Science.gov

Sample records for republiky za rok

  1. Characterization of DNA Binding Sites of RokB, a ROK-Family Regulator from Streptomyces coelicolor Reveals the RokB Regulon

    PubMed Central

    Bekiesch, Paulina; Forchhammer, Karl; Apel, Alexander Kristian

    2016-01-01

    ROK-family proteins have been described to act either as sugar kinases or as transcriptional regulators. Few ROK-family regulators have been characterized so far and most of them are involved in carbon catabolite repression. RokB (Sco6115) has originally been identified in a DNA-affinity capturing approach as a possible regulator of the heterologously expressed novobiocin biosynthetic gene cluster in Streptomyces coelicolor M512. Interestingly, both, the rokB deletion mutants as well as its overexpressing mutants showed significantly reduced novobiocin production in the host strain S.coelicolor M512. We identified the DNA-binding site for RokB in the promoter region of the novobiocin biosynthetic genes novH-novW. It overlaps with the novH start codon which may explain the reduction of novobiocin production caused by overexpression of rokB. Bioinformatic screening coupled with surface plasmon resonance based interaction studies resulted in the discovery of five RokB binding sites within the genome of S. coelicolor. Using the genomic binding sites, a consensus motif for RokB was calculated, which differs slightly from previously determined binding motifs for ROK-family regulators. The annotations of the possible members of the so defined RokB regulon gave hints that RokB might be involved in amino acid metabolism and transport. This hypothesis was supported by feeding experiments with casamino acids and L-tyrosine, which could also explain the reduced novobiocin production in the deletion mutants. PMID:27145180

  2. Characterization of the ROK-family transcriptional regulator RokA of Streptococcus pneumoniae D39.

    PubMed

    Shafeeq, Sulman; Kloosterman, Tomas G; Rajendran, Vijayanand; Kuipers, Oscar P

    2012-12-01

    The Gram-positive human pathogen Streptococcus pneumoniae possesses an unusually high number of gene clusters specific for carbohydrate utilization. This provides it with the ability to use a wide array of sugars, which may aid during infection and survival in different environmental conditions present in the host. In this study, the regulatory mechanism of transcription of a gene cluster, SPD0424-8, putatively encoding a cellobiose/lactose-specific phosphotransferase system is investigated. We demonstrate that this gene cluster is transcribed as one transcriptional unit directed by the promoter of the SPD0424 gene. Upstream of SPD0424, a gene was identified encoding a ROK-family transcriptional regulator (RokA: SPD0423). DNA microarray and transcriptional reporter analyses with a rokA mutant revealed that RokA acts as a transcriptional repressor of the SPD0424-8 operon. Furthermore, we identified a 25 bp AT-rich DNA operator site (5'-TATATTTAATTTATAAAAAATAAAA-3') in the promoter region of SPD0424, which was validated by promoter truncation studies, DNase I footprinting and electrophoretic mobility-shift assays. We tested a large range of different sugars for their effect on the expression of the SPD0424-8 operon, but only moderate variation in expression was observed in the conditions applied. Therefore, a co-factor for RokA-mediated transcriptional control could not be identified. PMID:23082033

  3. Description of Axial Detail for ROK Fuel

    SciTech Connect

    Trellue, Holly R; Galloway, Jack D

    2012-04-20

    For the purpose of NDA simulations of the ROK fuel assemblies, we have developed an axial burnup distribution to represent the pins themselves based on gamma scans of rods in the G23 assembly. For the purpose of modeling the G23 assembly (both at ORNL and LANL), the pin-by-pin burnup map as simulated by ROK is being assumed to represent the radial burnup distribution. However, both DA and NDA results indicate that this simulated estimate is not 100% correct. In particular, the burnup obtained from the axial gamma scan of 7 pins does not represent exactly the same 'average' pin burnup as the ROK simulation. Correction for this discrepancy is a goal of the well-characterized assembly task but will take time. For now, I have come up with a correlation for 26 axial points of the burnup as obtained by gamma scans of 7 different rods (C13, G01, G02, J11, K10, L02, and M04, neglecting K02 at this time) to the average burnup given by the simulation for each of the rods individually. The resulting fraction in each axial zone is then averaged for the 7 different rods so that it can represent every fuel pin in the assembly. The burnup in each of the 26 axial zones of rods in all ROK assemblies will then be directly adjusted using this fraction, which is given in Table 1. Note that the gamma scan data given by ROK for assembly G23 included a length of {approx}3686 mm, so the first 12 mm and the last 14 mm were ignored to give an actual rod length of {approx}366 cm. To represent assembly F02 in which no pin-by-pin burnup distribution is given by ROK, we must model it using infinitely-reflected geometry but can look at the effects of measuring in different axial zones by using intermediate burnup files (i.e. smaller burnups than 28 GWd/MTU) and determining which axial zone(s) each burnup represents. Details for assembly F02 are then given in Tables 2 and 3, which is given in Table 1 and has 44 total axial zones to represent the top meter in explicit detail in addition to the

  4. Evolutionary bases of carbohydrate recognition and substrate discrimination in the ROK protein family.

    PubMed

    Conejo, Maria S; Thompson, Steven M; Miller, Brian G

    2010-06-01

    The ROK (repressor, open reading frame, kinase) protein family (Pfam 00480) is a large collection of bacterial polypeptides that includes sugar kinases, carbohydrate responsive transcriptional repressors, and many functionally uncharacterized gene products. ROK family sugar kinases phosphorylate a range of structurally distinct hexoses including the key carbon source D: -glucose, various glucose epimers, and several acetylated hexosamines. The primary sequence elements responsible for carbohydrate recognition within different functional categories of ROK polypeptides are largely unknown due to a limited structural characterization of this protein family. In order to identify the structural bases for substrate discrimination in individual ROK proteins, and to better understand the evolutionary processes that led to the divergent evolution of function in this family, we constructed an inclusive alignment of 227 representative ROK polypeptides. Phylogenetic analyses and ancestral sequence reconstructions of the resulting tree reveal a discrete collection of active site residues that dictate substrate specificity. The results also suggest a series of mutational events within the carbohydrate-binding sites of ROK proteins that facilitated the expansion of substrate specificity within this family. This study provides new insight into the evolutionary relationship of ROK glucokinases and non-ROK glucokinases (Pfam 02685), revealing the primary sequence elements shared between these two protein families, which diverged from a common ancestor in ancient times. PMID:20512568

  5. 77 FR 36031 - ROK Entertainment Group, Inc., RussOil Corp., Tricell, Inc., Tunex International, Inc. (n/k/a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION ROK Entertainment Group, Inc., RussOil Corp., Tricell, Inc., Tunex International, Inc. (n/k/a Aone... accurate information concerning the securities of ROK Entertainment Group, Inc. because it has not...

  6. Identification of a putative DEAD-box RNA helicase and a zinc-finger protein in Candida albicans by functional complementation of the S. cerevisiae rok1 mutation.

    PubMed

    Kim, W I; Lee, W B; Song, K; Kim, J

    2000-03-30

    We identified two novel genes, CHR1 and CSR1, of the fungal pathogen Candida albicans, by functional complementation of the Saccharomyces cerevisiae rok1 mutation. The Rok1 protein is a member of the DEAD protein family of ATP-dependent RNA helicases. ROK1 is required for cell cycle progression and also for rRNA processing. The CHR1 gene product of 578 amino acids is highly homologous to the Rok1 protein (54% identity) and is considered to be a putative DEAD-box RNA helicase. We predict that the CSR1 gene encodes a 73 kDa protein of 612 amino acids with five zinc-finger motifs at the C-terminal region. CHR1 or CSR1 on a high-copy number plasmid showed a slow-growth phenotype in a condition where the ROK1 expression is turned on from the GAL1 promoter. This result is consistent with the lethality caused by the ROK1 overexpression. We conclude that CHR1 encodes a functional homologue of Rok1 protein and CSR1 is a heterologous suppressor of the rok1 mutation. PMID:10705369

  7. Forensic seismology and boundary element method application vis-à-vis ROKS Cheonan underwater explosion

    NASA Astrophysics Data System (ADS)

    Kim, So Gu

    2013-12-01

    On March 26, 2010 an underwater explosion (UWE) led to the sinking of the ROKS Cheonan. The official Multinational Civilian-Military Joint Investigation Group (MCMJIG) report concluded that the cause of the underwater explosion was a 250 kg net explosive weight (NEW) detonation at a depth of 6-9 m from a DPRK "CHT-02D" torpedo. Kim and Gitterman (2012a) determined the NEW and seismic magnitude as 136 kg at a depth of approximately 8m and 2.04, respectively using basic hydrodynamics based on theoretical and experimental methods as well as spectral analysis and seismic methods. The purpose of this study was to clarify the cause of the UWE via more detailed methods using bubble dynamics and simulation of propellers as well as forensic seismology. Regarding the observed bubble pulse period of 0.990 s, 0.976 s and 1.030 s were found in case of a 136 NEW at a detonation depth of 8 m using the boundary element method (BEM) and 3D bubble shape simulations derived for a 136 kg NEW detonation at a depth of 8 m approximately 5 m portside from the hull centerline. Here we show through analytical equations, models and 3D bubble shape simulations that the most probable cause of this underwater explosion was a 136 kg NEW detonation at a depth of 8m attributable to a ROK littoral "land control" mine (LCM).

  8. A Metafunctional Analysis of the News "ROK, DPRK Agree to Defuse Tension after Talks" on China Daily

    ERIC Educational Resources Information Center

    Xu, Bo

    2015-01-01

    On the basis of the three metafunctions in Systemic Functional Linguistics (SFL): experiential, interpersonal and textual, the paper makes an analysis of the current news "ROK, DPRK Agree to Defuse Tension after Talks" on China Daily. The paper finds out that the political news has unique features in terms of experiential, interpersonal…

  9. The Rock Geochemical Model (RokGeM) v0.9

    NASA Astrophysics Data System (ADS)

    Colbourn, G.; Ridgwell, A.; Lenton, T. M.

    2013-09-01

    A new model of terrestrial rock weathering - the Rock Geochemical Model (RokGeM) - was developed for incorporation into the GENIE Earth System modelling framework. In this paper we describe the model. We consider a range of previously devised parameterizations, ranging from simple dependencies on global mean temperature following Berner et al. (1983), to spatially explicit dependencies on run-off and temperature (GKWM, Bluth and Kump, 1994; GEM-CO2, Amiotte-Suchet et al., 2003) - fields provided by the energy-moisture balance atmosphere model component in GENIE. Using long-term carbon cycle perturbation experiments, we test the effects of a wide range of model parameters, including whether or not the atmosphere was "short-circuited" in the carbon cycle; the sensitivity and feedback strength of temperature and run-off on carbonate and silicate weathering; different river-routing schemes; 0-D (global average) vs. 2-D (spatially explicit) weathering schemes; and the lithology dependence of weathering. Included are details of how to run the model and visualize the results.

  10. The Rock Geochemical Model (RokGeM) v0.9

    NASA Astrophysics Data System (ADS)

    Colbourn, G.; Ridgwell, A.; Lenton, T. M.

    2012-07-01

    A new model of terrestrial rock weathering - The Rock Geochemical Model (RokGeM) - is developed for incorporation into the GENIE Earth System modelling framework. In this paper we describe the model. We consider a range of previously devised parameterizations, ranging from simple dependencies on global mean temperature following (Berner et al., 1983), to spatially-explicit dependencies on runoff and temperature (GKWM; Bluth and Kump, 1994; GEM-CO2 Amiotte-Suchet et al., 2003) - fields provided by the energy-moisture balance atmosphere model component in GENIE. Using long term carbon cycle perturbation experiments, we test the effects of a wide range of model parameters, including: whether or not the atmosphere was "short-circuited" in the carbon cycle; the sensitivity and feedback strength of temperature and runoff on carbonate and silicate weathering; different river-routing schemes; 0-D (global average) vs. 2-D (spatially explicit) weathering schemes; and the lithology dependence of weathering. Included are details of how to run the model and visualize the results.

  11. Structural studies of ROK fructokinase YdhR from Bacillus subtilis : insights into substrate binding and fructose specificity.

    SciTech Connect

    Nocek, B.; Stein, A.; Jedrzejczak, R.; Cuff, M.; Li, H.; Volkart, L.; Joachimiak, A.; Biosciences Division

    2011-02-18

    The main pathway of bacterial sugar phosphorylation utilizes specific phosphoenolpyruvate phosphotransferase system (PTS) enzymes. In addition to the classic PTS system, a PTS-independent secondary system has been described in which nucleotide-dependent sugar kinases are used for monosaccharide phosphorylation. Fructokinase (FK), which phosphorylates d-fructose with ATP as a cofactor, has been shown to be a member of this secondary system. Bioinformatic analysis has shown that FK is a member of the 'ROK' (bacterial Repressors, uncharacterized Open reading frames, and sugar Kinases) sequence family. In this study, we report the crystal structures of ROK FK from Bacillus subtilis (YdhR) (a) apo and in the presence of (b) ADP and (c) ADP/d-fructose. All structures show that YdhR is a homodimer with a monomer composed of two similar {alpha}/{beta} domains forming a large cleft between domains that bind ADP and d-fructose. Enzymatic activity assays support YdhR function as an ATP-dependent fructose kinase.

  12. Substrate Recognition Mechanism and Substrate-Dependent Conformational Changes of an ROK Family Glucokinase from Streptomyces griseus

    PubMed Central

    Miyazono, Ken-ichi; Tabei, Nobumitsu; Morita, Sho; Ohnishi, Yasuo; Horinouchi, Sueharu

    2012-01-01

    Carbon catabolite repression (CCR) is a widespread phenomenon in many bacteria that is defined as the repression of catabolic enzyme activities for an unfavorable carbon source by the presence of a preferable carbon source. In Streptomyces, secondary metabolite production often is negatively affected by the carbon source, indicating the involvement of CCR in secondary metabolism. Although the CCR mechanism in Streptomyces still is unclear, glucokinase is presumably a central player in CCR. SgGlkA, a glucokinase from S. griseus, belongs to the ROK family glucokinases, which have two consensus sequence motifs (1 and 2). Here, we report the crystal structures of apo-SgGlkA, SgGlkA in complex with glucose, and SgGlkA in complex with glucose and adenylyl imidodiphosphate (AMPPNP), which are the first structures of an ROK family glucokinase. SgGlkA is divided into a small α/β domain and a large α+β domain, and it forms a dimer-of-dimer tetrameric configuration. SgGlkA binds a β-anomer of glucose between the two domains, and His157 in consensus sequence 1 plays an important role in the glucose-binding mechanism and anomer specificity of SgGlkA. In the structures of SgGlkA, His157 forms an HC3-type zinc finger motif with three cysteine residues in consensus sequence 2 to bind a zinc ion, and it forms two hydrogen bonds with the C1 and C2 hydroxyls of glucose. When the three structures are compared, the structure of SgGlkA is found to be modified by the binding of substrates. The substrate-dependent conformational changes of SgGlkA may be related to the CCR mechanism in Streptomyces. PMID:22101842

  13. Identifying unstable taxa: Efficient implementation of triplet-based measures of stability, and comparison with Phyutility and RogueNaRok.

    PubMed

    Goloboff, Pablo A; Szumik, Claudia A

    2015-07-01

    This paper describes an efficient implementation of triplet-based measures of stability, in the program TNT. The only available implementations of such measures are much slower than the present one, either because of an inefficient implementation (Phyutility, Thor) or because the stability is evaluated with quartets (RogueNaRok, requiring O(t(4)), instead of the O(t(3)) possible for triplets). The method to quickly calculate triplets is applied to solving IterPCR (Pol and Escapa, 2009). It is shown that, in some cases, IterPCR or other algorithms in the program TNT (e.g. commands prunnelsen, prunmajor, or chkmoves) produce more informative results than analysis with RogueNaRok. PMID:25865266

  14. The Drosophila FHOD1-like formin Knittrig acts through Rok to promote stress fiber formation and directed macrophage migration during the cellular immune response.

    PubMed

    Lammel, Uwe; Bechtold, Meike; Risse, Benjamin; Berh, Dimitri; Fleige, Astrid; Bunse, Ingrid; Jiang, Xiaoyi; Klämbt, Christian; Bogdan, Sven

    2014-03-01

    A tight spatiotemporal control of actin polymerization is important for many cellular processes that shape cells into a multicellular organism. The formation of unbranched F-actin is induced by several members of the formin family. Drosophila encodes six formin genes, representing six of the seven known mammalian subclasses. Knittrig, the Drosophila homolog of mammalian FHOD1, is specifically expressed in the developing central nervous system midline glia, the trachea, the wing and in macrophages. knittrig mutants exhibit mild tracheal defects but survive until late pupal stages and mainly die as pharate adult flies. knittrig mutant macrophages are smaller and show reduced cell spreading and cell migration in in vivo wounding experiments. Rescue experiments further demonstrate a cell-autonomous function of Knittrig in regulating actin dynamics and cell migration. Knittrig localizes at the rear of migrating macrophages in vivo, suggesting a cellular requirement of Knittrig in the retraction of the trailing edge. Supporting this notion, we found that Knittrig is a target of the Rho-dependent kinase Rok. Co-expression with Rok or expression of an activated form of Knittrig induces actin stress fibers in macrophages and in epithelial tissues. Thus, we propose a model in which Rok-induced phosphorylation of residues within the basic region mediates the activation of Knittrig in controlling macrophage migration. PMID:24553290

  15. Structural Studies of ROK Fructokinase YdhR from Bacillus subtilis: Insights into substrates binding and fructose specificity

    PubMed Central

    Nocek, B.; Stein, A.J.; Jedrzejczak, R.; Cuff, M. E.; Li, H.; Volkart, L.; Joachimiak, A.

    2011-01-01

    The main pathway of bacterial sugar phosphorylation utilizes specific phosphoenolpyruvate phosphotransferase system (PTS) enzymes. In addition to the classic PTS system, a PTS-independent secondary system has been described in which nucleotide-dependent sugar kinases are used for monosaccharide phosphorylation. Fructokinase (FK) that phosphorylates d-fructose with ATP as a cofactor has been shown to be a member of this secondary system. Bioinformatics analysis has shown that FK is a member of the “ROK” (bacterial Repressors, uncharacterized Open reading frames, and sugar Kinases) sequence family. In this study, we report the crystal structures of ROK FK from Bacillus subtilis (YdhR) (a) apo and in the presence of (b) ADP and (c) ADP/dfructose. All structures show that YdhR is a homo-dimer with a monomer composed of two similar α/βdomains forming a large cleft between domains that bind ADP and d-fructose. Enzymatic activity assays support YdhR function as an ATP-dependent fructose kinase. PMID:21185308

  16. The RhoA-Rok-Myosin II Pathway is Involved in Extracellular Matrix-Mediated Regulation of Prolactin Signaling in Mammary Epithelial Cells

    PubMed Central

    Du, Jyun-Yi; Chen, Meng-Chi; Hsu, Tsai-Ching; Wang, Jen-Hsing; Brackenbury, Lisa; Lin, Ting-Hui; Wu, Yi-Ying; Yang, Zhihong; Streuli, Charles H; Lee, Yi-Ju

    2012-01-01

    In mammary epithelial cells (MECs), prolactin-induced signaling and gene expression requires integrin-mediated cell adhesion to basement membrane (BM). In the absence of proper cell–BM interactions, for example, culturing cells on collagen-coated plastic dishes, signal propagation is substantially impaired. Here we demonstrate that the RhoA-Rok-myosin II pathway accounts for the ineffectiveness of prolactin signaling in MECs cultured on collagen I. Under these culture conditions, the RhoA pathway is activated, leading to downregulation of prolactin receptor expression and reduced prolactin signaling. Enforced activation of RhoA in MECs cultured on BM suppresses prolactin receptor levels, and prevents prolactin-induced Stat5 tyrosine phosphorylation and β-casein expression. Overexpression of dominant negative RhoA in MECs cultured on collagen I, or inhibiting Rok activity, increases prolactin receptor expression, and enhances prolactin signaling. In addition, inhibition of myosin II ATPase activity by blebbistatin also exerts a beneficial effect on prolactin receptor expression and prolactin signaling, suggesting that tension exerted by the collagen substratum, in collaboration with the RhoA-Rok-myosin II pathway, contributes to the failure of prolactin signaling. Furthermore, MECs cultured on laminin-coated plastic have similar morphology and response to prolactin as those cultured on collagen I. They display high levels of RhoA activity and are inefficient in prolactin signaling, stressing the importance of matrix stiffness in signal transduction. Our results reveal that RhoA has a central role in determining the fate decisions of MECs in response to cell–matrix interactions. J. Cell. Physiol. 227: 1553–1560, 2012. © 2011 Wiley Periodicals, Inc. PMID:21678418

  17. An Analysis of Selected Properties of ZA Alloys

    NASA Astrophysics Data System (ADS)

    Gervais, E.; Barnhurst, R. J.; Loong, C. A.

    1985-11-01

    Zinc-aluminum (ZA) alloys are a relatively new family of zinc foundry alloys having superior melting and casting characteristics and attractive mechanical properties. The ZA-8 and ZA-12 alloys are moderate to high strength materials while ZA-27 is a high-strength alloy. All can be sand cast, permanent molded and pressure die cast. An extensive characterization program is being implemented to develop appropriate and reliable engineering data for designers. Property development in all aspects of ZA metallurgy is welladvanced. The data available on selected physical and mechanical properties of ZA alloys is compared here with the properties of traditional casting alloys.

  18. The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation

    PubMed Central

    Khoshnevis, Sohail; Askenasy, Isabel; Dattolo, Maria D.; Young-Erdos, Crystal L.; Stroupe, M. Elizabeth; Karbstein, Katrin

    2016-01-01

    DEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed “helicases,” their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S ribosomes. Interconversion between these two forms by ATP hydrolysis is required for release of Rrp5 from pre-40S ribosomes in vivo, thereby allowing Rrp5 to carry out its role in 60S subunit assembly. Furthermore, our data also strongly suggest that the previously described accumulation of snR30 upon Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked. PMID:27280440

  19. The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation.

    PubMed

    Khoshnevis, Sohail; Askenasy, Isabel; Johnson, Matthew C; Dattolo, Maria D; Young-Erdos, Crystal L; Stroupe, M Elizabeth; Karbstein, Katrin

    2016-06-01

    DEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S ribosomes. Interconversion between these two forms by ATP hydrolysis is required for release of Rrp5 from pre-40S ribosomes in vivo, thereby allowing Rrp5 to carry out its role in 60S subunit assembly. Furthermore, our data also strongly suggest that the previously described accumulation of snR30 upon Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked. PMID:27280440

  20. AMS Radiocarbon Dating of Large Za Baobabs (Adansonia za) of Madagascar

    PubMed Central

    Patrut, Adrian; Patrut, Roxana T.; Danthu, Pascal; Leong Pock-Tsy, Jean-Michel; Rakosy, Laszlo; Lowy, Daniel A.; von Reden, Karl F.

    2016-01-01

    The article reports the radiocarbon investigation of Anzapalivoro, the largest za baobab (Adansonia za) specimen of Madagascar and of another za, namely the Big cistern baobab. Several wood samples collected from the large inner cavity and from the outer part/exterior of the tree were investigated by AMS (accelerator mass spectrometry) radiocarbon dating. For samples collected from the cavity walls, the age values increase with the distance into the wood up to a point of maximum age, after which the values decrease toward the outer part. This anomaly of age sequences indicates that the inner cavity of Anzapalivoro is a false cavity, practically an empty space between several fused stems disposed in a ring-shaped structure. The radiocarbon date of the oldest sample was 780 ± 30 bp, which corresponds to a calibrated age of around 735 yr. Dating results indicate that Anzapalivoro has a closed ring-shaped structure, which consists of 5 fused stems that close a false cavity. The oldest part of the biggest za baobab has a calculated age of 900 years. We also disclose results of the investigation of a second za baobab, the Big cistern baobab, which was hollowed out for water storage. This specimen, which consists of 4 fused stems, was found to be around 260 years old. PMID:26760300

  1. AMS Radiocarbon Dating of Large Za Baobabs (Adansonia za) of Madagascar.

    PubMed

    Patrut, Adrian; Patrut, Roxana T; Danthu, Pascal; Leong Pock-Tsy, Jean-Michel; Rakosy, Laszlo; Lowy, Daniel A; von Reden, Karl F

    2016-01-01

    The article reports the radiocarbon investigation of Anzapalivoro, the largest za baobab (Adansonia za) specimen of Madagascar and of another za, namely the Big cistern baobab. Several wood samples collected from the large inner cavity and from the outer part/exterior of the tree were investigated by AMS (accelerator mass spectrometry) radiocarbon dating. For samples collected from the cavity walls, the age values increase with the distance into the wood up to a point of maximum age, after which the values decrease toward the outer part. This anomaly of age sequences indicates that the inner cavity of Anzapalivoro is a false cavity, practically an empty space between several fused stems disposed in a ring-shaped structure. The radiocarbon date of the oldest sample was 780 ± 30 bp, which corresponds to a calibrated age of around 735 yr. Dating results indicate that Anzapalivoro has a closed ring-shaped structure, which consists of 5 fused stems that close a false cavity. The oldest part of the biggest za baobab has a calculated age of 900 years. We also disclose results of the investigation of a second za baobab, the Big cistern baobab, which was hollowed out for water storage. This specimen, which consists of 4 fused stems, was found to be around 260 years old. PMID:26760300

  2. Isotopic geochemistry of acid thermal waters and volcanic gases from Zaō volcano in Japan

    NASA Astrophysics Data System (ADS)

    Kiyosu, Yasuhiro; Kurahashi, Makoto

    1984-08-01

    The chemical composition and D/H, {18O }/{16O } and {34S }/{32S } ratios have been determined for the acid hot waters and volcanic gases discharging from Zaō volcano in Japan. The thermal springs in Zaō volcano issue acid sulfate-chloride type waters (Zaō) and acid sulfate type waters (Kamoshika). Gases emitted at Kamoshika fumaroles are rich in CO 2, SO 2 and N 2, exclusive of H 2O. Chloride concentrations and oxygen isotope data indicate that the Zaō thermal waters issue a fluid mixture from an acid thermal reservoir and meteoric waters from shallow aquifers. The waters in the Zaō volcanic system have slight isotopic shifts from the respective local meteoric values. The isotopic evidence indicates that most of the water in the system is meteoric in origin. Sulfates in Zaō acid sulfate-chloride waters with δ34S values of around +15‰, are enriched in 34S compared to Zaō H 2S, while the acid sulfate waters at Kamoshika contain supergene light sulfate ( δ 34S = ˜ + 4‰ ) derived from volcanic sulfur dioxide from the volcanic exhalations. The sulfur species in Zaō acid waters are lighter in δ34S than those of other volcanic areas, reflecting the difference in total pressure.

  3. Stabilization in the ZaP Flow Z-Pinch

    NASA Astrophysics Data System (ADS)

    Shumlak, U.; Blakely, J. M.; Chan, B.-J.; Golingo, R. P.; Knecht, S. D.; Nelson, B. A.; Oberto, R. J.; Sybouts, M. R.; Vogman, G. V.; Den Hartog, D. J.

    2009-06-01

    The ZaP flow Z-pinch experiment at the University of Washington investigates the innovative plasma confinement concept of using sheared flows to stabilize an otherwise unstable configuration. The ZaP experiment generates an axially flowing Z-pinch that is 1 m long with a 1 cm radius with a coaxial accelerator coupled to a pinch assembly chamber. Magnetic probes measure the fluctuation levels of the azimuthal modes m = 1, 2, and 3. After assembly, the plasma is magnetically confined for an extended quiescent period where the mode activity is significantly reduced. Experimental measurements show a sheared flow profile that is coincident with the low magnetic fluctuations during the quiescent period. Recent experimental modifications produce more energetic Z-pinch plasmas that exhibit the same general behavior. The plasma equilibrium is characterized with a suite of diagnostics that measure the plasma density, magnetic field, ion and electron temperatures, in addition to plasma flow. The equilibrium is shown to satisfy radial force balance.

  4. Investigation of Heating Mechanisms in the ZaP Flow Z-Pinch

    NASA Astrophysics Data System (ADS)

    Knecht, S. D.; Shumlak, U.; Nelson, B. A.; Golingo, R. P.

    2010-11-01

    The ZaP Flow Z-Pinch at the University of Washington is a basic plasma physics experiment that investigates stabilizing a Z-pinch with a radially-varying axial flow, dvz/dr. ZaP consists of a coaxial accelerator region coupled to a pinch assembly region. It is hypothesized that the primary means of heating in ZaP is through adiabatic compression during pinch formation. The 10 cm inner electrode of ZaP is replaced with a 16 cm inner electrode to investigate this hypothesis. A four-chord HeNe interferometer is used to determine a pinch density profile as a function of time, and radial force balance and conservation of energy equations are used to determine temperature and magnetic field profiles. Temperature measurements are made with a 20-chord imaging spectrometer (Ti) and a Thomson-scattering system (Te) and compared to the calculated temperatures. The profiles are investigated for a range of accelerator densities and pinch currents for both electrode configurations. The possible effects of adiabatic compression, Ohmic heating and shock heating will be evaluated and reported.

  5. ZaP-HD: High Energy Density Z-Pinch Plasmas using Sheared Flow Stabilization

    NASA Astrophysics Data System (ADS)

    Golingo, R. P.; Shumlak, U.; Nelson, B. A.; Claveau, E. L.; Doty, S. A.; Forbes, E. G.; Hughes, M. C.; Kim, B.; Ross, M. P.; Weed, J. R.

    2015-11-01

    The ZaP-HD flow Z-pinch project investigates scaling the flow Z-pinch to High Energy Density Plasma, HEDP, conditions by using sheared flow stabilization. ZaP used a single power supply to produce 100 cm long Z-pinches that were quiescent for many radial Alfven times and axial flow-through times. The flow Z-pinch concept provides an approach to achieve HED plasmas, which are dimensionally large and persist for extended durations. The ZaP-HD device replaces the single power supply from ZaP with two separate power supplies to independently control the plasma flow and current in the Z-pinch. Equilibrium is determined by diagnostic measurements of the density with interferometry and digital holography, the plasma flow and temperature with passive spectroscopy, the magnetic field with surface magnetic probes, and plasma emission with optical imaging. The diagnostics fully characterize the plasma from its initiation in the coaxial accelerator, through the pinch, and exhaust from the assembly region. The plasma evolution is modeled with high resolution codes: Mach2, WARPX, and NIMROD. Experimental results and scaling analyses are presented. This work is supported by grants from the U.S. Department of Energy and the U.S. National Nuclear Security Administration.

  6. Aging characteristics of short glass fiber reinforced ZA-27 alloy composite materials

    NASA Astrophysics Data System (ADS)

    Sharma, S. C.; Girish, B. M.; Satish, B. M.; Kamath, R.

    1998-12-01

    Aging characteristics of short glass fiber reinforced ZA-27 alloy composite materials have been evaluated in the present study. The liquid metallurgy technique was used to fabricate the composites, in which preheated short glass fibers were introduced into the ZA-27 alloy melt above its liquidus temperature. The aging temperature employed was 125 °C for 6, 12,18, and 24 h. The aged alloy (no fibers) reached the peak hardness after 18 h, while the composites (regardless of filler content) reached the same hardness in 12 h. It is hypothesized that the aging treatment of a composite improves the strength of the interface between the short fibers and the matrix. This is confirmed by the tensile fractograph analysis, which indicates that at a given aging temperature, the composites aged for 18 h exhibit short fibers that remain attached to the metal matrix, while those aged for 6 h undergo debonding.

  7. Effects on asylum seekers of ill treatment in Zaïre.

    PubMed

    Peel, M R

    1996-02-01

    To describe the health effects of the political system in Zaïre on asylum seekers seen at the Medical Foundation for the Care of Victims of Torture a retrospective study was performed of the records of 92 asylum seekers from Zaïre who were seen for medical reports at the medical foundation in 1993 and 1994. Eighty one had been imprisoned; the others had been severely treated at home by the security services. Sixty six had been detained for up to one year. Prison conditions were invariably unsanitary, and food of poor quality when provided. All had been beaten on arrest, and all but two had been beaten repeatedly in prison. Nearly all the women and some of the men described sexual abuse. Almost all left prison through bribery or because a guard had a similar background. Seventy two asylum seekers had scarring, consider to be consistent with the history, and 70 were considered to have suffered persistent psychological damage. Asylum seekers from Zaïre will have health effects from experiences unimaginable to the ordinary Briton. An understanding of the background will help clinicians manage them. PMID:8611788

  8. Pak4 Is Required during Epithelial Polarity Remodeling through Regulating AJ Stability and Bazooka Retention at the ZA

    PubMed Central

    Walther, Rhian F.; Nunes de Almeida, Francisca; Vlassaks, Evi; Burden, Jemima J.; Pichaud, Franck

    2016-01-01

    Summary The ability of epithelial cells to assemble into sheets relies on their zonula adherens (ZA), a circumferential belt of adherens junction (AJ) material, which can be remodeled during development to shape organs. Here, we show that during ZA remodeling in a model neuroepithelial cell, the Cdc42 effector P21-activated kinase 4 (Pak4/Mbt) regulates AJ morphogenesis and stability through β-catenin (β-cat/Arm) phosphorylation. We find that β-catenin phosphorylation by Mbt, and associated AJ morphogenesis, is needed for the retention of the apical determinant Par3/Bazooka at the remodeling ZA. Importantly, this retention mechanism functions together with Par1-dependent lateral exclusion of Par3/Bazooka to regulate apical membrane differentiation. Our results reveal an important functional link between Pak4, AJ material morphogenesis, and polarity remodeling during organogenesis downstream of Par3. PMID:27052178

  9. Effect of copper addition at a rate of 4% weight on the machininability of ZA-21A1 cast alloy by CNC milling

    NASA Astrophysics Data System (ADS)

    Alqawabah, S. M. A.; Zaid, A. I. O.

    2014-06-01

    Little work is published on the effect of copper addition to zinc-aluminium ZA-21Al alloy on its surface quality machined by milling. In this paper, the effect of copper addition at a rate 4 % weight to the ZA-21Al alloy on its hardness and surface quality is investigated. It was found that the addition of 4% Cu resulted in 18.3% enhancement in microhardness whereas the mechanical characteristics were reduced (softening) about 14.5% at 0.2% strain. It was found that the best surface finish for this alloy before copper addition ZA21 was achieved at a feed rate of 100 mm/min and 1.25 mm depth of cut whereas the best surface finish for ZA21-4% Cu was achieved at feed rate 250 mm/min, 1600 rpm cutting velocity and 1.25 mm depth of cut.

