of HCC than TF patients (aHR = 0.48, CI 0.31-0.73), whereas treatment - regardless of outcome - reduced all-cause mortality (aHR = 0.45, CI 0.34-0.60 for SVR patients; aHR = 0.78, CI 0.65-0.93 for TF patients). PMID:27028626

  12. MAXI/GSC detection of a possible X-ray flare from an RS CVn star HR5110

    NASA Astrophysics Data System (ADS)

    Sasaki, R.; Tsuboi, Y.; Nakamura, Y.; Serino, M.; Ueno, S.; Tomida, H.; Nakahira, S.; Ishikawa, M.; Nakagawa, Y. E.; Sugawara, Y.; Mihara, T.; Sugizaki, M.; Iwakiri, W.; Shidatsu, M.; Sugimoto, J.; Takagi, T.; Matsuoka, M.; Kawai, N.; Isobe, N.; Sugita, S.; Yoshii, T.; Tachibana, Y.; Ono, Y.; Fujiwara, T.; Yoshida, A.; Sakamoto, T.; Kawakubo, Y.; Kitaoka, Y.; Tsunemi, H.; Shomura, R.; Negoro, H.; Nakajima, M.; Tanaka, K.; Masumitsu, T.; Kawase, T.; Ueda, Y.; Kawamuro, T.; Hori, T.; Tanimoto, A.; Yamauchi, M.; Furuya, K.; Yamaoka, K.

    2016-06-01

    MAXI/GSC observed a possible X-ray flare from an RS CVn star HR5110. The MAXI/GSC nova alert system triggered on the flare-like event from the position consistent with the RS CVn system HR5110 during a scan transit at 09:19:00 UT on June 12th 2016.

  13. 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. PMID:15587557

  14. 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

  15. Exploration adjustment by ant colonies.

    PubMed

    Doran, Carolina; Stumpe, Martin C; Sendova-Franks, Ana; Franks, Nigel R

    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

  16. The yellow hypergiant HR 5171 A: Resolving a massive interacting binary in the common envelope phase

    NASA Astrophysics Data System (ADS)

    Chesneau, O.; Meilland, A.; Chapellier, E.; Millour, F.; van Genderen, A. M.; Nazé, Y.; Smith, N.; Spang, A.; Smoker, J. V.; Dessart, L.; Kanaan, S.; Bendjoya, Ph.; Feast, M. W.; Groh, J. H.; Lobel, A.; Nardetto, N.; Otero, S.; Oudmaijer, R. D.; Tekola, A. G.; Whitelock, P. A.; Arcos, C.; Curé, M.; Vanzi, L.

    2014-03-01

    Context. Only a few stars are caught in the very brief and often crucial stages when they quickly traverse the Hertzsprung-Russell diagram, and none has yet been spatially resolved in the mass transfer phase. Aims: We initiated long-term optical interferometry monitoring of the diameters of massive and unstable yellow hypergiants (YHG) with the goal of detecting both the long-term evolution of their radius and shorter term formation of a possible pseudo-photosphere related to proposed large mass-loss events. Methods: We observed HR 5171 A with AMBER/VLTI. We also examined archival photometric data in the visual and near-IR spanning more than 60 years, as well as sparse spectroscopic data. Results: HR 5171 A exhibits a complex appearance. Our AMBER data reveal a surprisingly large star for a YHG R∗ = 1315 ± 260R⊙ (or ~6.1 AU) at the distance of 3.6 ± 0.5 kpc. The source is surrounded by an extended nebulosity, and these data also show a large level of asymmetry in the brightness distribution of the system, which we attribute to a newly discovered companion star located in front of the primary star. The companion's signature is also detected in the visual photometry, which indicates an orbital period of Porb = 1304 ± 6 d. Modeling the light curve with the NIGHTFALL program provides clear evidence that the system is a contact or possibly over-contact eclipsing binary. A total current system mass of 39+40-22 M⊙ and a high mass ratio q ≥ 10 is inferred for the system. Conclusions: The low-mass companion of HR 5171 A is very close to the primary star that is embedded within its dense wind. Tight constraints on the inclination and vsini of the primary are lacking, which prevents us from determining its influence precisely on the mass-loss phenomenon, but the system is probably experiencing a wind Roche-Lobe overflow. Depending on the amount of angular momentum that can be transferred to the stellar envelope, HR 5171 A may become a fast-rotating B

  17. 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.

  18. Transcription alterations of microRNAs, cytochrome P4501A1 and 3A65, and AhR and PXR in the liver of zebrafish exposed to crude microcystins.

