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Sample records for k-3 k-4 k-5

  1. Shikonin, vitamin K3 and vitamin K5 inhibit multiple glycolytic enzymes in MCF-7 cells.

    Science.gov (United States)

    Chen, Jing; Hu, Xun; Cui, Jingjie

    2018-05-01

    Glycolysis is the most important source of energy for the production of anabolic building blocks in cancer cells. Therefore, glycolytic enzymes are regarded as potential targets for cancer treatment. Previously, naphthaquinones, including shikonin, vitamin K 3 and vitamin K 5 , have been proven to decrease the rate of glycolysis in cancer cells, which is partly due to suppressed pyruvate kinase activity. In the present study, enzymatic assays were performed using MCF-7 cell lysate in order to screen the profile of glycolytic enzymes in cancer cells inhibited by shikonin, vitamin K 3 and vitamin K 5 , in addition to pyruvate kinase. Results revealed that hexokinase, phosphofructokinase-1, fructose bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase produced in the process of glycolysis were inhibited by shikonin, vitamin K 3 and vitamin K 5 . The results indicated that shikonin, vitamin K 3 and vitamin K 5 are chemical inhibitors of glycolytic enzymes in cancer cells and have potential uses in translational medical applications.

  2. Effects of Vitamin K3 and K5 on Daunorubicin-resistant Human T Lymphoblastoid Leukemia Cells.

    Science.gov (United States)

    Nakaoka, Eri; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Hirano, Toshihiko

    2015-11-01

    Anticancer efficacy of vitamin K derivatives on multidrug-resistant cancer cells has been scarcely investigated. The effects of vitamins K3 and K5 on proliferation of human leukemia MOLT-4 cells and on daunorubicin-resistant MOLT-4/DNR cells were estimated by a WST assay. Apoptotic cells were detected by Annexin V and propidium iodide staining, followed by flow cytometry. Vitamins K3 and K5 significantly inhibited proliferation of leukemic cells at 10 and 100 μM (pVitamin K3 induced cell apoptosis at 10 and 100 μM in both MOLT-4 and MOLT-4/DNR cells (pVitamin K5 also increased apoptotic cells, while rather inducing necrotic cell death. Vitamins K3 and K5 suppress MOLT-4 and MOLT-4/DNR cell-proliferation partially through induction of apoptosis, and these vitamin derivatives can overcome drug resistance due to P-glycoprotein expression. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells.

    Science.gov (United States)

    Ogawa, Mutsumi; Nakai, Seiji; Deguchi, Akihiro; Nonomura, Takako; Masaki, Tsutomu; Uchida, Naohito; Yoshiji, Hitoshi; Kuriyama, Shigeki

    2007-08-01

    Although a number of studies have shown that vitamin K possesses antitumor activities on various neoplastic cell lines, there are few reports demonstrating in vivo antitumor effects of vitamin K, and the antitumor effect on colorectal cancer (CRC) remains to be examined. Therefore, antitumor effects of vitamin K on CRC were examined both in vitro and in vivo. Vitamins K2, K3 and K5 suppressed the proliferation of colon 26 cells in a dose-dependent manner, while vitamin K1 did not. On flow cytometry, induction of apoptosis by vitamins K2, K3 and K5 was suggested by population in sub-G1 phase of the cell cycle. Hoechst 33342 staining and a two-color flow cytometric assay using fluorescein isothiocyanate-conjugated annexin V and propidium iodide confirmed that vitamins K2, K3 and K5 induced apoptotic death of colon 26 cells. Enzymatic activity of caspase-3 in colon 26 cells was significantly up-regulated by vitamins K2, K3 and K5. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, substantially prevented vitamin K-mediated apoptosis. In vivo study using syngeneic mice with subcutaneously established colon 26 tumors demonstrated that intravenous administration of vitamins K2, K3 and K5 significantly suppressed the tumor growth. The number of apoptotic tumor cells was significantly larger in the vitamin K-treated groups than in the control group. These results suggest that vitamins K2, K3 and K5 exerted effective antitumor effects on CRC in vitro and in vivo by inducing caspase-dependent apoptotic death of tumor cells, suggesting that these K vitamins may be promising agents for the treatment of patients with CRC.

  4. Differences in Physical Performance Measures Among Patients With Unilateral Lower-Limb Amputations Classified as Functional Level K3 Versus K4.

    Science.gov (United States)

    Sions, Jaclyn Megan; Beisheim, Emma Haldane; Manal, Tara Jo; Smith, Sarah Carolyn; Horne, John Robert; Sarlo, Frank Bernard

    2018-02-01

    To determine whether differences in physical function, assessed via self-report questionnaires and physical performance tests, exist between individuals with lower-limb loss using a prosthetic device classified as a K3 versus a K4 functional level. Cross-sectional study. A university physical therapy amputee clinic. Participants (N=55) were included if they (1) were aged ≥18 years with a unilateral transfemoral or transtibial amputation; (2) were classified as K3 or K4 functional level; (3) completed all relevant outcome measures; and (4) were currently using a prosthesis. Not applicable. Locomotor Capabilities Index (LCI), Prosthetic Evaluation Questionnaire-Mobility Section (PEQ-MS), Timed Up and Go (TUG), 10-Meter Walk Test (10MWT), Amputee Mobility Predictor (AMPPRO), and 6-Minute Walk Test (6MWT). K level was determined by group consensus based on a standardized clinical evaluation. After controlling for covariates, patients classified as K3 had slower TUG times (P=.002) and self-selected and fast gait speeds (Pclinical evaluations to help differentiate between individuals of higher functional mobility. The LCI and PEQ-MS may be less useful in classifying individuals as K3 versus K4 because of a ceiling effect. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  5. Vitamins K2, K3 and K5 exert in vivo antitumor effects on hepatocellular carcinoma by regulating the expression of G1 phase-related cell cycle molecules.

    Science.gov (United States)

    Kuriyama, Shigeki; Hitomi, Misuzu; Yoshiji, Hitoshi; Nonomura, Takako; Tsujimoto, Tatsuhiro; Mitoro, Akira; Akahane, Takami; Ogawa, Mutsumi; Nakai, Seiji; Deguchi, Akihiro; Masaki, Tsutomu; Uchida, Naohito

    2005-08-01

    A number of studies have shown that various vitamins K, specifically vitamin K2, possessed antitumor activity on various types of rodent- and human-derived neoplastic cell lines. However, there are only a small number of reports demonstrating in vivo antitumor effects of vitamins K. Furthermore, the mechanism of antitumor effects of vitamins K still remains to be examined. In the present study, we examined the antitumor effects of vitamins K2, K3 and K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vivo. Furthermore, to examine the mechanism of antitumor actions of these vitamins K, mRNA expression levels of various G1 phase-related cell cycle molecules were evaluated by using a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. HCC-bearing animals were produced by implanting PLC/PRF/5 cells subcutaneously into athymic nude mice, and drinking water containing vitamin K2, K3 or K5 was given to the animals. Treatments with vitamins K2, K3 and K5 were shown to markedly inhibit the growth of HCC tumors. To examine the mechanism of in vivo antitumor effects of vitamins K, total RNA was extracted from HCC tumors, and the expression of G1 phase-related cell cycle molecules was quantitatively examined. Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. Conversely, the expression of the cell cycle-suppressing molecules, Cdk inhibitor p16INK4a and retinoblastoma, in HCC was significantly enhanced by the treatments with vitamins K2, K3 and K5. These results indicate that vitamins K2, K3 and K5 exert antitumor effects on HCC by regulating the expression of G1 phase-related cell cycle molecules. These results also indicate that vitamins K2, K3 and K5 may be useful agents for the treatment of patients with HCC.

  6. Structural determinants of the outer shell of β-carboxysomes in Synechococcus elongatus PCC 7942: roles for CcmK2, K3-K4, CcmO, and CcmL.

    Directory of Open Access Journals (Sweden)

    Benjamin D Rae

    Full Text Available Cyanobacterial CO(2-fixation is supported by a CO(2-concentrating mechanism which improves photosynthesis by saturating the primary carboxylating enzyme, ribulose 1, 5-bisphosphate carboxylase/oxygenase (RuBisCO, with its preferred substrate CO(2. The site of CO(2-concentration is a protein bound micro-compartment called the carboxysome which contains most, if not all, of the cellular RuBisCO. The shell of β-type carboxysomes is thought to be composed of two functional layers, with the inner layer involved in RuBisCO scaffolding and bicarbonate dehydration, and the outer layer in selective permeability to dissolved solutes. Here, four genes (ccmK2-4, ccmO, whose products were predicted to function in the outer shell layer of β-carboxysomes from Synechococcus elongatus PCC 7942, were investigated by analysis of defined genetic mutants. Deletion of the ccmK2 and ccmO genes resulted in severe high-CO(2-requiring mutants with aberrant carboxysomes, whilst deletion of ccmK3 or ccmK4 resulted in cells with wild-type physiology and normal ultrastructure. However, a tandem deletion of ccmK3-4 resulted in cells with wild-type carboxysome structure, but physiologically deficient at low CO(2 conditions. These results revealed the minimum structural determinants of the outer shell of β-carboxysomes from this strain: CcmK2, CcmO and CcmL. An accessory set of proteins was required to refine the function of the pre-existing shell: CcmK3 and CcmK4. These data suggested a model for the facet structure of β-carboxysomes with CcmL forming the vertices, CcmK2 forming the bulk facet, and CcmO, a "zipper protein," interfacing the edges of carboxysome facets.

  7. A pharmacological profile of the high-affinity GluK5 kainate receptor

    DEFF Research Database (Denmark)

    Møllerud, Stine; Kastrup, Jette Sandholm Jensen; Pickering, Darryl S

    2016-01-01

    -hydroxyisoxazol-4-yl)propionate (ATPA), dihydrokainate and (2 S,4 R)−4-methyl-glutamate (SYM2081) have higher affinity at GluK3 compared to GluK5. Since some studies have indicated that GluK5 is associated with various diseases in the central nervous system (e.g. schizophrenia, temporal lobe epilepsy, bipolar...

  8. The Role of GluK4 in Synaptic Plasticity and Affective Behavior in Mice

    Science.gov (United States)

    Catches, Justin Samuel

    Kainate receptors (KARs) are glutamate-gated ion channels that signal through both ionotropic and metabotropic pathways (Contractor et al., 2011). Combinations of five KAR subunits (GluK1-5) form tetrameric receptors with GluK1, GluK2, and GluK3 able to form functional homomeric channels. The high-affinity subunits, GluK4 and GluK5, do not form homomeric channels but modify the properties of heteromeric receptors. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs modulate synaptic plasticity. In this study, ablation of Grik4, which encodes GluK4, in mice reduced KAR synaptic currents and altered activation properties of postsynaptic receptors but left two forms of presynaptic short-term plasticity intact. Disruption of both Grik4 and Grik5 caused complete loss of the postsynaptic ionotropic KAR current and impaired presynaptic frequency facilitation. Additionally, KAR surface expression was altered at pre- and postsynaptic sites at the MF synapse. Despite the loss of ionotropic signaling, KAR-mediated inhibition of the slow afterhyperpolarization current, which is dependent on metabotropic signaling, was intact in CA3 neurons. Long-term potentiation at the MF-CA3 synapse was reduced, likely through a loss of KAR modulation of excitability of the presynaptic MF axons. Genetic variants in the human GRIK4 gene alter the susceptibility for affective disorders (Bloss and Hunter, 2010). We found that ablation of Grik4 in mice resulted in reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, and in two anxiogenic tests, marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim, a test of learned helplessness used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting

  9. Optimizing Your K-5 Engineering Design Challenge

    Science.gov (United States)

    Coppola, Matthew Perkins; Merz, Alice H.