  10. Influence of Refiner in ZA-12 Alloys During Centrifugal Casting Process

    NASA Astrophysics Data System (ADS)

    Jyothi, P. N.; Shailesh, Rao A.; Jagath, M. C.; Channakeshavalu, K.

    2014-05-01

    The behavior of the molten melt plays a predominant role in determining the quality cast product. In continuous casting, addition of refiner 1% (Al+Ti+B2) onto the molten metal increases its mechanical properties as a result of the nucleation within the process. In this article, the effect of refiners in the centrifugal casting process was studied. Eutectic ZA-12 alloys were taken for our experiment and cast at various rotational speeds (400 rpm, 600 rpm, and 800 rpm) with and without the addition of refiners. Rather than increase in the solidification rate as in continuous casting, these refiners diminish the solidification rate, which in turn forms an irregular-shaped cast tube. The microstructure and hardness for the entire cast specimen were discussed finally.

  11. Effect of Ce melt treatment on solidification path of ZA8 alloy

    NASA Astrophysics Data System (ADS)

    Sudheer, R.; Vijeesh, V.; Prabhu, K. N.

    2016-03-01

    The solidification path of ZA8 alloy with Ce addition was characterized using Newtonian technique of thermal analysis. The solidification events were determined using cooling curve and its first derivative curve. The microstructure and chemical composition of various phases in the alloy were studied using EDS, SEM and XRD techniques. It was found that the addition of Ce did not cause formation of new phases. However, it hinders the nucleation of stable β dendrites in the alloy. The presence of Ce promotes the eutectoid phase transformation and increases the hardness of the alloy. Latent heat of solidification and heat of eutectoid transformation were found to increase on Ce addition. The upward solidification of the alloy against Cu chill was analysed. Chilling had significant influence on solidification parameters, and caused refinement of the microstructure. The addition of Ce to the melt had no effect during chill casting of the alloy.

  12. Investigating plasma viscosity with fast framing photography in the ZaP-HD Flow Z-Pinch experiment

    NASA Astrophysics Data System (ADS)

    Weed, Jonathan Robert

    The ZaP-HD Flow Z-Pinch experiment investigates the stabilizing effect of sheared axial flows while scaling toward a high-energy-density laboratory plasma (HEDLP > 100 GPa). Stabilizing flows may persist until viscous forces dissipate a sheared flow profile. Plasma viscosity is investigated by measuring scale lengths in turbulence intentionally introduced in the plasma flow. A boron nitride turbulence-tripping probe excites small scale length turbulence in the plasma, and fast framing optical cameras are used to study time-evolved turbulent structures and viscous dissipation. A Hadland Imacon 790 fast framing camera is modified for digital image capture, but features insufficient resolution to study turbulent structures. A Shimadzu HPV-X camera captures the evolution of turbulent structures with great spatial and temporal resolution, but is unable to resolve the anticipated Kolmogorov scale in ZaP-HD as predicted by a simplified pinch model.

  13. Dry Sliding Wear Behaviour of Flyash Reinforced ZA-27 Alloy Based Metal Matrix Composites

    NASA Astrophysics Data System (ADS)

    Sharma, S. C.; Krishna, M.; Bhattacharyya, D.

    In the present investigation, an attempt has been made to evaluate the wear rate of ZA-27 alloy composites reinforced with fly ash particles from 1 to 3 wt% in steps of 1 wt%. The compo-casting method has been used to fabricate the composites using Raichur fly ash of average size 3-5 microns. The wear specimens are tested under dry conditions using a pin-on-disc sliding wear testing machine with wear loads of 20-120 N in steps of 20 N, and the sliding distances in the range of 0.5 km to 2.5 km. The results indicate that the wear rate of the composites is less than that of the matrix alloy and it further decreases with the increase in fly ash content. However, the material loss in terms of wear rate and wear volume increases with the increase in load and sliding distance, both in the cases of composites and the matrix alloy. An increase in the applied load increases the wear severity by changing the wear mechanism from abrasion to particle-cracking induced delamination wear. It is found that with the increase in fly ash content, the wear resistance increases monotonically. The observations have been explained using scanning electron microscope (SEM) analysis of the worn surfaces of the composites.

  14. Overview and Recent Results from the ZaP Flow Z-Pinch

    NASA Astrophysics Data System (ADS)

    Shumlak, U.; Nelson, B. A.; Adams, C. S.; Chahim, D. M.; den Hartog, D. J.; Golingo, R. P.; Knecht, S. D.; Oberto, R.; Sybouts, M.; Vogman, G.

    2007-11-01

    The ZaP Flow Z-Pinch investigates a magnetic confinement configuration that relies on sheared flow for stability in an otherwise unstable configuration. An axially flowing Z-pinch is generated with a coaxial accelerator coupled to a pinch assembly chamber. Magnetic probes measure fluctuation levels. Plasma is magnetically confined for an extended quiescent period where the mode activity is reduced. Doppler shift measurements of impurity lines show sub-Alfvenic, sheared flow during the quiescent period and low shear profiles during periods of high mode activity. The plasma has a sheared axial flow that exceeds the theoretical threshold for stability during the quiescent period and is lower than the threshold during periods of high mode activity. A holographic interferometer measures radially peaked density profiles during the quiescent period. Density profiles are analyzed to determine equilibrium profiles. Internal magnetic fields have been determined by measuring the Zeeman splitting of impurity emission. Measurements are consistent with a magnetically confined plasma. Plasma lifetime appears to be limited by neutral gas supply.

  15. Overview and Recent Results from the ZaP Flow Z-Pinch

    NASA Astrophysics Data System (ADS)

    Shumlak, U.; Neslon, B. A.; Adams, C. S.; den Hartog, D. J.; Golingo, R. P.; Knecht, S. D.; Munson, K. A.; Newman, J.; Pasko, J.; Schmuland, D.; Sybouts, M.; Vogman, G.

    2006-10-01

    The ZaP Flow Z-Pinch Experiment at the University of Washington investigates a magnetic confinement configuration that relies on sheared flow for stability in an otherwise unstable configuration. An axially flowing Z-pinch is generated with a coaxial accelerator coupled to a pinch assembly chamber. Magnetic probes measure fluctuation levels. The plasma is magnetically confined for an extended quiescent period where the mode activity is reduced. Multichord Doppler shift measurements of impurity lines show a sub-Alfvenic, sheared flow during the quiescent period and low shear profiles during periods of high mode activity. The plasma has a sheared axial flow that exceeds the theoretical threshold for stability during the quiescent period and is lower than the threshold during periods of high mode activity. A holographic interferometer measures a radially peaked density profile during the quiescent period. Density profiles are analyzed to determine magnetic field and temperature profiles. Internal magnetic fields have been recently determined by measuring the Zeeman splitting of impurity carbon emission. The measurements are consistent with a magnetically confined pinch plasma. Recent experimental measurements will be presented. This work is supported by a grant from DOE.

  16. Overview and Recent Results from the ZaP Flow Z-Pinch

    NASA Astrophysics Data System (ADS)

    Shumlak, U.

    2005-10-01

    The ZaP Flow Z-Pinch Experiment at the University of Washington investigates sheared flow stabilization in an otherwise unstable configuration. An axially flowing Z-pinch is generated with a coaxial accelerator coupled to a pinch assembly chamber. Magnetic probes measure the fluctuation levels of the azimuthal modes m = 1, 2, and 3. The plasma is magnetically confined for an extended quiescent period where the mode activity is significantly reduced. Multichord Doppler shift measurements of impurity lines show a large, sheared flow during the quiescent period and low shear profiles during periods of high mode activity. The plasma has a sheared axial flow that exceeds the theoretical threshold for stability during the quiescent period and is lower than the threshold during periods of high mode activity. The Z-pinch plasmas are globally stable for approximately 2000 growth times. The end of the quiescent period corresponds to a drop in plasma density and a decrease in plasma acceleration. Recent experimental results suggest a means to extend the experiment to quasi steady state operation.

  17. Results of the ZaP Flow Z-Pinch Inner Electrode Upgrade

    NASA Astrophysics Data System (ADS)

    Knecht, Sean; Shumlak, Uri; Golingo, Raymond; Nelson, Brian

    2007-11-01

    The ZaP Flow Z-Pinch is a plasma physics experiment that investigates the stabilization of a plasma column using sheared flows. The experiment consists of a coaxial plasma accelerator coupled to a pinch assembly region. Recently, the 10 cm diameter inner electrode (cathode) of the experiment was replaced by a 15 cm diameter inner electrode with the goal of increasing the temperature of the pinch through adiabatic compression while also increasing the quiescent (stable) period of the plasma through increased control of neutral-gas injection. This increased control is a product of the larger number of neutral-gas puff valves located inside the inner electrode (eight in the present configuration, compared to one in the previous). Results obtained after this inner electrode upgrade will be presented. Special attention will be paid to the temperature, density, characteristic radius of the pinch and the length of the quiescent period. Comparisons will be drawn between the properties of the plasma when using the 10 cm inner electrode and the 15 cm inner electrode. Theoretical calculations have shown an increase in the temperature by a factor of two, a slight increase in number density and a decrease in the characteristic radius of the pinch. Plans for future efforts will also be reported.

  18. On the deuterium abundance at z_a = 3.514 towards APM 08279+5255

    NASA Astrophysics Data System (ADS)

    Levshakov, S. A.; Agafonova, I. I.; Kegel, W. H.

    2000-03-01

    A very low primordial deuterium abundance of D/H =~ 1.5*E-5 has recently been proposed by Molaro et al. in the Lyman limit system with log N_{H i} =~ 18.1 cm-2 at z_a = 3.514 towards the quasar APM 08279+5255. The D/H value was estimated through the standard Voigt fitting procedure utilizing a simple one-component model of the absorbing region. We have investigated this system using our new Monte Carlo inversion procedure which allows us to recover self-consistently both the physical parameters of the gas cloud and the projected velocity and density distributions along the line of sight. The absorption lines of H i, C ii, C iv, Si iii, and Si iv were analyzed simultaneously. The result obtained shows a considerably lower neutral hydrogen column density log N_{H i} =~ 15.7 cm-2. Hence, the measurement of the deuterium abundance in this system is rather uncertain. We find that the asymmetric blue wing of the hydrogen Lyalpha absorption is readily explained by H i alone. Thus, up to now, deuterium was detected in only four QSO spectra (Q 1937-1009, Q 1009+2956, Q 0130-4021, and Q 1718+4807) and all of them are in concordance with D/H =~ 4*E-5. Based on data obtained at the W. M. Keck Observatory, which is jointly operated by the California Institute of Technology, the University of California and the National Aeronautics and Space Administration.

  19. [The review of the composition of Za Liao Fang of Jinguiyaolue (Synopsis of Prescriptions of the Golden Chamber)].

    PubMed

    Zhao, Huai-Zhou; Liang, Yong-Xuan

    2012-05-01

    The contents of Jinguiyaolue (Synopsis of Prescriptions of the Golden Chamber) can mainly be divided into 2 parts, which are "text" and "attached formulas". It is mostly thought that the "text" has more content than the "attached formulas". After comparing the small character version of WU Qian's transcript, which was recently published,with the large character version of Jinguiyaolue, and doing textual research on the "attached formulas" in Za Liao Fang of Jinguiyaolue (Synopsis of Prescriptions of the Golden Chamber) according to the clues left by the Bureau of the Revision of Medical Books in Song Dynasty, we can find that there are only "chai hu decoction with addition or subtraction in four seasons" and "the Kele pear pill for taking for long periods" which belong to the Song masters' copy. However, another 22 prescriptions called "attached formulas" were added when the Song masters revised it. PMID:22883383

  20. Mechanical properties of as-cast and heat-treated ZA-27 alloy/short glass fiber composites

    SciTech Connect

    Sharma, S.C.; Girish, B.M.; Satish, B.M.; Kamath, R.

    1998-02-01

    This paper reports on the mechanical properties of as-cast and heat-treated ZA-27 alloy composites reinforced with glass fibers from 1 to 5 wt%. The composites were fabricated using the Compocasting method, in which short glass fibers were introduced into the vortex created in the molten alloy through an impeller rotated at 500 rpm. The molten mass was thoroughly stirred and poured into permanent molds and squeezed under pressure. The specimens were heat treated at 320 C for 1, 2, 3, and 4 h. The tests on the as-cast composites revealed that as the glass content in the composites was increased, the ultimate tensile strength (UTS), compressive strength, and hardness of the composite increased, while the ductility and impact strength were decreased. Heat treatment was found to improve significantly the ductility, compressive strength, and impact strength, while the hardness and UTS were reduced. This paper discusses the behavior of these composites.

  1. Assessing Global Transcriptome Changes in Response to South African Cassava Mosaic Virus [ZA-99] Infection in Susceptible Arabidopsis thaliana

    PubMed Central

    Pierce, Erica J.; Rey, M. E. Chrissie

    2013-01-01

    In susceptible plant hosts, co-evolution has favoured viral strategies to evade host defenses and utilize resources to their own benefit. The degree of manipulation of host gene expression is dependent on host-virus specificity and certain abiotic factors. In order to gain insight into global transcriptome changes for a geminivirus pathosystem, South African cassava mosaic virus [ZA:99] and Arabidopsis thaliana, 4×44K Agilent microarrays were adopted. After normalization, a log2 fold change filtering of data (p<0.05) identified 1,743 differentially expressed genes in apical leaf tissue. A significant increase in differential gene expression over time correlated with an increase in SACMV accumulation, as virus copies were 5-fold higher at 24 dpi and 6-fold higher at 36 dpi than at 14 dpi. Many altered transcripts were primarily involved in stress and defense responses, phytohormone signalling pathways, cellular transport, cell-cycle regulation, transcription, oxidation-reduction, and other metabolic processes. Only forty-one genes (2.3%) were shown to be continuously expressed across the infection period, indicating that the majority of genes were transient and unique to a particular time point during infection. A significant number of pathogen-responsive genes were suppressed during the late stages of pathogenesis, while during active systemic infection (14 to 24 dpi), there was an increase in up-regulated genes in several GO functional categories. An adaptive response was initiated to divert energy from growth-related processes to defense, leading to disruption of normal biological host processes. Similarities in cell-cycle regulation correlated between SACMV and Cabbage leaf curl virus (CaLCuV), but differences were also evident. Differences in gene expression between the two geminiviruses clearly demonstrated that, while some global transcriptome responses are generally common in plant virus infections, temporal host-specific interactions are required for

  2. Feeding ecology and nutrition of an eastern gorilla group in the Mt. Kahuzi Region (République du Zaïre).

    PubMed

    Casimir, M J

    1975-01-01

    An eastern gorilla group of the Mt. Kahuzi region (République du Zaïre) was studied over 15 months. Its migration route was determined, and the various biotopes it visited are described. A record was made of its main food plants, and of the plant parts eaten. For nine important food plants the protein content, the concentration of the individual amino acids and the water content were measured for the plant parts eaten and for those not eaten. For some of these plant parts the Na, K, Ca and Mg content were also determined. No general correlation between food selection and one or several of these factors could be found. The development and value of a traditionally determined mixed diet is discussed. PMID:1165081

  3. Geological constraints on the evolution of the Angolan margin based on reflection and refraction seismic data (ZaïAngo project)

    NASA Astrophysics Data System (ADS)

    Moulin, Maryline; Aslanian, Daniel; Olivet, Jean-Louis; Contrucci, Isabelle; Matias, Luis; Géli, Louis; Klingelhoefer, Frauke; Nouzé, Hervé; Réhault, Jean-Pierre; Unternehr, Patrick

    2005-09-01

    Deep penetration multichannel reflection and Ocean Bottom Seismometer wide-angle seismic data from the Congo-Angola margin were collected in 2000 during the ZaïAngo cruise. These data help constrain the deep structure of the continental margin, the geometry of the pre-salt sediment layers and the geometry of the Aptian salt layer. Dating the deposition of the salt relative to the chronology of the margin formation is an issue of fundamental importance for reconstructing the evolution of the margin and for the understanding of the crustal thinning processes. The data show that the crust thins abruptly, from a 30-40 km thickness to less than 10 km, over a lateral distance of less than 50 km. The transitional domain is a 180-km-wide basin. The pre-salt sediment layering within this basin is parallel to the base of the salt and hardly affected by tectonic deformation. In addition, the presence of a continuous salt cover, from the continental platform down to the presumed oceanic boundary, provides indications on the conditions of salt deposition that constrain the geometry of the margin at that time. These crucial observations imply shallow deposition environments during the rifting and suggest that vertical motions prevailed-compared to horizontal motions-during the formation of the basin.

  4. Centrifugal casting of ZA8 zinc alloy and composite A356/silicon carbide: Study and modeling of phases' and particles' segregation

    NASA Astrophysics Data System (ADS)

    Balout, Bahaa

    Centrifugation is a casting technology that allows the production of cylindrical and graduated parts with different mechanical properties through the section. The need for materials with good quality and specific mechanical properties has been driven this technology in order to produce different types of materials such as zinc alloys and graduated metal matrix composites reinforced by hard and wear resistant particles. The goal of this research project is to study and model the eutectic macrosegregation, the solidification speed, and the speeds of solidification fronts during centrifugal casting of ZA8 zinc-aluminum alloy in order to improve the part quality and increase its strength and field reliability. Moreover, the segregation of the particles during centrifugal casting of an aluminum matrix composite reinforced by silicon carbide particles (A356/SiC) is also studied to improve and control the graduation of the parts. The cooling rate, the speed, acceleration/deceleration, displacement, and segregation of the particles across the section will be modeled by discretization of Stokes' law in time in order to take into consideration the change in the centrifugal radius and melt viscosity during cooling process. This study will allow the control of the graduation degree of particles across the section in order to improve the properties and wear resistance of the composite. This composite can be used in systems where friction is critical and load is high (reinforcements of parts for the cylinders of pneumatic systems). The results show that the maximum macrosegregation zone of the eutectic across the casting section corresponds to the last point of solidification. The eutectic macrosegregation produced during centrifugal casting of thin walled part is a normal segregation which varies depending on the solidification speed and the ratio between the speeds of solidification fronts. On the other hand, it was found that the position and volume fraction of the particles

  5. US-ROK Action Sheet 34: Safeguards Application of a Hand-held Mechanically Cooled Germanium Spectrometer

    SciTech Connect

    Dreyer, J.; Burks, M.; Ham, Y.; Kwak, S.

    2015-10-20

    This report summarizes results of Action Sheet 34 - for the cooperative efforts on the field testing and evaluation of a high-resolution, hand-held, gamma-ray spectrometer, known as SPG (Spectroscopic Planar Germanium), for safeguards application such as short notice inspections, UF6 analysis, enrichment determination, and other potential applications. The Spectroscopic Planar Germanium (SPG) has been demonstrated IAEA Physical Inventory Verification (PIV) in South Korea. This field test was a success and the feedback provided by KINAC, IAEA, and national laboratory staff was used to direct efforts to improve the instrument this year. Key points in this report include measurement results from PIV, analysis of spectra with commercially available Ortec U235 and PC-FRAM, and completion of tripod and tungsten collimator and integration of user feedback.

  6. Comment on Underwater Explosion (UWE) Analysis of the ROKS Cheonan Incident by S.G. Kim and Y. Kitterman

    NASA Astrophysics Data System (ADS)

    Kim, Kwang Sup

    2013-03-01

    The analysis of the seismic and infrasound data recorded at the time of the Cheonan incident led Kim and Gitterman (this journal, published on line August 2012) to conclude that a non-contact underwater explosion had sunk the ship. They also concluded that one of the mines deployed by the South Korean Navy many years ago in the area and then abandoned sank the ship. Their mine theory that is based on the explosive charge weights they calculated by means of two methods using the bubble period determined by their analysis, however, appears to be invalid. Although the incident had occurred in a shallow sea with a depth of less than 50m, the authors used the methods that are applicable only to free-field underwater explosions. The consideration of the influence on the bubble period of the nearby sea surface and bottom and the nearby ship's hull would double the calculated weights. In addition, the authors ignored several evidences that support the torpedo theory. One of them is aluminum-containing white powder found in large quantities at certain substrates in the retrieved Cheonan. However, the conclusion of the official investigation group that the torpedo was made in North Korea is based on a circumstantial evidence and is yet to be proven with other more direct evidences.

  7. Investigating the compatibility of the biocontrol agent Clonostachys rosea IK726 with prodigiosin-producing Serratia rubidaea S55 and phenazine-producing Pseudomonas chlororaphis ToZa7.

    PubMed

    Kamou, Nathalie N; Dubey, Mukesh; Tzelepis, Georgios; Menexes, Georgios; Papadakis, Emmanouil N; Karlsson, Magnus; Lagopodi, Anastasia L; Jensen, Dan Funck

    2016-05-01

    This study was carried out to assess the compatibility of the biocontrol fungus Clonostachys rosea IK726 with the phenazine-producing Pseudomonas chlororaphis ToZa7 or with the prodigiosin-producing Serratia rubidaea S55 against Fusarium oxysporum f. sp. radicis-lycopersici. The pathogen was inhibited by both strains in vitro, whereas C. rosea displayed high tolerance to S. rubidaea but not to P. chlororaphis. We hypothesized that this could be attributed to the ATP-binding cassette (ABC) proteins. The results of the reverse transcription quantitative PCR showed an induction of seven genes (abcB1, abcB20, abcB26, abcC12, abcC12, abcG8 and abcG25) from subfamilies B, C and G. In planta experiments showed a significant reduction in foot and root rot on tomato plants inoculated with C. rosea and P. chlororaphis. This study demonstrates the potential for combining different biocontrol agents and suggests an involvement of ABC transporters in secondary metabolite tolerance in C. rosea. PMID:26860841

  8. Press Freedom in the Republic of Korea: Coping with the Authoritarian Structure.

    ERIC Educational Resources Information Center

    Salwen, Michael B.

    To examine press freedom in the Republic of Korea (ROK, South Korea) and the role the ROK's press plays as the advantages of democracy and authoritarianism are being publicly debated, this paper looks back at where the ROK has been in terms of its social and political freedoms and where it is going in its attempts to break from its authoritarian…

  9. Diagnosing magnetized liner inertial fusion experiments on Za)

    NASA Astrophysics Data System (ADS)

    Hansen, S. B.; Gomez, M. R.; Sefkow, A. B.; Slutz, S. A.; Sinars, D. B.; Hahn, K. D.; Harding, E. C.; Knapp, P. F.; Schmit, P. F.; Awe, T. J.; McBride, R. D.; Jennings, C. A.; Geissel, M.; Harvey-Thompson, A. J.; Peterson, K. J.; Rovang, D. C.; Chandler, G. A.; Cooper, G. W.; Cuneo, M. E.; Herrmann, M. C.; Hess, M. H.; Johns, O.; Lamppa, D. C.; Martin, M. R.; Porter, J. L.; Robertson, G. K.; Rochau, G. A.; Ruiz, C. L.; Savage, M. E.; Smith, I. C.; Stygar, W. A.; Vesey, R. A.; Blue, B. E.; Ryutov, D.; Schroen, D. G.; Tomlinson, K.

    2015-05-01

    Magnetized Liner Inertial Fusion experiments performed at Sandia's Z facility have demonstrated significant thermonuclear fusion neutron yields (˜1012 DD neutrons) from multi-keV deuterium plasmas inertially confined by slow (˜10 cm/μs), stable, cylindrical implosions. Effective magnetic confinement of charged fusion reactants and products is signaled by high secondary DT neutron yields above 1010. Analysis of extensive power, imaging, and spectroscopic x-ray measurements provides a detailed picture of ˜3 keV temperatures, 0.3 g/cm3 densities, gradients, and mix in the fuel and liner over the 1-2 ns stagnation duration.

  10. Climate Change Education and Education for Sustainable Development in the Republic of Korea: A Status Report

    ERIC Educational Resources Information Center

    Sung, Junghee

    2015-01-01

    The Republic of Korea (ROK) has officially declared its national vision of green growth, and actively develops and implements policies related to education for sustainable development (ESD), green growth education (GGE) and climate change education (CCE). Over the Decade of ESD, the ROK experienced three administrations which have taken different…

  11. Evaluation of infectivity, virulence and transmission of FDMV field strains of serotypes O and A isolated in 2010 from outbreaks in the Republic of Korea

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since the early 2000s outbreaks of foot-and-mouth disease (FMD) have been described in several previously FMD-free Asian nations, including the Republic of Korea (ROK). One outbreak with FMD virus (FDMV) serotype A and two with serotype O occurred in ROK in 2010/2011. The causative viruses belong t...

  12. Introduction of the Republic of Korea-the United States of America's Joint Exercise Against Biothreats in 2013: Able Response 13.

    PubMed

    Kim, Seong Sun; Oh, Dong Whan; Jo, Hyun Jung; Chu, Chaeshin

    2013-10-01

    The Republic of Korea (ROK) and the the United States of America (USA) has held joint exercises to respond to biothreats in the Korean Peninsula since 2011. The exercise was called Able Response (AR) and it aims to coordinate interministerial procedures inside Korea and international procedures in requesting the medical resources urgently between ROK and USA, and among ROK and the United Nations, and nongovernmental organizations. AR13 was a functional exercise with a scenario that presumed a series of attack by terrorists, dispersing Bacillus anthracis in Seoul. The participants conducted exercises with action cells and using point-to-point communication system. It was followed by Senior Leadership Seminar participated by high-ranking officials in ROK and USA to discuss possible collaboration in advance. AR and its following actions will fortify collaboration between ROK and USA and enhance the capability of countermeasures against biothreats in Korea. PMID:24298445

  13. United States - Republic of Korea security relations: Policy/strategy for the future. Executive summary report, March-June 1990

    SciTech Connect

    Kristick, D.M.

    1990-06-01

    US domestic budget difficulties, and growing East Asian economics might now require the US to change its relationship with South Korea. The ROK's growing global stature, its economic vitality, and military strength indicate it is ready to take a more pronounced role in its own self-defense. US-ROK relations must become more reciprocal, giving the ROK more decision-sharing opportunities. The Nunn-Warner report does not go far enough in prescribing a US strategy toward East Asia in the next century. US must take a more active role in diplomatic initiatives aimed at reducing tensions in East Asia, specifically the Korean peninsula. The US and the ROK should be developing combined strategies to deal with an eventual Korean unification. These two allies should also begin developing arms control strategies for the Korean peninsula. US should facilitate better ROK-Japan security relations. US should maintain diligence in Korea until North Korea opens.

  14. Life Skills Manual = Les Practiques d'une Vie Saine = Mwongozo wa Stadi za Maisha.

    ERIC Educational Resources Information Center

    Callahan, Kathleen

    The Peace Corps Information Collection and Exchange makes available its information resources to other organizations. This document, made available in English, French, and Swahili, is one such resource. The focus of this document is a comprehensive behavior change approach that concentrates on the development of skills needed for life, such as…

  15. Data processing of absorption spectra from photoionized plasma experiments at Za)

    NASA Astrophysics Data System (ADS)

    Hall, I. M.; Durmaz, T.; Mancini, R. C.; Bailey, J. E.; Rochau, G. A.

    2010-10-01

    We discuss the processing of x-ray absorption spectra from photoionized plasma experiments at Z. The data was recorded with an imaging spectrometer equipped with two elliptically bent potassium acid phthalate (KAP) crystals. Both time-integrated and time-resolved data were recorded. In both cases, the goal is to obtain the transmission spectra for quantitative analysis of plasma conditions.

  16. Evaluation of anti-malarial effects of mass chemoprophylaxis in the Republic of Korea army.

    PubMed

    Yeom, Joon-Sup; Ryu, Seung-Ho; Oh, Sejoong; Choi, Dong-Hyun; Song, Kyoung-Jun; Oh, Young-Ha; Lee, Jae-Hyun; Kim, Young-A; Ahn, Sun-Young; Yang, Hwa-Young; Cha, Je-Eun; Park, Jae-Won

    2005-10-01

    Vivax malaria was endemic on the Korean peninsula for many centuries until the late 1970's when the Republic of Korea (ROK) was declared "malaria free". Since its re-emergence in 1993, the number of malaria cases in the military increased exponentially through 2000 near the demilitarized zone. Chemoprophylaxis with chloroquine and primaquine has been used in the ROK Army since 1997 in an attempt to reduce the number of the malaria cases throughout the ROK. Data show that chemoprophylaxis contributed, in part, to the decrease in the number of malaria cases among military personnel. However, mass chemoprophylaxis on a large scale in the ROK Army is unprecedented and extensive supervision and monitoring is warranted to determine its effectiveness and to monitor the appearance of chloroquine tolerant/resistant strains of Plasmodium vivax. PMID:16224140

  17. [The War on "Red Drugs": Anticommunism and Drug Policy in Republic of Korea, 1945-1960].

    PubMed

    Park, Ji-Young

    2016-04-01

    This paper investigates the discourses and policies on narcotics in Republic of Korea from 1945 to 1960. Since the Liberation the narcotic problem was regarded as the vestige of Japanese imperialism. which was expected to be cleaned up. The image of narcotic crimes as the legacy of the colonial past was turned into as the result of the Red Army's tactics to attack on the liberalist camp around the Korean war. The government of ROK represented the source of the illegal drugs as the Red army and the spy from North Korea. The anticommunist discourse about narcotics described the spies, who introduced the enormous amount of poppies into ROK and brought about the addicts, as the social evil. Through this discourse on poppies from North Korea, the government of ROK emphasized the immorality of the communists reinforcing the anticommunist regime, which was inevitable for the government of ROK to legitimize the division of Korea and the establishment of the government alone. This paper examines how the discourses and policies on narcotics in ROK was shaped and transformed from 1945 to 1960 focusing the relationship between the them and the political context such as anticommunism, Korean war, the division of Korea, and etc. This approach would be helpful to reveal the effect of the ROK's own political situation to the public health system involving the management for drugs. PMID:27301856

  18. Republic of Korea's Health Aid Governance: Perspectives from Partner Countries.

    PubMed

    Alley, Allison Baer; Park, Eunhee; Lee, Jong-Koo; Kang, Minah; Oh, Juhwan

    2015-11-01

    The Republic of Korea (ROK) has a remarkable development history, including its status as the first country to transition from aid recipient to member of the Organization for Economic Cooperation and Development Development Assistance Committee (DAC). However, since becoming a donor country, the ROK has struggled to achieve internationally accepted agreements related to aid effectiveness and several evaluations have identified the ROK as being one of the weakest DAC member countries at providing good aid. A survey was conducted to assess partner countries' perceptions of the ROK's governance of health official development assistance (ODA). The survey was administered to government officials based in partner countries' Ministries of Health and therefore presents the unique perspective of ODA recipients. The survey questions focused on governance principles established in the internationally-accepted Paris Declaration on Aid Effectiveness. The total response rate was 13 responses out of 26 individuals who received the email request (50%). The survey results indicate that progress has been made since earlier international evaluations but the ROK has not overcome all areas of concern. This confirms that the ROK is continuing to develop its capacity as a good donor but has yet to achieve all governance-related targets. The results of this survey can be used to inform a future aid strategy. PMID:26617449

  19. Republic of Korea's Health Aid Governance: Perspectives from Partner Countries

    PubMed Central

    Alley, Allison Baer; Park, Eunhee; Lee, Jong-Koo; Kang, Minah

    2015-01-01

    The Republic of Korea (ROK) has a remarkable development history, including its status as the first country to transition from aid recipient to member of the Organization for Economic Cooperation and Development Development Assistance Committee (DAC). However, since becoming a donor country, the ROK has struggled to achieve internationally accepted agreements related to aid effectiveness and several evaluations have identified the ROK as being one of the weakest DAC member countries at providing good aid. A survey was conducted to assess partner countries' perceptions of the ROK's governance of health official development assistance (ODA). The survey was administered to government officials based in partner countries' Ministries of Health and therefore presents the unique perspective of ODA recipients. The survey questions focused on governance principles established in the internationally-accepted Paris Declaration on Aid Effectiveness. The total response rate was 13 responses out of 26 individuals who received the email request (50%). The survey results indicate that progress has been made since earlier international evaluations but the ROK has not overcome all areas of concern. This confirms that the ROK is continuing to develop its capacity as a good donor but has yet to achieve all governance-related targets. The results of this survey can be used to inform a future aid strategy. PMID:26617449

  20. Inhibition of Rho-associated kinase blocks agonist-induced Ca2+ sensitization of myosin phosphorylation and force in guinea-pig ileum

    PubMed Central

    Swärd, Karl; Dreja, Karl; Susnjar, Marija; Hellstrand, Per; Hartshorne, David J; Walsh, Michael P

    2000-01-01

    Ca2+ sensitization of smooth muscle contraction involves the small GTPase RhoA, inhibition of myosin light chain phosphatase (MLCP) and enhanced myosin regulatory light chain (LC20) phosphorylation. A potential effector of RhoA is Rho-associated kinase (ROK).The role of ROK in Ca2+ sensitization was investigated in guinea-pig ileum.Contraction of permeabilized muscle strips induced by GTPγS at pCa 6.5 was inhibited by the kinase inhibitors Y-27632, HA1077 and H-7 with IC50 values that correlated with the known Ki values for inhibition of ROK. GTPγS also increased LC20 phosphorylation and this was prevented by HA1077. Contraction and LC20 phosphorylation elicited at pCa 5.75 were, however, unaffected by HA1077.Pre-treatment of intact tissue strips with HA1077 abolished the tonic component of carbachol-induced contraction and the sustained elevation of LC20 phosphorylation, but had no effect on the transient or sustained increase in [Ca2+]i induced by carbachol.LC20 phosphorylation and contraction dynamics suggest that the ROK-mediated increase in LC20 phosphorylation is due to MLCP inhibition, not myosin light chain kinase activation.In the absence of Ca2+, GTPγS stimulated 35S incorporation from [35S]ATPγS into the myosin targeting subunit of MLCP (MYPT). The enhanced thiophosphorylation was inhibited by HA1077. No thiophosphorylation of LC20 was detected.These results indicate that ROK mediates agonist-induced increases in myosin phosphorylation and force by inhibiting MLCP activity through phosphorylation of MYPT. Under Ca2+-free conditions, ROK does not appear to phosphorylate LC20in situ, in contrast to its ability to phosphorylate myosin in vitro. In particular, ROK activation is essential for the tonic phase of agonist-induced contraction. PMID:10618150

  1. Simple graph-theoretical model for flavonoid binding to P-glycoprotein / Jednostavan graf-teorijski model vezivanja flavonoida za P-glikoprotein / Jednostavan graf-teorijski model vezivanja flavonoida za P-glikoprotein.