    PubMed

    Li, Xiaoyu; Ma, Junguo; Fang, Qian; Li, Yuanyuan

    2013-10-01

    MicroRNAs are small non-coding regulatory RNAs that not only control diverse cellular processes but also regulate gene expression induced by environmental chemicals. However, little is known about the role of microRNAs in liver response of fish to the exposure of cyanobacterial hepatotoxin microcystins (MCs). In the present study, the transcription levels of 4 miRNAs (dre-miR-21, dre-miR-122, dre-miR-27b, and dre-miR-148), cytochromes P450s CYP1A1 and CYP3A65, and their receptors, aryl hydrocarbon receptor (AhR, for CYP1A1) and pregnane X receptor (PXR, for CYP3A65), in the liver of zebrafish were evaluated after 24 h of 50, 200, or 800 μg/L of crude MCs exposure by using the quantitative real-time PCR method. The results showed that MCs-exposure elevated the transcription levels of dre-miR-21 and dre-miR-27b while down-regulated the expressions of dre-miR-122 and dre-miR-148. However, CYP1A1 transcription remained unchanged while mRNA levels of AhRR1 and AhR2 were significantly higher than that of control. Furthermore, the expressions of CYP3A65 and its receptor PXR were up-regulated by MCs-exposure at higher concentrations (200, or 800 μg/L of crude MCs). Therefore we suggest that CYP3A65 and PXR may be involved in the metabolization and detoxification of MCs in zebrafish, which may be regulated by dre-miR-27b. This work might be beneficial for the discovery of new potential diagnostic biomarker and drug target for hepatosis caused by MC. PMID:23851223

  19. 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.

  20. 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

    2016-01-01

    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

  1. Grand Portage Band Per Capita Adjustment Act

    THOMAS, 113th Congress

    Sen. Franken, Al [D-MN

    2014-04-10

    04/10/2014 Read twice and referred to the Committee on Finance. (All Actions) Notes: For further action, see H.R.3608, which became Public Law 113-290 on 12/19/2014. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  2. 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.

  3. 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.

  4. Asian immigrant settlement and adjustment in Australia.

    PubMed

    Khoo, S; Kee, P; Dang, T; Shu, J

    1994-01-01

    "This article provides a broad assessment of the settlement and adjustment of people born in the many countries of Asia who are resident in Australia, based on recently available data from the 1991 Census of Population and Housing. It examines some indicators of economic adjustment such as performance in the labor market, and some indicators of social adjustment, such as acquisition of English language proficiency." PMID:12289777

  5. Rate adjusters for Medicare under capitation

    PubMed Central

    Newhouse, Joseph P.

    1986-01-01

    This article addresses three issues related to capitation. First, the average adjusted per capita cost (AAPCC) fluctuates with the mix of risks in the fee-for-service system. More sensitive adjusters in the AAPCC are needed. Second, the AAPCC, as now estimated, exhibits large geographic variance; so-called shrinkage estimators may help. Third, the AAPCC requires new adjusters to yield more homogeneous risk classes. Otherwise, the portion of the Medicare population under capitation may experience access problems at alternative delivery systems: Until such adjusters are developed, it seems better to rely upon a blend of capitation and fee-for-service than the present AAPCC. PMID:10311926

  6. Techniques and applications of adjustable sutures.

    PubMed

    Fells, P

    1987-02-01

    The 'rediscovery' of adjustable sutures some 10 years ago has given the ophthalmic surgeon much more confidence in his ability to correct strabismus. Three methods of use are described: during surgery under general anaesthesia with adjustment during the operation using the 'springback' test to centralise the eye; during surgery under general anaesthesia and subsequent adjustment under local anaesthesia using the patient's subjective responses to obtain optimal positioning; and performance of the operation and adjustment under topical local anaesthesia in one procedure. Full details are given of each technique and the indications for their application to particular problems are discussed. PMID:3297111

  7. Factors associated with hospitalization for blood-borne viral infections among treatment-seeking illicit drug users.

    PubMed

    Onyeka, Ifeoma N; Olubamwo, Olubunmi; Beynon, Caryl M; Ronkainen, Kimmo; Föhr, Jaana; Tiihonen, Jari; Tuomola, Pekka; Tasa, Niko; Kauhanen, Jussi