    2017-01-01

    Today, elementary school teachers continue to revisit old lessons and seek out new ones, especially in engineering. Optimization is the process by which an existing product or procedure is revised and refined. Drawn from the authors' experiences working directly with students in grades K-5 and their teachers and preservice teachers, the…

  10. Bringing Inquiry Science to K-5 Classrooms

    Science.gov (United States)

    Schachtel, Paula L.; Messina, D. L.; McDermott, L. C.

    2006-12-01

    As a science coach in the Seattle School District, I am responsible for helping other elementary teachers teach science. For several years, I have been participating in a program that consists of intensive NSF Summer Institutes and an ongoing academic-year Continuation Course. Teachers in this program work through modules in Physics by Inquiry, a research-based curriculum developed by the Physics Education Group at the University of Washington.1 I will discuss how this type of professional development has deepened my understanding of topics in physical science, helped me to teach science by inquiry to my own students, and enabled me to assist my colleagues in implementing inquiry science in their K-5 classrooms. Sponsored by Lillian C. McDermott. 1. A research-based curriculum developed by L.C. McDermott and the Physics Education Group at the University of Washington, Physics by Inquiry, New York, NY, John Wiley & Sons, Inc. (1996.)

  11. One of the 10 cells of AA Injection Kicker K4

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The 3.5 GeV/c Antiproton Accumulator (AA) had 2 delay-line type injection kickers, K3 (12 cells) and K4 (10 cells). Here we see one of the K4 cells, with ferrite between stainless-steel plates. Pulse voltage: 61 kV; rise/fall-time 86 ns; flat-top 460 ns; top flatness +-2%. During injection, the open side of the C-shaped kickers was closed off with a fast shutter, so that their stray field would not perturb the stack of already accumulated antiprotons.

  12. K3 projective models in scrolls

    CERN Document Server

    Johnsen, Trygve

    2004-01-01

    The exposition studies projective models of K3 surfaces whose hyperplane sections are non-Clifford general curves. These models are contained in rational normal scrolls. The exposition supplements standard descriptions of models of general K3 surfaces in projective spaces of low dimension, and leads to a classification of K3 surfaces in projective spaces of dimension at most 10. The authors bring further the ideas in Saint-Donat's classical article from 1974, lifting results from canonical curves to K3 surfaces and incorporating much of the Brill-Noether theory of curves and theory of syzygies developed in the mean time.

  13. A modified K3M thinning algorithm

    Directory of Open Access Journals (Sweden)

    Tabedzki Marek

    2016-06-01

    Full Text Available The K3M thinning algorithm is a general method for image data reduction by skeletonization. It had proved its feasibility in most cases as a reliable and robust solution in typical applications of thinning, particularly in preprocessing for optical character recognition. However, the algorithm had still some weak points. Since then K3M has been revised, addressing the best known drawbacks. This paper presents a modified version of the algorithm. A comparison is made with the original one and two other thinning approaches. The proposed modification, among other things, solves the main drawback of K3M, namely, the results of thinning an image after rotation with various angles.

  14. D-branes on K3-fibrations

    International Nuclear Information System (INIS)

    Kaste, P.; Lerche, W.; Luetken, C.A.; Walcher, J.

    2000-01-01

    B-type D-branes are constructed on two different K3-fibrations over P 1 using boundary conformal field theory at the rational Gepner points of these models. The microscopic CFT charges are compared with the Ramond charges of D-branes wrapped on holomorphic cycles of the corresponding Calabi-Yau manifold. We study in particular D4-branes and bundles localized on the K3 fibers, and find from CFT that each irreducible component of a bundle on K3 gains one modulus upon fibration over P 1 . This is in agreement with expectations and so provides a further test of the boundary CFT approach to D-brane physics

  15. D-Branes on K3-Fibrations

    CERN Document Server

    Kaste, P.; Lutken, C.A.; Walcher, Johannes

    2000-01-01

    B-type D-branes are constructed on two different K3-fibrations over IP_1 using boundary conformal field theory at the rational Gepner points of these models. The microscopic CFT charges are compared with the Ramond charges of D-branes wrapped on holomorphic cycles of the corresponding Calabi-Yau manifold. We study in particular D4-branes and bundles localized on the K3 fibers, and find agreement with expectations. This provides a further test of the boundary CFT approach to $D$-brane physics.

  16. K3 surfaces and their moduli

    CERN Document Server

    Farkas, Gavril; Geer, Gerard

    2016-01-01

    This book provides an overview of the latest developments concerning the moduli of K3 surfaces. It is aimed at algebraic geometers, but is also of interest to number theorists and theoretical physicists, and continues the tradition of related volumes like “The Moduli Space of Curves” and “Moduli of Abelian Varieties,” which originated from conferences on the islands Texel and Schiermonnikoog and which have become classics. K3 surfaces and their moduli form a central topic in algebraic geometry and arithmetic geometry, and have recently attracted a lot of attention from both mathematicians and theoretical physicists. Advances in this field often result from mixing sophisticated techniques from algebraic geometry, lattice theory, number theory, and dynamical systems. The topic has received significant impetus due to recent breakthroughs on the Tate conjecture, the study of stability conditions and derived categories, and links with mirror symmetry and string theory. At the same time, the theory of irred...

  17. Cusps in K->3{pi} decays

    Energy Technology Data Exchange (ETDEWEB)

    Colangelo, G. [Institute for Theoretical Physics, University of Bern, Sidlerstr. 5, CH-3012 Bern (Switzerland); Gasser, J. [Institute for Theoretical Physics, University of Bern, Sidlerstr. 5, CH-3012 Bern (Switzerland); Kubis, B. [Helmholtz-Institut fuer Strahlen- und Kernphysik, Universitaet Bonn, Nussallee 14-16, D-53115 Bonn (Germany); Rusetsky, A. [Helmholtz-Institut fuer Strahlen- und Kernphysik, Universitaet Bonn, Nussallee 14-16, D-53115 Bonn (Germany)]. E-mail: rusetsky@itkp.uni-bonn.de

    2006-07-06

    pion mass difference generates a pronounced cusp in K->3{pi} decays. As has recently been pointed out by Cabibbo and Isidori, an accurate measurement of the cusp may allow one to pin down the S-wave {pi}{pi} scattering lengths to high precision. Here, we present and illustrate an effective field theory framework that allows one to determine the structure of this cusp in a straightforward manner. The strictures imposed by analyticity and unitarity are respected automatically.

  18. Cusps in K->3π decays

    International Nuclear Information System (INIS)

    Colangelo, G.; Gasser, J.; Kubis, B.; Rusetsky, A.

    2006-01-01

    The pion mass difference generates a pronounced cusp in K->3π decays. As has recently been pointed out by Cabibbo and Isidori, an accurate measurement of the cusp may allow one to pin down the S-wave ππ scattering lengths to high precision. Here, we present and illustrate an effective field theory framework that allows one to determine the structure of this cusp in a straightforward manner. The strictures imposed by analyticity and unitarity are respected automatically

  19. Anticancer Vitamin K3 Analogs: A Review.

    Science.gov (United States)

    Badave, Kirti D; Khan, Ayesha A; Rane, Sandhya Y

    2016-01-01

    Menadione (Vitamin K3) comprises of 1,4-naphthoquinone (NQ) moiety that can form redox isomers such as napthosemiquinone (NSQ) and catechol by accepting one or two electrons, respectively. The quinone redox cycling ability leads to the generation of "reactive oxygen species" (ROS) as well as arylation reactions, which are of biological relevance. This ability can be modulated with the help of suitable derivatization. A pharmacophore can be appended at suitable position of Vitamin K3 to have a synergistic or additive effect. In the present review, an attempt has been made to accrue such derivatives modified at 1 or 2 position and evaluated for their cytotoxicity activity on different series of human cancer cell lines such as HeLa, HL-60 and MCF- 7 etc. Production of reactive oxygen species (ROS) and mitochondrial dysfunction caused by Vitamin K3 derivatives leads to apoptosis and tumor inhibition. Recently, the CR-108 compound has shown to exhibit oxidative path together with non-oxidative phosphorylation of p38 MAP kinase in human breast cancer cells. Thus the chemical-biological interactions have been discussed which can be further extrapolated for the development of a potent anticancer drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Totally odd K-4-subdivisions in 4-chromatic graphs

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2001-01-01

    We prove the conjecture made by Bjarne Toft in 1975 that every 4-chromatic graph contains a subdivision of K-4 in which each edge of K-4 corresponds to a path of odd length. As an auxiliary result we characterize completely the subspace of the cycle space generated by all cycles through two fixed...

  1. Phosphorus K4 Crystal: A New Stable Allotrope

    OpenAIRE

    Jie Liu; Shunhong Zhang; Yaguang Guo; Qian Wang

    2016-01-01

    The intriguing properties of phosphorene motivate scientists to further explore the structures and properties of phosphorus materials. Here, we report a new allotrope named K 4 phosphorus composed of three-coordinated phosphorus atoms in non-layered structure which is not only dynamically and mechanically stable, but also possesses thermal stability comparable to that of the orthorhombic black phosphorus (A17). Due to its unique configuration, K 4 phosphorus exhibits exceptional properties: i...

  2. Math and Economics: Implementing Authentic Instruction in Grades K-5

    Science.gov (United States)

    Althauser, Krista; Harter, Cynthia

    2016-01-01

    The purpose of this study is to outline a partnership program that involved a local elementary school district, an institution of higher education, the local business community, and a state economic education advocacy group to integrate economics into math in grades K-5. The "Economics: Math in Real Life" program was provided in…

  3. Spectroscopic properties of K5Li2UF10

    International Nuclear Information System (INIS)

    Karbowiak, M.; Gajek, Z.; Drozdzynski, J.

    2005-01-01

    A new uranium (III) fluoro-complex of the formula K 5 Li 2 UF 10 has been synthesised and characterised by X-ray powder diffraction and electronic absorption spectra measurements. The compound crystallises in the orthorhombic system, space group Pnma, with a = 20.723, b = 7.809, c = 6.932 A, V = 1121.89 A 3 , Z = 4 and is isostructural with its K 5 Li 2 NdF 10 and K 5 Li 2 LaF 10 analogous. The absorption spectrum of a polycrystalline sample of K 5 Li 2 UF 10 was recorded at 4.2 K in the 3500-45,000 cm -1 range and is discussed. The observed crystal-field levels were assigned and fitted to parameters of the simplified angular overlap model (AOM) and next to those of a semi-empirical Hamiltonian, which was representing the combined atomic and one-electron crystal-field interactions. The starting values of the AOM parameters were obtained from ab initio calculations. The analysis of the spectra enabled the assignment of 71 crystal-field levels of U 3+ with a relatively small r.m.s. deviation of 37 cm -1 . The total splitting of 714 cm -1 was calculated for the 4 I 9/2 ground multiplet

  4. Spectroscopic properties of K 5Li 2UF 10

    Science.gov (United States)

    Karbowiak, M.; Gajek, Z.; Drożdżyński, J.

    2005-04-01

    A new uranium (III) fluoro-complex of the formula K 5Li 2UF 10 has been synthesised and characterised by X-ray powder diffraction and electronic absorption spectra measurements. The compound crystallises in the orthorhombic system, space group Pnma, with a = 20.723, b = 7.809, c = 6.932 Å, V = 1121.89 Å 3, Z = 4 and is isostructural with its K 5Li 2NdF 10 and K 5Li 2LaF 10 analogous. The absorption spectrum of a polycrystalline sample of K 5Li 2UF 10 was recorded at 4.2 K in the 3500-45,000 cm -1 range and is discussed. The observed crystal-field levels were assigned and fitted to parameters of the simplified angular overlap model (AOM) and next to those of a semi-empirical Hamiltonian, which was representing the combined atomic and one-electron crystal-field interactions. The starting values of the AOM parameters were obtained from ab initio calculations. The analysis of the spectra enabled the assignment of 71 crystal-field levels of U 3+ with a relatively small r.m.s. deviation of 37 cm -1. The total splitting of 714 cm -1 was calculated for the 4I 9/2 ground multiplet.