    PubMed

    Miličević, Ante; Raos, Nenad

    2016-03-01

    Three sets of flavonoid derivatives (N=32, 40, and 74) and logarithms of their dissociation constants (log Kd) that describe flavonoid affinity toward P-glycoprotein were modelled using six connectivity indices. The best results were obtained with the zero-order valence molecular connectivity index (0χv) for all three sets. Standard errors of the calibration models were around 0.3, and of the constants from the test sets even a little lower, 0.22 and 0.24. Despite using only one descriptor, our model proved better in internal (cross-validation) and especially in external (test set) statistics than much more demanding methods used in previous 3D QSAR modelling. PMID:27092640

  2. [Joining WHO of Republic of Korea and the projects in the 1950s].

    PubMed

    Lee, Sun Ho

    2014-04-01

    The Republic of Korea(ROK) and the World Health Organization(WHO) have done many projects successfully from 1949, in which the government of First Republic joined the WHO. However the relation between the ROK and the WHO have not been studied very much so far. The main purpose of this research, which could be done by the support of WHO, is connected with three questions. First research point would be "how could the ROK joined WHO in 1949 and what's the meaning of it? And the what's the difference in the process for the WHO between the ROK of 1949 and the DPRK(Democratic People's Republic of Korea) of 1973?" The first president of the ROK, Rhee Syngman, who had received his Ph. D.(about international politics) from Princeton University in 1910, was strongly interested in joining international institutes like UN, WHO. The ROK that could join WHO on 17 August 1949, with the approval of Assembly on 25 May 1949, was one of the founder members of the Western Pacific Region. By joining WHO, the ROK could get chance to increase the level of public health and its administration in 1950's. But the DPRK manage to became a member of WHO on 19 May 1973 and joined the South-East Asia Region. The joining of DPRK was influenced by the easing of the cold war after the Nixon Doctrine and the joining of the China(People's Republic of China). Second research point would be "What kind of roll did the WHO take in the First Republic?" Yet the public health administration of the First Republic that had been made in the period of US army military government was been strongly influenced by USA, the roll of WHO was also important in the 1950's. Last research point would be "What kind of the projects did the ROK and the WHO take part in during the period of he First Republic? How could evaluate the results?" The ROK and the WHO handled the projects including health services, communicable disease prevention and control, control of noncommunicable diseases, and protection of health. Specially

  3. Use of EBSD to study electropulsing induced reverse phase transformations in a Zn-Al alloy (ZA22).

    PubMed

    Zhu, Y H; To, S; Liu, X M

    2011-04-01

    Multi-phase identification and phase transformations in electropulsing treated Zn-Al based alloy wire specimens were studied using electron back-scattered diffraction, back-scattered scanning electron microscopy and X-ray diffraction techniques. By using electron back-scattered diffraction, two phases: η'(S) and η'(T) with a small difference of about 1% in lattice parameters (c(0)/a(0) ) were identified, based on the determined lattice parameters of the phases, and the reverse eutectoid phase transformations: η'(T) +ɛ'(T) +α'(T) →η'(S) and ɛ+α→T'+η were successfully detected. Electron back-scattered diffraction appeared to be an effective technique for studying complex electropulsing induced phase transformations. PMID:21118233

  4. Dobro Dosli U Sjedinjene Drzave. Prirucnik za Izbjeglice. (Welcome to the United States. A Guidebook for Refugees).

    ERIC Educational Resources Information Center

    Center for Applied Linguistics, Washington, DC. Refugee Service Center.

    This guidebook provides Bosnian, Croatian, and Serbian refugees being resettled in the United States with general information about what they will encounter and the services they can receive in their first months in the country. The book is distributed to overseas processing agencies, refugees overseas who have been approved for U.S. admission,…

  5. First report of Bluetongue virus isolation in the Republic of Korea and analysis of the complete coding sequence of the segment 2 gene.

    PubMed

    Seo, Hyun-Ji; Park, Jee-Yong; Cho, Yun Sang; Cho, In-Soo; Yeh, Jung-Yong

    2015-02-01

    This study investigated the possible presence of the Bluetongue virus (BTV) in the Republic of Korea (ROK). Cell cultures were used to test blood samples collected from abattoirs throughout the country. Testing identified a single BTV isolate, which was characterized as BTV serotype 1 based on a nucleotide sequence analysis of the segment 2 gene. This report therefore indicates that BTV serotype 1 is present in the ROK. The potential importance of BTV in the ROK has been overlooked because cattle are mostly unaffected by the virus and because sheep, the most severely infected hosts, are uncommon in the ROK. However, as recent BTV serotype 8 outbreaks in Europe have demonstrated, certain BTV strains have the potential to cause severe disease in cattle. Additionally, with climate change continuously expanding the regions in which Culicoides vectors are able to survive, there is an increased need to study BTV in the Far East and ROK. To better prepare for future outbreaks of BTV, a sustained and effective level of surveillance for BTV in livestock will need to be established. PMID:25384537

  6. Epidemiological observations of bovine viral diarrhea virus in Korean indigenous calves.

    PubMed

    Choi, Kyoung-Seong; Song, Moo-Chan

    2011-02-01

    Bovine viral diarrhea virus (BVDV) is an important worldwide disease in the livestock industry. To date, little research has been done on BVDV circulating in the Republic of Korea (ROK). The cases outlined in our research originated from rectal swabs taken from calves up to 80 days of age. Twenty-two of 99 Korean indigenous calves with diarrhea were identified as BVDV positive and 3 different 5'-untranslated region (UTR) sequences were determined. The results indicated that BVDV infections in the ROK were found mostly in winter and when calves were less than 20 days old. Phylogenetic analysis based on the 5'-UTR revealed that our cases from Korean indigenous calves belonged to BVDV-2a. Therefore, the result of this study will be useful to understand epidemiology and allow producers in the ROK to better protect their livestock. PMID:20978931

  7. First Isolation of Severe Fever with Thrombocytopenia Syndrome Virus from Haemaphysalis longicornis Ticks Collected in Severe Fever with Thrombocytopenia Syndrome Outbreak Areas in the Republic of Korea

    PubMed Central

    Yun, Seok-Min; Song, Bong Gu; Choi, WooYoung; Roh, Jong Yul; Lee, Ye-Ji; Park, Won Il; Han, Myung Guk; Ju, Young Ran

    2016-01-01

    Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease that is endemic to China, Japan, and the Republic of Korea (ROK). In this study, 8313 ticks collected from SFTS outbreak areas in the ROK in 2013 were used to detect the SFTS virus (SFTSV). A single SFTSV was isolated in cell culture from one pool of Haemaphysalis longicornis ticks collected from Samcheok-si, Gangwon Province, in the ROK. Phylogenetic analysis showed that the SFTSV isolate was clustered with the SFTSV strain from Japan, which was isolated from humans. To the best of our knowledge, this is the first isolation in the world of SFTSV in ticks collected from vegetation. PMID:26745758

  8. Summing up the Global Health Security Agenda 2015 High Level Meeting in Seoul.

    PubMed

    Ghsa Preparation Task Force Team

    2015-12-01

    The Second Global Health Security Agenda (GHSA) 2015 High Level Meeting was successfully held in September 7 to 9 in Seoul, the Republic of Korea (ROK). Delegations from 46 countries including 26 ministerial level officials and 9 international organizations participated in the meeting. ROK, one of the 10 steering group countries of GHSA, shared the importance of multi-sectoral response through the experiences of Able Response Exercise, and MERS outbreak countermeasure with international communities. ROK promised to input 10 billion USD to strengthen the capacities to respond infectious diseases in developing countries. Seoul Declaration, the first collaborative efforts on heal security, was announced at the end of the meeting. Seoul Declaration holds GHSA vision promising international collaboration and commitment. PMID:27429903

  9. Further Evidence of Increasing Diversity of Plasmodium vivax in the Republic of Korea in Recent Years

    PubMed Central

    Kim, Jung-Yeon; Goo, Youn-Kyoung; Zo, Young-Gun; Ji, So-Young; Trimarsanto, Hidayat; To, Sheren; Clark, Taane G.; Price, Ric N.; Auburn, Sarah

    2016-01-01

    Background Vivax malaria was successfully eliminated from the Republic of Korea (ROK) in the late 1970s but re-emerged in 1993. Two decades later as the ROK enters the final stages of malaria elimination, dedicated surveillance of the local P. vivax population is critical. We apply a population genetic approach to gauge P. vivax transmission dynamics in the ROK between 2010 and 2012. Methodology/Principal Findings P. vivax positive blood samples from 98 autochthonous cases were collected from patients attending health centers in the ROK in 2010 (n = 27), 2011 (n = 48) and 2012 (n = 23). Parasite genotyping was undertaken at 9 tandem repeat markers. Although not reaching significance, a trend of increasing population diversity was observed from 2010 (HE = 0.50 ± 0.11) to 2011 (HE = 0.56 ± 0.08) and 2012 (HE = 0.60 ± 0.06). Conversely, linkage disequilibrium declined during the same period: IAS = 0.15 in 2010 (P = 0.010), 0.09 in 2011 (P = 0.010) and 0.05 in 2012 (P = 0.010). In combination with data from other ROK studies undertaken between 1994 and 2007, our results are consistent with increasing parasite divergence since re-emergence. Polyclonal infections were rare (3% infections) suggesting that local out-crossing alone was unlikely to explain the increased divergence. Cases introduced from an external reservoir may therefore have contributed to the increased diversity. Aside from one isolate, all infections carried a short MS20 allele (142 or 149 bp), not observed in other studies in tropical endemic countries despite high diversity, inferring that these regions are unlikely reservoirs. Conclusions Whilst a number of factors may explain the observed population genetic trends, the available evidence suggests that an external geographic reservoir with moderate diversity sustains the majority of P. vivax infection in the ROK, with important implications for malaria elimination. PMID:26990869

  10. Agreed Framework and KEDO: The role of the United States in Korean security

    SciTech Connect

    Gamble, A.J.

    1999-06-01

    The US is moving from a leading security guarantor of the ROK to a mediator of the Korean dispute. The US should understand this fundamental change and adjust its relationship with the ROK and the DPRK to maintain the possibility of Korean reunification. The Agreed Framework is a deal between the US and the DPRK to stop the DPRK`s nuclear program in exchange for energy resources. The Agreed Framework forces the US to go beyond its traditional ROK supportive policy to deal with the DPRK`s nuclear ambition. The US should assess the goals of the PRC, ROK, DPRK, and Japan on the Korean peninsula to determine if a change in policy will enhance the probability of a soft landing by the DPRK. To conduct this assessment, the goals of all nations and the DPRK`s nuclear ambition have been developed. A graphical summary of the subjective analysis was used to pick the US policy option that shows the best credible and clear logic, and mitigates most effectively any international criticism that may dilute the sound reasoning of future policy. The US should change its current policy to mediate the Korean dispute and increase the probability that all concerned actors meet their goals on the Korean peninsula.

  11. Nuclear's role in 21. century Pacific rim energy use

    SciTech Connect

    Singer, Clifford; Taylor, J'Tia

    2007-07-01

    Extrapolations contrast the future of nuclear energy use in Japan and the Republic of Korea (ROK) to that of the Association of Southeast Asian Nations (ASEAN). Japan can expect a gradual rise in the nuclear fraction of a nearly constant total energy use rate as the use of fossil fuels declines. ROK nuclear energy rises gradually with total energy use. ASEAN's total nuclear energy use rate can rapidly approach that of the ROK if Indonesia and Vietnam make their current nuclear energy targets by 2020, but experience elsewhere suggests that nuclear energy growth may be slower than planned. Extrapolations are based on econometric calibration to a utility optimization model of the impact of growth of population, gross domestic product, total energy use, and cumulative fossil carbon use. Fractions of total energy use from fluid fossil fuels, coal, water-driven electrical power production, nuclear energy, and wind and solar electric energy sources are fit to market fractions data. Where historical data is insufficient for extrapolation, plans for non-fossil energy are used as a guide. Extrapolations suggest much more U.S. nuclear energy and spent nuclear fuel generation than for the ROK and ASEAN until beyond the first half of the twenty-first century. (authors)

  12. Association of temperature and historical dynamics of malaria in the Republic of Korea, including reemergence in 1993

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasmodium vivax malaria reemerged in the Republic of Korea (ROK) in 1993 after it had been declared malaria free in 1979. Malaria rapidly increased and peaked in 2000 with 4,142 cases. Lower but variable numbers of cases were reported through 2011. We examined the association of regional climate tr...

  13. Resurgence of Plasmodium vivax malaria in the Republic of Korea during 2006-2007.

    PubMed

    Jun, Gyo; Yeom, Joon-Sup; Hong, Jee-Young; Shin, E-Hyun; Chang, Kyu-Sik; Yu, Jae-Ran; Oh, Sejoong; Chung, Hyeok; Park, Jae-Won

    2009-10-01

    Plasmodium vivax malaria, which re-emerged in the Republic of Korea (ROK) in 1993, had decreased since 2001. However, case numbers began to increase again in 2005. The number of cases rose 54.0% in 2006, but the rate of increase slowed down in 2007. Among the total of 4,206 cases of P. vivax malaria during 2006-2007, 756 cases (18.0%) were ROK military personnel, 891 cases (21.2%) were veterans, and 2,559 cases (60.8%) were civilians. The rapid increase during this period was mostly contributed by the western part of the malaria-risk areas that is under the influence of adjacent North Korea. Local transmission cases in ROK have also increased gradually and the transmission period seemingly became longer. Chemoprophylaxis in the military should be re-assessed in view of chloroquine-resistance. Continuous surveillance and monitoring are warranted to prevent further expansion of P. vivax malaria caused by climate change in ROK. PMID:19815874

  14. 78 FR 12365 - Sunshine Act Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... electronic mail to FR_NOTICE_QUESTIONS@lsc.gov . ACCESSIBILITY: LSC complies with the Americans with... telephonically should contact Atitaya Rok, at (202) 295-1500 or FR_NOTICE_QUESTIONS@lsc.gov , at least 2 business... From the Federal Register Online via the Government Publishing Office LEGAL SERVICES...

  15. 78 FR 9430 - Sunshine Act Meeting Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

    ... person or telephonically should contact Atitaya Rok, at (202) 295-1500 or FR_NOTICE_QUESTIONS@lsc.gov... may be sent by electronic mail to FR_NOTICE_QUESTIONS@lsc.gov . ACCESSIBILITY: LSC complies with the... From the Federal Register Online via the Government Publishing Office LEGAL SERVICES...

  16. Fasudil hydrochloride induces osteoblastic differentiation of stromal cell lines, C3H10T1/2 and ST2, via bone morphogenetic protein-2 expression.

    PubMed

    Kanazawa, Ippei; Yamaguchi, Toru; Yano, Shozo; Yamauchi, Mika; Sugimoto, Toshitsugu

    2010-01-01

    Rho-kinase (ROK), downstream of the mevalonate pathway, is detrimental to vessels, and suppressing its activity is a target for the treatment of human disease such as coronary artery disease and pulmonary hypertension. Recent studies have shown that ROK has a crucial role in bone metabolism. However, the role of ROK in stromal cells is still unclear. The present study was undertaken to investigate the effect of a ROK inhibitor, fasudil hydrochloride, on stromal cell lines, C3H10T1/2 and ST2. In both cells, Fasudil significantly stimulated alkaline phosphatase activity and enhanced cell mineralization. Moreover, fasudil significantly increased the mRNA expression of collagen-I, osteocalcin, and bone morphogenetic protein-2 (BMP-2). Supplementation of noggin, a BMP-2 antagonist, significantly reversed the fasudil-induced collagen-I and osteocalcin mRNA expression in both cells. These findings suggest that fasudil induces the osteoblastic differentiation of stromal cells via enhancing BMP-2 expression, and that this drug might be beneficial for not only atherosclerosis but also osteoporosis by promoting bone formation. PMID:20154408

  17. 78 FR 4462 - Sunshine Act; Meeting Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-22

    ... sent by electronic mail to FR_NOTICE_QUESTIONS@lsc.gov . NON-CONFIDENTIAL MEETING MATERIALS: Non... telephonically should contact Atitaya Rok, at (202) 295-1500 or FR_NOTICE_QUESTIONS@lsc.gov , at least 2 business..., please refrain from placing the call on hold if doing so will trigger recorded music or other sound....

  18. Inclusive Music Education in the Republic of Korea: Policies and Adaptive Instruction for General Educators of Primary School Students with Disabilities

    ERIC Educational Resources Information Center

    Kim, Eun Jew

    2009-01-01

    The purposes of this study were to research the current inclusive practices in primary school music education in the Republic of Korea (ROK), identify issues that hamper optimal inclusion, and develop instructional strategies and recommendations to assist general educators in the accommodation of students with disabilities in their music classes.…

  19. Acne

    MedlinePlus

    ... can try different ones to see which helps. Products with benzoyl peroxide (say: BEN-zoil peh - ROK - side) or salicylic (say: sal-uh-SIL - ick) acid in them are usually pretty helpful for treating acne. Benzoyl peroxide kills the bacteria that can lead to acne and it also ...

  20. 78 FR 51750 - Sunshine Act Meeting; Cancellation-Institutional Advancement Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-21

    ... From the Federal Register Online via the Government Publishing Office LEGAL SERVICES CORPORATION...''). This announcement was published in the Federal Register on August 12, 2013, at 78 FR 48910. This... sent by electronic mail to FR_NOTICE_QUESTIONS@lsc.gov . Dated: August 16, 2013. Atitaya C. Rok,...

  1. Hyperosmotic stress activates Rho: differential involvement in Rho kinase-dependent MLC phosphorylation and NKCC activation.

    PubMed

    Di Ciano-Oliveira, Caterina; Sirokmány, Gábor; Szászi, Katalin; Arthur, William T; Masszi, András; Peterson, Mark; Rotstein, Ori D; Kapus, András

    2003-09-01

    Hyperosmotic stress initiates adaptive responses, including phosphorylation of myosin light chain (MLC) and concomitant activation of Na+-K+-Cl- cotransporter (NKCC). Because the small GTPase Rho is a key regulator of MLC phosphorylation, we investigated 1) whether Rho is activated by hyperosmotic stress, and if so, what the triggering factors are, and 2) whether the Rho/Rho kinase (ROK) pathway is involved in MLC phosphorylation and NKCC activation. Rho activity was measured in tubular epithelial cells by affinity pulldown assay. Hyperosmolarity induced rapid (<1 min) and sustained (>20 min) Rho activation that was proportional to the osmotic concentration and reversed within minutes upon restoration of isotonicity. Both decreased cell volume at constant ionic strength and elevated total ionic strength at constant cell volume were capable of activating Rho. Changes in [Na+] and [K+] at normal total salinity failed to activate Rho, and Cl- depletion did not affect the hyperosmotic response. Thus alterations in cellular volume and ionic strength but not individual ion concentrations seem to be the critical triggering factors. Hyperosmolarity induced mono- and diphosphorylation of MLC, which was abrogated by the Rho-family blocker Clostridium toxin B. ROK inhibitor Y-27632 suppressed MLC phosphorylation under isotonic conditions and prevented its rise over isotonic levels in hypertonically stimulated cells. ML-7 had a smaller inhibitory effect. In contrast, it abolished the hypertonic activation of NKCC, whereas Y-27632 failed to inhibit this response. Thus hyperosmolarity activates Rho, and Rho/ROK pathway contributes to basal and hyperosmotic MLC phosphorylation. However, the hypertonic activation of NKCC is ROK independent, implying that the ROK-dependent component of MLC phosphorylation can be uncoupled from NKCC activation. PMID:12748065

  2. Plasmodium vivax malaria: status in the Republic of Korea following reemergence.

    PubMed

    Park, Jae-Won; Jun, Gyo; Yeom, Joon-Sup

    2009-10-01

    The annual incidence of Plasmodium vivax malaria that reemerged in the Republic of Korea (ROK) in 1993 increased annually, reaching 4,142 cases in 2000, decreased to 864 cases in 2004, and once again increased to reach more than 2,000 cases by 2007. Early after reemergence, more than two-thirds of the total annual cases were reported among military personnel. However, subsequently, the proportion of civilian cases increased consistently, reaching over 60% in 2006. P. vivax malaria has mainly occurred in the areas adjacent to the Demilitarized Zone, which strongly suggests that malaria situation in ROK has been directly influenced by infected mosquitoes originating from the Democratic People's Republic of Korea (DPRK). Besides the direct influence from DPRK, local transmission within ROK was also likely. P. vivax malaria in ROK exhibited a typical unstable pattern with a unimodal peak from June through September. Chemoprophylaxis with hydroxychloroquine (HCQ) and primaquine, which was expanded from approximately 16,000 soldiers in 1997 to 200,000 soldiers in 2005, contributed to the reduction in number of cases among military personnel. However, the efficacy of the mass chemoprophylaxis has been hampered by poor compliance. Since 2000, many prophylactic failure cases due to resistance to the HCQ prophylactic regimen have been reported and 2 cases of chloroquine (CQ)-resistant P. vivax were reported, representing the first-known cases of CQ-resistant P. vivax from a temperate region of Asia. Continuous surveillance and monitoring are warranted to prevent further expansion of CQ-resistant P. vivax in ROK. PMID:19885334

  3. Molecular detection and genotyping of Japanese Encephalitis Virus in mosquitoes during a 2010 outbreak in the Republic of Korea

    USGS Publications Warehouse

    Seo, Hyun-Ji; Kim, Heung Chul; Klein, Terry A.; Ramey, Andrew M.; Lee, Ji-Hyee; Kyung, Soon-Goo; Park, Jee-Yong; Cho, In-Soo; Yeh, Jung-Yong

    2013-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis. To reduce the impact of Japanese encephalitis among children in the Republic of Korea (ROK), the government established a mandatory vaccination program in 1967. Through the efforts of this program only 0-7 (mean 2.1) cases of Japanese encephalitis were reported annually in the ROK during the period of 1984-2009. However, in 2010 there was an outbreak of 26 confirmed cases of Japanese encephalitis, including 7 deaths. This represented a >12-fold increase in the number of confirmed cases of Japanese encephalitis in the ROK as compared to the mean number reported over the last 26 years and a 3.7-fold increase over the highest annual number of cases during this same period (7 cases). Surveillance of adult mosquitoes was conducted during the 2010 outbreak of Japanese encephalitis in the ROK. A total of 6,328 culicine mosquitoes belonging to 12 species from 5 genera were collected at 6 survey sites from June through October 2010 and assayed by reverse-transcription polymerase chain reaction (RT-PCR) for the presence of JEV. A total of 34/371 pooled samples tested positive for JEV (29/121 Culex tritaeniorhynchus, 4/64 Cx. pipiens, and 1/26 Cx. bitaeniorhynchus) as confirmed by sequencing of the pre-membrane and envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 culicine vectors for Cx. tritaeniorhynchus, Cx. pipiens, and Cx. bitaeniorhynchus were 11.8, 5.6, and 2.8, respectively. Sequences of the JEV pre-membrane and envelope protein coding genes amplified from the culicine mosquitoes by RT-PCR were compared with those of JEV genotypes I-V. Phylogenetic analyses support the detection of a single genotype (I) among samples collected from the ROK in 2010.

  4. Molecular Detection and Genotyping of Japanese Encephalitis Virus in Mosquitoes during a 2010 Outbreak in the Republic of Korea

    PubMed Central

    Klein, Terry A.; Ramey, Andrew M.; Lee, Ji-Hye; Kyung, Soon-Goo; Park, Jee-Yong; Cho, Yun Sang; Cho, In-Soo; Yeh, Jung-Yong

    2013-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis. To reduce the impact of Japanese encephalitis among children in the Republic of Korea (ROK), the government established a mandatory vaccination program in 1967. Through the efforts of this program only 0–7 (mean 2.1) cases of Japanese encephalitis were reported annually in the ROK during the period of 1984–2009. However, in 2010 there was an outbreak of 26 confirmed cases of Japanese encephalitis, including 7 deaths. This represented a >12-fold increase in the number of confirmed cases of Japanese encephalitis in the ROK as compared to the mean number reported over the last 26 years and a 3.7-fold increase over the highest annual number of cases during this same period (7 cases). Surveillance of adult mosquitoes was conducted during the 2010 outbreak of Japanese encephalitis in the ROK. A total of 6,328 culicine mosquitoes belonging to 12 species from 5 genera were collected at 6 survey sites from June through October 2010 and assayed by reverse-transcription polymerase chain reaction (RT-PCR) for the presence of JEV. A total of 34/371 pooled samples tested positive for JEV (29/121 Culex tritaeniorhynchus, 4/64 Cx. pipiens, and 1/26 Cx. bitaeniorhynchus) as confirmed by sequencing of the pre-membrane and envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 culicine vectors for Cx. tritaeniorhynchus, Cx. pipiens, and Cx. bitaeniorhynchus were 11.8, 5.6, and 2.8, respectively. Sequences of the JEV pre-membrane and envelope protein coding genes amplified from the culicine mosquitoes by RT-PCR were compared with those of JEV genotypes I-V. Phylogenetic analyses support the detection of a single genotype (I) among samples collected from the ROK in 2010. PMID:23390520

  5. Intercultural Education: Proceedings of the 2nd International Scientific Conference=Obrazovanje za interkulturalizam: Zbornik radova S.2 Medunarodne znanstvene konferencije

    ERIC Educational Resources Information Center

    Peko, Andelka, Ed.; Sablic, Marija, Ed.; Jindra, Ranka, Ed.

    2010-01-01

    The democratic changes that occurred in Croatia within last two decades are oriented towards European values and multi-intercultural perspectives. Let us remember that, according to the census from 1991, Croatia was inhabited with people from 27 nations, with Croats being a majority. During the Homeland war, basically a defensive war against the…

  6. Intercultural Education: The Position of Roma in Education=Obrazovanje za interkulturalizam: Položaj Roma u odgoju i obrazovanju

    ERIC Educational Resources Information Center

    Mlinarevic, Vesnica, Ed.; Brust Nemet, Maja, Ed.; Bushati, Jozef, Ed.

    2015-01-01

    Faculty of Educational Sciences has recognized the importance of education for interculturalism, and it organizes the conference entitled "Education for interculturalism" every five years, so that all participants could gain new insights about interculturalism and strengthen their intercultural competencies. Modern interculturalism, as a…

  7. Geological Constraints on the Evolution of the Angolan Margin Based on Reflection and Refraction Seismic Data (ZaïAngo project)

    NASA Astrophysics Data System (ADS)

    Moulin, M.; Aslanian, D.; Olivet, J.; Contrucci, I.; Matias, L.; Geli, L.; Klingelhoefer, F.; Nouze, H.; Rabineau, M.; Labails, C.; Rehault, J.; Unternehr, P.

    2005-05-01

    Deep penetration multi-channel reflection and OBS wide-angle seismic data from the Congo-Angola margin were collected in 2000 during the ZaiAngo cruise (Ifremer and Total). These data help constrain the deep structure of the non-volcanic continental margin, the geometry of the pre-salt sediment layers and the geometry of the Aptian salt layer. Dating the deposition of the salt relative to the chronology of the margin formation is an issue of fundamental importance for reconstructing the evolution of the margin and for the understanding of the crustal thinning processes. The data show that the crust thins abruptly, from a 30 - 40km thickness to less than 10km, over a lateral distance of less than 50km. The transitional domain is a 180km wide basin with a thickness lower than 7 km. The pre-salt sediment layering within this basin is parallel to the base of the salt and hardly affected by tectonic deformation. In addition, the presence of a continuous salt cover, from the continental platform down to the presumed oceanic boundary, provides indications on the conditions of salt deposition that constrain the geometry of the margin at that time. These crucial observations imply shallow deposition environments during the rifting and suggest that vertical motions prevailed - compared to horizontal motions - during the formation of the basin.

  8. Zoledronic acid therapy impacts risk and frequency of skeletal complications and follow-up duration in prostate cancer patients with bone metastasis

    PubMed Central

    Hatoum, Hind T.; Lin, Swu-Jane; Guo, Amy; Lipton, Allan; Smith, Matthew R.

    2011-01-01

    Purpose To evaluate the effects of timing and length of zoledronic acid (ZA) treatment on outcomes for patients with prostate cancer in clinical practice. Materials and methods Patients with prostate cancer and first bone metastasis diagnosed from January 2003 to October 2006 were included. Patients were considered ‘untreated’ if no ZA was given, ‘early ZA-treated’ if ZA was initiated before skeletal complication (SC) occurrence or ‘late ZA-treated’ if one or more SC was documented before or at ZA initiation. Patients were classified with short (≤90 days), medium (91–180 days) or long (>180 days) treatment persistence. Assessments included follow-up duration (FUP) and risk of developing one or more SC. Results Among eligible patients, 847 were untreated, 243 were early ZA-treated and 218 were late ZA-treated. For untreated versus early ZA-treated groups, median FUP was 263 versus 357 days (p<0.0001), respectively, and time to first SC was 199 versus 273 days (p<0.0001), respectively. ZA treatment was associated with significantly longer FUP and lower SC risk. The early ZA-treated group had significantly longer FUP versus the late ZA-treated group (median days, 357 vs. 299.5); the late ZA-treated group experienced significantly higher SC risk vs. the early ZA-treated group (odds ratio, 1.51). Compared with the long-persistence group, FUP was 56% and 40% shorter in the short and medium groups, respectively (p<0.0001). Conclusion Treatment with and early initiation of ZA for patients with prostate cancer and bone metastasis significantly prolonged time to and reduced risk of developing SC, while extending FUP. PMID:21083514

  9. Genetic Diversity and Reassortment of Hantaan Virus Tripartite RNA Genomes in Nature, the Republic of Korea

    PubMed Central

    Kim, Jeong-Ah; Kim, Won-keun; No, Jin Sun; Lee, Seung-Ho; Lee, Sook-Young; Kim, Ji Hye; Kho, Jeong Hoon; Lee, Daesang; Song, Dong Hyun; Gu, Se Hun; Jeong, Seong Tae; Park, Man-Seong; Kim, Heung-Chul; Klein, Terry A.; Song, Jin-Won

    2016-01-01

    Background Hantaan virus (HTNV), a negative sense tripartite RNA virus of the Family Bunyaviridae, is the most prevalent hantavirus in the Republic of Korea (ROK). It is the causative agent of Hemorrhagic Fever with Renal Syndrome (HFRS) in humans and maintained in the striped field mouse, Apodemus agrarius, the primary zoonotic host. Clinical HFRS cases have been reported commonly in HFRS-endemic areas of Gyeonggi province. Recently, the death of a member of the ROK military from Gangwon province due to HFRS prompted an investigation of the epidemiology and distribution of hantaviruses in Gangwon and Gyeonggi provinces that border the demilitarized zone separating North and South Korea. Methodology and Principal Findings To elucidate the geographic distribution and molecular diversity of HTNV, whole genome sequences of HTNV Large (L), Medium (M), and Small (S) segments were acquired from lung tissues of A. agrarius captured from 2003–2014. Consistent with the clinical incidence of HFRS established by the Korea Centers for Disease Control & Prevention (KCDC), the prevalence of HTNV in naturally infected mice in Gangwon province was lower than for Gyeonggi province. Whole genomic sequences of 34 HTNV strains were identified and a phylogenetic analysis showed geographic diversity of the virus in the limited areas. Reassortment analysis first suggested an occurrence of genetic exchange of HTNV genomes in nature, ROK. Conclusion/Significance This study is the first report to demonstrate the molecular prevalence of HTNV in Gangwon province. Whole genome sequencing of HTNV showed well-supported geographic lineages and the molecular diversity in the northern region of ROK due to a natural reassortment of HTNV genomes. These observations contribute to a better understanding of the genetic diversity and molecular evolution of hantaviruses. Also, the full-length of HTNV tripartite genomes will provide a database for phylogeographic analysis of spatial and temporal

  10. The relationship between mosquito abundance and rice field density in the Republic of Korea

    PubMed Central

    2010-01-01

    Background Japanese encephalitis virus (JEV), the causative agent of Japanese encephalitis (JE), is endemic to the Republic of Korea (ROK) where unvaccinated United States (U.S.) military Service members, civilians and family members are stationed. The primary vector of the JEV in the ROK is Culex tritaeniorhynchus. The ecological relationship between Culex spp. and rice fields has been studied extensively; rice fields have been shown to increase the prevalence of Cx. tritaeniorhynchus. This research was conducted to determine if the quantification of rice field land cover surrounding U.S. military installations in the ROK should be used as a parameter in a larger risk model that predicts the abundance of Cx. tritaeniorhynchus populations. Mosquito data from the U.S. Forces Korea (USFK) mosquito surveillance program were used in this project. The average number of female Cx. tritaeniorhynchus collected per trap night for the months of August and September, 2002-2008, was calculated. Rice fields were manually digitized inside 1.5 km buffer zones surrounding U.S. military installations on high-resolution satellite images, and the proportion of rice fields was calculated for each buffer zone. Results Mosquito data collected from seventeen sample sites were analyzed for an association with the proportion of rice field land cover. Results demonstrated that the linear relationship between the proportion of rice fields and mosquito abundance was statistically significant (R2 = 0.62, r = .79, F = 22.72, p < 0.001). Conclusions The analysis presented shows a statistically significant linear relationship between the two parameters, proportion of rice field land cover and log10 of the average number of Cx. tritaeniorhynchus collected per trap night. The findings confirm that agricultural land cover should be included in future studies to develop JE risk prediction models for non-indigenous personnel living at military installations in the ROK. PMID:20573242

  11. Morning calm, nuclear sunset: South Korea`s atomic option

    SciTech Connect

    Pierce, A.D.

    1998-09-01

    US national security strategy sets nuclear nonproliferation as a high priority. However pursuing nonproliferation without regard for important traditional security relationships might yield undesired results. The Republic of Korea (ROK) requires a high degree of confidence in the US security guarantee one that includes an extended nuclear deterrent. The nuclear weapons program that South Korea began and abandoned in the 1970s was prompted by a decrease in confidence in US security commitments. Conciliatory actions taken recently by the United States toward the Democratic Peoples` Republic of Korea (DPRK) to prevent a possible nuclear weapons program may undermine the US-ROK security arrangement that has been in place for decades. This work examines perceived threats to South Korea and the US security commitment to Korea since 1945 to reveal how US nuclear nonproliferation policy affects Seoul`s propensity to develop nuclear weapons. Recommendations are provided for policy makers regarding strengthening of ROK confidence in the US commitment on the peninsula, with particular emphasis on preventing South Korea from pursuing a nuclear arsenal.