    2015-06-01

    Blood-borne viral infections (BBVIs) are important health consequences of illicit drug use. This study assessed predictors of inpatient hospital admissions for BBVIs in a cohort of 4817 clients seeking treatment for drug use in Finland. We examined clients' data on hospital admissions registered in the Finnish National Hospital Discharge Register from 1997 to 2010 with diagnoses of BBVIs. Cox proportional hazards regression analyses were separately conducted for each of the three BBVI groups to test for association between baseline variables and hospitalizations. Findings were reported as adjusted hazard ratios (aHRs). Based upon primary discharge diagnoses, 81 clients were hospitalized for HIV, 116 for hepatitis C, and 45 for other types of hepatitis. Compared to those admitted for hepatitis C and other hepatitis, drug users with HIV had higher total number of hospital admissions (294 versus 141 and 50 respectively), higher crude hospitalization rate (7.1 versus 3.4.and 1.2 per 1000 person-years respectively), and higher total length of hospital stay (2857 days versus 279 and 308 respectively). Trends in hospitalization for all BBVI groups declined at the end of follow-up. HIV positive status at baseline (aHR: 6.58) and longer duration of drug use (aHR: 1.11) were independently associated with increased risk for HIV hospitalization. Female gender (aHR: 3.05) and intravenous use of primary drug (aHR: 2.78) were significantly associated with HCV hospitalization. Having hepatitis B negative status at baseline (aHR: 0.25) reduced the risk of other hepatitis hospitalizations. Illicit drug use coexists with blood-borne viral infections. To address this problem, clinicians treating infectious diseases need to also identify drug use in their patients and provide drug treatment information and/or referral. PMID:25736625

  8. Work disability and state benefit claims in early rheumatoid arthritis: the ERAN cohort

    PubMed Central

    Varughese, Sneha; Young, Adam; Kiely, Patrick D.; Walsh, David A.

    2014-01-01

    Objective. RA is an important cause of work disability. This study aimed to identify predictive factors for work disability and state benefit claims in a cohort with early RA. Methods. The Early RA Network (ERAN) inception cohort recruited from 22 centres. At baseline, and during each annual visit, participants (n = 1235) reported employment status and benefits claims and how both were influenced by RA. Survival analysis derived adjusted hazard ratios (aHRs) and 95% CIs to predict associations between baseline factors and time until loss of employment due to RA or a state benefits claim due to RA. Results. At baseline, 47% of participants were employed and 17% reported claiming benefits due to RA. During follow-up, loss of employment due to RA was reported by 10% (49/475) of the participants and 20% (179/905) began to claim benefits. Independent predictors of earlier work disability were bodily pain (aHR 2.45, 95% CI 1.47, 4.08, P = 0.001) and low vitality (aHR 1.84, 95% CI 1.18, 2.85, P = 0.007). Disability (aHR 1.28, 95% CI 1.02, 1.61, P = 0.033), DAS28 (aHR 1.48, 95% CI 1.05, 2.09, P = 0.026) and extra-articular disease (aHR 1.77, 95% CI 1.17, 2.70, P = 0.007) predicted earlier benefits claims. Conclusion. Work disability and benefits claims due to RA were predicted by different baseline factors. Pain and low vitality predicted work disability. Baseline disability, extra-articular disease manifestations and disease activity predicted new benefits claims due to RA. Future research on interventions targeting these factors could investigate job retention and financial independence. PMID:24241033

  9. Direct Detection and Orbital Analysis of the Exoplanets HR 8799 bcd from Archival 2005 Keck/NIRC2 Data

    NASA Astrophysics Data System (ADS)

    Currie, Thayne; Fukagawa, Misato; Thalmann, Christian; Matsumura, Soko; Plavchan, Peter

    2012-08-01

    We present previously unpublished 2005 July 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 2010 October Keck data constrains the orbits of the planets. Analyzing the planets' astrometry separately, HR 8799 d's orbit is likely inclined at least 25° from face-on and the others may be on 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 face-on orbits. This Letter illustrates the significant science gain enabled with the release of the NIRC2 archive.

  10. 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.

  11. 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. PMID:26998601

  12. Ratios as a size adjustment in morphometrics.

    PubMed

    Albrecht, G H; Gelvin, B R; Hartman, S E

    1993-08-01

    Simple ratios in which a measurement variable is divided by a size variable are commonly used but known to be inadequate for eliminating size correlations from morphometric data. Deficiencies in the simple ratio can be alleviated by incorporating regression coefficients describing the bivariate relationship between the measurement and size variables. Recommendations have included: 1) subtracting the regression intercept to force the bivariate relationship through the origin (intercept-adjusted ratios); 2) exponentiating either the measurement or the size variable using an allometry coefficient to achieve linearity (allometrically adjusted ratios); or 3) both subtracting the intercept and exponentiating (fully adjusted ratios). These three strategies for deriving size-adjusted ratios imply different data models for describing the bivariate relationship between the measurement and size variables (i.e., the linear, simple allometric, and full allometric models, respectively). Algebraic rearrangement of the equation associated with each data model leads to a correctly formulated adjusted ratio whose expected value is constant (i.e., size correlation is eliminated). Alternatively, simple algebra can be used to derive an expected value function for assessing whether any proposed ratio formula is effective in eliminating size correlations. Some published ratio adjustments were incorrectly formulated as indicated by expected values that remain a function of size after ratio transformation. Regression coefficients incorporated into adjusted ratios must be estimated using least-squares regression of the measurement variable on the size variable. Use of parameters estimated by any other regression technique (e.g., major axis or reduced major axis) results in residual correlations between size and the adjusted measurement variable. Correctly formulated adjusted ratios, whose parameters are estimated by least-squares methods, do control for size correlations. The size-adjusted