  5. Effects of vitamin K3 and K5 on proliferation, cytokine production, and regulatory T cell-frequency in human peripheral-blood mononuclear cells.

    Science.gov (United States)

    Hatanaka, Hiroshige; Ishizawa, Hitomi; Nakamura, Yurie; Tadokoro, Hiroko; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Hirano, Toshihiko

    2014-03-18

    The effects of vitamin K (VK) derivatives VK3 and VK5 on human immune cells have not been extensively investigated. We examined the effects of VK3 and VK5 on proliferation, apoptosis, cytokine production, and CD4+CD25+Foxp3+ regulatory T (Treg) cell-frequency in human peripheral blood mononuclear cells (PBMCs) activated by T cell mitogen in vitro. Anti-proliferative effects of VK3 and VK5 on T-cell mitogen activated PBMCs were assessed by WST assay procedures. Apoptotic cells were determined as Annexin V positive/propidium iodide (PI) negative cells. Cytokine concentrations in the supernatant of the culture medium were measured with bead-array procedures followed by analysis with flow cytometry. The CD4+CD25+Foxp3+Treg cells in mitogen-activated PBMCs were stained with fluorescence-labeled specific antibodies followed by flow cytometry. VK3 and VK5 suppressed the mitogen-activated proliferation of PBMCs significantly at 10-100μM (p<0.05). The data also suggest that VK3 and VK5 promote apoptosis in the mitogen-activated T cells. VK3 and VK5 significantly inhibited the production of tumor necrosis factor (TNF) α, interleukin (IL)-4, -6, and -10 from the activated PBMCs at 10-100μM (p<0.05). In contrast, VK3 and VK5 significantly increased Treg cell-frequency in the activated PBMCs at concentrations more than 10μM (p<0.001). Our data suggest that VK3 and VK5 attenuate T cell mediated immunity by inhibiting the proliferative response and inducing apoptosis in activated T cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Bacterial Electrocatalysis of K4[Fe(CN)6] Oxidation

    DEFF Research Database (Denmark)

    Zheng, Zhiyong; Xiao, Yong; Wu, Ranran

    Shewanella oneidensis MR-1 (MR-1), a model strain of electrochemically active bacteria, can transfer electrons from cell to extracellular electron acceptors including Fe(III) (hydro)oxides. It has been reported that several redox species such as cytochromes in membranes and flavins assist...... in the electron transport (ET) processes. However, the oxidization of metal compounds was barely described. Here we report electrocatalysis of K4[Fe(CN)6] oxidation by MR-1. K4[Fe(CN)6] is a redox inorganic compound and shows a reversible redox process on bare glassy carbon (GCE). This is reflected by a pair...

  7. Ideas: NCTM Standards-Based Instruction, Grades K-4.

    Science.gov (United States)

    Hynes, Michael C., Ed.

    This document is a collection of activity-based mathematics lessons for grades K-4 from the "Ideas" department in "Arithmetic Teacher: Mathematics Education through the Middle Grades." Each lesson includes background information, objectives, directions, extensions, and student worksheets. A matrix is included which correlates…

  8. CCM key comparison CCM.D-K4 'Hydrometer'

    Science.gov (United States)

    Lorefice, S.; Becerra, L. O.; Lenard, E.; Lee, Y. J.; Lee, W. G.; Madec, T.; Meury, P. A.; Caceres, J.; Santos, C.; Vamossy, C.; Man, J.; Fen, K.; Toda, K.; Wright, J.; Bettin, H.; Toth, H.

    2016-01-01

    This report presents the comparison philosophy, methodology, analysis and the results of the designed CCM.D-K4 key comparison that covered the calibration of high resolution hydrometers for liquid and alcoholometers in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20°C. The main purpose of this comparison was not only to evaluate the degree of equivalence in the calibration of high accuracy hydrometers between NMI participants, but also to link, were it is possible, the results of previous comparisons to Key Comparison Reference Values (KCRVs) of CCM.D-K4. Eleven NMI laboratories took part in the CCM.D-K4 divided in two groups (petals). With the CCM.D-K4 purpose, two similar sets consisting of three hydrometers for liquid density determinations and an alcoholometer were circulated to the NMI participants as a travelling standard in the time interval from January 2011 to April 2012. Twelve Key Comparison Reference Values (KCRVs) for each petal have been obtained at the density values related to the tested density marks of the transfer standards by the results of participants. The KCRVs and corresponding uncertainties were calculated by the weighted mean in the case of consistent results, otherwise the median was used. The degree of equivalence (DoE) with respect to the corresponding KCRV was determined for each participant and, in this particular comparison, the Weighted Least Squares (WLS) method was used to link the individual DoE of each participant by a continuous function. Significant drift of the transfer standards was not detected. This report also gives instructions on calculating pair-wise degrees of equivalence, with the addition of any information on correlations that may be necessary to estimate more accurately as well as the procedure for linking international comparisons to the CCM.D-K4. Finally an example of linkage to the CCM.D-K4 is given by dealing with the results of the bilateral comparison between INRiM and NMIA, which was

  9. Symplectic S5 action on symplectic homotopy K3 surfaces

    Indian Academy of Sciences (India)

    HONGXIA LI

    Let X be a symplectic homotopy K3 surface and G = S5 act on X symplectically. In this paper, we give a weak classification of the G action on X by discussing the fixed-point set structure. Besides, we analyse the exoticness of smooth structures of X under the action of G. Keywords. K3 surfaces; symplectic actions; exotic ...

  10. Opportunities to Align California's PreK-3 Education System

    Science.gov (United States)

    Policy Analysis for California Education, PACE, 2016

    2016-01-01

    "PreK-3 Alignment in California's Education System: Obstacles and Opportunities" by Rachel Valentino and Deborah J. Stipek reviews the opportunities and challenges that must be addressed to better align PreK-3 education in California. The report describes policies and practices that districts have implemented to strengthen alignment, and…

  11. Kählerian K3 surfaces and Niemeier lattices. I

    International Nuclear Information System (INIS)

    Nikulin, V V

    2013-01-01

    Using the results obtained in [1], Remark 1.14.7, we clarify the relation between Kählerian K3 surfaces and Niemeier lattices. We emphasize that all 24 Niemeier lattices are important in the description of K3 surfaces, not only the one related to the Mathieu group

  12. Phosphotungstic acid binding in situ to K4Nb6O17 for the effective adsorption-photocatalytic removal of tetracycline

    Science.gov (United States)

    Gu, Huimin; Lang, Junyu; Ma, Yuli; Gu, Huayu; Song, Yanyong; Chai, Zhanli; Li, Guangshe; Wang, Xiaojing

    2018-05-01

    In this investigation, phosphotungstic acid (H3PW12O40) was successfully self-assembly implanted into the interspace of K4Nb6O17 nanosheet via an impregnation method to form an adsorption-photocatalytic composite, in which n-type semiconductor K4Nb6O17 was selected as photo-electron emitter and H3PW12O40 was particularly used as an electronic transmitter. By characterizing with X-ray diffraction (XRD), transmission (TEM), scan electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and FT-IR spectrum (FT-IR), it confirmed that H3PW12O40 (HPW) was converted to the insoluble tiny particles of K3PW12O40 (KPW) with the remained primary Keggin group via an ion-exchanged H+ of HPW with K+ in K4Nb6O17 in the implanted process and was firmly bound to the surface of K4Nb6O17 to form well sandwich structure. UV-vis diffuse reflectance spectroscopy revealed that the band gap of K4Nb6O17-K3PW12O40 have a slight red shift compared with the single K4Nb6O17. Its adsorption-photocatalytic properties were evaluated with the removal of tetracycline as model reaction. Compared with pure K4Nb6O17, tetracycline removal rate can be significantly improved for the as-prepared sandwich. Importantly, the removal could still maintain 70% after five reuses in recycle tests at an acidic solution, inferring a good stability which was mainly ascribed to the formation of water-insoluble K3PW12O40. The separation and transfer process of photogenerated electrons were investigated by surface photovoltage spectroscopy (SPV). It proposed that the KPW anchored firmly on the interlayers of K4Nb6O17 through a O-K-O bridge plays a significantly role in promoting the separation of the photogenerated carriers and preventing the leakage and agglomeration of HPW. The present results showed that the strategy of the phosphotungstic acid binding in situ to K4Nb6O17 was favorable to promote the hetero-photocatalytic efficiency as well as reusability. [Figure not available: see fulltext.

  13. Reading, Writing & Rings: Science Literacy for K-4 Students

    Science.gov (United States)

    McConnell, S.; Spilker, L.; Zimmerman-Brachman, R.

    2007-12-01

    Scientific discovery is the impetus for the K-4 Education program, "Reading, Writing & Rings." This program is unique because its focus is to engage elementary students in reading and writing to strengthen these basic academic skills through scientific content. As science has been increasingly overtaken by the language arts in elementary classrooms, the Cassini Education Program has taken advantage of a new cross-disciplinary approach to use language arts as a vehicle for increasing scientific content in the classroom. By utilizing the planet Saturn and the Cassini-Huygens mission as a model in both primary reading and writing students in these grade levels, young students can explore science material while at the same time learning these basic academic skills. Content includes reading, thinking, and hands-on activities. Developed in partnership with the Cassini-Huygens Education and Public Outreach Program, the Bay Area Writing Project/California Writing Project, Foundations in Reading Through Science & Technology (FIRST), and the Caltech Pre-College Science Initiative (CAPSI), and classroom educators, "Reading, Writing & Rings" blends the excitement of space exploration with reading and writing. All materials are teacher developed, aligned with national science and language education standards, and are available from the Cassini-Huygens website: http://saturn.jpl.nasa.gov/education/edu-k4.cfm Materials are divided into two grade level units. One unit is designed for students in grades 1 and 2 while the other unit focuses on students in grades 3 and 4. Each includes a series of lessons that take students on a path of exploration of Saturn using reading and writing prompts.

  14. In vitro comparison in a manikin model: increasing apical enlargement with K3 and K3XF rotary instruments.

    Science.gov (United States)

    Olivieri, Juan Gonzalo; Stöber, Eva; García Font, Marc; González, Jose Antonio; Bragado, Pablo; Roig, Miguel; Duran-Sindreu, Fernando

    2014-09-01

    The aim of the study was to compare the K3 and K3XF systems (SybronEndo, Glendora, CA) after 1 and 2 uses by evaluating apical transportation, working length loss, and working time in a manikin model. Mesial canals of 40 extracted first mandibular molars were instrumented. Radiographs taken after instrumentation with #25, #30, #35, and #40 files were superimposed on the preoperative image in both mesiodistal and buccolingual angulations. AutoCAD (Autodesk Inc, San Rafael, CA) was used to measure working length loss and apical transportation at 0, 0.5, and 1 mm from the working length (WL). The working time was measured. Group comparison was analyzed using post hoc Tukey honestly significant difference tests (P < .05). No significant differences were found in apical transportation, working length loss between K3 and K3XF systems, or between the number of uses. Significant differences were found when canal enlargement was performed to a #35-40 (P < .05). K3 instrumentation performed significantly faster (29.6 ± 15.4) than with the K3XF system (40.2 ± 17.7) (P < .05). No differences were observed in working time when comparing the number of uses. K3 and R-phase K3XF rotary systems shaped curved root canals safely with minimal apical transportation, even up to a 40/04 file. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor

    International Nuclear Information System (INIS)

    Fan Junkai; Xiao Tian; Gu Jinfa; Wei Na; He Lingfeng; Ding Miao; Liu Xinyuan

    2008-01-01

    Angiogenesis plays a key role in the development of a wide variety of malignant tumors. The approach of targeting antiangiogenesis has become an important field of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the kringle 5 of human plasminogen) has been mutated by changing leucine71 to arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus expressing mK5, was constructed. It showed stronger inhibition on proliferation of human umbilical vein endothelial cell. Moreover, in tube formation and embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious suppression on the growth of colorectal tumor xenografts and prolonged the life span of nude mice. These results indicate that ZD55-mK5 is a potent agent for inhibiting the tumor angiogenesis and tumor growth

  16. 26 CFR 1.401(k)-5 - Special rules for mergers, acquisitions and similar events. [Reserved

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Special rules for mergers, acquisitions and similar events. [Reserved] 1.401(k)-5 Section 1.401(k)-5 Internal Revenue INTERNAL REVENUE SERVICE... Bonus Plans, Etc. § 1.401(k)-5 Special rules for mergers, acquisitions and similar events. [Reserved] [T...