  12. Combover/CG10732, a Novel PCP Effector for Drosophila Wing Hair Formation

    PubMed Central

    Fagan, Jeremy K.; Dollar, Gretchen; Lu, Qiuheng; Barnett, Austen; Pechuan Jorge, Joaquin; Schlosser, Andreas; Pfleger, Cathie; Adler, Paul; Jenny, Andreas

    2014-01-01

    The polarization of cells is essential for the proper functioning of most organs. Planar Cell Polarity (PCP), the polarization within the plane of an epithelium, is perpendicular to apical-basal polarity and established by the non-canonical Wnt/Fz-PCP signaling pathway. Within each tissue, downstream PCP effectors link the signal to tissue specific readouts such as stereocilia orientation in the inner ear and hair follicle orientation in vertebrates or the polarization of ommatidia and wing hairs in Drosophila melanogaster. Specific PCP effectors in the wing such as Multiple wing hairs (Mwh) and Rho Kinase (Rok) are required to position the hair at the correct position and to prevent ectopic actin hairs. In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. Overexpression of Cmb causes the formation of a multiple hair cell phenotype (MHC), similar to loss of rok and mwh. This MHC phenotype is dominantly enhanced by removal of rok or of other members of the PCP effector gene family. Furthermore, we show that Cmb physically interacts with Mwh, and cmb null mutants suppress the MHC phenotype of mwh alleles. Our data indicate that Cmb is a novel PCP effector that promotes to wing hair formation, a function that is antagonized by Mwh. PMID:25207969

  13. Electrochemical/Pyrometallurgical Waste Stream Processing and Waste Form Fabrication

    SciTech Connect

    Steven Frank; Hwan Seo Park; Yung Zun Cho; William Ebert; Brian Riley

    2015-07-01

    This report summarizes treatment and waste form options being evaluated for waste streams resulting from the electrochemical/pyrometallurgical (pyro ) processing of used oxide nuclear fuel. The technologies that are described are South Korean (Republic of Korea – ROK) and United States of America (US) ‘centric’ in the approach to treating pyroprocessing wastes and are based on the decade long collaborations between US and ROK researchers. Some of the general and advanced technologies described in this report will be demonstrated during the Integrated Recycle Test (IRT) to be conducted as a part of the Joint Fuel Cycle Study (JFCS) collaboration between US Department of Energy (DOE) and ROK national laboratories. The JFCS means to specifically address and evaluated the technological, economic, and safe guard issues associated with the treatment of used nuclear fuel by pyroprocessing. The IRT will involve the processing of commercial, used oxide fuel to recover uranium and transuranics. The recovered transuranics will then be fabricated into metallic fuel and irradiated to transmutate, or burn the transuranic elements to shorter lived radionuclides. In addition, the various process streams will be evaluated and tested for fission product removal, electrolytic salt recycle, minimization of actinide loss to waste streams and waste form fabrication and characterization. This report specifically addresses the production and testing of those waste forms to demonstrate their compatibility with treatment options and suitability for disposal.

  14. Whole-Genome Sequencing Analysis of Sapovirus Detected in South Korea

    PubMed Central

    Choi, Hye Lim; Suh, Chang-Il; Park, Seung-Won; Jin, Ji-Young; Cho, Han-Gil; Paik, Soon-Young

    2015-01-01

    Sapovirus (SaV), a virus residing in the intestines, is one of the important causes of gastroenteritis in human beings. Human SaV genomes are classified into various genogroups and genotypes. Whole-genome analysis and phylogenetic analysis of ROK62, the SaV isolated in South Korea, were carried out. The ROK62 genome of 7429 nucleotides contains 3 open-reading frames (ORF). The genotype of ROK62 is SaV GI-1, and 94% of its nucleotide sequence is identical with other SaVs, namely Manchester and Mc114. Recently, SaV infection has been on the rise throughout the world, particularly in countries neighboring South Korea; however, very few academic studies have been done nationally. As the first whole-genome sequence analysis of SaV in South Korea, this research will help provide reference for the detection of recombination, tracking of epidemic spread, and development of diagnosis methods for SaV. PMID:26161646

  15. Measurements of radioxenon in ground level air in South Korea following the claimed nuclear test in North Korea on October 9, 2006

    SciTech Connect

    Ringbom, Anders; Elmgren, K.; Lindh, Karin; Peterson, Jenny; Bowyer, Ted W.; Hayes, James C.; McIntyre, Justin I.; Panisko, Mark E.; Williams, Richard M.

    2009-12-03

    Abstract Following the claimed nuclear test in the Democratic People’s Republic of Korea (DPRK) on October 9, 2006, and a reported seismic event, a mobile system for sampling of atmospheric xenon was transported to the Republic of South Korea (ROK) in an attempt to detect possible emissions of radioxenon in the region from a presumed test. Five samples were collected in the ROK during October 11–14, 2006 near the ROK–DPRK border, and thereafter transported to the Swedish Defense Research Agency (FOI) in Stockholm, Sweden, for analysis. Following the initial measurements, an automatic radioxenon sampling and analysis system was installed at the same location in the ROK, and measurements on the ambient atmospheric radioxenon background in the region were performed during November 2006 to February 2007. The measured radioxenon concentrations strongly indicate that the explosion in October 9, 2006 was a nuclear test. The conclusion is further strengthened by atmospheric transport models. Radioactive xenon measurement was the only independent confirmation that the supposed test was in fact a nuclear explosion and not a conventional (chemical) explosive.

  16. Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study.

    PubMed

    de Molon, Rafael Scaf; Hsu, Chingyun; Bezouglaia, Olga; Dry, Sarah M; Pirih, Flavia Q; Soundia, Akrivoula; Cunha, Fernando Queiroz; Cirelli, Joni Augusto; Aghaloo, Tara L; Tetradis, Sotirios

    2016-08-01

    Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J mice were divided into four groups: control, zoledronic acid (ZA), collagen-induced arthritis (CIA), and CIA-ZA. Animals were pretreated with vehicle or ZA. Bovine collagen II emulsified in Freund's adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8 weeks. ONJ indices were measured by micro-CT (µCT) and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by µCT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, periodontal ligament (PDL) space widening, lamina dura loss, and cortex thinning. ZA prevented these changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could

  17. Is administration of trastuzumab an independent risk factor for developing osteonecrosis of the jaw among metastatic breast cancer patients under zoledronic acid treatment?

    PubMed

    Pilanci, Kezban Nur; Alco, Gul; Ordu, Cetin; Sarsenov, Dauren; Celebi, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Tecimer, Coskun; Demir, Gokhan; Eralp, Yesim; Okkan, Sait; Ozmen, Vahit

    2015-05-01

    One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients' ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab. PMID:25950681

  18. Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements

    PubMed Central

    Tisdale, James E.; Allen, Matthew R.; Overholser, Brian R.; Jaynes, Heather A.; Kovacs, Richard J.

    2015-01-01

    Introduction Our objective was to determine effects of zoledronic acid (ZA) on atrial electrophysiological parameters and electrocardiographic measurements. Methods and Results Ex vivo perfusion study: Isolated guinea pig hearts were perfused with modified Krebs-Henseleit (K-H) buffer with or without ZA 0.07 mg/kg/L (each n=6). In ZA-perfused hearts, atrial action potential at 90% repolarization (APD90) decreased more from baseline than in controls (−23.2% ± −5.1% vs −2.1% ± −8.1%, p<0.0001), as did APD30 (−28.8% ± −3.8% vs −2.1% ± −2.1%, p<0.0001). In vivo dose-response study: Guinea pigs underwent intraperitoneal injections every two weeks in one of 4 groups (each n=8): ZA 0.007 mg/kg (low-dose), ZA 0.07 mg/kg (medium-dose), ZA 0.7 mg/kg (high-dose) or placebo. Hearts were excised at 8 weeks and perfused with modified K-H. Atrial effective refractory period (ERP) was lower with medium and high-dose ZA versus placebo (p=0.004). Atrial APD30 was lower with high-dose ZA versus placebo, low and medium doses (p<0.001). Canine ECG study: Mature female beagles received intravenous ZA 0.067 mg/kg or saline (placebo) (each n=6) every two weeks for 12 weeks. P wave dispersion was greater in the ZA group (7.7±3.7 vs. 3.4±2.6 ms, p=0.04). There were no significant differences in P wave index, maximum or minimum P wave duration, or PR interval. Conclusion ZA shortens left atrial APD and ERP and increases P wave dispersion. PMID:25684326

  19. Is Administration of Trastuzumab an Independent Risk Factor for Developing Osteonecrosis of the Jaw Among Metastatic Breast Cancer Patients Under Zoledronic Acid Treatment?

    PubMed Central

    Pilanci, Kezban Nur; Alco, Gul; Ordu, Cetin; Sarsenov, Dauren; Celebi, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Tecimer, Coskun; Demir, Gokhan; Eralp, Yesim; Okkan, Sait; Ozmen, Vahit

    2015-01-01

    Abstract One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect. Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients’ ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits. Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13–82) and the mean number of ZA infusions was 38 (range: 15–56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively). The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab. PMID:25950681

  20. La formation de l'inkisi (Supergroupe ouest-congolien) en Afrique centrale (Congo et Bas-Zaïre): un delta d'âge Paléozoïque comblant un bassin en extension

    NASA Astrophysics Data System (ADS)

    Alvarez, Philippe; Maurin, Jean-Christophe; Vicat, Jean-Paul

    1995-02-01

    The Inkisi Formation (West Congolian Supergroup) corresponds to a large deltaic body, which extends through Congo, Lower Zaire and Angola. In the Congo and Lower Zaire areas, the lower part of this formation is characterized by a fluvial conglomerate with elliptic pebbles. The red arkosic, channelized series from the Brazzaville-Kinshasa area involves delta plain distributary channels and delta front sequences. The transport direction of continental material is from north to south and the source area is the Chaillu basement. Glacial quartzitic pebbles are probably reworked from the fluvio-lacustrine Upper Diamictite Formation. The classical subdivisions of the Inkisi Formation - basal conglomerate (I 0), Lower part (I 1) and Upper part (I 2) - are not used. These subdivisions correspond to a fluvial conglomerate and to delta front and delta plain facies. The coastal onlap progressively covered the conglomerate and the distributary channels in the delta plain was prograding onto the delta front. The prodelta sequence could correspond to the Upper level of the Mpioka molassic Formation. The Inkisi delta was on the northern edge of an extensional basin controlled by NE-SW normal faults. The extension phase is dearly post Pan-African and occurred during the Palaeozoic, probably in relation to the Permian Karoo phase, and is also known in Angola.

  1. Some modern astronomical problem of creating television-measuring systems (ATVMS) for observations artificial earth satellites (Nekotoryye sovremennyye problemy sozdaniya astronomicheskikh televizionno-izmeritel'nykh sistem (ATVIS) dlya nablyudeniy za iskusstvennymi sputnikami Zemli, on Russian))

    NASA Astrophysics Data System (ADS)

    Prokof'yeva-Mikhaylovskaya, V. V.; Strígin, N. Z.; Sukhov, P. P.; Karpenko, G. F.

    History of the artificial satellite observations is briefly described. On objective reasons there is no enough perfected methodses of the creation astronomical television-measuring systems (ATVMS) on today. There are shown some problems methdological, technological, algorithmic and etc nature, which necessary to solve for development of this methods. Possible ways of the decision is specified for some problems.

  2. Modeling Water Balance of Dammed Lakes Using Computer Code Matlab-Simulink/ Modelowanie Bilansu Wodnego Piętrzonych Jezior Za Pomocą Programu Komputerowego Matlab-Simulink

    NASA Astrophysics Data System (ADS)

    Błażejewski, Ryszard; Murat-Błażejewska, Sadżide; Jędrkowiak, Martyna

    2014-09-01

    The paper presents a water balance of a flow-through, dammed lake, consisted of the following terms: surface inflow, underground inflow/outflow based on the Dupuit's equation, precipitation on the lake surface, evaporation from water surface and outflow from the lake at which a damming weir is located. The balance equation was implemented Matlab-Simulink®. Applicability of the model was assessed on the example of the Sławianowskie Lake of surface area 276 ha and mean depth - 6.6 m, Water balances, performed for month time intervals in the hydrological year 2009, showed good agreement for the first three months only. It is concluded that the balancing time interval should be shorter (1 day) to minimize the errors. For calibration purposes, measurements of ground water levels in the vicinity of the lake are also recommended. Praca przedstawia bilans wodny przepływowego piętrzonego jeziora, uwzględniający dopływ powierzchniowy, dopływ i odpływ podziemny opisany równaniem Dupuita, opad na powierzchnię jeziora, parowanie z powierzchni wody oraz odpływ w przekroju zamkniętym jazem piętrzącym. Z uwagi na nieliniowe związki wymienionych składników bilansu z poziomem wody w jeziorze, do obliczeń wykorzystano program komuterowy Matlab-Simulink®. Przydatność modelu sprawdzono na przykładzie Jeziora Sławianowskiego o powierzchni 276 ha i średniej głębokości - 6,6 m. Jezioro to zostało podzielone na dwa akweny o zróżnicowanej głębokości. Wyniki obliczeń miesięcznych bilansów wodnych dla roku hydrologicznego 2009, wykazały dobrą zgodność z pomiarami jedynie dla trzech pierwszych miesięcy. Stwierdzono, że dla zmniejszenia błędów obliczeniowych należałoby skrócić interwał bilansowania do jednej doby. Kalibracja modelu byłaby łatwiejsza i bardziej adekwatna, gdyby do oszacowania przewodności hydraulicznej przyległych do jeziora gruntów i osadów dennych wykorzystać badania poziomów wody w piezometrach, zlokalizowanych w kilku transektach, prostopadłych do linii brzegowej jeziora.

  3. Transient states of air parameters after a stoppage and re-start of the main fan / Stany przejściowe parametrów powietrza po postoju i załączeniu wentylatora głównego

    NASA Astrophysics Data System (ADS)

    Wasilewski, Stanisław

    2012-12-01

    A stoppage of the main ventilation fan constitutes a disturbance of ventilation conditions of a deepmine and its effects can cause serious hazards by generating transient states of air and gas flow. Main ventilation fans are the basic deep-mine facilities; therefore, under mining regulations it is only allowed to stop them with the consent and under the conditions specified by the mine maintenance manager. The stoppage of the main ventilation fan may be accompanied by transient air parameters, including the air pressure and flow patterns. There is even the likelihood of reversing the direction of air flow, which, in case of methane mines, can pose a major hazard, particularly in sections of the mine with fire fields or large goaf areas. At the same time, stoppages of deep-mine main ventilation fans create interesting research conditions, which if conducted under the supervision of the monitoring systems, can provide much information about the transient processes of pressure, air and gas flow in underground workings. This article is a discussion of air parameter observations in mine workings made as part of such experiments. It also presents the procedure of the experiments, conducted in three mines. They involved the observation of transient processes of mine air parameters, and most interestingly, the recording of pressure and air and gas flow in the workings of the mine ventilation networks by mine monitoring systems and using specialist recording instruments. In mining practice, both in Poland and elsewhere, software tools and computer modelling methods are used to try and reproduce the conditions prior to and during disasters based on the existing network model and monitoring system data. The use of these tools to simulate the alternatives of combating and liquidation of the gas-fire hazard after its occurrence is an important issue. Measurement data collected during the experiments provides interesting research material for the verification and validation of the software tools used for the simulation of processes occurring in deep-mine ventilation systems.

  4. Rac1/Pak1/p38/MMP-2 axis regulates angiogenesis in ovarian cancer

    PubMed Central

    Gonzalez-Villasana, Vianey; Fuentes-Mattei, Enrique; Ivan, Cristina; Dalton, Heather J.; Rodriguez-Aguayo, Cristian; Fernandez-de Thomas, Ricardo J.; Aslan, Burcu; Monroig, Paloma del C.; Velazquez-Torres, Guermarie; Previs, Rebecca A.; Pradeep, Sunila; Kahraman, Nermin; Wang, Huamin; Kanlikilicer, Pinar; Ozpolat, Bulent; Calin, George; Sood, Anil K.; Lopez-Berestein, Gabriel

    2015-01-01

    Purpose Zoledronic acid (ZA) is being increasingly recognized for its anti-tumor properties, but the underlying functions are not well understood. In this study, we hypothesized that ZA inhibits ovarian cancer (OC) angiogenesis preventing Rac1 activation. Experimental Design The biological effects of ZA were examined using a series of in vitro (cell invasion, cytokine production, Rac1 activation, reverse-phase protein array and in vivo (orthotopic mouse models) experiments. Results There was significant inhibition of OC (HeyA8-MDR and OVCAR-5) cell invasion as well as reduced production of pro-angiogenic cytokines in response to ZA treatment. Furthermore, ZA inactivated Rac1 and decreased the levels of Pak1/p-38/matrix metalloproteinase-2 in OC cells. In vivo, ZA reduced tumor growth, angiogenesis and cell proliferation and inactivated Rac1 in both HeyA8-MDR and OVCAR-5 models. These in vivo antitumor effects were enhanced in both models when ZA was combined with nab-paclitaxel. Conclusion ZA has robust anti-tumor and anti-angiogenic activity and merits further clinical development as OC treatment. PMID:25595279

  5. Sulfation mediates activity of zosteric acid against biofilm formation.

    PubMed

    Kurth, Caroline; Cavas, Levent; Pohnert, Georg

    2015-01-01

    Zosteric acid (ZA), a metabolite from the marine sea grass Zostera marina, has attracted much attention due to its attributed antifouling (AF) activity. However, recent results on dynamic transformations of aromatic sulfates in marine phototrophic organisms suggest potential enzymatic desulfation of metabolites like ZA. The activity of ZA was thus re-investigated using biofilm assays and simultaneous analytical monitoring by liquid chromatography/mass spectrometry (LC/MS). Comparison of ZA and its non-sulfated form para-coumaric acid (CA) revealed that the active substance was in all cases the non-sulfated CA while ZA was virtually inactive. CA exhibited a strong biofilm inhibiting activity against Escherichia coli and Vibrio natriegens. The LC/MS data revealed that the apparent biofilm inhibiting effects of ZA on V. natriegens can be entirely attributed to CA released from ZA by sulfatase activity. In the light of various potential applications, the (a)biotic transformation of ZA to CA has thus to be considered in future AF formulations. PMID:25915112

  6. Multicomponent Analysis of Junctional Movements Regulated by Myosin II Isoforms at the Epithelial Zonula Adherens

    PubMed Central

    Smutny, Michael; Wu, Selwin K.; Gomez, Guillermo A.; Mangold, Sabine; Yap, Alpha S.; Hamilton, Nicholas A.

    2011-01-01

    The zonula adherens (ZA) of epithelial cells is a site of cell-cell adhesion where cellular forces are exerted and resisted. Increasing evidence indicates that E-cadherin adhesion molecules at the ZA serve to sense force applied on the junctions and coordinate cytoskeletal responses to those forces. Efforts to understand the role that cadherins play in mechanotransduction have been limited by the lack of assays to measure the impact of forces on the ZA. In this study we used 4D imaging of GFP-tagged E-cadherin to analyse the movement of the ZA. Junctions in confluent epithelial monolayers displayed prominent movements oriented orthogonal (perpendicular) to the ZA itself. Two components were identified in these movements: a relatively slow unidirectional (translational) component that could be readily fitted by least-squares regression analysis, upon which were superimposed more rapid oscillatory movements. Myosin IIB was a dominant factor responsible for driving the unilateral translational movements. In contrast, frequency spectrum analysis revealed that depletion of Myosin IIA increased the power of the oscillatory movements. This implies that Myosin IIA may serve to dampen oscillatory movements of the ZA. This extends our recent analysis of Myosin II at the ZA to demonstrate that Myosin IIA and Myosin IIB make distinct contributions to junctional movement at the ZA. PMID:21799860

  7. Improvement in biocompatibility of ZrO2-Al2O3 nano-composite by addition of HA.

    PubMed

    Kong, Young-Min; Bae, Chang-Jun; Lee, Su-Hee; Kim, Hae-Won; Kim, Hyoun-Ee

    2005-02-01

    The biocompatibility of zirconia-alumina (ZA) nano-composites in load-bearing applications such as dental/orthopedic implants was significantly enhanced by the addition of bioactive HA. The ZA matrix was composed of nano-composite powder obtained from the Pechini process and had higher flexural strength than conventionally mixed zirconia-alumina composite. Because the ZA nano-composite powder effectively decreased the contact area between HA and zirconia for their reaction during the sintering process, the HA-added ZA nano-composites contained biphasic calcium phosphates (BCP) of HA/TCP and had higher flexural strength than conventionally mixed ZA-HA composite. From the in vitro test with osteoblastic cell-lines, the proliferation and the differentiation (as expressed by the alkaline phosphatase activity) of the cellular response on the HA-added ZA nano-composites gradually increased as the amount of HA added increased. From the mechanical and biological evaluations of the HA-added ZA nano-composites, 30HA (30 vol% HA + 70 vol% ZA) was found to be the optimal composition for load-bearing biological applications. PMID:15276359

  8. Effect of Y Addition on the Mechanical Properties and Microstructure of Zn-Al Alloys

    NASA Astrophysics Data System (ADS)

    Li, Mingyang; Lu, Shujing; Long, Fang; Sheng, Meng; Geng, Haoran; Liu, Wendi

    2015-05-01

    This article will discuss the influence of the rare earth Y on the microstructure and mechanical properties of Zn-Al alloys (ZA27, ZA35, and ZA40), and it will provide reference to rare-earth microalloying through the cast ingot metallurgy process. The results also suggest that the microstructure can be refined and mechanical properties can be improved obviously when adding the right amount of Y, and its tensile strength and brinell hardness increased by 9.1% and 11.7% compared with the unmodified ZA27 alloys, respectively. Compared with non-Y addition, the alloys will form dispersed YZn12 phase, which can strongly pin dislocations and subgrain boundary, inhibiting further recrystallization. On this basis, the impacts of Y on the microstructure and mechanical properties of ZA27, ZA35, and ZA40 have been explored. After adding Y, the microstructures of as-cast Zn-Al alloys are refined at different degree. However, with the increase of Al content, the microstructure shows a certain coarsening and the segregation and shrinkage porosity occur. The most effective refining appears in ZA27-0.4%Y.

  9. Fatigue of die cast zinc alloys

    SciTech Connect

    Schrems, K.K.; Dogan, O.N.; Goodwin, F.E.

    2006-04-01

    The rotating bending fatigue limit of die cast zinc alloy 2, alloy 3, alloy 5, AcuZinc 5, and ZA-8 were determined as a part of an on-going program by ILZRO into the mechanical properties of die cast zinc. The stress-life (S-N) curves of alloys 3, 5, AcuZinc 5, and ZA-8 were determined previously. This presentation reports the results of the S-N curve for Alloy 2 and the calculated fatigue limits for all five alloys. During the previous stress-life testing, the samples were stopped at 10 million cycles and the fatigue limit for alloy 3, alloy 5, and AcuZinc 5 appeared to be higher and the fatigue limit for ZA-8 appeared to be lower than the values reported in the literature. This was further investigated in alloy 5 and ZA-8 by testing continuous cast bulk alloy 5 and ZA-8.

  10. Effect of a Home Bleaching Agent on the Fracture Toughness of Resin Composites, Using Short Rod Design

    PubMed Central

    Bagheri, R.; Fani, M.; Barfi Ghasrodashti, AR.; Nouri Yadkouri, N.; Mousavi, SM.

    2014-01-01

    Statement of Problem: Resin composites are brittle materials and their major shortcomings are manifested in their sensitivity to flaws and defects. Although various mechanical properties of resin composites have been described, few studies are available on assessing the effect of bleaching agents on resin composites using the short rod design. Purpose: To place various resin composites into distilled water at 37°C for 21 days and determine the effect of immersion time in distilled water, with and without exposure to 10% carbamide peroxide by employing short rod design fracture toughness test. Materials and Method: Specimens were prepared from three resin composites; Rok (SDI), Esthet (Dentsply), and Estelite (Tokuyama). For each material, a total of 24 disc-shaped specimens were prepared using a custom-made mould. Specimens were randomly divided into 3 groups of 8 and conditioned in 37°C distilled water for either 24 hours, or 21 days. 21 day specimens were tested both with and without applying bleaching agent; Polanight (SDI). Study group specimens were bleached for 21 days, 2 hours a day. The specimens were loaded using a universal testing machine with a crosshead speed of 0.5 mm per minute. The maximum load at specimen failure was recorded and the KIc (MPa. M 0.5) was calculated. Results: Statistical analysis using two-way ANOVA showed a significant relationship between material and time (p< 0.05).Tukey’s test showed that after 24 h of immersion in distilled water, Rok revealed the highest KIc followed by Esthet and Estelite. The bleaching agent significantly improved the fracture toughness values of Esthet while it decreased that of Estelite. Conclusion: The fracture toughness of the resin composites was affected by the bleaching agent and distilled water. In comparison with Rok and Estelite, fracture toughness of Esthet was increased due to aging and application of bleaching agent. PMID:24883344

  11. Trends of Antibiotic Consumption in Korea According to National Reimbursement Data (2008–2012)

    PubMed Central

    Yoon, Young Kyung; Park, Gi Chan; An, Hyonggin; Chun, Byung Chul; Sohn, Jang Wook; Kim, Min Ja

    2015-01-01

    Abstract This study determined the trends in the quantities and patterns of nationwide antibiotic consumption in the Republic of Korea (ROK). This nationwide descriptive epidemiological study was conducted in the ROK between 2008 and 2012. The quantities and patterns of total systemic antibiotic prescriptions were analyzed using National Health Insurance claims data collected through the Health Insurance Review and Assessment service. Data concerning systemic antibiotics were collected using measurement units of the defined daily dose (DDD) per 1000 people per day according to the Anatomical Therapeutic Chemical classification. Over the 5-year study period, the annual consumption of systemic antibiotics ranged from 21.68 to 23.12 DDD per 1000 people per day. Outpatient antibiotic use accounted for 80.9% of total consumption. A regression model with autoregressive errors showed significant increased consumption of major antibiotic subgroups, including 3rd-generation cephalosporins, carbapenems, and glycopeptides (P < 0.001). However, the antibiotic use of 1st- (P = 0.003), 2nd- (P = 0.004), and 3rd-generation (P = 0.018) cephalosporins among patients who underwent surgery under monitoring by the antimicrobial stewardship programs for perioperative prescription was significantly lower than in those who underwent surgery without monitoring programs. In time-series analysis, total antibiotic consumption demonstrated significant seasonality (P < 0.001). The consumption of broad-spectrum antibiotics was noted to have increased in the ROK from 2008 to 2012, providing a possible explanation for the changing epidemiology of multidrug resistance. Larger prospective studies are needed to investigate the impact on public health of monitoring programs of perioperative antibiotic usage. PMID:26579825

  12. Design of Wireless GPIB Interface Module Based on Bluetooth

    NASA Astrophysics Data System (ADS)

    Fu, P.; Ma, W. J.; Huang, C. J.

    2006-10-01

    GPIB interface is widely used in the testing and control field. In this paper a wireless GPIB interface module based on Bluetooth is developed. Programming with Verilog HDL language on the hardware of ROK 101 008 and a FPGA chip, the complicated logical design of GPIB interface and the Bluetooth data processing unit are implemented. On basis of Bluetooth specifications, the software for the control computer is developed. In order to provide a standard software interface for users, a VISA library that is compatible with the VPP specifications is also designed.

  13. Doses effects of zoledronic acid on mineral apatite and collagen quality of newly-formed bone in the rat's calvaria defect.

    PubMed

    Olejnik, Cécile; Falgayrac, Guillaume; During, Alexandrine; Cortet, Bernard; Penel, Guillaume

    2016-08-01

    Due to their inhibitory effects on resorption, bisphosphonates are widely used in the treatment of diseases associated to an extensive bone loss. Yet, little is known about bisphosphonates effects on newly-formed bone quality. In the present study, adult male Sprague-Dawley rats (n=80) with a bone defect calvaria area were used and short-term effects of zoledronic acid (ZA) were studied on the healing bone area. Three ZA treatments were tested by using either: 1°) a low single dose (120μgZA/kg, n=10; equivalent to human osteoporosis treatment), 2°) a low fractionated doses (20μgZA/kg daily for 6days either a total of 120μg/kg, n=15), and 3°) a high fractionated doses, (100μgZA/kg weekly for 6weeks, n=15; equivalent to 6months of human bone metastasis treatment). For each treatment, a control "vehicle" treatment was performed (with an identical number of rats). After ZA administration, the intrinsic bone material properties were evaluated by quantitative backscattered electron imaging (qBEI) and Raman microspectroscopy. Neither single nor fractionated low ZA doses modify the intrinsic bone material properties of the newly-formed bone compared to their respective control animals. On the opposite, the high ZA treatment resulted in a significant decrease of the crystallinity (-25%, P< 0.05) and of the hydroxyproline-to-proline ratio (-30%, P<0.05) in newly-formed bones. Moreover, with the high ZA treatment, the crystallinity was positively correlated with the hydroxyproline-to-proline ratio (ρ=0.78, P<0.0001). The present data highlight new properties for ZA on bone formation in a craniofacial defect model. As such, ZA at high doses disrupted the apatite crystal organization. In addition, we report here for the first time that high ZA doses decreased the hydroxyproline-to-proline ratio suggesting that ZA may affect the early collagen organization during the bone healing. PMID:27168397

  14. Zoledronic acid causes γδ T cells to target monocytes and down-modulate inflammatory homing

    PubMed Central

    Fowler, Daniel W; Copier, John; Dalgleish, Angus G; Bodman-Smith, Mark D

    2014-01-01

    Zoledronic acid (ZA) is a potential immunotherapy for cancer because it can induce potent γδ T-cell-mediated anti-tumour responses. Clinical trials are testing the efficacy of intravenous ZA in cancer patients; however, the effects of systemic ZA on the activation and migration of peripheral γδ T cells remain poorly understood. We found that γδ T cells within ZA-treated peripheral blood mononuclear cells were degranulating, as shown by up-regulated expression of CD107a/b. Degranulation was monocyte dependent because CD107a/b expression was markedly reduced in the absence of CD14+ cells. Consistent with monocyte-induced degranulation, we observed γδ T-cell-dependent induction of monocyte apoptosis, as shown by phosphatidylserine expression on monocytes and decreased percentages of monocytes in culture. Despite the prevailing paradigm that ZA promotes tumour homing in γδ T cells, we observed down-modulation of their tumour homing capacity, as shown by decreased expression of the inflammatory chemokine receptors CCR5 and CXCR3, and reduced migration towards the inflammatory chemokine CCL5. Taken together our data suggest that ZA causes γδ T cells to target monocytes and down-modulate the migratory programme required for inflammatory homing. This study provides novel insight into how γδ T cells interact with monocytes and the possible implications of systemic use of ZA in cancer. PMID:24912747

  15. Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection.

    PubMed

    Lee, Chia Min; Weight, Alisha K; Haldar, Jayanta; Wang, Ling; Klibanov, Alexander M; Chen, Jianzhu

    2012-12-11

    Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance. PMID:23185023

  16. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    PubMed

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  17. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

    PubMed Central

    Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  18. Anabolic and antiresorptive drugs improve trabecular microarchitecture and reduce fracture risk following radiation therapy.

    PubMed

    Arrington, Sarah A; Fisher, Erica R; Willick, Gordon E; Mann, Kenneth A; Allen, Matthew J

    2010-09-01

    Many patients with symptomatic bone metastases receive radiation therapy, even though radiation is known to have potential adverse effects on bone. We hypothesized that the concurrent use of a bisphosphonate drug (zoledronic acid, ZA) or a combination of ZA plus an anabolic agent (parathyroid hormone, PTH) would lead to improvements in the microarchitecture and mechanical properties of irradiated bone. Human breast cancer cells were injected into the distal femur of 56 female nude mice, which were then divided into four groups: no treatment (0 Gy), radiation administered 4 weeks postinjection (20 Gy), radiation plus ZA (12.5 microg/kg weekly from weeks 4 to 12) (20 Gy + ZA), and radiation followed by ZA (25 microg/kg weekly from weeks 4 to 8) and PTH(1-34) (100 microg microg/kg daily from weeks 8 to 12) (20 Gy + ZA + PTH). Left limbs served as normal control bones. Bone loss over the 12-week study was tracked with serial radiography and bone densitometry. At the end of the study, micro-computed tomography and mechanical testing were used to quantify bone microarchitecture and bone strength. Radiation alone failed to prevent tumor-induced decreases in bone mineral density (BMD), trabecular bone volume, and bone strength. Treatment with 20 Gy + ZA or 20 Gy + ZA + PTH as adjuncts to radiation was effective at preserving trabecular bone architecture and bone strength at normal levels. ZA reduced the risk of mechanical fragility following irradiation of a lytic bone lesion. Supplemental use of PTH did not result in further increases in bone strength but was associated with significant increases in BMD and bone mass, suggesting that it may be beneficial in enhancing bone architecture following radiation therapy. PMID:20563797

  19. Chemical sterilisation of Bos indicus bull calves following intratesticular injection of zinc acetate: effects on semen quality and testicular changes.

    PubMed

    Cavalieri, J; Wang, M; Johnson, L

    2015-05-01

    The aim of this study was to determine the effects in Bos indicus bull calves of intratesticular administration of 1mL of either saline (n=9) or one of the two doses of zinc acetate (ZA1, 57.75mg, n=10 or ZA2, 71.75mg, n=10) on semen quality and testicular changes. Semen was collected by electroejaculation on Days 343, 524 and 783 and animals were slaughtered on Day 860. Treatment reduced median maximum number of progressively motile and morphologically normal sperm collected (P=0.001) and the percentage of animals in which sperm were recovered (saline: 100%, 9/9; ZA1: 44.9%, 4/9 and ZA2: 40.0%, 4/10; P=0.013). Compared to saline treated controls, treatment with ZA reduced the mean diameter of the testes after Day 34 of treatment (treatment×time, P=0.013) and total testicular weight at slaughter (treatment: mean±SEM; saline: 569.4±59.0g, ZA1: 249.3±72.9g, ZA2: 247.5±68.1g; P=0.004). Histological changes in testes of bulls treated with ZA were characterized by germ cell depletion, vacuolation of Sertoli cells, interstitial fibrosis, epididymal duct atrophy with variable remnants of testicular tissue and degeneration. We conclude that intratesticular administration of two doses of ZA in B. indicus calves is able to severely impair spermatogenesis and cause varying degrees of testicular degeneration and a reduction in testicular diameter and mass. Further investigation is required to determine ways of obtaining more consistent results from treatment. PMID:25752498

  20. The effect of a moderate zinc deficiency and dietary fat source on the activity and expression of the Δ(3)Δ (2)-enoyl-CoA isomerase in the liver of growing rats.