  13. Deep Thermal Infrared Imaging of HR 8799 bcde: New Atmospheric Constraints and Limits on a Fifth Planet

    NASA Astrophysics Data System (ADS)

    Currie, Thayne; Burrows, Adam; Girard, Julien H.; Cloutier, Ryan; Fukagawa, Misato; Sorahana, Satoko; Kuchner, Marc; Kenyon, Scott J.; Madhusudhan, Nikku; Itoh, Yoichi; Jayawardhana, Ray; Matsumura, Soko; Pyo, Tae-Soo

    2014-11-01

    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 MJ (7 MJ ), 7 MJ (10 MJ ), or 12 MJ (13 MJ ) at r 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.

  14. 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. PMID:10688326

  15. 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.

  16. A Critical Role of the Nuclear Receptor HR3 in Regulation of Gonadotrophic Cycles of the Mosquito Aedes aegypti

    PubMed Central

    Mane-Padros, Daniel; Cruz, Josefa; Cheng, Andrew; Raikhel, Alexander S.

    2012-01-01

    The orphan nuclear receptor HR3 is essential for developmental switches during insect development and metamorphosis regulated by 20-hydroxyecdysone (20E). Reproduction of female mosquitoes of the major vector of Dengue fever, Aedes aegypti, is cyclic because of its dependence on blood feeding. 20E is an important hormone regulating vitellogenic events in this mosquito; however, any role for HR3 in 20E-driven reproductive events has not been known. Using RNA interference (RNAi) approach, we demonstrated that Aedes HR3 plays a critical role in a timely termination of expression of the vitellogenin (Vg) gene encoding the major yolk protein precursor. It is also important for downregulation of the Target-of-Rapamycin pathway and activation of programmed autophagy in the Aedes fat body at the end of vitellogenesis. HR3 is critical in activating betaFTZ-F1, EcRB and USPA, the expressions of which are highly elevated at the end of vitellogenesis. RNAi depletion of HR3 (iHR3) prior to the first gonadotrophic cycle affects a normal progression of the second gonadotrophic cycle. Most of ovaries 24 h post second blood meal from iHR3 females in the second cycle were small with follicles that were only slightly different in length from of those of resting stage. In addition, these iHR3 females laid a significantly reduced number of eggs per mosquito as compared to those of iMal and the wild type. Our results indicate an important role of HR3 in regulation of 20E-regulated developmental switches during reproductive cycles of A. aegypti females. PMID:23049766

  17. 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

  18. 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.

  19. 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.

  20. Identification of Metastasis-Associated Metabolic Profiles of Tumors by (1)H-HR-MAS-MRS.

    PubMed

    Gorad, Saurabh S; Ellingsen, Christine; Bathen, Tone F; Mathiesen, Berit S; Moestue, Siver A; Rofstad, Einar K

    2015-10-01

    Tumors develop an abnormal microenvironment during growth, and similar to the metastatic phenotype, the metabolic phenotype of cancer cells is tightly linked to characteristics of the tumor microenvironment (TME). In this study, we explored relationships between metabolic profile, metastatic propensity, and hypoxia in experimental tumors in an attempt to identify metastasis-associated metabolic profiles. Two human melanoma xenograft lines (A-07, R-18) showing different TMEs were used as cancer models. Metabolic profile was assessed by proton high resolution magic angle spinning magnetic resonance spectroscopy ((1)H-HR-MAS-MRS). Tumor hypoxia was detected in immunostained histological preparations by using pimonidazole as a hypoxia marker. Twenty-four samples from 10 A-07 tumors and 28 samples from 10 R-18 tumors were analyzed. Metastasis was associated with hypoxia in both A-07 and R-18 tumors, and (1)H-HR-MAS-MRS discriminated between tissue samples with and tissue samples without hypoxic regions in both models, primarily because hypoxia was associated with high lactate resonance peaks in A-07 tumors and with low lactate resonance peaks in R-18 tumors. Similarly, metastatic and non-metastatic R-18 tumors showed significantly different metabolic profiles, but not metastatic and non-metastatic A-07 tumors, probably because some samples from the metastatic A-07 tumors were derived from tumor regions without hypoxic tissue. This study suggests that (1)H-HR-MAS-MRS may be a valuable tool for evaluating the role of hypoxia and lactate in tumor metastasis as well as for identification of metastasis-associated metabolic profiles. PMID:26585232