  17. Synergistic cytotoxic action of vitamin C and vitamin K3.

    Science.gov (United States)

    Zhang, W; Negoro, T; Satoh, K; Jiang, Y; Hashimoto, K; Kikuchi, H; Nishikawa, H; Miyata, T; Yamamoto, Y; Nakano, K; Yasumoto, E; Nakayachi, T; Mineno, K; Satoh, T; Sakagami, H

    2001-01-01

    We investigated the combination effect of sodium ascorbate (vitamin C) and menadione (vitamin K3) on the viability of various cultured cells. Human oral squamous cell carcinoma (HSC-2, HSC-3) and human promyelocytic leukemia (HL-60) cells were more sensitive to these vitamins as compared to normal cells (human gingival fibroblast HGF, human periodontal ligament fibroblast HPLF, human pulp cell HPC). The combination of vitamin C and vitamin K3 produced synergistic cytotoxicity against all these 6 cell lines. Treatment with vitamin C or vitamin K3, or their combination, induced internucleosomal DNA fragmentation only in HL-60 cells, but not in the oral tumor cell lines (HSC-2, HSC-3, HSG). ESR spectroscopy showed that vitamins C and K3 produce radicals under alkaline conditions and that the combination of these two vitamins synergistically enhanced their respective radical intensities.

  18. Landau-Ginzburg orbifolds and symmetries of K3 CFTs

    International Nuclear Information System (INIS)

    Cheng, Miranda C. N.; Ferrari, Francesca; Harrison, Sarah M.; Paquette, Natalie M.

    2017-01-01

    Recent developments in the study of the moonshine phenomenon, including umbral and Conway moonshine, suggest that it may play an important role in encoding the action of finite symmetry groups on the BPS spectrum of K 3 string theory. To test and clarify these proposed K 3 -moonshine connections, we study Landau-Ginzburg orbifolds that flow to conformal field theories in the moduli space of K 3 sigma models. We compute K 3 elliptic genera twined by discrete symmetries that are manifest in the UV description, though often inaccessible in the IR. We obtain various twining functions coinciding with moonshine predictions that have not been observed in physical theories before. These include twining functions arising from Mathieu moonshine, other cases of umbral moonshine, and Conway moonshine. For instance, all functions arising from M 11 c 2.M 12 moonshine appear as explicit twining genera in the LG models, which moreover admit a uniform description in terms of its natural 12-dimensional representation. Finally, our results provide strong evidence for the relevance of umbral moonshine for K 3 symmetries, as well as new hints for its eventual explanation.

  19. Landau-Ginzburg orbifolds and symmetries of K3 CFTs

    Science.gov (United States)

    Cheng, Miranda C. N.; Ferrari, Francesca; Harrison, Sarah M.; Paquette, Natalie M.

    2017-01-01

    Recent developments in the study of the moonshine phenomenon, including umbral and Conway moonshine, suggest that it may play an important role in encoding the action of finite symmetry groups on the BPS spectrum of K3 string theory. To test and clarify these proposed K3-moonshine connections, we study Landau-Ginzburg orbifolds that flow to conformal field theories in the moduli space of K3 sigma models. We compute K3ellipticgeneratwinedbydiscretesymmetriesthataremanifestintheUVdescription, though often inaccessible in the IR. We obtain various twining functions coinciding with moonshine predictions that have not been observed in physical theories before. These include twining functions arising from Mathieu moonshine, other cases of umbral moonshine, and Conway moonshine. For instance, all functions arising from M 11 ⊂ 2 .M 12 moonshine appear as explicit twining genera in the LG models, which moreover admit a uniform description in terms of its natural 12-dimensional representation. Our results provide strong evidence for the relevance of umbral moonshine for K3 symmetries, as well as new hints for its eventual explanation.

  20. The Amazing COS FUV (1320 - 1460 A) Spectrum of (lambda) Vel (K4Ib-II)

    Science.gov (United States)

    Carpenter, Kenneth

    2010-01-01

    The FUV spectrum (1320-1460 A) of the K4 lb-11 supergiant (lambda) Vel was observed with the Cosmic Origins Spectrograph (COS) on HST, as part of the Ayres and Redfield Cycle 17 SNAP program "SNAPing Coronal Iron". This spectrum covers a region not previously recorded in (lambda) Vel at high resolution and, in a mere 20 minutes of exposure, reveals a treasure trove of information. It shows a wide variety of strong emission lines, superposed on a bright continuum, with contributions from both atomic and molecular species. Multiple absorptions, including numerous Ni II and Fe II lines, are visible over this continuum, which is likely generated in the chromosphere of the star. Evidence of the stellar wind is seen in the P Cygni profiles of the CII lines near 1335 A and the results of fluorescence processes are visible throughout the region. The spectrum has remarkable similarities to that of (alpha) Boo (K1.5 III), but significant differences as well, including substantial FUV continuum emission, reminiscent of the M2 Iab supergiant (alpha) Ori, but minus the CO fundamental absorption bands seen in the spectrum of the latter star. However, fluoresced CO emission is present, as in the K-giant stars (alpha) Boo and (alpha) Tau (K5 III). The presence of hot plasma in the atmosphere of the star, indicated by previous GHRS observations of Si III] and C III] lines near 1900 A and FUSE observations of O VI 1032 A, is further confirmed by the detection in this COS spectrum of the Si IV UV 1 lines near 1400 A, though both lines are contaminated by overlying fluorescent H2 emission. We present the details of this spectrum, in comparison with stars of similar temperature or luminosity and discuss the implications for the structure of, and the radiative processes active in, the outer atmospheres of these stars.

  1. Supersymmetry Constraints and String Theory on K3

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ying-Hsuan; Shao, Shu-Heng [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States); Wang, Yifan [Center for Theoretical Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Yin, Xi [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States)

    2015-12-22

    We study supervertices in six dimensional (2,0) supergravity theories, and derive supersymmetry non-renormalization conditions on the 4- and 6-derivative four-point couplings of tensor multiplets. As an application, we obtain exact non-perturbative results of such effective couplings in type IIB string theory compactified on K3 surface, extending previous work on type II/heterotic duality. The weak coupling limit thereof, in particular, gives certain integrated four-point functions of half-BPS operators in the nonlinear sigma model on K3 surface, that depend nontrivially on the moduli, and capture worldsheet instanton contributions.

  2. Note on twisted elliptic genus of K3 surface

    Energy Technology Data Exchange (ETDEWEB)

    Eguchi, Tohru, E-mail: eguchi@yukawa.kyoto-u.ac.j [Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan); Hikami, Kazuhiro, E-mail: KHikami@gmail.co [Department of Mathematics, Naruto University of Education, Tokushima 772-8502 (Japan)

    2011-01-03

    We discuss the possibility of Mathieu group M{sub 24} acting as symmetry group on the K3 elliptic genus as proposed recently by Ooguri, Tachikawa and one of the present authors. One way of testing this proposal is to derive the twisted elliptic genera for all conjugacy classes of M{sub 24} so that we can determine the unique decomposition of expansion coefficients of K3 elliptic genus into irreducible representations of M{sub 24}. In this Letter we obtain all the hitherto unknown twisted elliptic genera and find a strong evidence of Mathieu moonshine.

  3. Note on twisted elliptic genus of K3 surface

    International Nuclear Information System (INIS)

    Eguchi, Tohru; Hikami, Kazuhiro

    2011-01-01

    We discuss the possibility of Mathieu group M 24 acting as symmetry group on the K3 elliptic genus as proposed recently by Ooguri, Tachikawa and one of the present authors. One way of testing this proposal is to derive the twisted elliptic genera for all conjugacy classes of M 24 so that we can determine the unique decomposition of expansion coefficients of K3 elliptic genus into irreducible representations of M 24 . In this Letter we obtain all the hitherto unknown twisted elliptic genera and find a strong evidence of Mathieu moonshine.

  4. Eta products, BPS states and K3 surfaces

    Energy Technology Data Exchange (ETDEWEB)

    He, Yang-Hui [Department of Mathematics, City University,London, EC1V 0HB (United Kingdom); School of Physics, NanKai University,Tianjin, 300071 (China); Merton College, University of Oxford,Oxford, OX14JD (United Kingdom); McKay, John [Department of Mathematics and Statistics, Concordia University,1455 de Maisonneuve Blvd. West, Montreal, Quebec, H3G 1M8 (Canada)

    2014-01-22

    Inspired by the multiplicative nature of the Ramanujan modular discriminant, Δ, we consider physical realizations of certain multiplicative products over the Dedekind eta-function in two parallel directions: the generating function of BPS states in certain heterotic orbifolds and elliptic K3 surfaces associated to congruence subgroups of the modular group. We show that they are, after string duality to type II, the same K3 surfaces admitting Nikulin automorphisms. In due course, we will present identities arising from q-expansions as well as relations to the sporadic Mathieu group M{sub 24}.

  5. K3-fibered Calabi-Yau threefolds II, singular fibers

    OpenAIRE

    Hunt, Bruce

    1999-01-01

    In part I of this paper we constructed certain fibered Calabi-Yaus by a quotient construction in the context of weighted hypersurfaces. In this paper look at the case of K3 fibrations more closely and study the singular fibers which occur. This differs from previous work since the fibrations we discuss have constant modulus, and the singular fibers have torsion monodromy.

  6. N=4 superconformal bootstrap of the K3 CFT

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ying-Hsuan; Shao, Shu-Heng [Jefferson Physical Laboratory, Harvard University,17 Oxford Street, Cambridge, MA 02138 (United States); Simmons-Duffin, David [School of Natural Sciences, Institute for Advanced Study,1 Einstein Drive, Princeton, NJ 08540 (United States); Wang, Yifan [Center for Theoretical Physics, Massachusetts Institute of Technology,77 Massachusetts Ave, Cambridge, MA 02139 (United States); Yin, Xi [Jefferson Physical Laboratory, Harvard University,17 Oxford Street, Cambridge, MA 02138 (United States)

    2017-05-23

    We study two-dimensional (4,4) superconformal field theories of central charge c=6, corresponding to nonlinear sigma models on K3 surfaces, using the superconformal bootstrap. This is made possible through a surprising relation between the BPS N=4 superconformal blocks with c=6 and bosonic Virasoro conformal blocks with c=28, and an exact result on the moduli dependence of a certain integrated BPS 4-point function. Nontrivial bounds on the non-BPS spectrum in the K3 CFT are obtained as functions of the CFT moduli, that interpolate between the free orbifold points and singular CFT points. We observe directly from the CFT perspective the signature of a continuous spectrum above a gap at the singular moduli, and find numerically an upper bound on this gap that is saturated by the A{sub 1}N=4 cigar CFT. We also derive an analytic upper bound on the first nonzero eigenvalue of the scalar Laplacian on K3 in the large volume regime, that depends on the K3 moduli data. As two byproducts, we find an exact equivalence between a class of BPS N=2 superconformal blocks and Virasoro conformal blocks in two dimensions, and an upper bound on the four-point functions of operators of sufficiently low scaling dimension in three and four dimensional CFTs.