    PubMed

    Justus, Jennifer; Weigand, Edgar

    2014-06-01

    Auxiliary enzymes participate in β-oxidation of unsaturated fatty acids. The objective of the study was to investigate the impact of a moderate zinc deficiency and a high intake of polyunsaturated fat on Δ(3)Δ(2)-enoyl-CoA isomerase (ECI) in the liver and other tissues. Five groups of eight weanling rats each were fed moderately zinc-deficient (ZD) or zinc-adequate (ZA) semisynthetic diets (7 or 50 mg Zn/kg) enriched with 22 % cocoa butter (CB) or 22 % safflower oil (SO) for 4 weeks: (1) ZD-CB, fed free choice; (2) ZA-CBR, ZA-CB diet fed in equivalent amounts consumed by the ZD-CB group; (3) ZD-SO, fed free choice; (4) ZA-SOR, ZA-SO diet fed in equivalent amounts consumed by the ZD-SO group; and (5) ZA-SO, fed free choice. Growth and Zn status markers were markedly reduced in the ZD groups. ECI activity in the liver of the animals fed the ZD- and ZA-SO diets were significantly higher (approximately 2- and 3-fold, respectively) as compared with the CB-fed animals, whereas activities in extrahepatic tissues (kidneys, heart, skeletal muscle, testes, adipose tissue) were not altered by dietary treatments. Transcript levels of the mitochondrial Eci gene in the liver did not significantly differ between ZD and ZA rats, but were 1.6-fold higher in the ZA-SO- than in the ZD-CB-fed animals (P < 0.05). It is concluded that diets enriched with safflower oil as a source high in linoleic acid induce markedly increased hepatic ECI activities and that a moderate Zn deficiency does not affect transcription of the mitochondrial Eci gene in the liver. PMID:24682920

  1. Chemical sterilisation of Bos indicus bull calves following intratesticular injection of zinc acetate: Effects on growth and concentrations of testosterone.

    PubMed

    Cavalieri, J; Wang, M

    2015-08-01

    The aim of this study was to determine the effects in Bos indicus calves of intra-testicular injection of either saline (n=9) or one of two doses of zinc acetate ((ZA1, 57.75mg, n=10, or ZA2, 71.75mg, n=10) or surgical castration (n=9) on circulating concentrations of testostosterone and liveweight. Human chorionic gonadotrophin (hCG, 1500IU) was administered 202 and 525 days after treatment on Day 0 and animals were slaughtered on Day 860. In animals left intact treatment with ZA reduced mean serum concentrations of testosterone (Saline: 5.58±0.79ng/mL, ZA1: 1.28±0.27ng/mL, ZA2: 1.01±0.17ng/mL; P<0.001) and concentrations 48h following administration of hCG. The maximum concentration of testosterone recorded throughout the study in six out of 19 animals treated with ZA was ≤0.21ng/mL. Treatment with ZA did not significantly affect live weights or carcass weights or result in any detectable scrotal lesions. Animals with concentrations of testosterone ≥1.0ng/mL exhibited greater liveweights throughout most of the study and yielded heavier carcass weights (340.9±7.02 versus 309.3±6.17kg, P=0.002). It is concluded that a single, intra-testicular administration of either 57.75mg or 71.75mg of ZA was able to similarly reduce circulating concentrations of testosterone without significantly affecting liveweights or carcass weights. Treatment with ZA can result in variation in circulating concentrations of testosterone which could lead to differences in behaviour, liveweights and carcass characteristics. PMID:26130602

  2. The isoprenoid pathway and transcriptional response to its inhibitors in the yeast Saccharomyces cerevisiae.

    PubMed

    Kuranda, Klaudia; François, Jean; Palamarczyk, Grazyna

    2010-02-01

    This review presents new insights into the regulation of the isoprenoid pathway in the yeast Saccharomyces cerevisiae, in particular the short-term transcriptional response to two inhibitors, lovastatin and zaragozic acid (ZA). Whereas lovastatin blocks whole isoprenoid pathway, ZA only blocks the sterol branch. Consequently, their effects on the cellular level of farnesyl diphosphate (FPP) are different. Lovastatin decreases the FPP level, whereas ZA, by inhibiting the main FPP-consuming enzyme, increases FPP availability in the cell. We discuss the role of genes whose expression is affected by both inhibitors and consider possible association of these genes with the regulation of the isoprenoid pathway. PMID:19744247

  3. Capillary liquid chromatographic fingerprint used for discrimination of Zingiber montanum from related species.

    PubMed

    Rafi, Mohamad; Lim, Lee Wah; Takeuchi, Toyohide; Darusman, Latifah Kosim

    2013-08-01

    Fingerprint analysis using capillary liquid chromatography (CLC) has been developed for discrimination of Zingiber montanum (ZM) from related species, for example Z. americans (ZA) and Z. zerumbet (ZZ). By comparing the fingerprint chromatograms of ZM, ZA, and ZZ we could identify ZM samples and discriminate them from ZA and ZZ by using their marker peaks. We also combined CLC fingerprint with multivariate analysis, including principal-component analysis (PCA) and canonical variate analysis (CVA); all three species were discriminated successfully. This result indicates that CLC fingerprint analysis in combination with PCA and CVA can be used for discrimination of ZM samples from samples of related species. PMID:23760136

  4. The confluent hypergeometric functions M(a,b;z) and U(a,b;z) for large b and z

    NASA Astrophysics Data System (ADS)

    López, José L.; Pagola, Pedro J.

    2010-01-01

    We obtain new and complete asymptotic expansions of the confluent hypergeometric functions M(a,b;z) and U(a,b;z) for large b and z. The expansions are different in the three different regions: z+a+1-b>0, z+a+1-b<0 and z+a+1-b=0. The expansions are not of Poincaré type and we give explicit expressions for the terms of the expansions. In some cases, the expansions are valid for complex values of the variables too. We give numerical examples which show the accuracy of the expansions.

  5. Zoledronic acid increases the circulating soluble RANKL level in mice, with a further increase in lymphocyte-derived soluble RANKL in zoledronic acid- and glucocorticoid-treated mice stimulated with bacterial lipopolysaccharide.

    PubMed

    Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Hori, Naoko; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

    2016-07-01

    The nitrogen-containing bisphosphonate (BP) zoledronic acid (ZA) is a potent antiresorptive drug used in conjunction with standard cancer therapy to treat osteolysis or hypercalcemia due to malignancy. However, it is unclear how ZA influences the circulating levels of bone remodeling factors. The aim of this study was to evaluate the effects of ZA on the serum levels of soluble receptor activator of NF-kB ligand (sRANKL) and osteoprotegerin (OPG). The following four groups of C57BL/6 mice were used (five mice per group): (1) the placebo+phosphate-buffered saline (PBS) group, in which placebo-treated mice were injected once weekly with PBS for 4weeks; (2) the placebo+ZA group, in which placebo-treated mice were injected once weekly with ZA for 4weeks; (3) the prednisolone (PSL)+PBS group, in which PSL-treated mice were injected once weekly with PBS for 4weeks; and (4) the PSL+ZA group, in which PSL-treated mice were injected once weekly with ZA for 4weeks. At the 3-week time point, all mice were subjected to oral inflammatory stimulation with bacterial lipopolysaccharide (LPS). The sera of these mice were obtained every week and the levels of sRANKL and OPG were measured using enzyme-linked immunosorbent assay. At the time of sacrifice, femurs were prepared for micro-computed tomography (micro-CT), histological, and histomorphometric analyses. Our data indicated that ZA administration remarkably reduced bone turnover and significantly increased the basal level of sRANKL. Interestingly, the PSL+ZA group showed a dramatically elevated sRANKL level after LPS stimulation. In contrast, the PSL+ZA group in nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice), which are characterized by the absence of functional T- and B-lymphocytes, showed no increase in the sRANKL level. Our data suggest that, particularly with combination treatment of ZA and glucocorticoids, surviving lymphocytes might be the source of inflammation-induced sRANKL. Thus

  6. Dynamic myosin phosphorylation regulates contractile pulses and tissue integrity during epithelial morphogenesis

    PubMed Central

    Vasquez, Claudia G.; Tworoger, Mike

    2014-01-01

    Apical constriction is a cell shape change that promotes epithelial bending. Activation of nonmuscle myosin II (Myo-II) by kinases such as Rho-associated kinase (Rok) is important to generate contractile force during apical constriction. Cycles of Myo-II assembly and disassembly, or pulses, are associated with apical constriction during Drosophila melanogaster gastrulation. It is not understood whether Myo-II phosphoregulation organizes contractile pulses or whether pulses are important for tissue morphogenesis. Here, we show that Myo-II pulses are associated with pulses of apical Rok. Mutants that mimic Myo-II light chain phosphorylation or depletion of myosin phosphatase inhibit Myo-II contractile pulses, disrupting both actomyosin coalescence into apical foci and cycles of Myo-II assembly/disassembly. Thus, coupling dynamic Myo-II phosphorylation to upstream signals organizes contractile Myo-II pulses in both space and time. Mutants that mimic Myo-II phosphorylation undergo continuous, rather than incremental, apical constriction. These mutants fail to maintain intercellular actomyosin network connections during tissue invagination, suggesting that Myo-II pulses are required for tissue integrity during morphogenesis. PMID:25092658

  7. Functional Classification of Natural Resources for Valuing Natural Resources in Korea

    NASA Astrophysics Data System (ADS)

    Choi, H.; Lee, W.; Kwak, H.

    2013-12-01

    The ecosystem services concept emphasizes not only regulating services, but also supporting, provisioning, and cultural/social services according to the Millennium Ecosystem Assessment (MA). While the spatial and quantifying of ecosystem services is becoming increasingly recognized for natural resources conservation, however, due to methodological challenges, ecosystem services quantification is rarely considered in Republic of Korea (ROK). This study matches appropriate indicators, data and mapping for describing respective states, quantification and ecosystem valuation. The results were analyzed with statistical and GIS-based techniques. We classified the ecosystem services function based on reference to the literature, interviews and a modified approach compared to the MA, the Economics of Ecosystems and Biodiversity (TEEB). For quantifying values, we subdivided land cover types using ecological features and normalized numerical information of provisioning services, regulating services and cultural services. Resulting hotspots of ecosystem services are related to landscape features and land cover types in ROK. The mapping results show hotspots of ecosystem services where high level of ecosystem services is distributed - around Baekdudaegan protected area (Gangwon, Gyeongbuk Province, Chungbuk, Jeonam Province). n addition, the results of our study show that ecosystem services function - especially, fostering water resources, erosion control, air quality and pollution control in terrestrial ecosystems - can contribute to planning management policy for ecosystem based management at regional scale.

  8. Ticks Collected from Selected Mammalian Hosts Surveyed in the Republic of Korea During 2008-2009

    PubMed Central

    Kim, Heung Chul; Han, Sang Hoon; Chong, Sung Tae; Klein, Terry A.; Choi, Chang-Yong; Nam, Hyun-Young; Chae, Hee-Young; Lee, Hang; Ko, Sungjin; Kang, Jun-Gu

    2011-01-01

    A tick survey was conducted to determine the relative abundance and distribution of ticks associated with selected mammals in the Republic of Korea (ROK) during 2008-2009. A total of 918 ticks were collected from 76 mammals (6 families, 9 species) captured at 6 provinces and 3 Metropolitan Cities in ROK. Haemaphysalis longicornis (54.4%) was the most frequently collected tick, followed by Haemaphysalis flava (28.5%), Ixodes nipponensis (7.6%), Ixodes pomerantzevi (4.8%), Ixodes persulcatus (4.6%), and Haemaphysalis japonica (0.1%). Adults (57.0%) and nymphs (28.7%) of Ixodes and Haemaphysalis spp. were collected most frequently from medium or large mammals in this survey, while few larvae (14.3%) were collected. Hydropotes inermis was the most frequently captured mammal (52.6%), with a 16.4 tick index and 5 of 6 species of ticks collected during this survey. H. longicornis (69.7%) was the predominant tick collected from H. inermis, followed by H. flava (22.2%), I. persulcatus (6.1%), I. nipponensis (1.8%), and H. japonica (0.2%). PMID:22072840

  9. Dynamic myosin phosphorylation regulates contractile pulses and tissue integrity during epithelial morphogenesis.

    PubMed

    Vasquez, Claudia G; Tworoger, Mike; Martin, Adam C

    2014-08-01

    Apical constriction is a cell shape change that promotes epithelial bending. Activation of nonmuscle myosin II (Myo-II) by kinases such as Rho-associated kinase (Rok) is important to generate contractile force during apical constriction. Cycles of Myo-II assembly and disassembly, or pulses, are associated with apical constriction during Drosophila melanogaster gastrulation. It is not understood whether Myo-II phosphoregulation organizes contractile pulses or whether pulses are important for tissue morphogenesis. Here, we show that Myo-II pulses are associated with pulses of apical Rok. Mutants that mimic Myo-II light chain phosphorylation or depletion of myosin phosphatase inhibit Myo-II contractile pulses, disrupting both actomyosin coalescence into apical foci and cycles of Myo-II assembly/disassembly. Thus, coupling dynamic Myo-II phosphorylation to upstream signals organizes contractile Myo-II pulses in both space and time. Mutants that mimic Myo-II phosphorylation undergo continuous, rather than incremental, apical constriction. These mutants fail to maintain intercellular actomyosin network connections during tissue invagination, suggesting that Myo-II pulses are required for tissue integrity during morphogenesis. PMID:25092658

  10. Leptospirosis in the republic of Korea: historical perspectives, current status and future challenges.

    PubMed

    Kim, Min Ja

    2013-06-01

    Leptospirosis is an important public health problem in the Republic of Korea (ROK), occurring sporadically or in outbreaks during the autumn season. Wild rodents, Apodemus agrarius, have been mainly involved in human leptospirosis. The majority of carrier animals are infected with Leptospira interrogans serovar lai. The characteristic pulmonary involvement or hemorrhage may increase the clinical severity or result in fatal outcomes, and these aspects continue to be a threat to people in endemic areas. While the disease incidence has been relatively low in recent years, there have been newer findings of livestock (zoo animals and racing horses) and rats (Rattus norvegicus) captured in urban environments as potential animal carriers. Many avenues of research are still open to define current changes in ecology, epidemiology, and the disease burden in both humans and animals in the ROK, together with global warming and climate change issues. In addition, national policy regarding the weighted wildlife monitoring system and the enhanced disease surveillance program is required to facilitate better monitoring and understanding of this disease. PMID:24265962

  11. Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms

    PubMed Central

    Schimizzi, Gregory V.; Maher, Meghan T.; Loza, Andrew J.; Longmore, Gregory D.

    2016-01-01

    The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin. PMID:27454609

  12. Seasonal Distribution of Ticks in Four Habitats near the Demilitarized Zone, Gyeonggi-do (Province), Republic of Korea

    PubMed Central

    Chong, Sung Tae; Kim, Heung Chul; Lee, In-Yong; Kollars, Thomas M.; Sancho, Alfredo R.; Sames, William J.; Chae, Joon-Seok

    2013-01-01

    This study describes the seasonal distribution of larvae, nymph, and adult life stages for 3 species of ixodid ticks collected by tick drag and sweep methods from various habitats in the Republic of Korea (ROK). Grasses less than 0.5 m in height, including herbaceous and crawling vegetation, and deciduous, conifer, and mixed forests with abundant leaf/needle litter were surveyed at United States (US) and ROK operated military training sites and privately owned lands near the demilitarized zone from April-October, 2004 and 2005. Haemaphysalis longicornis Neumann adults and nymphs were more frequently collected from April-August, while those of Haemaphysalis flava Neumann and Ixodes nipponensis Kitaoka and Saito were collected more frequently from April-July and again during October. H. longicornis was the most frequently collected tick in grass habitats (98.9%), while H. flava was more frequently collected in deciduous (60.2%) and conifer (57.4%) forest habitats. While more H. flava (54.1%) were collected in mixed forest habitats than H. longicornis (35.2%), the differences were not significant. I. nipponensis was more frequently collected from conifer (mean 8.8) compared to deciduous (3.2) and mixed (2.4) forests. PMID:23864743

  13. Leptospirosis in the Republic of Korea: Historical Perspectives, Current Status and Future Challenges

    PubMed Central

    2013-01-01

    Leptospirosis is an important public health problem in the Republic of Korea (ROK), occurring sporadically or in outbreaks during the autumn season. Wild rodents, Apodemus agrarius, have been mainly involved in human leptospirosis. The majority of carrier animals are infected with Leptospira interrogans serovar lai. The characteristic pulmonary involvement or hemorrhage may increase the clinical severity or result in fatal outcomes, and these aspects continue to be a threat to people in endemic areas. While the disease incidence has been relatively low in recent years, there have been newer findings of livestock (zoo animals and racing horses) and rats (Rattus norvegicus) captured in urban environments as potential animal carriers. Many avenues of research are still open to define current changes in ecology, epidemiology, and the disease burden in both humans and animals in the ROK, together with global warming and climate change issues. In addition, national policy regarding the weighted wildlife monitoring system and the enhanced disease surveillance program is required to facilitate better monitoring and understanding of this disease. PMID:24265962

  14. Selection of the Methods of Soil Analysis for Phyto-available Arsenic

    NASA Astrophysics Data System (ADS)

    Yoon, Junghwan; Lee, Dan-Bi; Kim, Kwon-Rae; Kim, Won-Il; Kim, Kye-Hoon

    2016-04-01

    Arsenic (As) is a trace element of major public health concern. Many of As contaminated agricultural lands in the Republic of Korea (ROK) are located at the areas nearby abandoned mines. Therefore, management of contaminated agricultural lands is important for safe crop cultivation. In ROK, soils contaminated with As have managed according to the As concentration determined after aqua regia digestion (total As). Many soil scientists reported that management of As in soils by phyto-available As is more effective than that by total As for safety of the crop cultivation point-of-view since As concentration in crops has a significant correlation with phyto-available As. Therefore, this study was carried out to select method of soil analysis for phyto-available As. For that purpose, five extracting solutions (0.1M Ca(NO?), 0.1M (NH?)?HPO?), 0.5M EDTA, Mehlich 3, 0.5M NaHCO?) were examined with 35 soil samples used for cultivation of three crops (bean, red pepper, rice). Correlation analysis was conducted between phyto-available As concentrations in soils and As concentration in edible part of the crops. Results of the correlation analysis showed that phyto-available As concentrations in soils using Mehlich 3 solution and As concentrations in edible part of red pepper and rice were significantly correlated. For soils used for bean cultivation, Mehlich 3 (R

  15. Report on Project Action Sheet PP05 task 3 between the U.S. Department of Energy and the Republic of Korea Ministry of Education, Science, and Technology (MEST).

    SciTech Connect

    Snell, Mark Kamerer

    2013-01-01

    This report documents the results of Task 3 of Project Action Sheet PP05 between the United States Department of Energy (DOE) and the Republic of Korea (ROK) Ministry of Education, Science, and Technology (MEST) for Support with Review of an ROK Risk Evaluation Process. This task was to have Sandia National Laboratories collaborate with the Korea Institute of Nuclear Nonproliferation and Control (KINAC) on several activities concerning how to determine the Probability of Neutralization, PN, and the Probability of System Effectiveness, PE, to include: providing descriptions on how combat simulations are used to determine PN and PE; comparisons of the strengths and weaknesses of two neutralization models (the Neutralization.xls spreadsheet model versus the Brief Adversary Threat-Loss Estimator (BATLE) software); and demonstrating how computer simulations can be used to determine PN. Note that the computer simulation used for the demonstration was the Scenario Toolkit And Generation Environment (STAGE) simulation, which is a stand-alone synthetic tactical simulation sold by Presagis Canada Incorporated. The demonstration is provided in a separate Audio Video Interleave (.AVI) file.

  16. Surveillance of Rift Valley Fever Virus in Mosquito Vectors of the Republic of Korea.

    PubMed

    Kim, Hyun-Joo; Lyoo, Hye-Rhyoung; Park, Jee-Yong; Choi, Jeong-Soo; Lee, Ji-Youn; Jeoung, Hye-Young; Cho, Yun-Sang; Cho, In-Soo; Yoo, Han Sang

    2016-02-01

    Rift Valley fever (RVF) is an acute mosquito-borne viral zoonotic disease that affects mainly domestic ruminants and humans. RVF virus (RVFV) was first identified in Kenya in 1931 and was reported to be endemic in Africa but has recently spread to the Arabian Peninsula. With increasing climate change and globalization of trade in animals and animal products, there is great concern that the disease will spread worldwide to regions such as Europe, Asia, and the Americas. Although RVFV has not been reported in the Republic of Korea (ROK), the possibility of RVFV introduction is increasing because transmissible mosquito vectors are present and direct flights to Africa were added in 2012. For these reasons, we conducted a surveillance study to detect RVFV in mosquito vectors collected around the airport and harbor from 2012 to 2013. A total of 36,734 mosquitoes were collected and tested by real-time RT-PCR. A total of 1837 mosquito pools were used, and all were confirmed to be negative. This is the first report in the ROK concerning RVFV surveillance in mosquito vectors, and continuous surveillance will be conducted for the early warning of RVFV introduction. PMID:26771529

  17. Prediction of Excited-State Energies and Singlet-Triplet Gaps of Charge-Transfer States Using a Restricted Open-Shell Kohn-Sham Approach.

    PubMed

    Hait, Diptarka; Zhu, Tianyu; McMahon, David P; Van Voorhis, Troy

    2016-07-12

    Organic molecules with charge-transfer (CT) excited states are widely used in industry and are especially attractive as candidates for fabrication of energy efficient OLEDs, as they can harvest energy from nonradiative triplets by means of thermally activated delayed fluorescence (TADF). It is therefore useful to have computational protocols for accurate estimation of their electronic spectra in order to screen candidate molecules for OLED applications. However, it is difficult to predict the photophysical properties of TADF molecules with LR-TDDFT, as semilocal LR-TDDFT is incapable of accurately modeling CT states. Herein, we study absorption energies, emission energies, zero-zero transition energies, and singlet-triplet gaps of TADF molecules using a restricted open-shell Kohn-Sham (ROKS) approach instead and discover that ROKS calculations with semilocal hybrid functionals are in good agreement with experiments-unlike TDDFT, which significantly underestimates energy gaps. We also propose a cheap computational protocol for studying excited states with large CT character that is found to give good agreement with experimental results without having to perform any excited-state geometry optimizations. PMID:27267803

  18. In-situ Measurements of the Cosmic Radiation on the Aircraft Altitude over Korean Peninsula

    NASA Astrophysics Data System (ADS)

    Lee, J.; Park, I.; Lee, J.; Oh, S.; Kim, Y. C.

    2014-12-01

    This study presents the comparison between the measured and modeled cosmic radiation on aircraft altitude over Korean peninsula. We performed the measurement with a radiation spectrometer, Liulin-6K on board a Republic of Korea (ROK) Air Force aircraft accomplishing the high-altitude (above 9 km) flight over Korea, and the modeled data was obtained from the operational modeling program, CARI-6M developed by FAA. A number of measurements for the flight mission at high-altitude have been executed to evaluate the exposed dose of cosmic radiation. Both the measured and the calculated data show that the exposed radiation dose enhances dramatically as the altitude increases. The results reveal that the exposed dose rate of aircrews at high-altitude flight is 2-3 orders of magnitude (1-2 mSv/hour) higher than the exposure rate at sea level. It is inferred that the annual total dose of radiation for the aircrews at high-altitude could be higher than the annually public limit (1 mSv) recommended by ICRP. Finally, since neutrons are the dominant components reflecting among total cosmic radiation above 9 km, we try to analyze the relationship between the neutron count from the neutron monitor on the ground and the effective dose from the on board spectrometer. Based on these results, it is suggested that the annual criterion and the proper managing procedure of exposed dose for the flight aircrews of ROK Air Force should be regulated.

  19. Maltose-Dependent Transcriptional Regulation of the mal Regulon by MalR in Streptococcus pneumoniae

    PubMed Central

    Afzal, Muhammad; Shafeeq, Sulman; Manzoor, Irfan; Kuipers, Oscar P.

    2015-01-01

    The maltose regulon (mal regulon) has previously been shown to consist of the mal gene cluster (malMP, malXCD and malAR operons) in Streptococcus pneumoniae. In this study, we have further elucidated the complete mal regulon in S. pneumoniae D39 using microarray analyses and β-galactosidase assays. In addition to the mal gene cluster, the complete mal regulon of S. pneumoniae D39 consists of a pullulanase (PulA), a glucosidase (DexB), a glucokinase (RokB), a PTS component (PtsG) and an amylase (AmyA2). Our microarray studies and β-galactosidase assays further showed that the LacI-family transcriptional regulator MalR represses the expression of the mal regulon in the absence of maltose. Furthermore, the role of the pleiotropic transcriptional regulator CcpA in the regulation of the mal regulon in the presence of maltose was explored. Our microarray analysis with a ΔccpA strain showed that CcpA only represses the expression of the malXCD operon and the pulA gene in the presence of maltose. Hence, we extend the mal regulon now consisting of pulA, dexB, rokB, ptsG and amyA2 in addition to malMP, malXCD and malAR operons. PMID:26030923

  20. Maltose-Dependent Transcriptional Regulation of the mal Regulon by MalR in Streptococcus pneumoniae.

    PubMed

    Afzal, Muhammad; Shafeeq, Sulman; Manzoor, Irfan; Kuipers, Oscar P

    2015-01-01

    The maltose regulon (mal regulon) has previously been shown to consist of the mal gene cluster (malMP, malXCD and malAR operons) in Streptococcus pneumoniae. In this study, we have further elucidated the complete mal regulon in S. pneumoniae D39 using microarray analyses and β-galactosidase assays. In addition to the mal gene cluster, the complete mal regulon of S. pneumoniae D39 consists of a pullulanase (PulA), a glucosidase (DexB), a glucokinase (RokB), a PTS component (PtsG) and an amylase (AmyA2). Our microarray studies and β-galactosidase assays further showed that the LacI-family transcriptional regulator MalR represses the expression of the mal regulon in the absence of maltose. Furthermore, the role of the pleiotropic transcriptional regulator CcpA in the regulation of the mal regulon in the presence of maltose was explored. Our microarray analysis with a ΔccpA strain showed that CcpA only represses the expression of the malXCD operon and the pulA gene in the presence of maltose. Hence, we extend the mal regulon now consisting of pulA, dexB, rokB, ptsG and amyA2 in addition to malMP, malXCD and malAR operons. PMID:26030923

  1. Synergistic anti-tumor effects of zoledronic acid and radiotherapy against metastatic hepatocellular carcinoma.

    PubMed

    Morii, Kazuhiko; Aoyama, Yuhki; Nakamura, Shinichiro; Okushin, Hiroaki

    2015-01-01

    A 72-year-old man with advanced hepatocellular carcinoma and decompensated hepatitis C virus-related cirrhosis suffered from a metastatic femoral fracture. After undergoing radiotherapy, he was only treated with supportive care, except for the administration of zoledronic acid (ZA). Thereafter, the initially elevated serum α-fetoprotein and des-gamma carboxyprothrombin levels declined to within the normal ranges. Hepatic and metastatic adrenal tumors, distant from the radiation field, exhibited a surprising regression. ZA is known to inhibit the activity of osteoclasts, bone-residential macrophages, and has been reported to have a direct anti-tumor effect. ZA may adjust the immunological milieu in tumor microenvironments by inhibiting the tumor-associated macrophages. Because radiotherapy can enhance the presentation of tumor-associated antigens, ZA and radiotherapy may exert synergistic anti-tumor effects. PMID:26466697

  2. Optic glioma

    MedlinePlus

    ... et al. Optic Glioma in Children: A Retrospective Analysis of 101 Cases. American Journal of Clinical Oncology. 2013; 36(3):287-292. Karcioglu ZA, Haik BG. Eye, orbit, and adnexal structures. In: Abeloff MD, Armitage JO, ...

  3. Lacrimal gland tumor

    MedlinePlus

    ... specializes in problems with the bony eye socket (orbit). Tests most often include a CT or MRI ... 2013:chap 40. Karcioglu ZA, Haik BG. Eye, orbit, and adnexal structures. In: Niederhuber JE, Armitage JO, ...

  4. 50 CFR Appendix A to Chapter I - Codes for the Representation of Names of Countries (Established by the International Organization...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... Burundi BI. Canada CA. Cape Verde CV. Central African Empire CF. Chad TD. Chile CL. China CN. Colombia CO... SO. South Africa ZA. Spain ES. Sri Lanka LK. Sudan SD. Suriname SR. Swaziland SZ. Sweden...

  5. Campylobacter infection

    MedlinePlus

    ... eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 303. Bhutta ZA. Acute gastroenteritis ... Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 340. DuPont HL. Approach to the ...

  6. 75 FR 10464 - Broadband Technology Opportunities Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-08

    ... National Telecommunications and Information Administration RIN 0660-ZA28 Broadband Technology Opportunities Program AGENCY: National Telecommunications and Information Administration, U.S. Department of Commerce... Register announcing general policy and application procedures for the second round of BTOP funding. 75...

  7. Antibacterial activity of extracts from Zostera marina against pathogens of Apostichopus japonicus skin ulceration disease

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Jiang, Guoliang; Wu, Zhiqiang

    2010-03-01

    The purpose of this study was to investigate the antibacterial activity of extracts from Zostera marina against the pathogens of Apostichopus japonicus skin ulceration disease. When 95% ethanol (v/v) solvent was used to extract Zostera marina at 50°C, aqueous extract (ZA) showed obvious bacteriostatic effects on the tested bacterial strains (inhibition halo diameters between 8.23 mm and 13.62 mm), whereas the ethyl acetate extract (ZE) was almost inactive. The minimal inhibitory concentration (MIC) of ZA against four pathogens were homogeneous at 12.8 g L-1. ZA components were analyzed by thin layer chromatography (TLC) assay and six fractions were obtained. In another study, the six fractions showed inhibitory effects against the tested bacteria while their functions seemed to counteract the ZA activity.

  8. Supersaturation of zafirlukast in fasted and fed state intestinal media with and without precipitation inhibitors.

    PubMed

    Madsen, Cecilie Maria; Boyd, Ben; Rades, Thomas; Müllertz, Anette

    2016-08-25

    Poor water solubility is a bottle neck in the development of many new drug candidates, and understanding and circumventing this is essential for a more effective drug development. Zafirlukast (ZA) is a leukotriene antagonist marketed for the treatment of asthma (Accolate®). ZA is poorly water soluble, and is formulated in an amorphous form (aZA) to improve its solubility and oral bioavailability. It has been shown that upon dissolution of aZa, the concentration of ZA in solution is supersaturated with respect to its stable crystalline form (ZA monohydrate), and thus, in theory, the bioavailability increases upon amorphization of ZA. The polymers hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidone (PVP), often used as stabilizers of the supersaturated state, are in the excipient list of Accolate®. It is not recommended to take Accolate® with food, as this reduces the bioavailability by 40%. The aim of this study was to investigate the effect of simulated fasted and fed state intestinal media as well as the effect of HPMC and PVP on the supersaturation and precipitation of ZA in vitro. Supersaturation of aZA was studied in vitro in a small scale setup using the μDiss Profiler™. Several media were used for this study: One medium simulating the fasted state intestinal fluids and three media simulating different fed state intestinal fluids. Solid state changes of the drug were investigated by small angle x-ray scattering. The duration wherein aZA was maintained at a supersaturated state was prolonged in the presence of HPMC and lasted more than 20h in the presence of PVP in a fasted state intestinal medium. The presence of PVP increased the concentration of drug dissolved in the supersaturated state. The duration of supersaturation was shorter in fed than in a fasted state simulated intestinal media, but the concentration during supersaturation was higher. It was thus not possible to predict any positive or negative food effects from the dissolution

  9. Retinoblastoma

    MedlinePlus

    ... It is especially important when more than 1 family member has had the disease, or if retinoblastoma occurs in both ... 8.1. Karcioglu ZA, Haik BG. Eye, orbit, and adnexal structures. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ...

  10. Cardiac Catheterization

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Catheterization? Cardiac catheterization (KATH-eh-ter-ih-ZA-shun) is a ... disease. Doctors also can use ultrasound during cardiac catheterization to see blockages in the coronary arteries. Ultrasound ...

  11. Effects of Dietary Supplementation with the Combination of Zeolite and Attapulgite on Growth Performance, Nutrient Digestibility, Secretion of Digestive Enzymes and Intestinal Health in Broiler Chickens

    PubMed Central

    Zhou, P.; Tan, Y. Q.; Zhang, L.; Zhou, Y. M.; Gao, F.; Zhou, G. H.

    2014-01-01

    This study was designed to investigate the effects of basal diets supplemented with a clay product consisting of zeolite and attapulgite (ZA) at 1:1 ratio on growth performance, digestibility of feed nutrients, activities of digestive enzymes in small intestine and intestinal health in broiler chickens. In experiment 1, 112 one-day-old male chickens were randomly divided into 2 groups with 8 replicates of 7 chickens each. In experiment 2, 84 one-day-old male chickens were randomly allocated into 2 groups consisting 6 replicates of 7 chickens each. The experimental diets both consisted of a maize-soybean basal control diet supplemented with 0% or 2% ZA. The diets were fed from 1 to 42 days of age. The results showed that ZA supplementation could increase body weight gain (BWG) and feed intake (FI), but had no significant effect on feed conversion ratio. The apparent digestibility values of crude protein and gross energy were significantly increased (p<0.05) by ZA from 14 to 16 d and 35 to 37 d. Dietary ZA treatment significantly increased (p<0.05) the activities of amylase, lipase and trypsin in jejunal digesta and the activities of maltase and sucrase in jejunal mucosa on days 21 and 42. The ZA supplementation also significantly increased (p<0.05) the catalase activity, reduced (p<0.05) the malondialdehyde concentration in the jejunal mucosa. In addition, a decrease of serum diamine oxidase activity and an increase (p<0.05) in concentration of secretory immunoglobulin A in jejunal mucosa were observed in birds treated with ZA on 21 and 42 days. It is concluded that ZA supplementation (2%) could partially improve the growth performance by increasing BWG and FI. This improvement was achieved through increasing the secretion of digestive enzymes, enhancing the digestibilites of nutrients, promoting intestinal health of broiler chickens. PMID:25178375

  12. Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts

    PubMed Central

    KOMATSU, YUKO; IBI, MIHO; CHOSA, NAOYUKI; KYAKUMOTO, SEIKO; KAMO, MASAHARU; SHIBATA, TOSHIYUKI; SUGIYAMA, YOSHIKI; ISHISAKI, AKIRA

    2016-01-01

    Bisphosphonates (BPs) are analogues of pyro-phosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF-β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF-β-induced promotion of cell viability, ii) the TGF-β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF-β-induced migratory activity of hGFs and iv) the expression level of TGF-β type I receptor on the surfaces of hGFs, as well as the TGF-β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF-β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad-dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level. PMID:27176567

  13. Controlled Directional Crystallization of Oligothiophenes Using Zone Annealing of Preseeded Thin Films.

    PubMed

    Ye, Changhuai; Zhang, Lei; Fu, Guopeng; Karim, Alamgir; Kyu, Thein; Briseno, Alejandro L; Vogt, Bryan D

    2015-10-21

    We demonstrate a simple route to directionally grow crystals of oligothiophenes, based on 2,5-bis(3-alkylthiophen-2-yl)thieno[3,2-b]thiophene with degrees of polymerization of 2 (BTTT-2) and 4 (BTTT-4) via zone annealing (ZA) of preseeded films. ZA of spun-cast films of BTTT-2 does not yield highly aligned crystals. However, if the film is oven-annealed briefly prior to ZA, highly aligned crystals that are millimeters in length can be grown, whose length depends on the velocity of the ZA front. The precrystallized region provides existing nuclei that promote crystal growth and limit nucleation of new crystals in the melted region. Aligned crystals of BTTT-2 can be obtained even when the moving velocity for ZA is an order of magnitude greater than the crystal growth rate. The relative nucleation rate to the crystallization rate for BTTT-4 is greater than that for BTTT-2, which decreases the length over which BTTT-4 can be aligned to ∼500 μm for the conditions examined. The temperature gradient and moving velocity of ZA enable control of the length of the aligned crystalline structure at the macroscale. PMID:26414104

  14. Characterization of a Siberian Virus Isolated from a Patient with Progressive Chronic Tick-Borne Encephalitis

    PubMed Central

    Gritsun, T. S.; Frolova, T. V.; Zhankov, A. I.; Armesto, M.; Turner, S. L.; Frolova, M. P.; Pogodina, V. V.; Lashkevich, V. A.; Gould, E. A.