  1. Discovery of a strong magnetic field in the rapidly rotating B2Vn star HR 7355

    NASA Astrophysics Data System (ADS)

    Oksala, M. E.; Wade, G. A.; Marcolino, W. L. F.; Grunhut, J.; Bohlender, D.; Manset, N.; Townsend, R. H. D.; Mimes Collaboration

    2010-06-01

    We report the detection of a strong, organized magnetic field in the He-variable early B-type star HR 7355 using spectropolarimetric data obtained with ESPaDOnS on the 3.6-m Canada-France-Hawaii Telescope within the context of the Magnetism in Massive Stars (MiMeS) Large Program. HR 7355 is both the most rapidly rotating known main-sequence magnetic star and the most rapidly rotating He-strong star, with v sin i = 300 +/- 15 km s-1 and a rotational period of 0.5214404+/-0.0000006 d. We have modelled our eight longitudinal magnetic field measurements assuming an oblique dipole magnetic field. Constraining the inclination of the rotation axis to be between 38° and 86°, we find the magnetic obliquity angle to be between 30° and 85°, and the polar strength of the magnetic field at the stellar surface to be between 13-17 kG. The photometric light curve constructed from HIPPARCOS archival data and new CTIO measurements shows two minima separated by 0.5 in rotational phase and occurring 0.25 cycles before/after the magnetic extrema. This photometric behaviour, coupled with previously reported variable emission of the Hα line (which we confirm), strongly supports the proposal that HR 7355 harbours a structured magnetosphere similar to that in the prototypical He-strong star, σ Ori E. Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France and the University of Hawaii.

  2. 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

  3. Infrared spectrum and proper motion of the brown dwarf companion of HR 7329 in Tucanae

    NASA Astrophysics Data System (ADS)

    Guenther, E. W.; Neuhäuser, R.; Huélamo, N.; Brandner, W.; Alves, J.

    2001-01-01

    Up to now only four brown dwarf companions to normal stars have been found and confirmed by both spectroscopy and proper motion (namely Gl 229 B, G 196-3 B, Gl 570 D, and CoD-33 deg 7795 B). On the basis of an optical spectrum taken with HST/STIS Lowrance et al. (2000) recently pointed out another possible candidate companion. The companion candidate is located at a distance of 4{' '} from the A0-star HR 7329, which is considered as a member of a moving group of young stars in Tucanae located at a distance of only ~ 48 pc. In order to confirm or disregard the companion nature of the candidate, we have determined the proper motion of the brown dwarf candidate with an epoch difference of 1.8 years, and found that it is consistent with a co-moving companion of HR 7329. Additional to the proper motion measurement, we have also taken an H-band spectrum using ISAAC on the ESO-VLT. From this spectrum, we conclude that the companion candidate has spectral type M 7 to M 8, which is in agreement with the optical spectrum. We thus conclude that HR 7329 B is most likely a brown dwarf companion. The mass ratio of this pair (A0 to M 7-8, i.e. ~ 100:1) is the largest known among brown dwarf companions, which is relevant for studying the formation of brown dwarfs as companions. Based on observations obtained at the European Southern Observatory on Cerro Paranal and La Silla in program\\break 65.L-0144.

  4. Photometric calibrations after Hipparcos or: the fine structure of the HR-diagram revealed

    NASA Astrophysics Data System (ADS)

    Grenon, Michel

    The Hipparcos parallaxes allow us to revisit photometric calibrations in terms of Mv and to evaluate the effects of the overall metallicity across the HR-diagram. For evolved stars the spread in mass remains the major and irreducible source of errors in the photometric Mv. If the relative location of open cluster main-sequences are fully explained by the ΔMv versus Δ[M/H] relation, the residual scatter in the lower main sequence appears due to additional parameters such as rotation or gravitational settling of the heavy elements. These cannot readily be studied by a purely photometric approach.

  5. 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

  6. An analysis of the spectrum of the Hg-Mn star HR 4072.

    NASA Astrophysics Data System (ADS)

    Dobrichev, V. M.; Klochkova, V. G.; Panchuk, V. E.; Rajkova, D. V.

    The Hg-Mn extremely sharp line star HR 4072 has been studied. In the spectral range 3600 - 4800 Å the lines of the primary and the secondary have been identified and their equivalent widths have been measured. Fundamental parameters (T0 = 10100K, lg g = 3.8, ξt = 2.2 km/s) and chemical composition of the atmospheres have been determined. The particularities of the chemical abundance pattern (enhancement of the heavy element abundance, infringement of the odd-even effect) agree qualitatively with the hypothesis about diffuse separation of the elements.