  7. N=4 Superconformal Bootstrap of the K3 CFT

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    We study two-dimensional (4,4) superconformal field theories of central charge c=6, corresponding to nonlinear σ models on K3 surfaces, using the superconformal bootstrap. This is made possible through a surprising relation between the BPS N=4 superconformal blocks with c=6 and bosonic Virasoro conformal blocks with c=28, and an exact result on the moduli dependence of a certain integrated BPS 4-point function. Nontrivial bounds on the non-BPS spectrum in the K3 CFT are obtained as functions of the CFT moduli, that interpolate between the free orbifold points and singular CFT points. We observe directly from the CFT perspective the signature of a continuous spectrum above a gap at the singular moduli, and find numerically an upper bound on this gap that is saturated by the A1 N=4 cigar CFT. We also derive an analytic upper bound on the first nonzero eigenvalue of the scalar Laplacian on K3 in the large volume regime, that depends on the K3 moduli data. As two byproducts, we find an exact equivalence...

  8. A Primary Grade (K-3) Earth Science Program

    Science.gov (United States)

    Schwartz, Maurice L.; Slesnick, Irwin L.

    1973-01-01

    Describes the rationale and structure of a newly developed earth science program for elementary school children (K-3). The activities involve pre-operational and concrete operational stages, progressing from one to the other. Children show sustained interest and enthusiasm as they investigate landforms, the moon, fossils, and weather phenomena.…

  9. Exploring Parents’ Perceptions of Student Absenteeism in K-3

    OpenAIRE

    Karpilovski, Margarita

    2017-01-01

    Chronic absenteeism affects students’ academic achievement as well as their social and emotional wellbeing. In early elementary school, the primary responsibility for school attendance rests with parents and guardians. This thesis investigates parents’ perceptions of factors related to school attendance. The study was conducted in BC’s largest school district within the context of an absenteeism reduction program. Fifty-four parents of students in K-3 from 15 inner-city schools participated i...

  10. Association between H3K4 methylation and cancer prognosis: A meta-analysis.

    Science.gov (United States)

    Li, Simin; Shen, Luyan; Chen, Ke-Neng

    2018-05-08

    Histone H3 lysine 4 methylation (H3K4 methylation), including mono-methylation (H3K4me1), di-methylation (H3K4me2), or tri-methylation (H3K4me3), is one of the epigenetic modifications to histone proteins, which are related to the transcriptional activation of genes. H3K4 methylation has both tumor inhibiting and promoting effects, and the prognostic value of H3K4 methylation in cancer remains controversial. Therefore, we performed a systematic review and meta-analysis to examine the association between H3K4 methylation and cancer prognosis. A comprehensive search of PubMed, Web of Science, ScienceDirect, Embase, and Ovid databases was conducted to identify studies investigating the association between H3K4 methylation and prognosis of patients with malignant tumors. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. A total of 1474 patients in 10 studies were enrolled in this meta-analysis. The pooled HR of 1.52 (95% CI 1.02-2.26) indicated that patients with a lower level of H3K4me2 expression were expected to have shorter overall survival, while the pooled HR of 0.45 (95% CI 0.27-0.74) indicated that patients with a lower level of H3K4me3 expression were expected to have longer overall survival. This meta-analysis indicates that increased H3K4me3 expression and decreased H3K4me2 expression might be predictive factors of poor prognosis in cancer. Further large cohort studies are needed to confirm these findings. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  11. Topotactic dehydration of the lamellar oxide HK2Ti5NbO14 x H2O: the oxide K4Ti10Nb2O27

    International Nuclear Information System (INIS)

    Grandin, A.; Borel, M.M.; Hervieu, M.; Raveau, B.

    1987-01-01

    The lamellar oxide HK 2 Ti 5 NbO 14 x H 2 O can be topotactically dehydrated to K 4 Ti 10 Nb 2 O 27 . Electron diffraction and X-ray diffraction studies of this phase lead to a monoclinic cell with the parameters a = 17.005, b = 3.78, c = 9.01 A and β 92.14 0 . Diffusion streaks on the electron diffraction patterns indicate disorder whereas the existence of two sets of lattices on the same crystal give evidence of the topotactic character of the reaction. A structural model is proposed for K 4 Ti 10 Nb 2 O 27 , which corresponds to the intergrowth of K 3 TiNbO 14 layers with the K 2 Ti 6 O 13 tunnel structure. The possibility of formation of various intergrowths such as (KTi 5 NbO 13 )/sub n/ (HK 2 Ti 5 NbO 14 )/sub n/' is suggested

  12. High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

    2006-09-01

    The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

  13. A SNAPshot of the FUV (1320 - 1460 A) Spectrum of Lambda Vel (K4Ib-II)

    Science.gov (United States)

    Carpenter, Kenneth G.

    2010-01-01

    The FUV spectrum (l330-1460A) of the K4Ib-II supergiant Lambda Vel was observed with the Cosmic Origins Spectrograph (COS) on HST, as part of the Ayres and Redfield Cycle 17 SNAP program "SNAPing Coronal Iron". This spectrum covers a region not previously seen in Lambda Vel at high resolution and reveals a rich emission-line spectrum superposed on a bright continuum, with contributions from a variety of atomic and molecular sources. Evidence of the stellar wind is seen in the P Cygni profiles of selected lines and the results of fluorescence processes are visible throughout the region. The spectrum has remarkable similarities to that of Alpha Boo (K1.5 III), but significant differences as well, including substantial FUV continuum emission, reminiscent of the M2 lab supergiant Alpha Ori, but minus the CO fundamental absorption bands seen in the latter star. However, fluoresced CO emission is present and strong, as in the K-giant stars Alpha Boo and Alpha Tau (K5 III). We present the details of this spectrum, in comparison to stars of similar temperature or luminosity and discuss the implications for the structure of and the radiative processes active in, the outer atmospheres of these stars.

  14. Effects of nickel treatment on H3K4 trimethylation and gene expression.

    Directory of Open Access Journals (Sweden)

    Kam-Meng Tchou-Wong

    Full Text Available Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl(2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3, a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq. The effect of NiCl(2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl(2. This study may provide insights into the epigenetic mechanism(s underlying the carcinogenicity of nickel compounds.

  15. Genome-Wide H3K4me3 Analysis in Angus Cattle with Divergent Tenderness.

    Directory of Open Access Journals (Sweden)

    Chunping Zhao

    Full Text Available Tenderness is one of the most important properties of meat quality, which is influenced by genetic and environmental factors. As an intensively studied epigenetic marker, histone methylation, occurring on arginine and lysine residues, has pivotal regulatory functions on gene expression. To examine whether histone methylation involves in beef tenderness variation, we analyzed the transcriptome and H3K4me3 enrichment profiles of muscle strips obtained from the longissimus dorsi (LD of Angus steers previously classify to the tender or tough group. We first plotted a global bovine H3K4me3 map on chromosomes and called peak-enriched regions and genes. We found that majorities of H3K4me3 on genes were occupying the first intron and intergenic regions and its maps displayed similar patterns in tender and tough groups, with high H3K4me3 enrichment surrounding the transcription start site (TSS. We also explored the relationship of H3K4me3 and gene expression. The results showed that H3K4me3 enrichment is highly positively correlated with gene expression across the whole genome. Cluster analysis results confirmed the relationship of H3K4me3 enrichment and gene expression. By using a pathway-based approach in genes with H3K4me3 enrichment in promoter regions from the tender cluster, we revealed that those genes involved in the development of different tissues-connective tissue, skeletal and muscular system and functional tissues-; while in tough group those genes engaged in cell death, lipid metabolism and small molecule biochemistry. The results from this study provide a deep insight into understanding of the mechanisms of epigenetic regulations in meat quality and beef tenderness.

  16. CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes

    Directory of Open Access Journals (Sweden)

    Chao Yu

    2017-08-01

    Full Text Available Trimethylation of histone H3 at lysine-4 (H3K4me3 is associated with eukaryotic gene promoters and poises their transcriptional activation during development. To examine the in vivo function of H3K4me3 in the absence of DNA replication, we deleted CXXC finger protein 1 (CFP1, the DNA-binding subunit of the SETD1 histone H3K4 methyltransferase, in developing oocytes. We find that CFP1 is required for H3K4me3 accumulation and the deposition of histone variants onto chromatin during oocyte maturation. Decreased H3K4me3 in oocytes caused global downregulation of transcription activity. Oocytes lacking CFP1 failed to complete maturation and were unable to gain developmental competence after fertilization, due to defects in cytoplasmic lattice formation, meiotic division, and maternal-zygotic transition. Our study highlights the importance of H3K4me3 in continuous histone replacement for transcriptional regulation, chromatin remodeling, and normal developmental progression in a non-replicative system.

  17. Signal transduction of vitamin K3 for pancreas cancer therapy

    Directory of Open Access Journals (Sweden)

    Toshiyuki Tanahashi

    2011-10-01

    Full Text Available We characterized molecular mechanisms of vitamin K3 (VK3-induced inhibition of proliferation to evaluate VK3 effectiveness in treating advanced pancreatic cancer. A novel endoscopic drug delivery system, ultrasound injection technique, was used to study local effects of VK3. VK3 inhibited pancreas cancer cell growth by rapid phosphorylation of growth factor receptor and cellular signal factors such as extracellular signal-regulated kinase. VK3 also activated apoptosis, and apoptosis inhibitor antagonized the apoptosis pathway without inhibiting cell growth. Thiol antioxidant treatment completely abrogated VK3-induced ERK but not JNK phosphorylation or inhibition of proliferation. Non-thiol antioxidant did not affect ERK phosphorylation or growth inhibitory actions. Arylation was considered the main mechanism of VK3-induced growth inhibition through ERK activation. VK3 may lead to favorable outcomes in the treatment of pancreatic tumors. Detection of ERK phosphorylation in tissue is important to predict VK3 effect. Endoscopic ultrasound-guided fine-needle injection may be beneficial for treating pancreatic cancer with VK3.

  18. Vitamin K3 analogs induce selective tumor cytotoxicity in neuroblastoma.

    Science.gov (United States)

    Kitano, Toru; Yoda, Hiroyuki; Tabata, Keiichi; Miura, Motofumi; Toriyama, Masaharu; Motohashi, Shigeyasu; Suzuki, Takashi

    2012-01-01

    We investigated the cytotoxicity of eight vitamin K3 (VK3) analogs against neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, and SK-N-SH) and normal cell lines (human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF)) using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. 2-[(2-Methoxy)ethylthio]-3-methyl-1,4-naphthoquinone (VK3-OCH(3)) showed especially potent cytotoxic activities against neuroblastoma cells compared with normal cells. In a Hoechst 33342 staining experiment, apoptotic morphologies characterized by cell shrinkage, nuclear condensation, and nuclear fragmentation were observed in IMR-32 and LA-N-1 cells after 48 h of treatment with 10(-5) M of VK3-OCH(3). To clarify the molecular mechanisms of apoptosis induced by VK3-OCH(3), we examined the expression of apoptosis related proteins using a Proteome Profiler Array and western blotting. Heme oxygenase (HO)-1 was remarkably increased by VK3-OCH(3) compared with the control (173% in IMR-32 and 170% in LA-N-1 at 24 h). Moreover, caveolin-1 was induced by VK3-OCH(3) at 48 h. In addition, VK3-OCH(3) arrested the cell cycle at the G2/M phase in IMR-32 cells. These results suggest that VK3-OCH(3) exhibited a selective antitumor activity via HO-1-related mechanisms.

  19. Prepotential, Mirror Map and F-Theory on K3

    CERN Document Server

    Lerche, W.

    1998-01-01

    We compute certain one-loop corrections to F^4 couplings of the heterotic string compactified on T^2, and show that they can be characterized by holomorphic prepotentials. We then discuss how some of these couplings can be obtained in F-theory, or more precisely from 7-brane geometry in type IIB language. We in particular study theories with E_8 x E_8 and SO(8)^4 gauge symmetry, on certain one-dimensional sub-spaces of the moduli space that correspond to constant IIB coupling. For these theories, the relevant geometry can be mapped to Riemann surfaces. Physically, the computations amount to non-trivial tests of the basic F-theory -- heterotic duality in eight dimensions. Mathematically, they mean to associate holomorphic 5-point couplings of the form (del_t)^5 G = sum[ g_l l^5 q^l/(1-q^l) ] to K3 surfaces. This can be seen as a novel manifestation of the mirror map, acting here between open and closed string sectors.