    2003-01-01

    A strain of Tick-borne encephalitis virus designated Zausaev (Za) was isolated in Siberia from a patient who died of a progressive (2-year) form of tick-borne encephalitis 10 years after being bitten by a tick. The complete genomic sequence of this virus was determined, and an attempt was made to correlate the sequence with the biological characteristics of the virus. Phylogenetic analysis demonstrated that this virus belongs to the Siberian subtype of Tick-borne encephalitis virus. Comparison of Za virus with two related viruses, a Far Eastern isolate, Sofjin, and a Siberian isolate, Vasilchenko, revealed differences among the three viruses in pathogenicity for Syrian hamsters, cytopathogenicity for PS cells, plaque morphology, and the electrophoretic profiles of virus-specific nonstructural proteins. Comparative amino acid alignments revealed 10 individual amino acid substitutions in the Za virus polyprotein sequence that were different from those of other tick-borne flaviviruses. Notably, the dimeric form of the Za virus NS1 protein migrated in polyacrylamide gels as a heterogeneous group of molecules with a significantly higher electrophoretic mobility than those of the Sofjin and Vasilchenko viruses. Two amino acid substitutions, T277→V and E279→G, within the NS1 dimerization domain are probably responsible for the altered oligomerization of Za virus NS1. These studies suggest that the patient from whom Za virus was isolated died due to increased pathogenicity of the latent virus following spontaneous mutagenesis. PMID:12477807

  15. Determination of Dynamic Loads of Sprocket Drum Teeth and Seats by Means of a Mathematical Model of the Longwall Conveyor / Wyznaczenie Obciążeń Dynamicznych Zębów I Gniazd Bębna Łańcuchowego Za Pomocą Modelu Matematycznego Przenośnika Ścianowego

    NASA Astrophysics Data System (ADS)

    Dolipski, Marian; Remiorz, Eryk; Sobota, Piotr

    2012-12-01

    Scraper conveyors are one of the key machines forming part of mechanised longwall systems. They are currently the only means of transporting the mined rock from longwalls in hard coal mines. The hauling force caused by the drive is transmitted onto a link chain through drive wheels with their external shape corresponding to a geometric polygon. The number of teeth (seats) in such wheels ranges between 5 and 8. The horizontal links running on the drum are arranged in the drive wheel seats and are meshing with the teeth segments. The geometric relationships between the sprocket drum and the links are decisive for the position of the chain links in the seats. The abrasive wear of the chain parts and of the drive drum parts occurring due to conveyor operation is increasing the chain pitch and decreasing the wheel pitch. The position of a link in the seats changes as a result along with the load on the sprocket drum teeth and seats. Sprocket drums are the weakest element in longwall conveyors. It is, therefore, urgently necessary to determine the dynamic loads of such drums' teeth and seats. The article presents a physical model and a mathematical model of a longwall conveyor created for the purpose of determination of dynamic loads of the sprocket drum teeth and seats. The results of computer simulations are also presented (dynamic loads: in chains, dynamic loads of sprocket drums and dynamic loads of sprocket drums' teeth and seats) carried out using the created mathematical model for a 350 m long face conveyor.

  16. Determination of Two-Liquid Mixture Composition by Assessing Dielectric Parameters 1. Precise Measuring System / Divu Šķidrumu Maisījuma Sastāva Noteikšana, Izvērtējot to Dielektriskos Parametrus 1. Precīza Mērīšanas Sistēma

    NASA Astrophysics Data System (ADS)

    Vilitis, O.; Shipkovs, P.; Merkulovs, D.

    2013-08-01

    Concentration measurements are important in bioethanol industries, in the R&D areas, for chemical, medical and microbiological analyses and processing as well as for diagnostics, manufacturing, etc. The overview shows development of the structural design of a system for measuring the concentration of solutions and mixtures consisting of two dielectric liquids. The basic principles of the system's design are given along with relevant equations. The concentration of dielectric liquids is measured using devices with capacitive sensors (1-300 pF). The operational frequency of the developed measuring system is 100.000 kHz. Configuration of the system excludes some errors usually arising at measurements, and broadens its applicability. For testing, the system was calibrated for measuring the concentration of anhydrous ethanol + de-ionized water mixture. Experimental results have shown a stable resolution of ±0.005 pF at measuring the sensor capacitance and a reproducible resolution better than ±0.01% at measuring the ethanol volume concentration Rakstā esam parādījuši iespējas izveidot augstas precizitātes, kompaktu, lētu un ērtu lietošanai dielektrisku šķidrumu mērīšanas sistēmu koncentrācijas noteikšanai. Šī sistēma ir piemērojama kapacitīviem sensoriem, kuru kapacitāte ir atkarīga no sensora izveidojuma kā arī mērāmā šķidruma dielektriskās konstantes vērtības, un kapacitāte var tikt noteikta pie frekvences 100,000 kHz robežās no 1 F līdz 300 pF. Mērīšanas sistēmas pārbaudei, sistēma tika kalibrēta etanola koncentrācijas mērīšanai tilpuma procentos sertificēta bezūdens etanola un dejonizēta ūdens maisījumiem. Pārbaužu rezultāti pierādīja, ka sensora kapacitātes vērtības ir stabili nosakāmas ar izšķirtspēju ne mazāku par ±0,005 pF. Sensora kapacitāšu vērtībām atbilstošā etanola tilpuma koncentrācijas atkārtojamu mērījumu izšķirtspēja visā mērīšanas diapazonā nebija mazāka par ±0,01%. Šajā darbā piedāvātajā jaunajā mērīšanas sistēmas struktūras risinājumā iekļautas divas tiešas signālu digitālās sintēzes mikrosistēmas, kas ar augstu precizitāti ģenerē mērīšanai nepieciešamās formas, fāzes un amplitūdas signālus ar 100,000 kHz frekvenci un tiek vadītas no mikrokontrolera. Mērīšanas sistēmā izmantota mērsignālu sinhronizētās detektēšanas tehnika. Izstrādātās sistēmas konigurācija, mērīšanas režīma uzstādījums un vadība automātiski praktiski izslēdz virkni mērīšanas signālu parazītisko fāzes nobīžu un fāzes uzstādījumu kļūdas. Izstrādātā mērīšanas sistēma ērti piemērojama vispārējai izmantošanai kapacitātes vai impedances mērierīcēs. Samērā nelielā prognozējamā mērīšanas sistēmas pašizmaksa un kompaktā, portatīvā konstrukcija, kā arī iepriekš minētās priekšrocības paplašina sistēmas lietojumu ne tikai etanola koncentrācijas mērīanai bioetanola ražošanas procesā, bet šī sistēma var tikt izmantota arī eļļas, benzīna un citu degvielu testēšanai, ķīmiskajā, farmācijas un pārtikas industrijā, mikrobioloģijā un medicīnā, lai noteiktu glikozes, antigēnu, antivielu, proteīna, DNS fragmentu un citu vielu saturu šķīdumos u.c.

  17. Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats.

    PubMed

    Li, Guan-Wu; Xu, Zheng; Chang, Shi-Xin; Zhou, Lei; Wang, Xiao-Yan; Nian, Hua; Shi, Xiao

    2014-12-01

    Although the primary target cell of bisphosphonates is the osteoclast, increasing attention is being given to other effector cells influenced by bisphosphonates, such as osteoblasts and marrow adipocytes. Early zoledronic acid (ZA) treatment to ovariectomized (OVX) rats has been found to fully preserve bone microarchitecture over time. However, little is known regarding the influence of ZA on marrow adipogenesis. The purpose of this study was to monitor the ability of early administration of ZA in restoring marrow adiposity in an estrogen-deficient rat model. Thirty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX + vehicle, and OVX + ZA groups (n=10/group). Dual-energy x-ray absorptiometry and water/fat magnetic resonance imaging were performed at baseline, 6 weeks, and 12 weeks after treatment to assess bone mineral density and marrow fat fraction. Serum biochemical markers, bone remodeling, and marrow adipocyte parameters were analyzed using biochemistry, histomorphometry, and histopathology, respectively. The expression levels of osteoblast, adipocyte, and osteoclast-related genes in bone marrow were assessed using RT-PCR. The OVX rats showed marked bone loss, first detected at 12 weeks, but estrogen deficiency resulted in a remarked increase in marrow fat fraction, first detected at 6 weeks compared with the SHAM rats (all P < .001). Similarly, the OVX rats had a substantially larger percent adipocyte area (+163.0%), mean diameter (+29.5%), and higher density (+57.3%) relative to the SHAM rats. Bone histomorphometry, levels of osteoclast-related gene expression, and a serum resorption marker confirmed that ZA significantly suppressed bone resorption activities. Furthermore, ZA treatment returned adipocyte-related gene expression and marrow adipocyte parameters toward SHAM levels. These data suggest that a single dose of early ZA treatment acts to reverse marrow adipogenesis occurring during estrogen deficiency, which may

  18. Enhanced repellency of binary mixtures of Zanthoxylum armatum seed oil, vanillin, and their aerosols to mosquitoes under laboratory and field conditions.

    PubMed

    Kwon, Hyung Wook; Kim, Soon-Il; Chang, Kyu-Sik; Clark, J Marshall; Ahn, Young-Joon

    2011-01-01

    The repellency of Zanthoxylum armatum seed oil (ZA-SO), alone or in combination with vanillin (VA), its six major constituents, and another four major previously known Zanthoxylum piperitum fruit oil constituents, as well as aerosol products containing 5 or 10% ZA-SO and 5% VA, was evaluated against female Aedes aegypti in laboratory and field studies. Results were then compared with those of N,N-diethyl-3-methylbenzamide (DEET) as a standard. Hand in cage laboratory tests showed that 0.2, 0.1, and 0.05 mg/cm2 ZA-SO resulted in > 92% protection through 30-min postexposure and was not significantly different than 0.05 mg/cm2 DEET. Skin treated with linalool and limonene (from Z. armatum) provided > 80% repellency to female Ae. aegypti at 10-min exposure, whereas cuminaldehyde, citronellal, geranyl acetate, and cuminyl alcohol (from Zanthoxylum piperitum) provided > 90% protection during this same time period. Only cuminaldehyde and citronellal provided complete protection comparable to DEET at 10-min postexposure. After that time, repellency of all plant constituents to mosquitoes was considerably decreased (< approximately 65%). An increase in repellency and duration of effectiveness was produced by a binary 1:4 mixture of ZA-SO and VA (0.05:0.2 mg/cm2) that was significantly more effective than 0.05 mg/cm2 DEET through 90 min. In field tests, an aerosol formulation containing 5 or 10% ZA-SO plus 5% VA gave 100% repellency at 60-min postexposure. Although these formulations were equal to the level of protection afforded by 10% DEET, repellency to the binary ZA-SO aerosol formulations at 90 min was significantly less effective than DEET. However, mixtures formulated from ZA-SO and VA merit further study as potential repellents for protection of humans and domestic animals from biting and nuisance caused by mosquitoes. PMID:21337949

  19. Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing’s sarcoma via inhibition of cell migration

    PubMed Central

    2014-01-01

    Background Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties. Methods Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 106 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 μg/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology. Results ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and −9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases. Conclusion These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs. PMID:24612486

  20. Emergence of new alleles of the MSP-3alpha gene in Plasmodium vivax isolates from Korea.

    PubMed

    Nam, Deok Hwa; Oh, Jun Seo; Nam, Myoung Hyun; Park, Hae Chul; Lim, Chae Seung; Lee, Won Ja; Sattabongkot, Jetsumon; Klein, Terry A; Ayala, Francisco J

    2010-04-01

    Nucleotide sequence analysis of the Plasmodium vivax PvMSP-3alpha gene was conducted on blood from 143 malaria patients admitted to Korea University Medical Center from 1996 to 2007 in the Republic of Korea (ROK). From 1996 to 2002, the PvMSP-3alpha alleles were of two types, SKOR-67 (2.53 kb) and SKOR-69 (1.78 kb), which differed in length and amino acid sequence. Two new variants with similar size to SKOR-67 were first observed in 2002 and in 2006-2007 accounted for nearly 50% (25/51) of the sampled isolates. The new variants had the same amino acid sequence as SKOR-69 in the N-terminal region, but in Blocks I and II and in the C-terminal region, they were similar to previously reported isolates from Thailand, Papua New Guinea, India, Brazil, and Ecuador strains. PMID:20348492

  1. Ornithodoros sawaii (Ixodida: Argasidae) Larvae Collected from Hydrobates monorhis on Sogugul and Gaerin Islands, Jeollanam-do (Province), Republic of Korea

    PubMed Central

    Kim, Heung-Chul; Choi, Chang-Yong; Kwon, Young-Soo; Yun, Seok-Min; Lee, Won-Ja; Chong, Sung-Tae; Robbins, Richard G.; Klein, Terry A.

    2016-01-01

    The 65th Medical Brigade and Public Health Command District-Korea, in collaboration with the Migratory Bird Research Center, National Park Research Institute, conducted migratory bird tick surveillance at Sogugul and Gaerin Islands (small rocky bird nesting sites), Jeollanam-do (Province), Republic of Korea (ROK), on 30 July and 1 August 2009. Breeding seabirds captured by hands in their nesting burrows were banded, identified to species, and carefully examined for ticks during the nesting season. A total of 9 Ornithodoros sawaii larvae were removed from 4 adult Hydrobates monorhis (Swinhoe’s storm petrel). The identification of the larvae of O. sawaii collected from migratory seabirds were molecularly confirmed using mitochondrial 16S rDNA primer sets. PMID:27180585

  2. Detection of Hantaan virus RNA from anti-Hantaan virus IgG seronegative rodents in an area of high endemicity in Republic of Korea.

    PubMed

    No, Jin Sun; Kim, Won-Keun; Kim, Jeong-Ah; Lee, Seung-Ho; Lee, Sook-Young; Kim, Ji Hye; Kho, Jeong Hoon; Lee, Daesang; Song, Dong Hyun; Gu, Se Hun; Jeong, Seong Tae; Kim, Heung-Chul; Klein, Terry A; Song, Jin-Won

    2016-04-01

    Hantaan virus (HTNV), of the family Bunyaviridae, causes hemorrhagic fever with renal syndrome (HFRS) in humans. Although the majority of epidemiologic studies have found that rodents are seropositive for hantavirus-specific immunoglobulin, the discovery of hantavirus RNA in seronegative hosts has led to an investigation of the presence of HTNV RNA in rodents captured in HFRS endemic areas. HTNV RNA was detected in seven (3.8%) of 186 anti-HTNV IgG seronegative rodents in Republic of Korea (ROK) during 2013-2014. RT-qPCR for HTNV RNA revealed dynamic virus-host interactions of HTNV in areas of high endemicity, providing important insights into the epidemiology of hantaviruses. PMID:26917012

  3. Ornithodoros sawaii (Ixodida: Argasidae) Larvae Collected from Hydrobates monorhis on Sogugul and Gaerin Islands, Jeollanam-do (Province), Republic of Korea.

    PubMed

    Kim, Heung-Chul; Choi, Chang-Yong; Kwon, Young-Soo; Yun, Seok-Min; Lee, Won-Ja; Chong, Sung-Tae; Robbins, Richard G; Klein, Terry A

    2016-04-01

    The 65th Medical Brigade and Public Health Command District-Korea, in collaboration with the Migratory Bird Research Center, National Park Research Institute, conducted migratory bird tick surveillance at Sogugul and Gaerin Islands (small rocky bird nesting sites), Jeollanam-do (Province), Republic of Korea (ROK), on 30 July and 1 August 2009. Breeding seabirds captured by hands in their nesting burrows were banded, identified to species, and carefully examined for ticks during the nesting season. A total of 9 Ornithodoros sawaii larvae were removed from 4 adult Hydrobates monorhis (Swinhoe's storm petrel). The identification of the larvae of O. sawaii collected from migratory seabirds were molecularly confirmed using mitochondrial 16S rDNA primer sets. PMID:27180585

  4. A hexokinase with broad sugar specificity from a thermophilic bacterium.

    PubMed

    Bae, Jungdon; Kim, Dooil; Choi, Yongseok; Koh, Sukhoon; Park, Jung Eun; Su Kim, Joong; Moon, Seong Hoon; Park, Bo-Hyun; Park, Miri; Song, Hye-Eun; Hong, Suk-In; Lee, Dae-Sil

    2005-09-01

    A recombinant thermophilic Thermus caldophilus GK24 hexokinase, one of the ROK-type (repressor protein, open reading frames, and sugar kinase) proteins, exists uniquely as a 120 kDa molecule with four subunits (31 kDa), in contrast to eukaryotic and bacterial sugar kinases which are monomers or dimers. The optimal temperature and pH for the enzyme reaction are 70-80 degrees C and 7.5, respectively. This enzyme shows broad specificity toward glucose, mannose, glucosamine, allose, 2-deoxyglucose, and fructose. To understand the sugar specificity at a structural level, the enzyme-ATP/Mg2+-sugar binding complex models have been constructed. It has been shown that the sugar specificity is probably dependent on the interaction energy occurred by the positional proximity of sugars bound in the active site of the enzyme, which exhibits a tolerance to modification at C2 or C3 of glucose. PMID:16053915

  5. Myotonic dystrophy protein kinase (DMPK) and its role in the pathogenesis of myotonic dystrophy 1.

    PubMed

    Kaliman, Perla; Llagostera, Esther

    2008-11-01

    Myotonic dystrophy 1 (DM1) is an autosomal, dominant inherited, neuromuscular disorder. The DM1 mutation consists in the expansion of an unstable CTG-repeat in the 3'-untranslated region of a gene encoding DMPK (myotonic dystrophy protein kinase). Clinical expression of DM1 is variable, presenting a progressive muscular dystrophy that affects distal muscles more than proximal and is associated with the inability to relax muscles appropriately (myotonia), cataracts, cardiac arrhythmia, testicular atrophy and insulin resistance. DMPK is a Ser/Thr protein kinase homologous to the p21-activated kinases MRCK and ROCK/rho-kinase/ROK. The most abundant isoform of DMPK is an 80 kDa protein mainly expressed in smooth, skeletal and cardiac muscles. Decreased DMPK protein levels may contribute to the pathology of DM1, as revealed by gene target studies. Here we review current understanding of the structural, functional and pathophysiological characteristics of DMPK. PMID:18583094

  6. A self-organized biomechanical network drives shape changes during tissue morphogenesis.

    PubMed

    Munjal, Akankshi; Philippe, Jean-Marc; Munro, Edwin; Lecuit, Thomas

    2015-08-20

    Tissue morphogenesis is orchestrated by cell shape changes. Forces required to power these changes are generated by non-muscle myosin II (MyoII) motor proteins pulling filamentous actin (F-actin). Actomyosin networks undergo cycles of assembly and disassembly (pulses) to cause cell deformations alternating with steps of stabilization to result in irreversible shape changes. Although this ratchet-like behaviour operates in a variety of contexts, the underlying mechanisms remain unclear. Here we investigate the role of MyoII regulation through the conserved Rho1-Rok pathway during Drosophila melanogaster germband extension. This morphogenetic process is powered by cell intercalation, which involves the shrinkage of junctions in the dorsal-ventral axis (vertical junctions) followed by junction extension in the anterior-posterior axis. While polarized flows of medial-apical MyoII pulses deform vertical junctions, MyoII enrichment on these junctions (planar polarity) stabilizes them. We identify two critical properties of MyoII dynamics that underlie stability and pulsatility: exchange kinetics governed by phosphorylation-dephosphorylation cycles of the MyoII regulatory light chain; and advection due to contraction of the motors on F-actin networks. Spatial control over MyoII exchange kinetics establishes two stable regimes of high and low dissociation rates, resulting in MyoII planar polarity. Pulsatility emerges at intermediate dissociation rates, enabling convergent advection of MyoII and its upstream regulators Rho1 GTP, Rok and MyoII phosphatase. Notably, pulsatility is not an outcome of an upstream Rho1 pacemaker. Rather, it is a self-organized system that involves positive and negative biomechanical feedback between MyoII advection and dissociation rates. PMID:26214737

  7. Extracellular signal regulated kinase and GEF-H1 mediate depolarization-induced Rho activation and paracellular permeability increase

    PubMed Central

    Waheed, Faiza; Speight, Pam; Kawai, Glenn; Dan, Qinghong; Kapus, András; Szászi, Katalin

    2011-01-01

    Plasma membrane depolarization activates the Rho/Rho kinase (ROK) pathway and thereby enhances myosin light chain (MLC) phosphorylation, which in turn is thought to be a key regulator of paracellular permeability. However, the upstream mechanisms that couple depolarization to Rho activation and permeability changes are unknown. Here we show that three different depolarizing stimuli (high extracellular [K+], the lipophilic cation tetraphenylphosphonium or L-alanine, which is taken up by electrogenic Na+-cotransport) all provoke robust phosphorylation of Extracellular Signal Regulated Kinase (ERK) in LLC-PK1 and MDCK cells. Importantly, inhibition of ERK prevented the depolarization-induced activation of Rho. Searching for the underlying mechanism, we have identified GEF-H1 as the ERK-regulated critical exchange factor, responsible for the depolarization-induced Rho activation. This conclusion is based on our findings that a) depolarization activated GEF-H1, but not p115RhoGEF; b) siRNA-mediated GEF-H1 silencing eliminated the activation of the Rho pathway; c) ERK inhibition prevented the activation of GEF-H1. Moreover, we found that the Na+/K+ pump inhibitor ouabain also caused ERK, GEF-H1 and Rho activation, partially due to its depolarizing effect. Regarding functional consequences of this newly identified pathway, we found that depolarization increased paracellular permeability in LLC-PK1 and MDCK cells, and this effect was mitigated by inhibiting myosin using blebbistatin or a dominant negative (phosphorylation-incompetent) MLC. Taken together, we propose, that the ERK/GEF-H1/Rho/ROK/pMLC pathway could be a central mechanism whereby electrogenic transmembrane transport processes control myosin phosphorylation and regulate paracellular transport in the tubular epithelium. PMID:20237148

  8. Epidemiologic Aspects of Medical Retirement from the Republic of Korea Army due to Visual Impairment.

    PubMed

    Jeong, Jae Hoon; Chun, Yeoun Sook; Park, Ki Ho

    2016-04-01

    This study was done to report the epidemiologic characteristics of medical retirement from the Republic of Korea (ROK) Army due to visual impairment and to suggest a practical screening system for the draft. The medical records of 423 eyes of 301 patients who retired from the ROK Army due to visual impairment were reviewed retrospectively between January 2010 and December 2014. The patients were grouped by the presence of trauma, and each group was subdivided by military rank. We analyzed demographic and ophthalmic data, including the etiology of ophthalmologic disease. The etiology was classified into 5 anatomical categories (ocular surface, lens, retina, optic nerve and extraocular visual pathway, and extraocular muscle and orbit), which were then subdivided into the type of disease. The mean age was 24.5 years, and non-traumatic mechanisms accounted for 81.1% (343/423 eyes) of medical retirements. Visual acuity was better in patients without trauma. In enlisted soldiers, disease in the optic nerve and extraocular visual pathway was the most common anatomical category (40.5%), and primary open angle glaucoma (30.8%), retinal dystrophy (18.3%), congenital cataract (14.5%), and retinal detachment (9.7%) were the four most common diseases. Most medical retirements due to visual impairment resulted from non-traumatic mechanisms, even though patients were young. The fundus examination and visual field test would be more useful tools than a conventional vision test for large-scale draft screening for the most common two disease types: primary open angle glaucoma and retinal dystrophy. PMID:27051249

  9. Chemoprophylaxis and the epidemiological characteristics of re-emergent P. vivax malaria in the Republic of Korea.

    PubMed Central

    Kim, Changsoo; Shin, Dong Chun; Yong, Tai Soon; Oh, Dae Kyu; Kim, Rock Kwon; Park, Keeho; Suh, I. L.

    2006-01-01

    OBJECTIVE: In the Republic of Korea (ROK), soldiers stationed where there is a risk of contracting malaria have received antimalarial chemoprophylaxis since 1997. However, chemoprophylaxis may facilitate the development of drug resistance, and late primary attacks in individuals who have received chemoprophylaxis are becoming more frequent. We investigated the association between chemoprophylaxis and the epidemiological characteristics and effectiveness of treatment for re-emergent Plasmodium vivax malaria, using a nationwide malaria database. METHODS: Among soldiers at risk of malaria between 1999 and 2001, we reviewed all P. vivax malaria cases (1158) that occurred before 31 December 2003. Early and late primary attacks were defined as cases occurring 2 months after the last day of exposure to risk of malaria, respectively. FINDINGS: Of these cases, 634 (72.0%) had received chemoprophylaxis, and 324 (28.0%) had not. Cases occurred mostly in summer, with a peak in July-August. Stratification by chemoprophylaxis history revealed different times to onset. Early primary attacks were more prevalent in the group not receiving chemoprophylaxis, while in the group receiving chemoprophylaxis most cases were late primary attacks. Of the latter, 312 out of 461 (67.7%) did not take primaquine regularly. After treatment of the first attack, 14 (1.2%) of 1158 were re-treated; all re-treated cases were cured using the same doses and regimen used for the first treatment. CONCLUSION: In ROK, the increase in late primary episodes of re-emergent P. vivax malaria is associated with the use of antimalarial chemoprophylaxis. PMID:17128363

  10. Structure-Function Studies of the Staphylococcal Methicillin Resistance Antirepressor MecR2*

    PubMed Central

    Arêde, Pedro; Botelho, Tiago; Guevara, Tibisay; Usón, Isabel; Oliveira, Duarte C.; Gomis-Rüth, F. Xavier

    2013-01-01

    Methicillin resistance in Staphylococcus aureus is elicited by the MecI-MecR1-MecA axis encoded by the mec locus. Recently, MecR2 was also identified as a regulator of mec through binding of the methicillin repressor, MecI. Here we show that plasmid-encoded full-length MecR2 restores resistance in a sensitive S. aureus mecR2 deletion mutant of the resistant strain N315. The crystal structure of MecR2 reveals an N-terminal DNA-binding domain, an intermediate scaffold domain, and a C-terminal dimerization domain that contributes to oligomerization. The protein shows structural similarity to ROK (repressors, open reading frames, and kinases) family proteins, which bind DNA and/or sugar molecules. We found that functional cell-based assays of three point mutants affecting residues participating in sugar binding in ROK proteins had no effect on the resistance phenotype. By contrast, MecR2 bound short double-stranded DNA oligonucleotides nonspecifically, and a deletion mutant affecting the N-terminal DNA-binding domain showed a certain effect on activity, thus contributing to resistance less than the wild-type protein. Similarly, a deletion mutant, in which a flexible segment of intermediate scaffold domain had been replaced by four glycines, significantly reduced MecR2 function, thus indicating that this domain may likewise be required for activity. Taken together, these results provide the structural basis for the activity of a methicillin antirepressor, MecR2, which would sequester MecI away from its cognate promoter region and facilitate its degradation. PMID:23733184

  11. Epidemiologic Aspects of Medical Retirement from the Republic of Korea Army due to Visual Impairment

    PubMed Central

    2016-01-01

    This study was done to report the epidemiologic characteristics of medical retirement from the Republic of Korea (ROK) Army due to visual impairment and to suggest a practical screening system for the draft. The medical records of 423 eyes of 301 patients who retired from the ROK Army due to visual impairment were reviewed retrospectively between January 2010 and December 2014. The patients were grouped by the presence of trauma, and each group was subdivided by military rank. We analyzed demographic and ophthalmic data, including the etiology of ophthalmologic disease. The etiology was classified into 5 anatomical categories (ocular surface, lens, retina, optic nerve and extraocular visual pathway, and extraocular muscle and orbit), which were then subdivided into the type of disease. The mean age was 24.5 years, and non-traumatic mechanisms accounted for 81.1% (343/423 eyes) of medical retirements. Visual acuity was better in patients without trauma. In enlisted soldiers, disease in the optic nerve and extraocular visual pathway was the most common anatomical category (40.5%), and primary open angle glaucoma (30.8%), retinal dystrophy (18.3%), congenital cataract (14.5%), and retinal detachment (9.7%) were the four most common diseases. Most medical retirements due to visual impairment resulted from non-traumatic mechanisms, even though patients were young. The fundus examination and visual field test would be more useful tools than a conventional vision test for large-scale draft screening for the most common two disease types: primary open angle glaucoma and retinal dystrophy. PMID:27051249

  12. Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton.

    PubMed

    Ly, Donald L; Waheed, Faiza; Lodyga, Monika; Speight, Pam; Masszi, András; Nakano, Hiroyasu; Hersom, Maria; Pedersen, Stine F; Szászi, Katalin; Kapus, András

    2013-01-15

    Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF translocation, since siRNA-mediated GEF-H1 downregulation suppresses these responses. While the osmotically induced RhoA activation promotes nuclear MRTF accumulation, the concomitant activation of p38 MAP kinase mitigates this effect. Moderate hyperosmotic stress (600 mosM) drives MRTF-dependent transcription through the cis-element CArG box. Silencing or pharmacological inhibition of MRTF prevents the osmotic stimulation of CArG-dependent transcription and renders the cells susceptible to osmotic shock-induced structural damage. Interestingly, strong hyperosmolarity promotes proteasomal degradation of MRTF, concomitant with apoptosis. Thus, MRTF is an osmosensitive and osmoprotective transcription factor, whose intracellular distribution is regulated by the GEF-H1/RhoA/ROK and p38 pathways. However, strong osmotic stress destabilizes MRTF, concomitant with apoptosis, implying that hyperosmotically induced cell death takes precedence over epithelial-myofibroblast transition, a potential consequence of MRTF-mediated phenotypic reprogramming. PMID:23054059

  13. The development of loop-mediated isothermal amplification targeting alpha-tubulin DNA for the rapid detection of Plasmodium vivax

    PubMed Central

    2014-01-01

    Background Malaria that is caused by Plasmodium vivax is the most widely distributed human malaria. Its recent resurgence in many parts of the world, including the Republic of Korea (ROK), emphasizes the importance of improved access to the early and accurate detection of P. vivax to reduce disease burden. In this study, a rapid and efficient loop-mediated isothermal amplification (LAMP)-based method was developed and validated using blood samples from malaria-suspected patients. Method A LAMP assay targeting the α-tubulin gene for the detection of P. vivax was developed with six primers that recognize different regions of the target gene. The diagnostic performance of the α-tubulin LAMP assay was compared to three other tests: microscopic examinations, rapid diagnostic tests (RDTs), and nested polymerase chain reactions (PCRs) using 177 whole blood specimens obtained from ROK military personnel from May to December 2011. Results The α-tubulin LAMP assay was highly sensitive with a detection limit of 100 copies of P. vivax α-tubulin gene per reaction within 50 min. It specifically amplified the target gene only from P. vivax. Validation of the α-tubulin LAMP assay showed that the assay had the highest sensitivity (P < 0.001 versus microscopy; P = 0.0023 versus RDT) when nested PCR was used as the gold standard and better agreement (concordance: 94.9%, kappa value: 0.865) with nested PCR than RDT and microscopy. A Receiver Operation Characteristics analysis showed that the diagnostic accuracy of the α-tubulin LAMP assay for vivax malaria was higher (Area Under Curve = 0.908) than RDT and microscopy. Conclusion This study showed that the P. vivax α-tubulin LAMP assay, which can be used to diagnose early infections of vivax malaria, is an alternative molecular diagnostic tool and a point-of-care test that may help to prevent transmission in endemic areas. PMID:24981710

  14. Syndromic Surveillance System for Korea-US Joint Biosurveillance Portal: Design and Lessons Learned.

    PubMed

    Rhee, Chulwoo; Burkom, Howard; Yoon, Chang-Gyo; Stewart, Miles; Elbert, Yevgeniy; Katz, Aaron; Tak, Sangwoo

    2016-01-01

    Driven by the growing importance of situational awareness of bioterrorism threats, the Republic of Korea (ROK) and the United States have constructed a joint military capability, called the Biosurveillance Portal (BSP), to enhance biosecurity. As one component of the BSP, we developed the Military Active Real-time Syndromic Surveillance (MARSS) system to detect and track natural and deliberate disease outbreaks. This article describes the ROK military health data infrastructure and explains how syndromic data are derived and made available to epidemiologists. Queries corresponding to 8 syndromes, based on published clinical effects of weaponized pathogens, were used to classify military hospital patient records to form aggregated daily syndromic counts. A set of ICD-10 codes for each syndrome was defined through literature review and expert panel discussion. A study set of time series of national daily counts for each syndrome was extracted from the Defense Medical Statistical Information System between January 1, 2011, and May 31, 2014. A stratified, adjusted cumulative summation algorithm was implemented for each syndrome group to signal alerts prompting investigation. The algorithm was developed by calculating sensitivity to sets of 1,000 artificial outbreak signals randomly injected in the dataset, with each signal injected in a separate trial. Queries and visualizations were adapted from the Suite for Automated Global bioSurveillance. Findings indicated that early warning of outbreaks affecting fewer than 50 patients will require analysis at subnational levels, especially for common syndrome groups. Developing MARSS to improve sensitivity will require modification of underlying syndromic diagnosis codes, engineering to coordinate alerts among subdivisions, and enhanced algorithms. The bioterrorist threat in the Korean peninsula mandates these efforts. PMID:27314655

  15. Detection of Severe Fever with Thrombocytopenia Syndrome Virus from Wild Animals and Ixodidae Ticks in the Republic of Korea.