  7. Automatic home care system for monitoring HR/RR during sleep.

    PubMed

    Zhu, Xin; Chen, Wenxi; Tang, Zunyi; Nemoto, Tetsu; Wei, Daming

    2008-01-01

    This paper described an automatic home care system for monitoring HR/RR during sleep. Pressure signal is measured with a completely unconstrained pressure sensor beneath a pillow; then the signal is digitalized and the data are transmitted to a remote server using TCP/IP via a netbox. The data are processed and analyzed with a wavelet-based algorithm to obtain the heart rate and respiration rhythm during sleep. Through analyzing 180 days' data obtained from a female subject, it was found that this system can be used for daily monitoring heart rate and respiration rhythm during sleep and evaluating the quality of sleep at home. PMID:19162708

  8. Water Extent Monitoring Exploiting MR and HR Remote Sensing Data: Synergy, Constraints and Limits

    NASA Astrophysics Data System (ADS)

    Huber, C.; Uribe, C.; Lai, X.; Huang, S.; Yesou, H.

    2013-01-01

    EO MR and HR imagery, particularly SAR data, are powerful tools to monitor water extent that allow to understand the mechanism of complex key ecosystems such as Poyang Lake, considered as a key element for flood natural control and reduction as well as major resources within the Yangtze middle basin. To assess and validate a such long monitoring (2000 to 2011 with an image every 10 days), a particular attention was paid on data quality : the assessment of water extent synergy derived from multi-resolution dataset, and the impact of meteorological conditions, wind (inducing an increasing of surface roughness) and rain, on the SAR signal quality with bands C and X.

  9. 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.

  10. 15 CFR 6.5 - Effective date of adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INFLATION ADJUSTMENTS § 6.5 Effective date of adjustments. The adjustments made by § 6.4 of this part, of... December 11, 2008, and before the effective date of any future inflation adjustment thereto made...

  11. 15 CFR 6.5 - Effective date of adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... INFLATION ADJUSTMENTS § 6.5 Effective date of adjustments. The adjustments made by § 6.4 of this part, of... December 7, 2012, and before the effective date of any future inflation adjustment thereto made...

  12. 15 CFR 6.5 - Effective date of adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... INFLATION ADJUSTMENTS § 6.5 Effective date of adjustments. The adjustments made by § 6.4 of this part, of... December 11, 2008, and before the effective date of any future inflation adjustment thereto made...

  13. 15 CFR 6.5 - Effective date of adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INFLATION ADJUSTMENTS § 6.5 Effective date of adjustments. The adjustments made by § 6.4 of this part, of... December 11, 2008, and before the effective date of any future inflation adjustment thereto made...

  14. 15 CFR 6.5 - Effective date of adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... INFLATION ADJUSTMENTS § 6.5 Effective date of adjustments. The adjustments made by § 6.4 of this part, of... December 7, 2012, and before the effective date of any future inflation adjustment thereto made...

  15. Stimulation of orphan nuclear receptor HR38 gene expression by PTTH in prothoracic glands of the silkworm, Bombyx mori.

    PubMed

    Gu, Shi-Hong; Hsieh, Yun-Chih; Lin, Pei-Ling

    2016-07-01

    A complex signaling network appears to be involved in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in insect prothoracic glands (PGs). Less is known about the genomic action of PTTH signaling. In the present study, we investigated the effect of PTTH on the expression of Bombyx mori HR38, an immediate early gene (IEG) identified in insect systems. Our results showed that treatment of B. mori PGs with PTTH in vitro resulted in a rapid increase in HR38 expression. Injection of PTTH into day-5 last instar larvae also greatly increased HR38 expression, verifying the in vitro effect. Cycloheximide did not affect induction of HR38 expression, suggesting that protein synthesis is not required for PTTH's effect. A mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), and a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002), partially inhibited PTTH-stimulated HR38 expression, implying the involvement of both the ERK and PI3K signaling pathways. When PGs were treated with agents that directly elevate the intracellular Ca(2+) concentration (either A23187 or thapsigargin), an increase in HR38 expression was also detected, indicating that Ca(2+) is involved in PTTH-stimulated HR38 gene expression. A Western blot analysis showed that PTTH treatment increased the HR38 protein level, and protein levels showed a dramatic increase during the later stages of the last larval instar. Expression of HR38 transcription in response to PTTH appeared to undergo development-specific changes. Treatment with ecdysone in vitro did not affect HR38 expression. However, 20-hydroxyecdysone treatment decreased HR38 expression. Taken together, these results demonstrate that HR38 is a PTTH-stimulated IEG that is, at least in part, induced through Ca(2+)/ERK and PI3K signaling. The present study proposes a potential cross talk mechanism between PTTH and ecdysone signaling to regulate insect development and lays a

  16. 7 CFR 718.110 - Adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Adjustments. 718.110 Section 718.110 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE FARM... Determination of Acreage and Compliance § 718.110 Adjustments. (a) The farm operator or other...