  20. Overcoming Pedagogical, Social/Cultural, and Attitudinal Barriers to Technology Integration in K-5 Schools

    Science.gov (United States)

    Durff, Lisa

    2017-01-01

    Technology engages and increases academic achievement for K-5 students, but teachers face attitudinal, social/cultural, and pedagogical barriers when they integrate technology for student learning. Although some teachers overcome these barriers, it remains unclear how they do so. The purpose of this qualitative multiple case study was to analyze…

  1. 29 CFR 71.52 - Specific exemptions pursuant to subsection (k)(5) of the Privacy Act.

    Science.gov (United States)

    2010-07-01

    ... (Investigative Case Tracking Systems/Audit Information Reporting Systems, USDOL/OIG), a system of records... AND ACCESS TO RECORDS UNDER THE PRIVACY ACT OF 1974 Exemption of Records Systems Under the Privacy Act § 71.52 Specific exemptions pursuant to subsection (k)(5) of the Privacy Act. (a) The following systems...

  2. The utility of vitamin K3 (menadione) against pancreatic cancer.

    Science.gov (United States)

    Osada, Shinji; Tomita, Hiroyuki; Tanaka, Yoshihiro; Tokuyama, Yasuharu; Tanaka, Hidenori; Sakashita, Fumio; Takahashi, Takao

    2008-01-01

    To evaluate the efficacy of vitamin K3 (VK3) against pancreatic cancer, the molecular mechanism of VK3 or gemcitabine (GEM)-induced inhibition of proliferation was characterized. The cell viability was determined using the 3-[4,5-dimethylthiazol]-2,5-diphenyl tetrazolium bromide (MTT) test method. The expressions of cellular proteins were evaluated by Western blot analysis. For morphological studies of the in vivo transplanted cancer cells, the tissues were stained with hematoxylin and eosin. The IC50 of VK3 for pancreatic cancer cells was calculated for 42.1 +/- 3.5 microM. Western blot analysis showed that VK3 induced rapid phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) 30 minutes after application. ERK but not JNK phosphorylation was maintained for at least 12 hours. Activation of apoptosis by VK3, as shown by molecular weight shifts of the pro-activated 32-kDa form of caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage of the 112-kDa form, was found. Treatment with the thiol antioxidant, L-cysteine (>0.2 mM), completely abrogated the VK3-induced phosphorylation of ERK, but not the JNK, and inhibition of proliferation. A caspase-3 inhibitor antagonized caspase-3 activation, but had no inhibitory effect on the proliferative activity of VK3. GEM at concentrations >0.1 microg/ml was found to inhibit cell proliferation after 24 hours. GEM also induced phosphorylation of JNK, activation of caspase-3 and accumulation of cyclin B1. Local application of VK3 was found to induce extensive tumor tissue necrosis, but slight hematemesis without necrosis was observed 48 hours after GEM injection. In Western blot, ERK but not JNK phosphorylation, was clearly detected in response to VK3 injection into the tumor tissue. The action of VK3 may lead to a favorable outcome against pancreatic cancer, and the detection of ERK phosphorylation in the tissue is important for predicting this effect.

  3. Role of H3K4 demethylases in complex neurodevelopmental diseases.

    Science.gov (United States)

    Wynder, Christopher; Stalker, Leanne; Doughty, Martin L

    2010-06-01

    Significant neurological disorders can result from subtle perturbations of gene regulation that are often linked to epigenetic regulation. Proteins that regulate the methylation of lysine 4 of histone H3 (H3K4) and play a central role in epigenetic regulation, and mutations in genes encoding these enzymes have been identified in both autism and Rett syndrome. The H3K4 demethylases remove methyl groups from lysine 4 leading to loss of RNA polymerase binding and transcriptional repression. When these proteins are mutated, brain development is altered. Currently, little is known regarding how these gene regulators function at the genomic level. In this article, we will discuss findings that link H3K4 demethylases to neurodevelopment and neurological disease.

  4. IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification

    Directory of Open Access Journals (Sweden)

    Yu L

    2018-01-01

    Full Text Available Lei Yu,1 Na Li,1 Jisheng Zhang,2 Yan Jiang1 1Department of Otorhinolaryngology, 2Key Laboratory of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, China Introduction: Epigenetic regulation has been shown to play an important role in the development of inflammatory diseases, including chronic rhinosinusitis and nasal polyps. The latter are characterized by epithelial mis-differentiation and infiltration of inflammatory cytokines. H3K4me3 has been shown to be involved in regulating lineage commitment. However, the underlying mechanisms, especially in human nasal epithelial cells (HNEpC, remain underexplored. The objective of this study was to investigate the role of H3K4me3 in HNEpC differentiation treated with the Th2 cytokine IL-13. Patients and methods: The expression levels of mRNA and proteins were investigated using reverse transcription-polymerase chain reaction (RT-PCR assays and Western blot in nasal polyp tissues and human nasal epithelial cells respectively. We measured these levels of H3K4me3, MLL1 and targeted genes compared with control subjects.Results: We demonstrate that expression of H3K4me3 and its methyltransferase MLL1 was significantly upregulated in IL-13-treated HNEpC. This elevation was also observed in nasal polyps. Expression of cilia-related transcription factors FOXJ1 and DNAI2 decreased, while goblet cell-derived genes CLCA1 and MUC5a increased upon IL-13 treatment. Mechanistically, knockdown of MLL1 restored expression of these four genes induced by IL-13. Conclusion: These findings suggest that H3K4me3 is a critical regulator in control of nasal epithelial cell differentiation. MLL1 may be a potential therapeutic target for nasal inflammatory diseases. Keywords: IL-13, H3K4me3 modification, nasal epithelial cell, differentiation 

  5. K4 Fe(CN)6 as a spectrophotometric agent for uranium analysis

    International Nuclear Information System (INIS)

    Soedyartomo; Tarwita.

    1976-01-01

    The properties of K 4 Fe(CN) 6 as a spectrophotometric agent for Uranium analysis was observed by putting some experiment into practice. The experiment covers the observation of expanding colour stability, the optimization of operating condition (p,H. and wavelength), the effect of K 4 Fe(CN) 6 concentration and the preparation of its standard curves (transmitansion vs uranium concentration) and the observation of the interfering metal spectra s (Cu ++ , Fe ++ ) either of its mixtures or themselves alone, has been carried out. The result and discussion on it are given. (author)

  6. Interaction of Escherichia coli K1 and K5 with Acanthamoeba castellanii Trophozoites and Cysts

    OpenAIRE

    Matin, Abdul; Jung, Suk-Yul

    2011-01-01

    The existence of symbiotic relationships between Acanthamoeba and a variety of bacteria is well-documented. However, the ability of Acanthamoeba interacting with host bacterial pathogens has gained particular attention. Here, to understand the interactions of Escherichia coli K1 and E. coli K5 strains with Acanthamoeba castellanii trophozoites and cysts, association assay, invasion assay, survival assay, and the measurement of bacterial numbers from cysts were performed, and nonpathogenic E. ...

  7. Genome Sequences of Subcluster K5 Mycobacteriophages AlleyCat, Edugator, and Guillsminger.

    Science.gov (United States)

    King, Rodney A; Slowan-Pomeroy, Tina M; Thomas, Jodi E; Ahmed, Tithe; Alexander, Katie L; Biddle, James M; Daniels, Makenzie K; Rowlett, Jenna R; Senay, Taylor E; Rinehart, Claire A; Staples, Amanda K; Rowland, Naomi S; Gaffney, Bobby L; Emmons, Christine B; Hauk, Maya D; Nguyen, Rebecca L; Naegele, Leonard; Strickland, Summer S; Briggs, Laura A; Rush, Alexander N; Saha, Sanghamitra; Sadana, Rachna; Cresawn, Steven G; Russell, Daniel A; Garlena, Rebecca A; Pope, Welkin H; Jacobs-Sera, Deborah; Hatfull, Graham F

    2017-11-09

    Bacteriophages AlleyCat, Edugator, and Guillsminger were isolated on Mycobacterium smegmatis mc 2 155 from enriched soil samples. All are members of mycobacteriophage subcluster K5, with genomes of 62,112 to 63,344 bp. Each genome contains 92 to 99 predicted protein-coding genes and one tRNA. Guillsminger is the first mycobacteriophage to carry an IS 1380 family transposon. Copyright © 2017 King et al.

  8. Heterotrophic nitrogen removal in Bacillus sp. K5: involvement of a novel hydroxylamine oxidase.

    Science.gov (United States)

    Yang, Yunlong; Lin, Ershu; Huang, Shaobin

    2017-12-01

    An aerobic denitrifying bacterium isolated from a bio-trickling filter treating NOx, Bacillus sp. K5, is able to convert ammonium to nitrite, in which hydroxylamine oxidase (HAO) plays a critical role. In the present study, the performance for simultaneous nitrification and denitrification was investigated with batch experiments and an HAO was purified by an anion-exchange and gel-filtration chromatography from strain K5. The purified HAO's molecular mass was determined by SDS-PAGE and its activity by measuring the change in the concentration of ferricyanide, the electron acceptor. Results showed that as much as 87.8 mg L -1 ammonium-N was removed without nitrite accumulation within 24 hours in the sodium citrate medium at C/N of 15. The HAO isolated from the strain K5 was approximately 71 KDa. With hydroxylamine (NH 2 OH) as a substrate and potassium ferricyanide as an electron acceptor, the enzyme was capable of oxidizing NH 2 OH to nitrite in vitro when the pH varied from 7 to 9 and temperature ranged from 25 °C to 40 °C. This is the first time that an HAO has been purified from the Bacillus genus, and the findings revealed that it is distinctive in its molecular mass and enzyme properties.

  9. Electrochemical studies on Li /K ion exchange behaviour in K4Fe(CN)

    Indian Academy of Sciences (India)

    based,24 sol-gel,17–21 and solid-state16 meth- ods. There are a .... Double potential step chronoamper- ometry was ... removal of moisture as well as water of crystallisa- tion and the .... active material, K4Fe(CN)6, carbon black and graphite.

  10. [Energy pooling collisions for K(4P) + Cs(5D) in a K-Cs mixture].

    Science.gov (United States)

    Aihemaiti, Pulati; Dai, Kang; Lu, Xin-hong; Shen, Yi-fan

    2005-04-01

    The rate coefficients for energy-pooling collisions K(4P) + Cs(5D) --> Cs(6S) + K(4D, 6S) in the K-Cs vapor mixture were measured relative to a known energy-pooling rate coefficient of a homonuclear reaction [i. e., Cs(6P) + Cs(5D) --> Cs(6S) + Cs (7D(J))]. Populations of the Cs(6P, 5D) and K(4P) states were produced by photodissociation of K2 and Cs2 molecules through the use of a dye laser radiation. The resulting fluorescence included the direct components emitted in the decay of the excited states produced by photodissociation and the induced components arising from the collisionally populated states. By combining relative intensities of the components with the effective lifetimes of Cs(6P) and K(4P) states, the rate coefficients (in units of 10(-9) cm3 x s(-1)) for the heteronuclear energy-pooling were found to be 2.6 and 3.6, respectively. The contribution to the rate coefficients from other processes are discussed.

  11. Synthesis and characterization of the ternary telluroargentate K4[Ag18Te11

    KAUST Repository

    Davaasuren, Bambar; Dashjav, Enkhtsetseg; Rothenberger, Alexander

    2014-01-01

    The ternary potassium telluroargentate(I), K4[Ag18Te11], was prepared by solvothermal synthesis in ethylenediamine at 160 °C. It crystallizes in the cubic space group Fm3¯ m (no. 225) with the cell parameter a = 18.6589(6) Å. The crystal structure

  12. MLL2 conveys transcription-independent H3K4 trimethylation in oocytes

    Czech Academy of Sciences Publication Activity Database

    Hanna, C. W.; Taudt, A.; Huang, J.; Gahurová, Lenka; Kranz, A.; Andrews, S.; Dean, W.; Francis Stewart, A.; Colomé-Tatché, M.; Kelsey, G.