    PubMed

    Oh, Sung-Suck; Chae, Jeong-Byoung; Kang, Jun-Gu; Kim, Heung-Chul; Chong, Sung-Tae; Shin, Jeong-Hwa; Hur, Moon-Suk; Suh, Jae-Hwa; Oh, Myoung-Don; Jeong, Soo-Myoung; Shin, Nam-Shik; Choi, Kyoung-Seong; Chae, Joon-Seok

    2016-06-01

    Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic to central-northeastern China, southern Japan, and the Republic of Korea (ROK). To investigate SFTSV infections, we collected serum samples and ticks from wild animals. Using serum samples and ticks, SFTSV-specific genes were amplified by one-step RT-PCR and nested PCR and sequenced. Indirect immunofluorescence assay (IFA) was performed to analyze virus-specific antibody levels in wild animals. Serum samples were collected from a total of 91 animals: 21 Korean water deer (KWD), 3 Siberian roe deer, 5 gorals, 7 raccoon dogs, 54 wild boars (WBs), and 1 carrion crow. The SFTSV infection rate in wild animals was 3.30% (3 of 91 animals: 1 KWD and 2 WBs). The seropositive rate was 6.59% (6 of 91 animals: 5 KWD and 1 WB). A total of 891 ticks (3 species) were collected from 65 wild animals (9 species). Of the attached tick species, Haemaphysalis longicornis (74.86%) was the most abundant, followed by Haemaphysalis flava (20.20%) and Ixodes nipponensis (4.94%). The average minimum infection rate (MIR) of SFTSV in ticks was 4.98%. The MIRs of H. longicornis, H. flava, and I. nipponensis were 4.51%, 2.22%, and 22.73%, respectively. The MIRs of larvae, nymphs, and adult ticks were 0.68%, 6.88%, and 5.53%, respectively. In addition, the MIRs of fed and unfed ticks were 4.67% and 4.96%, respectively. We detected a low SFTSV infection rate in wild animals, no differences in SFTSV infection rate with respect to bloodsucking in ticks, and SFTSV infection for all developmental stages of ticks. This is the first report describing the detection of SFTSV in wild animals in the ROK. PMID:27043361

  16. Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

    PubMed Central

    Ly, Donald L.; Waheed, Faiza; Lodyga, Monika; Speight, Pam; Masszi, András; Nakano, Hiroyasu; Hersom, Maria; Pedersen, Stine F.; Szászi, Katalin

    2013-01-01

    Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF translocation, since siRNA-mediated GEF-H1 downregulation suppresses these responses. While the osmotically induced RhoA activation promotes nuclear MRTF accumulation, the concomitant activation of p38 MAP kinase mitigates this effect. Moderate hyperosmotic stress (600 mosM) drives MRTF-dependent transcription through the cis-element CArG box. Silencing or pharmacological inhibition of MRTF prevents the osmotic stimulation of CArG-dependent transcription and renders the cells susceptible to osmotic shock-induced structural damage. Interestingly, strong hyperosmolarity promotes proteasomal degradation of MRTF, concomitant with apoptosis. Thus, MRTF is an osmosensitive and osmoprotective transcription factor, whose intracellular distribution is regulated by the GEF-H1/RhoA/ROK and p38 pathways. However, strong osmotic stress destabilizes MRTF, concomitant with apoptosis, implying that hyperosmotically induced cell death takes precedence over epithelial-myofibroblast transition, a potential consequence of MRTF-mediated phenotypic reprogramming. PMID:23054059

  17. Avian survey and field guide for Osan Air Base, Korea.

    SciTech Connect

    Levenson, J.

    2006-12-05

    This report summarizes the results of the avian surveys conducted at Osan Air Base (AB). This ongoing survey is conducted to comply with requirements of the Environmental Governing Standards (EGS) for the Republic of Korea, the Integrated Natural Resources Management Plan (INRMP) for Osan AB, and the 51st Fighter Wing's Bird Aircraft Strike Hazard (BASH) Plan. One hundred ten bird species representing 35 families were identified and recorded. Seven species are designated as Natural Monuments, and their protection is accorded by the Korean Ministry of Culture and Tourism. Three species appear on the Korean Association for Conservation of Nature's (KACN's) list of Reserved Wild Species and are protected by the Korean Ministry of Environment. Combined, ten different species are Republic of Korea (ROK)-protected. The primary objective of the avian survey at Osan AB was to determine what species of birds are present on the airfield and their respective habitat requirements during the critical seasons of the year. This requirement is specified in Annex J.14.c of the 51st Fighter BASH Plan 91-212 (51 FW OPLAN 91-212). The second objective was to initiate surveys to determine what bird species are present on Osan AB throughout the year and from the survey results, determine if threatened, endangered, or other Korean-listed bird species are present on Osan AB. This overall census satisfies Criterion 13-3.e of the EGS for Korea. The final objective was to formulate management strategies within Osan AB's operational requirements to protect and enhance habitats of known threatened, endangered, and ROK-protected species in accordance with EGS Criterion 13-3.a that are also favorable for the reproduction of indigenous species in accordance with the EGS Criterion 13-3.h.

  18. Avian Field guide and checklist for Kunsan Air Base, Korea.

    SciTech Connect

    Levenson, J. B.; Environmental Assessment

    2005-11-15

    This report summarizes the results of the avian surveys conducted at Kunsan Air Base (AB). This on-going survey is conducted to comply with requirements of the Environmental Governing Standards (EGS) for the Republic of Korea, the Integrated Natural Resources Management Plan (INRMP) for Kunsan AB, and the 8th Fighter Wing's Bird Aircraft Strike Hazard (BASH) Plan. One hundred sixteen bird species representing 34 families were identified and recorded. Seven species are designated as Cultural Property Monuments, and their protection is accorded by the Korean Ministry of Culture and Tourism. Six species appear on the Korean Association for Conservation of Nature's(KACN's) list of Reserved Wild Species and are protected by the Korean Ministry of Environment. Combined, only ten different species are Republic of Korea (ROK)-protected because the Eurasian Spoonbill, Peregrine Falcon, and Eurasian Oystercatcher are listed by both agencies. The primary objective of the avian survey at Kunsan AB was to determine what species of birds are present on the airfield and their respective habitat requirements during the critical seasons of the year. This requirement is specified in Annex C.4.a.(1-4) of the 8th Fighter Wing BASH Plan(8FWOPLAN 91-202). The second objective was to initiate surveys to determine what bird species are present on Kunsan AB throughout the year, and from the survey results determine if threatened, endangered, or other Korean-listed bird species are present on Kunsan AB. This overall census satisfies Criterion 13-3.e of the EGS for Korea. The final objective was to formulate management strategies within Kunsan AB's operational requirements to protect and enhance habitats of known threatened, endangered, and ROK-protected species in accordance with EGS Criterion 13-3.a and also that are favorable for the reproduction of indigenous species in accordance with the EGS Criterion 13-3.h.

  19. OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice

    PubMed Central

    de Molon, Rafael Scaf; Shimamoto, Hiroaki; Bezouglaia, Olga; Pirih, Flavia Q; Dry, Sarah M; Kostenuik, Paul; Boyce, Rogely W; Dwyer, Denise; Aghaloo, Tara L; Tetradis, Sotirios

    2016-01-01

    Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by µCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a “drug holiday” in managing the ONJ patient. PMID:25727550

  20. Unravelling the Structural and Molecular Basis Responsible for the Anti-Biofilm Activity of Zosteric Acid

    PubMed Central

    Cattò, Cristina; Dell’Orto, Silvia; Villa, Federica; Villa, Stefania; Gelain, Arianna; Vitali, Alberto; Marzano, Valeria; Baroni, Sara; Forlani, Fabio; Cappitelli, Francesca

    2015-01-01

    The natural compound zosteric acid, or p-(sulfoxy)cinnamic acid (ZA), is proposed as an alternative biocide-free agent suitable for preventive or integrative anti-biofilm approaches. Despite its potential, the lack of information concerning the structural and molecular mechanism of action involved in its anti-biofilm activity has limited efforts to generate more potent anti-biofilm strategies. In this study a 43-member library of small molecules based on ZA scaffold diversity was designed and screened against Escherichia coli to understand the structural requirements necessary for biofilm inhibition at sub-lethal concentrations. Considerations concerning the relationship between structure and anti-biofilm activity revealed that i) the para-sulfoxy ester group is not needed to exploit the anti-biofilm activity of the molecule, it is the cinnamic acid scaffold that is responsible for anti-biofilm performance; ii) the anti-biofilm activity of ZA derivatives depends on the presence of a carboxylate anion and, consequently, on its hydrogen-donating ability; iii) the conjugated aromatic system is instrumental to the anti-biofilm activities of ZA and its analogues. Using a protein pull-down approach, combined with mass spectrometry, the herein-defined active structure of ZA was matrix-immobilized, and was proved to interact with the E. coli NADH:quinone reductase, WrbA, suggesting a possible role of this protein in the biofilm formation process. PMID:26132116

  1. Zoledronic acid in vivo increases in vitro proliferation of rat mesenchymal stromal cells.

    PubMed

    Heino, Terhi J; Alm, Jessica J; Halkosaari, Heikki J; Välimäki, Ville-Valtteri

    2016-08-01

    Background and purpose - Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods - A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro-computed tomography (μCT), and histology. Results - Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA-treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation - Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms. PMID:27196705

  2. OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice.

    PubMed

    de Molon, Rafael Scaf; Shimamoto, Hiroaki; Bezouglaia, Olga; Pirih, Flavia Q; Dry, Sarah M; Kostenuik, Paul; Boyce, Rogely W; Dwyer, Denise; Aghaloo, Tara L; Tetradis, Sotirios

    2015-09-01

    Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by μCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a "drug holiday" in managing the ONJ patient. PMID:25727550

  3. Transverse zones controlling the structural evolution of the Zipaquira Anticline (Eastern Cordillera, Colombia): Regional implications

    NASA Astrophysics Data System (ADS)

    García, Helbert; Jiménez, Giovanny

    2016-08-01

    We report paleomagnetic, magnetic fabric and structural results from 21 sites collected in Cretaceous marine mudstones and Paleogene continental sandstones from the limbs, hinge and transverse zones of the Zipaquira Anticline (ZA). The ZA is an asymmetrical fold with one limb completely overturned by processes like gravity and salt tectonics, and marked by several axis curvatures. The ZA is controlled by at least two (2) transverse zones known as the Neusa and Zipaquira Transverse Zones (NTZ and ZTZ, respectively). Magnetic mineralogy methods were applied at different sites and the main carriers of the magnetic properties are paramagnetic components with some sites being controlled by hematite and magnetite. Magnetic fabric analysis shows rigid-body rotation for the back-limb in the ZA, while the forelimb is subjected to internal deformation. Structural and paleomagnetic data shows the influence of the NTZ and ZTZ in the evolution of the different structures like the ZA and the Zipaquira, Carupa, Rio Guandoque, Las Margaritas and Neusa faults, controlling several factors as vergence, extension, fold axis curvature and stratigraphic detatchment. Clockwise rotations unraveled a block segmentation following a discontinuos model caused by transverse zones and one site reported a counter clockwise rotation associated with a left-lateral strike slip component for transverse faults (e.g. the Neusa Fault). We propose that diverse transverse zones have been active since Paleogene times, playing an important role in the tectonic evolution of the Cundinamarca sub-basin and controlling the structural evolution of folds and faults with block segmentation and rotations.

  4. Zoledronic Acid–Induced Interface Dermatitis

    PubMed Central

    Succaria, Farah; Collier, Mary

    2015-01-01

    Abstract: Zoledronic acid (ZA) is a bisphosphonate given intravenously, most commonly for the treatment of postmenopausal osteoporosis. Increase in usage of ZA because it was FDA-approved has resulted in increasing reports of side effects. For the most part, these are systemic. Cutaneous side effects associated with ZA are infrequent and limited to 2 reports of dermatomyositis to date. In both, patients presented with clinical and laboratory stigmata of dermatomyositis soon after initiation of therapy. In this report, we describe a 62-year-old woman who presented with diffuse, erythematous scaly plaques over the right thigh after 12 hours of infusion of ZA. Histopathologic examination of a skin biopsy from the right thigh revealed patchy scale crust containing neutrophils and inspissated serum, interface change with scattered individually necrotic keratinocytes, and a mild, superficial perivascular lymphocytic infiltrate with scattered eosinophils and pigment incontinence—findings consistent with an interface dermatitis. Given that the patient had no other systemic manifestations or laboratory abnormalities, to the best of our knowledge, ours is the first report of interface dermatitis secondary to ZA with the caveat that longer follow-up is required to definitively exclude the development of drug-induced connective tissue disease. PMID:26588338

  5. Zoledronic Acid-Induced Interface Dermatitis.

    PubMed

    Succaria, Farah; Collier, Mary; Mahalingam, Meera

    2015-12-01

    Zoledronic acid (ZA) is a bisphosphonate given intravenously, most commonly for the treatment of postmenopausal osteoporosis. Increase in usage of ZA because it was FDA-approved has resulted in increasing reports of side effects. For the most part, these are systemic. Cutaneous side effects associated with ZA are infrequent and limited to 2 reports of dermatomyositis to date. In both, patients presented with clinical and laboratory stigmata of dermatomyositis soon after initiation of therapy. In this report, we describe a 62-year-old woman who presented with diffuse, erythematous scaly plaques over the right thigh after 12 hours of infusion of ZA. Histopathologic examination of a skin biopsy from the right thigh revealed patchy scale crust containing neutrophils and inspissated serum, interface change with scattered individually necrotic keratinocytes, and a mild, superficial perivascular lymphocytic infiltrate with scattered eosinophils and pigment incontinence-findings consistent with an interface dermatitis. Given that the patient had no other systemic manifestations or laboratory abnormalities, to the best of our knowledge, ours is the first report of interface dermatitis secondary to ZA with the caveat that longer follow-up is required to definitively exclude the development of drug-induced connective tissue disease. PMID:26588338

  6. Evaluation of Acute and Chronic Toxicities of the Water Extract from Ziziphus attopensis Pierre

    PubMed Central

    Sireeratawong, Seewaboon; Vannasiri, Supaporn; Nanna, Urarat; Singhalak, Tipaya; Jaijoy, Kanjana

    2012-01-01

    We studied an acute and chronic oral toxicity of the extract from Ziziphus attopensis (ZA) in male and female SD rats according to the OECD guidelines. After a single oral administration of ZA 5 g/kg body weight, measurement of the body and organs, necropsy, and health monitoring were performed. The body and organ weights and behavior were not changed relative to the control rats indicating that ZA does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with ZA at the doses of 1, 2, 4, and 8 g/kg body weight for 180 days. Body weight changes, hematological and biochemical parameters, organ weights, gross finding, and histopathology examination were monitored during the experimental period. The results did not show any differences from the control groups. Analyses of these results with the information of signs, behavior, and health monitoring can lead to a conclusion that the long-term oral administration of ZA for 180 days does not cause chronic toxicity. PMID:22474597

  7. Binding Modes of Zaragozic Acid A to Human Squalene Synthase and Staphylococcal Dehydrosqualene Synthase*

    PubMed Central

    Liu, Chia-I; Jeng, Wen-Yih; Chang, Wei-Jung; Ko, Tzu-Ping; Wang, Andrew H.-J.

    2012-01-01

    Zaragozic acids (ZAs) belong to a family of fungal metabolites with nanomolar inhibitory activity toward squalene synthase (SQS). The enzyme catalyzes the committed step of sterol synthesis and has attracted attention as a potential target for antilipogenic and antiinfective therapies. Here, we have determined the structure of ZA-A complexed with human SQS. ZA-A binding induces a local conformational change in the substrate binding site, and its C-6 acyl group also extends over to the cofactor binding cavity. In addition, ZA-A effectively inhibits a homologous bacterial enzyme, dehydrosqualene synthase (CrtM), which synthesizes the precursor of staphyloxanthin in Staphylococcus aureus to cope with oxidative stress. Size reduction at Tyr248 in CrtM further increases the ZA-A binding affinity, and it reveals a similar overall inhibitor binding mode to that of human SQS/ZA-A except for the C-6 acyl group. These structures pave the way for further improving selectivity and development of a new generation of anticholesterolemic and antimicrobial inhibitors. PMID:22474324

  8. Binding modes of zaragozic acid A to human squalene synthase and staphylococcal dehydrosqualene synthase.

    PubMed

    Liu, Chia-I; Jeng, Wen-Yih; Chang, Wei-Jung; Ko, Tzu-Ping; Wang, Andrew H-J

    2012-05-25

    Zaragozic acids (ZAs) belong to a family of fungal metabolites with nanomolar inhibitory activity toward squalene synthase (SQS). The enzyme catalyzes the committed step of sterol synthesis and has attracted attention as a potential target for antilipogenic and antiinfective therapies. Here, we have determined the structure of ZA-A complexed with human SQS. ZA-A binding induces a local conformational change in the substrate binding site, and its C-6 acyl group also extends over to the cofactor binding cavity. In addition, ZA-A effectively inhibits a homologous bacterial enzyme, dehydrosqualene synthase (CrtM), which synthesizes the precursor of staphyloxanthin in Staphylococcus aureus to cope with oxidative stress. Size reduction at Tyr(248) in CrtM further increases the ZA-A binding affinity, and it reveals a similar overall inhibitor binding mode to that of human SQS/ZA-A except for the C-6 acyl group. These structures pave the way for further improving selectivity and development of a new generation of anticholesterolemic and antimicrobial inhibitors. PMID:22474324

  9. Impact of Actinomyces naeslundii on bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats with periodontitis.

    PubMed

    Li, Chun Lei; Seneviratne, Chaminda Jayampath; Huo, Lei; Lu, Weijia William; Zheng, Li Wu

    2015-10-01

    Bisphosphonates-related osteonecrosis of the jaws (BRONJ) is a severe complication of BPs therapy with unknown pathogenesis. This study aimed to evaluate the impact of Actinomyces naeslundii (A. naeslundii) on the progression of BRONJ in ovariectomized (OVX) rat model with periodontal diseases. Sixty rats were randomly assigned into four groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, animals with periodontitis induced by ligature placement were administrated with normal saline (NS), NS &A. naeslundii inoculation, zolecdronic acid (ZA) and ZA &A. naeslundii inoculation for 12 weeks, respectively. Loads of total bacteria and A. naeslundii in the mouth were assessed by real time PCR. After sacrifice, the mandibles were harvested for micro-computed tomography (micro-CT) and histological examination. Real-time PCR demonstrated that A. naeslundii was not routinely found in the rats and ZA treatment did not promote its accumulation. Micro-CT examination disclosed that ligature placement induced significant alveolar bone loss, which was greatly attenuated by ZA treatment and aggravated by A. naeslundii. Histological assessment demonstrated that ZA treatment increased the risk of developing BRONJ-like disease but this condition was not worsen with the presence of A. naeslundii. Our study suggested that oral A. naeslundii inoculation aggravated periodontal disease but not BRONJ in our animal model. PMID:26293192

  10. Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering.

    PubMed

    Cheng, Tegan L; Murphy, Ciara M; Ravarian, Roya; Dehghani, Fariba; Little, David G; Schindeler, Aaron

    2015-01-01

    Sucrose acetate isobutyrate (SAIB) is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and found synergy when co-delivering zoledronic acid (ZA) and hydroxyapatite (HA) nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP) nor Bioglass (BG) 45S5 had a significant effect on bone volume (BV) alone or in combination with the ZA. (14)C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%), and BV was further increased with ZA-adsorbed micro-HA and nano-HA (+530% and +889%). These data support the use of ZA-adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering. PMID:26668709

  11. The anti-tumour effects of zoledronic acid

    PubMed Central

    Zekri, Jamal; Mansour, Maged; Karim, Syed Mustafa

    2014-01-01

    Bone is the most common site for metastasis in patients with solid tumours. Bisphosphonates are an effective treatment for preventing skeletal related events and preserving quality of life in these patients. Zoledronic acid (ZA) is the most potent osteoclast inhibitor and is licensed for the treatment of bone metastases. Clodronate and pamidronate are also licensed for this indication. In addition, ZA has been demonstrated to exhibit antitumour effect. Direct and indirect mechanisms of anti-tumour effect have been postulated and at many times proven. Evidence exists that ZA antitumour effect is mediated through inhibition of tumour cells proliferation, induction of apoptosis, synergistic/additive to inhibitory effect of cytotoxic agents, inhibition of angiogenesis, decrease tumour cells adhesion to bone, decrease tumour cells invasion and migration, disorganization of cell cytoskeleton and activation of specific cellular antitumour immune response. There is also clinical evidence from clinical trials that ZA improved long term survival outcome in cancer patients with and without bone metastases. In this review we highlight the preclinical and clinical studies investigating the antitumour effect of bisphosphonates with particular reference to ZA. PMID:26909294

  12. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.

    PubMed Central

    James, Nicholas; Pirrie, Sarah; Pope, Ann; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; McLaren, Duncan; O'Sullivan, Joe; Parker, Chris; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Russell, Martin; Billingham, Lucinda

    2016-01-01

    BACKGROUND: Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. METHODS: Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. RESULTS: PATIENTS: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression

  13. Seismic analyses of equipment in 2736-Z complex. Revision 1

    SciTech Connect

    Ocoma, E.C.

    1995-04-01

    This report documents the structural qualification for the existing equipment when subjected to seismic loading in the Plutonium Storage Complex. It replaces in entirety Revision 0 and reconciles the U.S. Department of Energy (DOE) comments on Revision 0. The Complex consists of 2736-Z Building (plutonium storage vault), 2736-ZA Building (vault ventilation equipment building), and 2736-ZB Building (shipping/receiving, repackaging activities). The existing equipment structurally qualified in this report are the metal storage racks for 7 inch and lard cans in room 2 of Building 2736-Z; the cubicles, can holders and pedestals in rooms 1, 3, and 4 of Building 2736-Z; the ventilation duct including exhaust fans/motors, emergency diesel generator, and HEPA filter housing in Building 2736-ZA; the repackaging glovebox in Building 2736-ZB; and the interface duct between Buildings 2736-Z and 2736-ZA.

  14. Inhibition of squalene synthase upregulates PCSK9 expression in rat liver.

    PubMed

    Bedi, Mohini; Niesen, Melissa; Lopez, Dayami

    2008-02-15

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol metabolism by enhancing the degradation of the LDL receptor protein in the liver. It has previously been shown that administration of zaragozic acid A (ZA), a potent inhibitor of squalene synthase, also significantly increases the rate of degradation of hepatic LDL receptor protein. Thus, we decided to determine whether ZA administration might act to up regulate hepatic expression of the rat PCSK9 gene. Administration of ZA resulted in increased PCSK9 mRNA and protein levels in rat liver surprisingly in concert with an increase in hepatic LDL receptor mRNA levels, LDL receptor protein turnover, and decreased serum cholesterol levels. These observations suggest an involvement of PCSK9 in hepatic LDL receptor protein degradation and perhaps, in increasing the rate of LDL receptor cycling resulting in lower serum cholesterol levels in response to cholesterol biosynthesis inhibitors. PMID:18054775

  15. Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease.

    PubMed

    Soundia, Akrivoula; Hadaya, Danny; Esfandi, Navid; de Molon, Rafael Scaf; Bezouglaia, Olga; Dry, Sarah M; Pirih, Flavia Q; Aghaloo, Tara; Tetradis, Sotirios

    2016-09-01

    Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and in vivo micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but

  16. Biocomposite macroporous cryogels as potential carrier scaffolds for bone active agents augmenting bone regeneration.

    PubMed

    Raina, Deepak Bushan; Isaksson, Hanna; Teotia, Arun Kumar; Lidgren, Lars; Tägil, Magnus; Kumar, Ashok

    2016-08-10

    Osteoinduction can be enhanced by combining scaffolds with bone morphogenic protein-2 (BMP-2). However, BMP's are known to also cause bone resorption. This can be controlled using bisphosphonates like zoledronic acid (ZA). In this study, we produced two different scaffolds containing silk-fibroin, chitosan, agarose and hydroxyapatite (HA) with and without bioactive glass. The aims of the study were to fabricate, physico-chemically characterize and evaluate the carrier properties of the scaffolds for recombinant human BMP-2 (rhBMP-2) and ZA. Scaffolds were characterized using various methods to confirm their composition. During cell-material interactions, both scaffolds exhibited gradual but sustained proliferation of both C2C12 and MSCs for a period of 6weeks with augmentative effects on their phenotype indicated by elevated levels of alkaline phosphatase (ALP) cuing towards osteogenic differentiation. In-vitro effects of rhBMP-2 and ZA contained within both the scaffolds was assessed on MC3T3 preosteoblast cells and the results show a significant increase in the ALP activity of the cells seeded on scaffolds with rhBMP-2. Further, the scaffold with both HA and bioactive glass was considered for the animal study. In-vitro, this scaffold released nearly 25% rhBMP-2 in 21-days and the addition of ZA did not affect the release. In the animal study, the scaffolds were combined with rhBMP-2 and ZA, rhBMP-2 or implanted alone in an ectopic muscle pouch model. Significantly higher bone formation was observed in the scaffold loaded with both rhBMP-2 and ZA as seen from micro-computed tomography, histomorphometry and energy dispersive X-ray spectroscopy. PMID:27252151

  17. Effect of surfactants on the emission properties of ZnO: Mn3O4 nanocomposites

    NASA Astrophysics Data System (ADS)

    Senthilkumar, P.; Rajeswari, P.; Dhanuskodi, S.

    2015-02-01

    Nanocomposite of metal oxide semiconductors are multifunctional and one such nanocomposite ZnO/ Mn3O4 (2:1) was synthesized ZMA4 (ZnO: Mn3O4 using ammonia), ZMH4 (ZnO: Mn3O4 using hexamine) by the coprecipitation route. In addition pure ZnO was prepared using ammonia (ZA) and hexamine (ZH). XRD reveals the crystal structure of ZnO/Mn3O4 and the average crystallite size is estimated as 43, 12, 42 and 18 nm for ZA, ZMA4, ZH and ZMH4 respectively. FTIR bands at 440-490 and 616-621cm-1 are due to Zn-O and Mn-O vibrational bands. Presence of manganese in nanocomposites is confirmed by EDS. SEM micrographs indicate the formation of nanoparticles (ZA and ZMA4) and nanorods (ZH-98 nm length, 63 nm dia). Excitonic absorption peaks at 370 and 290 nm in the UV-Vis spectra are attributed to ZnO/Mn3O4 nanocomposite. The bandgap is estimated as 2.7, 2.3, 2.6 and 3.0 eV for ZA, ZMA4, ZH and ZMH4 respectively. FL spectra of ZA, ZMA4 expose the emission at 366 and 396 nm owing to the near band edge (NBE) and zinc interstitial at 468 nm. ZH nanorods show the emission at 386, 468 and 558 nm which are attributed to NBE, zinc interstitial and oxygen vacancy respectively. The reduction of oxygen vacancy is observed in ZMH4 as manganese effectively changes the morphology from nanorod to nanoparticle. The second harmonic generation efficiency measured for ZA and ZH is 0.6 and 0.9 times KDP using Q - switched Nd: YAG laser (1064nm, 10 Hz, 9 ns).

  18. A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

    PubMed Central

    Kenney, Jessica; Rodríguez, Aixa; Kizima, Larisa; Seidor, Samantha; Menon, Radhika; Jean-Pierre, Ninochka; Pugach, Pavel; Levendosky, Keith; Derby, Nina; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Paglini, Gabriela; Zydowsky, Thomas M.; Robbiani, Melissa

    2013-01-01

    We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2. PMID:23752515

  19. [Excess of thiocyanate and selenium deficiency: cofactors in the etiology of endemic goiter and cretinism in North Zaire].

    PubMed

    Thilly, C H; Contempre, B; Vanderpas, J B

    1990-01-01

    Endemic goitre is accompanied by a spectrum of iodine deficiency disorders (IDD). From work undertaken by CEMUBAC in Ubangui Zaïre, the role of thiocyanate overload is recalled while this work demonstrates for the first time in man an action of selenium supplementation (and thus deficiency) on thyroid function in iodine deficient areas. The extreme severity of the selenium deficiency may intervene either on the central and/or peripheral deiodination of thyroxine, or on the synthesis of the thyroid hormones. Together with thiocyanate overload, selenium deficiency may be responsible of the high frequency of myxedematous cretins in Zaïre. PMID:2099229

  20. Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts.

    PubMed

    Komatsu, Yuko; Ibi, Miho; Chosa, Naoyuki; Kyakumoto, Seiko; Kamo, Masaharu; Shibata, Toshiyuki; Sugiyama, Yoshiki; Ishisaki, Akira

    2016-07-01

    Bisphosphonates (BPs) are analogues of pyrophosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF‑β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF‑β-induced promotion of cell viability, ii) the TGF‑β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF‑β-induced migratory activity of hGFs and iv) the expression level of TGF‑β type I receptor on the surfaces of hGFs, as well as the TGF‑β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF‑β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad‑dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level. PMID:27176567

  1. Data in support of the bone analysis of NOD-SCID mice treated with zoledronic acid and prednisolone.

    PubMed

    Hori, Naoko; Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

    2016-06-01

    This paper reports data on the bone, specifically the tibia and mandible, of nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice) treated with zoledronic acid (ZA) and prednisolone (PSL). The data described here are related to the research article titled "Zoledronic acid basically increases circulating soluble RANKL level in mice, and in glucocorticoid-administrated mice, more increases lymphocytes derived sRANKL by bacterial endotoxic stimuli" [1]. The present data and the NOD-SCID mice experiments described contain insights into the role of bone-remodeling factors induced by ZA treatment. PMID:27182545

  2. Transverse Zones in the Eastern Cordillera (Colombia): An example in the Zipaquira Anticline

    NASA Astrophysics Data System (ADS)

    Garcia Delgado, H. S.; Jimenez, G.

    2014-12-01

    Lateral connectors are expressed in map view by along-strike terminations of thrust faults and ramp anticlines; by curves and offsets in strike; and by along-strike changes in angle and direction of plunge, dip of fold limbs, direction of vergence, stratigraphic level of detachment, and structural style. Such lateral connectors could be formed from reactivated transform faults, transverse faults or lateral ramps. The Zipaquira Anticline (ZA) is a salt-cored structure, with a NE-SW axial axis direction, a clear defined map-view curvature. The Neusa Transverse Zone (NTZ) controls the kinematicof faults and folds. The Zipaquirá Transverse Zone (ZTZ) is located to the southern of the ZA. This transverse zone is a key feature in the area, controlling the ZA and allowing the ascend of diapirs and salt sheets to shallow deeps. Our study was focused on Cretaceous marine sediments and Cenozoic transitional to continental sedimentary sequence around the ZA. 224 oriented cores were collected using a gas portable drill. At each site we collected 10 cores, spaced in order to try to average out secular variation. All samples were oriented using a magnetic compass, corrected to account for the local magnetic field declination. Cores were cut into standard cylindrical specimens and magnetic fabric, rock magnetic and paleomagnetic measurements were done in the shielded room of the paleomagnetic laboratory of in the IAG in the Sao Paulo University. We measured the low-field (AMS) in a Kappabridge (MFK1-FA, AGICO). All samples were thermally demagnetized up to 680°C by a shielded oven, and the natural remanent magnetization (NRM) of the specimens was measured. Magnetic mineralogy analyses were carried out to identify and characterize the main magnetic carriers. The ZA is an important example of natural connection between multiple factors controlling deformation and geological evolution. Interaction between salt, transverse zones and folding, the ZA could be considered as a scale

  3. Data in support of the bone analysis of NOD–SCID mice treated with zoledronic acid and prednisolone

    PubMed Central

    Hori, Naoko; Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

    2016-01-01

    This paper reports data on the bone, specifically the tibia and mandible, of nonobese diabetic mice with severe combined immunodeficiency disease (NOD–SCID mice) treated with zoledronic acid (ZA) and prednisolone (PSL). The data described here are related to the research article titled “Zoledronic acid basically increases circulating soluble RANKL level in mice, and in glucocorticoid-administrated mice, more increases lymphocytes derived sRANKL by bacterial endotoxic stimuli” [1]. The present data and the NOD–SCID mice experiments described contain insights into the role of bone-remodeling factors induced by ZA treatment. PMID:27182545

  4. Geometric supergravity in D=11 and its hidden supergroup

    NASA Astrophysics Data System (ADS)

    D'Auria, R.; Fré, P.

    1982-06-01

    In this paper we address two questions: the geometrical formulation of D = 11 supergravity and the derivation of the super Lie algebra it is based on. The solutions of the two problems are intimately related and are obtained via the introduction of the new concept of a Cartan integrable system described in this paper. The previously developed group manifold framework can be naturally extended to a Cartan integrable system manifold approach. Within this scheme we obtain a geometric action for D = 11 supergravity based on a suitable Cartan system. This latter turns out to be a compact description of a two-element class of supergroups containing, besides Lorentz Jab, translation Pa and ordinary supersymmetry Q, the following extra generators: two- and five-index skew-symmetric tensors Za1 a2 , Za1… a5 and a further spinorial charge Q'. Q' commutes with itself and everything Jab. It appears in the commutators of Q with Pa, Za1 a2 , Za1 … a5.

  5. Synthesis, biocompatibility and mechanical properties of ZrO2-Al2O3 ceramics composites.

    PubMed

    Nevarez-Rascon, Alfredo; González-Lopez, Santiago; Acosta-Torres, Laura Susana; Nevarez-Rascon, Martina Margarita; Orrantia-Borunda, Erasmo

    2016-01-01

    This study evaluated cell viability, microhardness and flexural strength of two ceramic composites systems (ZA and AZ), pure alumina and zirconia. There were prepared homogeneous mixtures of 78wt%Al2O3+20wt%3Y-TZP+2wt%Al2O3w (AZ) and 80wt%3YTZP+18wt%Al2O3+2wt%Al2O3w (ZA), as well as 3Y-TZP (Z), pure Al2O3 (A) and commercial monolithic 3Y-TZP (Zc). Also mouse fibroblast cells 3T3-L1 and a MTT test was carried out at 24, 48 and 72 h. The surfaces were observed with SEM and the microhardness and three-point flexural strength values were estimated. The absolute microhardness values were: A>AZ>Z>Zc>ZA. Flexural strength of Zc, Z, and ZA were around double than AZ and A. All groups showed high biocompatibility trough cell viability values at 24, 48 and 72 h. Factors like grain shape, grain size and homogeneous or heterogeneous grain distributions may play an important role in physical, mechanical and biological properties of the ceramic composites. PMID:27251994

  6. 75 FR 4006 - Emergency Restoration Plan (ERP)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ...; ] DEPARTMENT OF AGRICULTURE Rural Utilities Service 7 CFR Part 1730 RIN 0572-ZA00 Emergency Restoration Plan... Activities Excluded from Executive Order 12372'' (50 FR 47034). Information Collection and Recordkeeping... Executive Order. Background The Agency published a final rule on October 12, 2004, at 69 FR 60541...