  17. 7 CFR 718.110 - Adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Adjustments. 718.110 Section 718.110 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE FARM... Determination of Acreage and Compliance § 718.110 Adjustments. (a) The farm operator or other...

  18. 7 CFR 718.110 - Adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Adjustments. 718.110 Section 718.110 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE FARM... Determination of Acreage and Compliance § 718.110 Adjustments. (a) The farm operator or other...

  19. 45 CFR 84.44 - Academic adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Academic adjustments. 84.44 Section 84.44 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Postsecondary Education § 84.44 Academic adjustments. (a)...

  20. 22 CFR 142.44 - Academic adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Academic adjustments. 142.44 Section 142.44 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Postsecondary Education § 142.44 Academic adjustments. (a) Academic requirements. A...

  1. 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.

  2. Marital Adjustment among Housestaff and New Attorneys.

    ERIC Educational Resources Information Center

    Spendlove, David C.; And Others

    1990-01-01

    This study, involving 116 housestaff physicians, 106 new attorneys, and the spouses of both groups, identified the factors that significantly affected their marital adjustments. No differences were found. The most important factor associated with adjustment was perceived level of emotional support from one's spouse. (Author/MLW)

  3. 15 CFR 6.6 - Subsequent adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Subsequent adjustments. 6.6 Section 6.6 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION... once every four years after October 23, 1996, make the inflation adjustment, described in Section...

  4. Religiousity, Spirituality and Adolescents' Self-Adjustment

    ERIC Educational Resources Information Center

    Japar, Muhammad; Purwati

    2014-01-01

    Religiuosity, spirituality, and adolescents' self-adjustment. The objective of this study is to test the correlation among religiosity, spirituality and adolescents' self-adjustment. A quantitative approach was employed in this study. Data were collected from 476 junior high schools students of 13 State Junior High Schools and one Junior High…

  5. Adjustable Optical Mount Is More Rigid

    NASA Technical Reports Server (NTRS)

    Asbury, Bill G.; Coombs, David S.; Jones, Irby W.; Moore, Alvah S., Jr.

    1994-01-01

    Improved mount for lens or mirror in laser offers rigidity similar to that of nonadjustable optical mount. In comparison with older adjustable optical mounts, this one less susceptible to movements and distortions caused by vibrations and by thermal expansions and contractions. Mount contains neither adjustment rods (which grow or shrink as temperature varies) nor springs (which transmit vibrations to mounted optic).

  6. 24 CFR 9.155 - Housing adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Housing adjustments. 9.155 Section 9.155 Housing and Urban Development Office of the Secretary, Department of Housing and Urban... THE DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT § 9.155 Housing adjustments. (a) The agency...

  7. 15 CFR 6.6 - Subsequent adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Subsequent adjustments. 6.6 Section 6.6 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION... once every four years after October 23, 1996, make the inflation adjustment, described in Section...

  8. 15 CFR 6.6 - Subsequent adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Subsequent adjustments. 6.6 Section 6.6 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION... once every four years after October 23, 1996, make the inflation adjustment, described in Section...

  9. 15 CFR 6.6 - Subsequent adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Subsequent adjustments. 6.6 Section 6.6 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION... once every four years after October 23, 1996, make the inflation adjustment, described in Section...

  10. 15 CFR 6.6 - Subsequent adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Subsequent adjustments. 6.6 Section 6.6 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION... once every four years after October 23, 1996, make the inflation adjustment, described in Section...

  11. 14 CFR 254.6 - Periodic adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Periodic adjustments. 254.6 Section 254.6 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS DOMESTIC BAGGAGE LIABILITY § 254.6 Periodic adjustments. The Department of Transportation...

  12. Affect and Status Dimensions of Marital Adjustment

    ERIC Educational Resources Information Center

    Fineberg, Beth L.; Joseph Lowman

    1975-01-01

    The interactions of 10 maritally adjusted and 10 maladjusted couples were compared using a coding system based on the Leary circumplex. Major findings are (1) adjusted couples communicated more affection and submission than did maladjusted ones, (2) all couples were more likely to show complementary sequencing patterns with some interesting…

  13. 24 CFR 902.24 - Database adjustment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Database adjustment. 902.24 Section 902.24 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED... PUBLIC HOUSING ASSESSMENT SYSTEM Physical Condition Indicator § 902.24 Database adjustment....

  14. 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...

  15. 24 CFR 902.24 - Database adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Database adjustment. 902.24 Section 902.24 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED... PUBLIC HOUSING ASSESSMENT SYSTEM Physical Condition Indicator § 902.24 Database adjustment....

  16. 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...

  17. 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...