    2018-01-01

    Roč. 25, č. 1 (2018), s. 73-82 ISSN 1545-9993 Institutional support: RVO:67985904 Keywords : H3K4 trimethylation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 12.595, year: 2016

  13. Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation

    Science.gov (United States)

    Jaiswal, Deepika; Jezek, Meagan; Quijote, Jeremiah; Lum, Joanna; Choi, Grace; Kulkarni, Rushmie; Park, DoHwan; Green, Erin M.

    2017-01-01

    The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono, di, and trimethylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied, and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription, and is often dependent on the H3K4me2 mark. We show that Set1, and particularly the H3K4me2 mark, are implicated in repression of a subset of middle sporulation genes during vegetative growth. In the absence of Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the associated histone deacetylase Hst1 from chromatin in a locus-specific manner. This is linked to increased H4K5ac at these loci and aberrant middle gene expression. These data indicate that, in addition to DNA sequence, histone modification status also contributes to proper localization of Sum1. Our results also show that the role for Set1 in middle gene expression control diverges as cells receive signals to undergo meiosis. Overall, this work dissects an unexplored role for Set1 in gene-specific repression, and provides important insights into a new mechanism associated with the control of gene expression linked to meiotic differentiation. PMID:29066473

  14. Targeted deletion of Atg5 reveals differential roles of autophagy in keratin K5-expressing epithelia

    Energy Technology Data Exchange (ETDEWEB)

    Sukseree, Supawadee [Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna (Austria); Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok (Thailand); Rossiter, Heidemarie; Mildner, Michael [Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna (Austria); Pammer, Johannes [Institute of Clinical Pathology, Medical University of Vienna, Vienna (Austria); Buchberger, Maria; Gruber, Florian [Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna (Austria); Watanapokasin, Ramida [Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok (Thailand); Tschachler, Erwin [Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna (Austria); Eckhart, Leopold, E-mail: leopold.eckhart@meduniwien.ac.at [Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna (Austria)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer We generated mice lacking Atg5 and autophagy in keratin K5-positive epithelia. Black-Right-Pointing-Pointer Suppression of autophagy in thymic epithelium was not associated with signs of autoimmunity. Black-Right-Pointing-Pointer Autophagy was required for normal terminal differentiation of preputial gland cells. Black-Right-Pointing-Pointer Autophagy-deficient cells of the preputial glands degraded nuclear DNA prematurely. -- Abstract: Autophagy contributes to the homeostasis of many tissues, yet its role in epithelia is incompletely understood. A recent report proposed that Atg5-dependent autophagy in thymic epithelial cells is essential for their function in the negative selection of self-reactive T-cells and, thus, for the suppression of tissue inflammation. Here we crossed mice carrying floxed alleles of the Atg5 gene with mice expressing the Cre recombinase under the control of the keratin K5 promoter to suppress autophagy in all K5-positive epithelia. The efficiency of autophagy abrogation was confirmed by immunoanalyses of LC3, which was converted to the autophagy-associated LC3-II form in normal but not Atg5-deficient cells, and of p62, which accumulated in Atg5-deficient cells. Mice carrying the epithelium-specific deletion of Atg5 showed normal weight gain, absence of tissue inflammation, and a normal morphology of the thymic epithelium. By contrast, autophagy-deficient epithelial cells of the preputial gland showed aberrant eosinophilic staining in histology and premature degradation of nuclear DNA during terminal differentiation. Taken together, the results of this study suggest that autophagy is dispensable for the suppression of autoimmunity by thymic epithelial cells but essential for normal differentiation of the preputial gland in mice.

  15. In vitro vitamin K3 effect on conjunctival fibroblast migration and proliferation.

    Science.gov (United States)

    Pinilla, I; Izaguirre, L B; Gonzalvo, F J; Piazuelo, E; Garcia-Gonzalez, M A; Sanchez-Cano, A I; Sopeña, F

    2014-01-01

    To evaluate the dose effect of vitamin K3 on wound healing mechanisms. Conjunctival fibroblasts were incubated for 24 hours. An artificial wound was made and the cells were incubated with fresh medium plus doses of vitamin K3 to be tested. Wound repair was monitored at 0, 18, 24, and 48 hours. Proliferation was measured in actively dividing cells by [(3)H]thymidine uptake. Six different groups were tested: group 1/no drugs added, group 2/ethanol 0.1%, group 3/vitamin K3 1 mg/L, group 4/vitamin K3 2 mg/L, group 5/vitamin K3 4 mg/L, and group 6/vitamin K3 6 mg/L. Each experiment was carried out in triplicate and 4 times. There were no differences among groups at the initial time. In vitro wound repair was slower in groups 4, 5, and 6. There were no differences between control and ethanol groups and between control and vitamin K3 1 mg/L groups. Fibroblast mitogenic activity was statistically decreased in all vitamin K groups; statistical differences were found among vitamin K3 1 mg/mL and higher doses too. In groups 5 and 6, cellular toxicity was presented. Vitamin K3 is able to inhibit fibroblast proliferation. Vitamin K3 2 mg/L or higher doses inhibit wound healing repair, exhibiting cellular toxicity at 4 and 6 mg/L.

  16. In Vitro Vitamin K3 Effect on Conjunctival Fibroblast Migration and Proliferation

    Directory of Open Access Journals (Sweden)

    I. Pinilla

    2014-01-01

    Full Text Available Purpose. To evaluate the dose effect of vitamin K3 on wound healing mechanisms. Methods. Conjunctival fibroblasts were incubated for 24 hours. An artificial wound was made and the cells were incubated with fresh medium plus doses of vitamin K3 to be tested. Wound repair was monitored at 0, 18, 24, and 48 hours. Proliferation was measured in actively dividing cells by [3H]thymidine uptake. Six different groups were tested: group 1/no drugs added, group 2/ethanol 0.1%, group 3/vitamin K3 1 mg/L, group 4/vitamin K3 2 mg/L, group 5/vitamin K3 4 mg/L, and group 6/vitamin K3 6 mg/L. Each experiment was carried out in triplicate and 4 times. Results. There were no differences among groups at the initial time. In vitro wound repair was slower in groups 4, 5, and 6. There were no differences between control and ethanol groups and between control and vitamin K3 1 mg/L groups. Fibroblast mitogenic activity was statistically decreased in all vitamin K groups; statistical differences were found among vitamin K3 1 mg/mL and higher doses too. In groups 5 and 6, cellular toxicity was presented. Conclusions. Vitamin K3 is able to inhibit fibroblast proliferation. Vitamin K3 2 mg/L or higher doses inhibit wound healing repair, exhibiting cellular toxicity at 4 and 6 mg/L.

  17. Molecular Basis for the Regulation of the H3K4 Methyltransferase Activity of PRDM9

    Directory of Open Access Journals (Sweden)

    Hong Wu

    2013-10-01

    Full Text Available PRDM9, a histone lysine methyltransferase, is a key determinant of the localization of meiotic recombination hot spots in humans and mice and the only vertebrate protein known to be involved in hybrid sterility. Here, we report the crystal structure of the PRDM9 methyltransferase domain in complex with a histone H3 peptide dimethylated on lysine 4 (H3K4me2 and S-adenosylhomocysteine (AdoHcy, which provides insights into the methyltransferase activity of PRDM proteins. We show that the genuine substrate of PRDM9 is histone H3 lysine 4 (H3K4 and that the enzyme possesses mono-, di-, and trimethylation activities. We also determined the crystal structure of PRDM9 in its autoinhibited state, which revealed a rearrangement of the substrate and cofactor binding sites by a concerted action of the pre-SET and post-SET domains, providing important insights into the regulatory mechanisms of histone lysine methyltransferase activity.

  18. Control system for a heavy-ion accelerator complex K4 - K10

    International Nuclear Information System (INIS)

    Kotov, V.M.; Pose, R.

    1992-01-01

    Control systems for newly created accelerators, perhaps for the first time, may be designed almost only around international standards for communication and control techniques. This is also true for the project of a control system for the accelerator complex K4-K10 at the Joint Institute for Nuclear Research Dubna. Nevertheless, open systems architecture with construction principles being essential for modern systems of such big devices as particle accelerators leaves designers enough possibilities for solving even very sophisticated problems. (author)

  19. Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

    Science.gov (United States)

    Lorefice, S.; Becerra, L. O.

    2017-01-01

    Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Drosophila KDM2 is a H3K4me3 demethylase regulating nucleolar organization

    Directory of Open Access Journals (Sweden)

    Birchler James A

    2009-10-01

    Full Text Available Abstract Background CG11033 (dKDM2 is the Drosophila homolog of the gene KDM2B. dKDM2 has been known to possess histone lysine demethylase activity towards H3K36me2 in cell lines and it regulates H2A ubiquitination. The human homolog of the gene has dual activity towards H3K36me2 as well as H3K4me3, and plays an important role in cellular senescence. Findings We have used transgenic flies bearing an RNAi construct for the dKDM2 gene. The knockdown of dKDM2 gene was performed by crossing UAS-RNAi-dKDM2 flies with actin-Gal4 flies. Western blots of acid extracted histones and immunofluoresence analysis of polytene chromosome showed the activity of the enzyme dKDM2 to be specific for H3K4me3 in adult flies. Immunofluoresence analysis of polytene chromosome also revealed the presence of multiple nucleoli in RNAi knockdown mutants of dKDM2 and decreased H3-acetylation marks associated with active transcription. Conclusion Our findings indicate that dKDM2 is a histone lysine demethylase with specificity for H3K4me3 and regulates nucleolar organization.

  1. Comparative Analyses of H3K4 and H3K27 Trimethylations Between the Mouse Cerebrum and Testis

    KAUST Repository

    Cui, Peng; Liu, Wanfe; Zhao, Yuhui; Lin, Qiang; Zhang, Daoyong; Ding, Feng; Xin, Chengqi; Zhang, Zhang; Song, Shuhui; Sun, Fanglin; Yu, Jun; Hu, Songnian

    2012-01-01

    The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K

  2. Vitamins C and K3 sensitize human urothelial tumors to gemcitabine.

    Science.gov (United States)

    Kassouf, Wassim; Highshaw, Ralph; Nelkin, Gina M; Dinney, Colin P; Kamat, Ashish M

    2006-10-01

    We evaluated the antitumor effects of vitamins C and K3 for human urothelial carcinoma and the potential use of the combination of vitamins C plus K3 as a sensitizing agent for conventional chemotherapy for urothelial carcinoma. The antiproliferative and apoptotic effects of vitamin C alone, vitamin K3 alone, vitamins C plus K3, gemcitabine alone and gemcitabine plus vitamins C plus K3 were assessed in vitro by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, propidium iodide staining and flow cytometry. For in vivo studies we implanted UMUC-14 tumorigenic urothelial carcinoma cells into the subcutis of nude mice. One week later we treated 10 mice each with saline (control), vitamins C plus K3, gemcitabine or gemcitabine plus vitamins C plus K3. Treatment was continued for 4 weeks, followed by necropsy. Tumor volume was measured and tumor kinetics were established. Apoptosis and proliferation were evaluated in tumor sections using immunohistochemistry and TUNEL assay. Vitamins C plus K3 induced cytostasis and caused apoptosis to a greater degree than either vitamin alone (p Vitamins C plus K3 also substantially augmented the effects of gemcitabine in vitro. There were 32.3% apoptosis with gemcitabine plus vitamins C plus K3, 5.3% with gemcitabine alone and 15.8% with vitamins C plus K3 alone (p vitamins C plus K3 compared with that in the control or for either agent alone. Mean tumor weight and growth rate in the gemcitabine plus vitamins C plus K3 group (237 mg and 11.3 mm3 daily) were decreased compared with those in the control (530 mg and 34.3 mm3 daily), and those for vitamins C plus K3 alone (490 mg and 25.2 mm3 daily) and gemcitabine alone (400 mg and 21.3 mm3 daily) (p Vitamins C and K3 have significant antiproliferative and apoptotic effects when used in combination. This combination enhances the efficacy of gemcitabine against bladder cancer in vivo.