  7. 76 FR 56682 - Sunscreen Drug Products for Over-the-Counter Human Use; Request for Data and Information...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    .... SUPPLEMENTARY INFORMATION: I. Background In the Federal Register of June 17, 2011 (76 FR 35669) (the June 17... Effectiveness Testing final rule that published in the Federal Register of June 17, 2011 (76 FR 35620). FDA is...-ZA40 Sunscreen Drug Products for Over-the-Counter Human Use; Request for Data and Information...

  8. 76 FR 35669 - Sunscreen Drug Products for Over-the-Counter Human Use; Request for Data and Information...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-17

    ... (ANPR) (43 FR 38206 at 38207, 38223, 38224, 38229, and 38239) as lip protectants, which are allowed to... products (72 FR 49070), several submissions recommended that we include the following dosage forms in the... Food and Drug Administration 21 CFR Part 352 RIN 0910-ZA40 Sunscreen Drug Products for...

  9. Examination of the Factors Influencing the Exam Results

    ERIC Educational Resources Information Center

    Sitku-Görömbei, Cecília

    2009-01-01

    The defectiveness of the effectiveness of the Hungarian general education revealed in the PISA survey appears in the higher education as well. The "Introduction to Informatics" subject has one of the lowest exam results among the students of the College of Nyíregyháza majoring in Computer Program Designer and Teacher of Computer Science.…

  10. 75 FR 7591 - Guidance on Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-22

    ... (75 FR 984), the deadline for the public to provide its comments was February 26, 2010. The purpose of... January 7, 2010 (75 FR 984), was for 50 days. Therefore, the new deadline will now be April 2, 2010. Dated... AGENCY RIN 2050-ZA05 Guidance on Recommended Interim Preliminary Remediation Goals for Dioxin in Soil...

  11. 75 FR 984 - Draft Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and RCRA Sites

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ... AGENCY RIN 2050-ZA05 Draft Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA...) developed in the Draft Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at Comprehensive... draft recommended interim PRGs for dioxin in soil. These draft recommended interim PRGs were...

  12. Isolation of novel Pseudomonas syringae promoters and functional characterization in polyhydroxyalkanoate-producing pseudomads

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A library of genomic DNA fragments of Pseudomonas syringae pv. tomato DC3000 was constructed in a lacZa-containing plasmid, pBS29. The library was used in a preliminary alpha-complementation-based screen to identify clones with promoter activity in Escherichia coli. Ten positive clones were sequen...

  13. Fabrication and Mechanical Characterization of Al2O3/ZrO2 Layered Composites with Graded Microstructure

    NASA Astrophysics Data System (ADS)

    Park, Sang-Hyun; Kang, Ji-Hun; Jung, Yeon-Gil; Paik, Ungyu

    2008-02-01

    Microstructure evaluation has been performed and related mechanical properties have been investigated and characterized in functionally graded materials (FGMs) using alumina and zirconia. Two kinds of FGM, one with a compositional variation from an alumina substrate to an outer layer of zirconia (AZ FGM) and an inverse one (ZA FGM), were prepared by dip-coating with substrates prepared by gel-casting. The slip composition for the coating was controlled with 10 vol.% variation. The microstructure changed from the substrate to the outer layer, showing smooth variation in hardness. The coating thickness of AZ FGM, with abnormal grain growth in the substrate, was thicker than that of ZA FGM, with grain growth inhibition, showing about 300 and about 200 μm for AZ FGM and ZA FGM, respectively. Well developed cracks with anisotropic crack propagation were observed in AZ FGM, but no cracking was observed in ZA FGM. The fracture strength of monolithic materials decreased as coating layers were applied onto the monolithic materials. Based on the results of mechanical properties and microstructure evaluation, the fracture mechanism in each FGM is proposed and discussed.

  14. Maize pathogens suppress inducible phytoalexin production to thwart innate plant immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kauralexins (KA) and zealexins (ZA) are newly described secondary metabolites in maize that serve as inducible chemical defenses against insects and pathogens. In contrast to the abundance of terpene volatiles in leaves, these non-volatile terpenoid phytoalexins are only mildly produced in response ...

  15. SigmaPlot 2000, Version 6.00, SPSS Inc. Computer Software Project Management, Requirements, and Design Document

    SciTech Connect

    HURLBUT, S.T.

    2000-10-24

    SigmaPlot is a vendor software product that will be used to convert the area under an absorbance curve generated by a Fourier transform infrared spectrometer (FTIR) to a relative area. SigmaPlot will be used in conjunction with procedure ZA-565-301, ''Determination of Moisture by Supercritical Fluid Extraction and Infrared Detection.''

  16. 75 FR 58329 - Federal Travel Regulation (FTR); Relocation Expenses Test Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... 3090-ZA01 Federal Travel Regulation (FTR); Relocation Expenses Test Programs AGENCY: Office of... relocation expenses test programs for Federal employees, made by the passage of Public Law 111-112 on... General Services to authorize Federal agencies to test new and innovative methods of...

  17. 75 FR 27984 - Broadband Technology Opportunities Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ... National Telecommunications and Information Administration RIN 0660-ZA28 Broadband Technology Opportunities... Applications, 75 FR 3792 (Jan. 22, 2010). \\2\\ Notice of Funds Availability; Extension of Application Closing Deadline for Comprehensive Community Infrastructure (CCI) Projects, 75 FR 10464 (Mar. 8, 2010); Notice...

  18. 75 FR 6627 - Broadband Technology Opportunities Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-10

    .../ . SUPPLEMENTARY INFORMATION: On January 22, 2010, NTIA published a Notice of Funds Availability (NOFA) (75 FR 3792... National Telecommunications and Information Administration RIN 0660-ZA28 Broadband Technology Opportunities Program AGENCY: National Telecommunications and Information Administration, U.S. Department of...

  19. 75 FR 14131 - Broadband Technology Opportunities Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ... National Telecommunications and Information Administration RIN 0660-ZA28 Broadband Technology Opportunities... procedures for the second round of BTOP funding. (75 FR 3792, Jan. 22, 2010). In the Second NOFA, NTIA... http://www.broadbandusa.gov . (75 FR at 3805). NTIA established an application window for BTOP...

  20. 76 FR 13508 - Ninth Coast Guard District Sector Realignment; Northern Lake Michigan and Lake Huron

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ... SECURITY Coast Guard 33 CFR Part 3 RIN 1625-ZA29 Ninth Coast Guard District Sector Realignment; Northern Lake Michigan and Lake Huron AGENCY: Coast Guard, DHS. ACTION: Final Rule. SUMMARY: This rule makes..., call or e-mail Mr. Doug McCann, Ninth District Resources Planning Branch, U.S. Coast Guard,...

  1. Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer.

    PubMed

    Zhang, Qian; Du, Yang; Jing, Lijia; Liang, Xiaolong; Li, Yaqian; Li, Xiaofeng; Dai, Zhifei; Tian, Jie

    2016-03-01

    Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near-infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA. PMID:27280247

  2. The LAOM Multidimensional Anxiety Scale for Measuring Anxiety in Children and Adolescents: Addressing the Psychometric Properties of the Scale

    ERIC Educational Resources Information Center

    Kozina, Ana

    2012-01-01

    The article introduces a new anxiety scale, called the LAOM (Lestvica anksioznosti za otroke in mladostnike [The anxiety scale for children and adolescents]) for measuring self-reported multidimensional anxiety. The scale has been developed with a special focus on the school setting, using one sample from an elementary school which is…

  3. 75 FR 80073 - Reasonable Break Time for Nursing Mothers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-21

    ... Hour Division RIN 1235-ZA00 Reasonable Break Time for Nursing Mothers AGENCY: Wage and Hour Division... Standards Act (FLSA) that requires employers to provide reasonable break time and a place for nursing... are the Department's preliminary interpretations of the new break time amendment to the FLSA....

  4. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    NASA Astrophysics Data System (ADS)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  5. 78 FR 72843 - Freedom of Information

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... Budget at 52 FR 10012 (Mar. 27, 1987) (``OMB Guidelines''). Sec. 706.2 Policy. It is OPIC's policy to... CORPORATION 22 CFR Part 706 RIN 3420-ZA00 Freedom of Information AGENCY: Overseas Private Investment... Private Investment Corporation's (``OPIC'') Freedom of Information Act (FOIA) regulations by...

  6. zeldovich-PLT: Zel'dovich approximation initial conditions generator

    NASA Astrophysics Data System (ADS)

    Eisenstein, Daniel; Garrison, Lehman

    2016-05-01

    zeldovich-PLT generates Zel'dovich approximation (ZA) initial conditions (i.e. first-order Lagrangian perturbation theory) for cosmological N-body simulations, optionally applying particle linear theory (PLT) corrections. The code uses double precision internally, but output format can be set to single or double precision.

  7. 78 FR 77601 - Adjustment of Monetary Threshold for Reporting Rail Equipment Accidents/Incidents for Calendar...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... Federal agencies to prepare a Statement of Energy Effects for any ``significant energy action.'' 66 FR... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Railroad Administration 49 CFR Part 225 RIN 2130-ZA12 Adjustment of Monetary Threshold...

  8. 76 FR 777 - National Wetland Plant List

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-06

    ... basis for the names included within the proposed list, National List of Vascular Plant Species that... Department of the Army, Corps of Engineers ZRIN 0710-ZA06 National Wetland Plant List AGENCY: U. S. Army Corps of Engineers, Department of Defense. ACTION: Notice. SUMMARY: The National Wetland Plant...

  9. 77 FR 35295 - Methyl Bromide; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... AGENCY 40 CFR Part 180 RIN 2070-ZA16 Methyl Bromide; Pesticide Tolerances AGENCY: Environmental... methyl bromide in or on cotton, undelinted seed under the Federal Food, Drug, and Cosmetic Act (FFDCA.... Background In the Federal Register of April 6, 2012 (77 FR 20752) (FRL-9345- 1), EPA issued a proposed...

  10. Sternbilder - Sternsagen. Mythen und Legenden um Sternbilder.

    NASA Astrophysics Data System (ADS)

    Bonov, A.

    This book is a German translation (translator L. Korniljew) of the Bulgarian original "Mitove i legendi za s'zvezdiyata"; Sofia 1978.It describes in detail how starsand star constellations were named and presents accounts of the mythological legends associated with these names.

  11. THE BISPHOSPHONATE ZOLEDRONIC ACID DECREASES TUMOR GROWTH IN BONE IN MICE WITH DEFECTIVE OSTEOCLASTS*

    PubMed Central

    Hirbe, Angela C.; Roelofs, Anke J.; Floyd, Desiree H.; Deng, Hongju; Becker, Stephanie N.; Lanigan, Lisa G.; Apicelli, Anthony J.; Xu, Zhiqiang; Prior, Julie L.; Eagleton, Mark C.; Piwnica-Worms, David; Rogers, Michael J.; Weilbaecher, Katherine

    2009-01-01

    Bisphosphonates (BPs), bone targeted drugs that disrupt osteoclast function, are routinely used to treat complications of bone metastasis. Studies in preclinical models of cancer have shown that BPs reduce skeletal tumor burden and increase survival. Similarly, we observed in the present study that administration of the Nitrogen-containing BP (N-BP), zoledronic acid (ZA) to osteolytic tumor-bearing Tax+ mice beginning at 6 months of age led to resolution of radiographic skeletal lesions. N-BPs inhibit farnesyl diphosphate (FPP) synthase, thereby inhibiting protein prenylation and causing cellular toxicity. We found that ZA decreased Tax+ tumor and B16 melanoma viability and caused the accumulation of unprenylated Rap1a proteins in vitro. However, it is presently unclear whether N-BPs exert anti-tumor effects in bone independent of inhibition of osteoclast (OC) function in vivo. Therefore, we evaluated the impact of treatment with ZA on B16 melanoma bone tumor burden in irradiated mice transplanted with splenic cells from src-/- mice, which have non-functioning OCs. OC-defective mice treated with ZA demonstrated a significant 88% decrease in tumor growth in bone compared to vehicle-treated OC-defective mice. These data support an osteoclast-independent role for N-BP therapy in bone metastasis. PMID:19442620

  12. 76 FR 14679 - Prevailing Wage Rates for Construction Occupations on Guam for Purposes of the H-2B Temporary...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-17

    .... Based on its own analysis and input from the public, USCIS will determine whether the prevailing wage... SECURITY U.S. Citizenship and Immigration Services RIN 1615-ZA98 Prevailing Wage Rates for Construction... comments from the public on the system that the Governor of Guam is using to determine prevailing...

  13. 76 FR 33993 - Exchange Visitor Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ... Part 62 RIN 1400-ZA20 Exchange Visitor Program AGENCY: Department of State. ACTION: Notice of... Sector Exchange, 2200 C Street NW., SA-5, 5th Floor, Washington, DC 20522; e-mail JExchanges@state.gov . SUPPLEMENTARY INFORMATION: Recent political turmoil in Libya has affected Exchange Visitor Program college...

  14. Efficacy of zoledronic acid for chronic low back pain associated with Modic changes in magnetic resonance imaging

    PubMed Central

    2014-01-01

    Background Modic changes (MC) are associated with low back pain (LBP), but effective treatments are lacking. The aim of this randomized, placebo-controlled, double-blinded trial was to evaluate the efficacy of zoledronic acid (ZA) for chronic LBP among patients with MC in magnetic resonance imaging (MRI). Methods Inclusion criteria were LBP lasting ≥3 months, with an intensity of ≥6 on a 10-cm VAS or an Oswestry Disability Index (ODI) of ≥30%, and MC in MRI. Patients were randomized into single intravenous infusion of ZA 5 mg (n = 20), or placebo (n = 20) groups. The primary outcome was LBP intensity, secondary outcomes leg pain intensity, ODI, health-related quality of life (RAND-36), lumbar flexibility, sick leaves and use of pain medication. The treatment differences at one month and one year were analysed using ANCOVA with adjustment for the baseline score. Results The mean difference (MD) between the groups in the primary outcome, intensity of LBP, was 1.4 (95% confidence intervals (CI) 0.01 to 2.9) in favour of ZA at one month. We observed no significant between-group difference in the intensity of LBP at one year (MD 0.7; 95% CI −1.0 to 2.4) or in secondary outcomes at any time point except that 20% of patients in the ZA group used non-steroidal anti-inflammatory drugs at one year compared to 60% in the placebo group (P = 0.022). Acute phase reactions (fever, flu-like symptoms, arthralgia) emerged in 95% of the patients in the ZA group, compared to 35% in the placebo group. Conclusions ZA was effective in reducing the intensity of LBP in the short term and in reducing the use of NSAIDs within the time span of one year among patients with chronic LBP and MC confirmed in MRI. Although the results seem encouraging, larger studies are required to analyse the effectiveness and safety of ZA for patients with MC. Trial registration ClinicalTrial.gov identifier NCT01330238. PMID:24588905

  15. Properties of the cosmological density distribution function

    NASA Astrophysics Data System (ADS)

    Bernardeau, Francis; Kofman, Lev

    1995-04-01

    The properties of the probability distribution function (PDF) of the cosmological continuous density field are studied. We focus our analysis on the quasi-linear regime where various calculations, based on dynamically motivated methods, have been presented: either by using the Zel'dovich approximation (ZA) or by using the perturbation theory to evaluate the behavior of the moments of the distribution function. We show how these two approaches are related to each other and that they can be used in a complementary way. For that respect, the one-dimensional dynamics, where the ZA is exact solution, has first been used as a testing ground. In particular, we show that, when the density PDF obtained with the ZA is regularized, its various moments exhibit the behavior expected by the perturbation theory applied to the ZA. We show that ZA approach can be used for arbitrary initial conditions (not only Gaussian) and that the nonlinear evolution of the moments can be obtained. The perturbation theory can be used for the exact dynamics. We take into account the final filtering of the density field both for ZA and perturbation theory. Applying these techniques, we got the generating function of the moments for the one-dimensional dynamics, the three-dimensional ZA, with and without smoothing effects. We also suggest methods to build PDFs. One is based on the Laplace inverse transform of the moment generating function. The other, the Edgeworth expansion, is obtained when the previous generating function is truncated at a given order and allows evaluation of the PDF out of limited number of moments. It provides insight on the relationship between the moments and the shape of the density PDF. In particular, it provides an alternative method to evaluate the skewness and kurtosis by measuring the PDF around its maximum. Eventually, results obtained from a numerical simulation with cold dark matter initial conditions have been used to validate the accuracy of the considered

  16. A novel soft-tissue in vitro model for bisphosphonate-associated osteonecrosis

    PubMed Central

    2010-01-01

    Background Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) has been reported in patients receiving intravenous BP, particularly zoledronic acid (ZA). The purpose of this study was to develop an in vitro model representative of the effects BP has on soft tissue secondary to its release from bone. Human gingival fibroblasts and oral epithelial cell lines were exposed to various concentrations (0-10 μM) of ZA using dentine discs (DDs) as a direct carrier of BP, which were exposed for 24 hours to ZA in normal medium (NM), washed in phosphate-buffered saline (PBS) and placed in a new co-culture with the cells. The cells were allowed to proliferate until they grew over the bone discs and then the discs either were left unchelated, or were chelated using 0.001% EDTA or EGTA to release BP from the discs and to observe the cellular effects. Direct effects were determined using direct and fluorescent imaging. Apoptotic effects were determined by vital stain, terminal dUTP nick-end labeling, and annexin V studies. The effect on cell proliferation was determined by mitochondrial tetrazolium salt assay. The level of BP release was determined based on the effect of BP directly on cells, using the DDs or the supernatant fluids resulting from chelation. Results A dose-response effect was seen on imaging, and effects on apoptosis and cell proliferation were observed with increasing ZA concentrations liberated from the DDs, particularly after calcium cleavage and release of ZA from the DDs with a variety of chelating agents. Apoptotic effects were observed microscopically after chelation at 24 hours. Release of ZA was confirmed by extracting medium from non-chelated and chelated cell culture models with DDs and applying this medium to untreated fresh cell cultures, providing appropriate controls. Conclusions The results from this study demonstrate that low concentrations of ZA released from bone can rapidly and directly affect the oral mucosal tissues, initially

  17. Osteoclasts but not osteoblasts are affected by a calcified surface treated with zoledronic acid in vitro

    SciTech Connect

    Schindeler, Aaron . E-mail: AaronS@chw.edu.au; Little, David G.

    2005-12-16

    Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. Recent interest has centered on the effects of bisphosphonates on osteoblasts. Chronic dosing of osteoblasts with solubilized bisphosphonates has been reported to enhance osteogenesis and mineralization in vitro. However, this methodology poorly reflects the in vivo situation, where free bisphosphonate becomes rapidly bound to mineralized bone surfaces. To establish a more clinically relevant cell culture model, we cultured bone cells on calcium phosphate coated quartz discs pre-treated with the potent nitrogen-containing bisphosphonate, zoledronic acid (ZA). Binding studies utilizing [{sup 14}C]-labeled ZA confirmed that the bisphosphonate bound in a concentration-dependent manner over the 1-50 {mu}M dose range. When grown on ZA-treated discs, the viability of bone-marrow derived osteoclasts was greatly reduced, while the viability and mineralization of the osteoblastic MC3T3-E1 cell line were largely unaffected. This suggests that only bone resorbing cells are affected by bound bisphosphonate. However, this system does not account for transient exposure to unbound bisphosphonate in the hours following a clinical dosing. To model this event, we transiently treated osteoblasts with ZA in the absence of a calcified surface. Osteoblasts proved highly resistant to all transitory treatment regimes, even when utilizing ZA concentrations that prevented mineralization and/or induced cell death when dosed chronically. This study represents a pharmacologically more relevant approach to modeling bisphosphonate treatment on cultured bone cells and implies that bisphosphonate therapies may not directly affect osteoblasts at bone surfaces.

  18. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer.

    PubMed

    Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

    2016-01-01

    Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients. PMID:27152244

  19. 5-year Follow-up of a Randomized Controlled Trial of Immediate versus Delayed Zoledronic Acid for Prevention of Bone Loss in Postmenopausal Women with Breast Cancer Starting Letrozole after Tamoxifen: N03CC (Alliance)

    PubMed Central

    Wagner-Johnston, Nina D.; Sloan, Jeff A.; Liu, Heshan; Kearns, Ann E.; Hines, Stephanie L.; Puttabasavaiah, Suneetha; Dakhil, Shaker R.; Lafky, Jacqueline M.; Perez, Edith A.; Loprinzi, Charles L.

    2015-01-01

    Background Postmenopausal women with breast cancer (BC) receiving aromatase inhibitors are at increased risk for bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report describes the 5-year follow-up results. Methods 551 postmenopausal women with BC completing tamoxifen and undergoing daily letrozole treatment were randomized to upfront (274) or delayed (277) ZA 4 mg IV every 6 months. In the delayed arm, ZA was initiated for post-baseline bone mineral density (BMD) T-score < -2.0 or fracture. Results The incidence of a 5% decrease in total lumbar spine BMD at 5 years was 10.2% in the upfront arm versus 41.2% in the delayed arm, p < 0.0001. 41 patients in the delayed arm were eventually started on ZA. With the exception of increased grade 1/2 elevated creatinine and fever in the upfront arm and cerebrovascular ischemia in the delayed arm, there were no significant differences between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront arm (2 versus 8 cumulative cases) though this difference was not statistically significant. Bone fractures occurred in 24 patients in the upfront arm versus 25 patients in the delayed arm. Conclusions Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women on letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not different between arms. PMID:25930719

  20. Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model.

    PubMed

    Qiao, H; Wang, T-y; Yu, Z-f; Han, X-g; Liu, X-q; Wang, Y-g; Fan, Q-m; Qin, A; Tang, T-t

    2016-01-01

    The treatment of breast cancer-induced osteolysis remains a challenge in clinical settings. Here, we explored the effect and mechanism of combined treatment with zoledronic acid (ZA) and plumbagin (PL), a widely investigated component derived from Plumbago zeylanica, against breast cancer-induced osteoclastogenesis. We found that the combined treatment with PL and ZA suppressed cell viability of precursor osteoclasts and synergistically inhibited MDA-MB-231-induced osteoclast formation (combination index=0.28) with the abrogation of recombinant mouse receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of NF-κB/MAPK (nuclear factor-κB/mitogen-activated protein kinase) pathways. Molecular docking suggested a putative binding area within c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk) protease active sites through the structural mimicking of adenosine phosphate (ANP) by the spatial combination of PL with ZA. A homogeneous time-resolved fluorescence assay further illustrated the direct competitiveness of the dual drugs against ANP docking to phosphorylated JNK/Erk, contributing to the inhibited downstream expression of c-Jun/c-Fos/NFATc-1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1). Then, in vivo testing demonstrated that the combined administration of PL and ZA attenuated breast cancer growth in the bone microenvironment. Additionally, these molecules prevented the destruction of proximal tibia, with significant reduction of tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast cells and potentiation of apoptotic cancer cells, to a greater extent when combined than when the drugs were applied independently. Altogether, the combination treatment with PL and ZA could significantly and synergistically suppress osteoclastogenesis and inhibit tumorigenesis both in vitro and in vivo by simulating the spatial structure of ANP to inhibit competitively phosphorylation of c-Jun N

  1. Relationship between zinc malnutrition and alterations in murine peripheral blood leukocytes

    SciTech Connect

    King, L.E.; Morford, L.A.; Fraker, P.J. )

    1991-03-15

    Studies using a murine model have shown that the immune system responds rapidly and adversely to zinc deficiency. The extent of alteration of peripheral blood leukocytes (PBL) and immunoglobulin levels were investigated in four zinc dietary groups: zinc adequate (ZA); restricted fed zinc adequate (RZA); marginal zinc deficient (MZD, 72-76% of ZA mouse weight); and severely zinc deficient. The peripheral white blood cell count was 3.66 {plus minus} 1.08 {times} 10{sup 6} cells/ml for ZA mice decreasing by 21%, 28% and 54% for RZA, MZD and SZD mice respectively. An equally dramatic change in the flow cytometric light scatter profile was found. ZA mice had 66% lymphocytes and 21% polymorphonuclear granulocytes (PMN) in their peripheral blood while MZD and SZD mice contained 43% and 30% lymphocytes and 40% and 60% PMNs respectively. Analysis of the phenotypic distribution of specific classes of lymphocytes revealed ZA blood contained 25% B-cells and 40% T-cells (CD5{sup +}). B-cells decreased 40-50% for RZA and MZD mice and 60-70% for SZD mice. The decline in CD5{sup +} T-cells was more modest at 30% and 45% for MZD and SZD mice. A nearly 40% decline in both T{sub h} and T{sub c/s} cells was noted for both MZD and SZD mice. Radioimmunoassay of serum for changes in IgM and IgG content revealed no change among dietary groups while serum zinc decreased 10% for RZA mice and 50% for both MZD and SZD mice. The authors conclude that peripheral blood differential counts in concert with total B and T-cell phenotype may serve as indicators of zinc status while serum zinc and Ig will not.

  2. Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model

    PubMed Central

    Qiao, H; Wang, T-y; Yu, Z-f; Han, X-g; Liu, X-q; Wang, Y-g; Fan, Q-m; Qin, A; Tang, T-t

    2016-01-01

    The treatment of breast cancer-induced osteolysis remains a challenge in clinical settings. Here, we explored the effect and mechanism of combined treatment with zoledronic acid (ZA) and plumbagin (PL), a widely investigated component derived from Plumbago zeylanica, against breast cancer-induced osteoclastogenesis. We found that the combined treatment with PL and ZA suppressed cell viability of precursor osteoclasts and synergistically inhibited MDA-MB-231-induced osteoclast formation (combination index=0.28) with the abrogation of recombinant mouse receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of NF-κB/MAPK (nuclear factor-κB/mitogen-activated protein kinase) pathways. Molecular docking suggested a putative binding area within c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk) protease active sites through the structural mimicking of adenosine phosphate (ANP) by the spatial combination of PL with ZA. A homogeneous time-resolved fluorescence assay further illustrated the direct competitiveness of the dual drugs against ANP docking to phosphorylated JNK/Erk, contributing to the inhibited downstream expression of c-Jun/c-Fos/NFATc-1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1). Then, in vivo testing demonstrated that the combined administration of PL and ZA attenuated breast cancer growth in the bone microenvironment. Additionally, these molecules prevented the destruction of proximal tibia, with significant reduction of tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast cells and potentiation of apoptotic cancer cells, to a greater extent when combined than when the drugs were applied independently. Altogether, the combination treatment with PL and ZA could significantly and synergistically suppress osteoclastogenesis and inhibit tumorigenesis both in vitro and in vivo by simulating the spatial structure of ANP to inhibit competitively phosphorylation of c-Jun N

  3. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone.

    PubMed

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-01-01

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm(3)) as compared to rhBMP-2 alone (10.9 ± 2.1 mm(3)) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

  4. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    PubMed Central

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-01-01

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

  5. Spatial interpolation of precipitation indexes in Sierra Nevada (Spain): comparing the performance of some interpolation methods

    NASA Astrophysics Data System (ADS)

    Pereira, Paulo; Oliva, Marc; Misiune, Ieva

    2015-08-01

    The objective of this paper is to examine the spatial distribution of several precipitation indexes in Sierra Nevada, Spain: mean annual number of wet days (R ≥ 1 mm), mean annual number of heavy rainy days (R ≥ 10 mm) and mean annual number of very heavy precipitation days (R ≥ 20 mm) and test the performance of several interpolation methods using these variables. In total, 17 univariate and multivariate methods were tested. A set of 36 metereological stations distributed in Sierra Nevada and neighbouring areas was analysed in this study. The original data did not followed the normal distribution; thus, a logarithm was applied to data meet normality purposes. Interpolator's performance was assessed using the root mean square error generated from cross-validation. The results showed that the mean annual R ≥ 10 mm and R ≥ 20 mm have a higher variability than R ≥ 1 mm. While the elevation and longitude did not show a significant correlation with the studied indexes, the latitude (i.e. distance to the sea) showed a significant negative correlation. The regressions carried out confirmed that elevation was the covariate with higher capacity to explain the variability of the indexes. The incorporation of elevation and longitude slightly increased the explanation capacity of the models. The data of LogR ≥ 1 mm, LogR ≥ 10 mm and LogR ≥ 20 mm displayed a clustered pattern, especially the last two indexes that also showed a strong spatial dependency attributed to the effects of local topography, slope, aspect and valley orientation. The best fitted variogram model to LogR ≥ 1 mm was the linear one while for the LogR ≥ 10 mm and LogR ≥ 20 mm, the Gaussian was the most appropriate. The best interpolator for LogR ≥ 1 mm was the local polinomyal with the power of 1, whereas for LogR ≥ 10 mm and LogR ≥ 20 mm, regression kriging (ROK) using as auxiliary variables the elevation, latitude and longitude was the most accurate. ROK methods significantly

  6. A Randomised Controlled Trial of Intravenous Zoledronic Acid in Malignant Pleural Disease: A Proof of Principle Pilot Study

    PubMed Central

    Clive, Amelia O.; Hooper, Clare E.; Edey, Anthony J.; Morley, Anna J.; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P.; Sequeiros, Iara; Lyen, Stephen M.; Milton, Tim; Kahan, Brennan C.; Maskell, Nick A.

    2015-01-01

    Introduction Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. Methods We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Results Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI −4.7 to 13.0)) or change in DCE-MRI iAUC (AMD −15.4 (95%CI −58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. Conclusions This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. Trial Registration UK Clinical

  7. Cranes in East Asia; Proceedings of the symposium held in Harbin, People's Republic of China, June 9-18, 1998

    USGS Publications Warehouse

    2001-01-01

    Introductory Remarks (R.C. Stendell): I appreciate the opportunity to be in Harbin and participate in the International Scientific Workshop on Cranes in East Asia. I would like to provide some background information on how this meeting came to be. Almost one year ago, in July 1997, Dr. Kun John of the Seoul National University contacted the U.S. Geological Survey’s Midcontinent Ecological Science Center (MESC) requesting that we host a meeting of scientists from the Republic of Korea (ROK) and the Democratic People’s Republic of Korea (DPRK) to discuss the biology and ecology of cranes on the Korean peninsula. Dr. John and his colleagues expressed concern about three species of cranes that migrate up and down the Korean peninsula and use the Demilitarized Zone. The species of interest are the Red-crowned Crane, White-naped Crane, and the Hooded Crane. The primary question was the conservation of these species in this part of the world. Another concern involved exploring potential economic values and opportunities associated with these species. Richard Johnson, an economist at MESC, assumed responsibility as the primary MESC contact to help bring about this meeting.

  8. Characterization of 16 novel human genes showing high similarity to yeast sequences.

    PubMed

    Stanchi, F; Bertocco, E; Toppo, S; Dioguardi, R; Simionati, B; Cannata, N; Zimbello, R; Lanfranchi, G; Valle, G

    2001-01-15

    The entire set of open reading frames (ORFs) of Saccharomyces cerevisiae has been used to perform systematic similarity searches against nucleic acid and protein databases: with the aim of identifying interesting homologies between yeast and mammalian genes. Many similarities were detected: mostly with known genes. However: several yeast ORFs were only found to match human partial sequence tags: indicating the presence of human transcripts still uncharacterized that have a homologous counterpart in yeast. About 30 such transcripts were further studied and named HUSSY (human sequence similar to yeast). The 16 most interesting are presented in this paper along with their sequencing and mapping data. As expected: most of these genes seem to be involved in basic metabolic and cellular functions (lipoic acid biosynthesis: ribulose-5-phosphate-3-epimerase: glycosyl transferase: beta-transducin: serine-threonine-kinase: ABC proteins: cation transporters). Genes related to RNA maturation were also found (homologues to DIM1: ROK1-RNA-elicase and NFS1). Furthermore: five novel human genes were detected (HUSSY-03: HUSSY-22: HUSSY-23: HUSSY-27: HUSSY-29) that appear to be homologous to yeast genes whose function is still undetermined. More information on this work can be obtained at the website http://grup.bio.unipd.it/hussy PMID:11124703

  9. Computational Assessment of the GT-MHR Graphite Core Support Structural Integrity in Air-Ingress Accident Condition

    SciTech Connect

    Jong B. Lim; Eung S. Kim; Chang H. Oh; Richard R. Schultz; David A. Petti

    2008-10-01

    The objective of this project was to perform stress analysis for graphite support structures of the General Atomics’ 600 MWth GT-MHR prismatic core design using ABAQUS ® (ver. 6.75) to assess their structural integrity in air-ingress accident conditions where the structure weakens over time due to oxidation damages. The graphite support structures of prismatic type GT-MHR was analyzed based on the change of temperature, burn-off and corrosion depth during the accident period predicted by GAMMA, a multi-dimensional gas multi-component mixture analysis code developed in the Republic of Korea (ROK)/United States (US) International –Nuclear Engineering Research Initiative (I-NERI) project. Both the loading and thermal stresses were analyzed, but the thermal stress was not significant, leaving the loading stress to be the major factor. The mechanical strengths are exceeded between 11 to 11.5 days after loss-of-coolant-accident (LOCA), corresponding to 5.5 to 6 days after the start of natural convection.

  10. Exposure of Bacillus subtilis to Low Pressure (5 Kilopascals) Induces Several Global Regulons, Including Those Involved in the SigB-Mediated General Stress Response

    PubMed Central

    Waters, Samantha M.; Robles-Martínez, José A.

    2014-01-01

    Studies of how microorganisms respond to pressure have been limited mostly to the extreme high pressures of the deep sea (i.e., the piezosphere). In contrast, despite the fact that the growth of most bacteria is inhibited at pressures below ∼2.5 kPa, little is known of microbial responses to low pressure (LP). To study the global LP response, we performed transcription microarrays on Bacillus subtilis cells grown under normal atmospheric pressure (∼101 kPa) and a nearly inhibitory LP (5 kPa), equivalent to the pressure found at an altitude of ∼20 km. Microarray analysis revealed altered levels of 363 transcripts belonging to several global regulons (AbrB, CcpA, CodY, Fur, IolR, ResD, Rok, SigH, Spo0A). Notably, the highest number of upregulated genes, 86, belonged to the SigB-mediated general stress response (GSR) regulon. Upregulation of the GSR by LP was confirmed by monitoring the expression of the SigB-dependent ctc-lacZ reporter fusion. Measuring transcriptome changes resulting from exposure of bacterial cells to LP reveals insights into cellular processes that may respond to LP exposure. PMID:24878601