  18. 24 CFR 902.24 - Database adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Database adjustment. 902.24 Section 902.24 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED... PUBLIC HOUSING ASSESSMENT SYSTEM Physical Condition Indicator § 902.24 Database adjustment....

  19. 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...

  20. 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...

  1. 24 CFR 902.24 - Database adjustment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Database adjustment. 902.24 Section 902.24 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED... PUBLIC HOUSING ASSESSMENT SYSTEM Physical Condition Indicator § 902.24 Database adjustment....

  2. 10 CFR 905.34 - Adjustment provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Adjustment provisions. 905.34 Section 905.34 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Power Marketing Initiative § 905.34 Adjustment... continue to take place based on existing contract/marketing criteria principles....

  3. 10 CFR 905.34 - Adjustment provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Adjustment provisions. 905.34 Section 905.34 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Power Marketing Initiative § 905.34 Adjustment... continue to take place based on existing contract/marketing criteria principles....

  4. 10 CFR 905.34 - Adjustment provisions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Adjustment provisions. 905.34 Section 905.34 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Power Marketing Initiative § 905.34 Adjustment... continue to take place based on existing contract/marketing criteria principles....

  5. 10 CFR 905.34 - Adjustment provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Adjustment provisions. 905.34 Section 905.34 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Power Marketing Initiative § 905.34 Adjustment... continue to take place based on existing contract/marketing criteria principles....

  6. 10 CFR 905.34 - Adjustment provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Adjustment provisions. 905.34 Section 905.34 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Power Marketing Initiative § 905.34 Adjustment... continue to take place based on existing contract/marketing criteria principles....

  7. 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…

  8. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... for a contract that otherwise would be approved by RUS. See 7 CFR part 1753. ... 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...

  9. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... for a contract that otherwise would be approved by RUS. See 7 CFR part 1753. ... 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...

  10. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... for a contract that otherwise would be approved by RUS. See 7 CFR part 1753. ... 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...

  11. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... for a contract that otherwise would be approved by RUS. See 7 CFR part 1753. ... 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...

  12. 7 CFR 1744.64 - Budget adjustment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... for a contract that otherwise would be approved by RUS. See 7 CFR part 1753. ... 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...

  13. 7 CFR 15b.32 - Academic adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Academic adjustments. 15b.32 Section 15b.32 Agriculture Office of the Secretary of Agriculture NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Postsecondary Education § 15b.32 Academic adjustments. (a) Academic requirements. A recipient...

  14. A Digital Game for International Students' Adjustment

    ERIC Educational Resources Information Center

    Bisadi, Maryam; Chua, Alton Y. K; Keong, Lee Chu

    2013-01-01

    Although digital games have been developed for various subject areas, little attention has been focused on using digital games to address international students' adjustment issues. For this reason, this paper endeavors to explore the use of a digital game in facilitating international students acquire adjustment-related information. Specifically,…

  15. Marital Adjustment Correlates in Young Couples.

    ERIC Educational Resources Information Center

    Haskell, Samuel D.

    The Locke-Wallace Marital Adjustment Scale was administered to 35 Caucasian, Protestant couples who were married an average of nine years, largely middle class, and lived in Knoxville, Tennessee. Significant correlates of marital adjustment were organized into groups of similar variables. Correlate groups that were the same for the husband and…

  16. 24 CFR 886.112 - Rent adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Adjustment Factor most recently published by HUD in the Federal Register in accordance with 24 CFR part 888... unassisted housing in the area to ensure that adjustments in the Contract Rents shall not result in material differences between the rents charged for assisted and comparable unassisted units. Contract Rents may...

  17. 24 CFR 886.112 - Rent adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Adjustment Factor most recently published by HUD in the Federal Register in accordance with 24 CFR part 888... unassisted housing in the area to ensure that adjustments in the Contract Rents shall not result in material differences between the rents charged for assisted and comparable unassisted units. Contract Rents may...

  18. 24 CFR 886.112 - Rent adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Adjustment Factor most recently published by HUD in the Federal Register in accordance with 24 CFR part 888... unassisted housing in the area to ensure that adjustments in the Contract Rents shall not result in material differences between the rents charged for assisted and comparable unassisted units. Contract Rents may...

  19. 24 CFR 886.112 - Rent adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Adjustment Factor most recently published by HUD in the Federal Register in accordance with 24 CFR part 888... unassisted housing in the area to ensure that adjustments in the Contract Rents shall not result in material differences between the rents charged for assisted and comparable unassisted units. Contract Rents may...

  20. 24 CFR 886.112 - Rent adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Adjustment Factor most recently published by HUD in the Federal Register in accordance with 24 CFR part 888... unassisted housing in the area to ensure that adjustments in the Contract Rents shall not result in material differences between the rents charged for assisted and comparable unassisted units. Contract Rents may...