  3. Structure of stable degeneration of K3 surfaces into pairs of rational elliptic surfaces

    Science.gov (United States)

    Kimura, Yusuke

    2018-03-01

    F-theory/heterotic duality is formulated in the stable degeneration limit of a K3 fibration on the F-theory side. In this note, we analyze the structure of the stable degeneration limit. We discuss whether stable degeneration exists for pairs of rational elliptic surfaces. We demonstrate that, when two rational elliptic surfaces have an identical complex structure, stable degeneration always exists. We provide an equation that systematically describes the stable degeneration of a K3 surface into a pair of isomorphic rational elliptic surfaces. When two rational elliptic surfaces have different complex structures, whether their sum glued along a smooth fiber admits deformation to a K3 surface can be determined by studying the structure of the K3 lattice. We investigate the lattice theoretic condition to determine whether a deformation to a K3 surface exists for pairs of extremal rational elliptic surfaces. In addition, we discuss the configurations of singular fibers under stable degeneration. The sum of two isomorphic rational elliptic surfaces glued together admits a deformation to a K3 surface, the singular fibers of which are twice that of the rational elliptic surface. For special situations, singular fibers of the resulting K3 surface collide and they are enhanced to a fiber of another type. Some K3 surfaces become attractive in these situations. We determine the complex structures and the Weierstrass forms of these attractive K3 surfaces. We also deduce the gauge groups in F-theory compactifications on these attractive K3 surfaces times a K3. E 6, E 7, E 8, SU(5), and SO(10) gauge groups arise in these compactifications.

  4. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    International Nuclear Information System (INIS)

    Khan, Maruf H.; Hart, Matthew J.; Rea, Shane L.

    2012-01-01

    Highlights: ► Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. ► Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. ► Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation – when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

  5. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Maruf H. [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Hart, Matthew J., E-mail: HartMJ@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Rea, Shane L., E-mail: reas3@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. Black-Right-Pointing-Pointer Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. Black-Right-Pointing-Pointer Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation - when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

  6. Plasminogen fragments K 1-3 and K 5 bind to different sites in fibrin fragment DD.

    Science.gov (United States)

    Grinenko, T V; Kapustianenko, L G; Yatsenko, T A; Yusova, O I; Rybachuk, V N

    2016-01-01

    Specific plasminogen-binding sites of fibrin molecule are located in Аα148-160 regions of C-terminal domains. Plasminogen interaction with these sites initiates the activation process of proenzyme and subsequent fibrin lysis. In this study we investigated the binding of plasminogen fragments K 1-3 and K 5 with fibrin fragment DD and their effect on Glu-plasminogen interaction with DD. It was shown that the level of Glu-plasminogen binding to fibrin fragment DD is decreased by 50-60% in the presence of K 1-3 and K 5. Fragments K 1-3 and K 5 have high affinity to fibrin fragment DD (Kd is 0.02 for K 1-3 and 0.054 μМ for K 5). K 5 interaction is independent and K 1-3 is partly dependent on C-terminal lysine residues. K 1-3 interacts with complex of fragment DD-immobilized K 5 as well as K 5 with complex of fragment DD-immobilized K 1-3. The plasminogen fragments do not displace each other from binding sites located in fibrin fragment DD, but can compete for the interaction. The results indicate that fibrin fragment DD contains different binding sites for plasminogen kringle fragments K 1-3 and K 5, which can be located close to each other. The role of amino acid residues of fibrin molecule Аα148-160 region in interaction with fragments K 1-3 and K 5 is discussed.

  7. On the Vertex-Distinguishing Proper Edge-Coloring of K4,4∨Kt%图K4,4∨Kt的点可区别正常边染色

    Institute of Scientific and Technical Information of China (English)

    魏甲静; 王治文; 陈祥恩

    2012-01-01

    讨论了图K4,4∨Kt的点可区别正常边染色及其色数.利用正多边形的对称性构造染色以及组合分析的方法.确定了图K4,4∨Kt的点可区别正常边色数,得到了:当t是奇数且t≥3以及t是偶数且2≤t≤32时,χ′s(K4,4∨Kt)=t+8;当t是偶数且t≥34时,χ′s(K4,4∨Kt)=t+9.%In this paper, the authors discuss the vertex-distinguishing proper edge colorings of K4,4∨Kt,and using the symmetry of regular polygons to construct coloring and the methods of combinatorial analysis, determine the vertex-distinguishing proper edge chromatic number of K4,4∨Kt. Finally, the authors show that χ:(K4,4∨Kt):t+8 when t is odd with t≥3 and when t is even with 2≤t≤32, and that xs(K4,4∨Kt) =t+9 when t is even with t≥34.

  8. Inactivation of bacteria via photosensitization of vitamin K3 by UV-A light.

    Science.gov (United States)

    Xu, Fei; Vostal, Jaroslav G

    2014-09-01

    This study investigated inactivation of bacteria with ultraviolet light A irradiation in combination with vitamin K3 as a photosensitizer. Six bacteria including Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, and Escherichia coli suspended in vitamin K3 aqueous solution were exposed to ultraviolet light A. Five of six bacteria, with the exception of Pseudomonas aeruginosa, were reduced by eight logs with 1600 μM of vitamin K3 and 5.8 J cm(-2) UV-A irradiation. Pseudomonas aeruginosa was reduced by four logs under these conditions. Reactive oxygen species including singlet oxygen, hydroxyl radical and superoxide anion radical were generated in vitamin K3 aqueous solution under UV-A irradiation. These results suggest that vitamin K3 and UV-A irradiation may be effective for bacterial inactivation in environmental and medical applications. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  9. Synthesis and characterization of the ternary telluroargentate K4[Ag18Te11

    KAUST Repository

    Davaasuren, Bambar

    2014-10-19

    The ternary potassium telluroargentate(I), K4[Ag18Te11], was prepared by solvothermal synthesis in ethylenediamine at 160 °C. It crystallizes in the cubic space group Fm3¯ m (no. 225) with the cell parameter a = 18.6589(6) Å. The crystal structure can be described as a [Ag18Te11]4- three-dimensional anionic framework with the voids accommodating potassium cations. Chemical bonding analysis reveals polar covalent Ag-Te bonds and considerable Ag-Ag interactions, which support the complex anionic character of the structure. The compound is thermally stable up to 450 °C in an inert atmosphere.

  10. Engineering Computer Games: A Parallel Learning Opportunity for Undergraduate Engineering and Primary (K-5 Students

    Directory of Open Access Journals (Sweden)

    Mark Michael Budnik

    2011-04-01

    Full Text Available In this paper, we present how our College of Engineering is developing a growing portfolio of engineering computer games as a parallel learning opportunity for undergraduate engineering and primary (grade K-5 students. Around the world, many schools provide secondary students (grade 6-12 with opportunities to pursue pre-engineering classes. However, by the time students reach this age, many of them have already determined their educational goals and preferred careers. Our College of Engineering is developing resources to provide primary students, still in their educational formative years, with opportunities to learn more about engineering. One of these resources is a library of engineering games targeted to the primary student population. The games are designed by sophomore students in our College of Engineering. During their Introduction to Computational Techniques course, the students use the LabVIEW environment to develop the games. This software provides a wealth of design resources for the novice programmer; using it to develop the games strengthens the undergraduates

  11. An unexpected oxidation: NaK5Cl2(S2O62 revisited

    Directory of Open Access Journals (Sweden)

    William T. A. Harrison

    2017-02-01

    Full Text Available The title compound, NaK5Cl2(S2O62 [systematic name: sodium pentapotassium dichloride bis(dithionate], arose as an unexpected product from an organic synthesis that used dithionite (S2O42− ions as a reducing agent to destroy excess permanganate ions. Compared to the previous study [Stanley (1953. Acta Cryst. 6, 187–196], the present tetragonal structure exhibits a root 2a × root 2a × c super-cell due to subtle changes in the orientations of the dithionate anions. The structure can be visualized as a three-dimensional framework of [001] columns of alternating trans-NaO4Cl2 and KO4Cl2 octahedra cross-linked by the dithionate ions with the interstices occupied by KO6Cl2 polyhedra to generate a densely packed three-dimensional framework. The asymmetric unit comprises two sodium ions (site symmetries 4 and -4, four potassium ions (site symmetries = -4, 4, 1 and 1, three chloride ions (site symmetries = 4, 4 and 2 and two half-dithionate ions (all atoms on general positions. Both dithionate ions are completed by crystallographic inversion symmetry. The crystal chosen for data collection was found to be rotationally twinned by 180° about the [100] axis in reciprocal space with a 0.6298 (13:0.3702 (13 domain ratio.

  12. The Noether-Lefschetz problem and gauge-group-resolved landscapes: F-theory on K3 × K3 as a test case

    Energy Technology Data Exchange (ETDEWEB)

    Braun, A.P. [Department of Mathematics, King’s College,London WC2R 2LS (United Kingdom); Kimura, Y. [Yukawa Institute for Theoretical Physics, Kyoto University,Kyoto 606-8502 (Japan); Watari, T. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwano-ha 5-1-5, 277-8583 (Japan)

    2014-04-07

    Four-form flux in F-theory compactifications not only stabilizes moduli, but gives rise to ensembles of string vacua, providing a scientific basis for a stringy notion of naturalness. Of particular interest in this context is the ability to keep track of algebraic information (such as the gauge group) associated with individual vacua while dealing with statistics. In the present work, we aim to clarify conceptual issues and sharpen methods for this purpose, using compactification on K3×K3 as a test case. Our first approach exploits the connection between the stabilization of complex structure moduli and the Noether-Lefschetz problem. Compactification data for F-theory, however, involve not only a four-fold (with a given complex structure) Y{sub 4} and a flux on it, but also an elliptic fibration morphism Y{sub 4}⟶B{sub 3}, which makes this problem complicated. The heterotic-F-theory duality indicates that elliptic fibration morphisms should be identified modulo isomorphism. Based on this principle, we explain how to count F-theory vacua on K3×K3 while keeping the gauge group information. Mathematical results reviewed/developed in our companion paper are exploited heavily. With applications to more general four-folds in mind, we also clarify how to use Ashok-Denef-Douglas’ theory of the distribution of flux vacua in order to deal with statistics of sub-ensembles tagged by a given set of algebraic/topological information. As a side remark, we extend the heterotic/F-theory duality dictionary on flux quanta and elaborate on its connection to the semistable degeneration of a K3 surface.

  13. Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia.

    Science.gov (United States)

    Roth Flach, Rachel J; Danai, Laura V; DiStefano, Marina T; Kelly, Mark; Menendez, Lorena Garcia; Jurczyk, Agata; Sharma, Rohit B; Jung, Dae Young; Kim, Jong Hun; Kim, Jason K; Bortell, Rita; Alonso, Laura C; Czech, Michael P

    2016-07-29

    Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced β cell mass, fewer proliferating β cells and reduced islet-specific gene mRNA expression compared with controls, although insulin content was normal. Interestingly, the reduced plasma insulin in M4K4 iKO mice exposed to chronic (16 weeks) HFD was not observed in response to acute HFD challenge or short term treatment with the insulin receptor antagonist S961. Furthermore, the improved insulin sensitivity in obese M4K4 iKO mice was abrogated by high exogenous insulin over the course of a euglycemic clamp study, indicating that hypoinsulinemia promotes insulin sensitivity in chronically obese M4K4 iKO mice. These results demonstrate that protein kinase Map4k4 drives obesity-induced hyperinsulinemia and insulin resistance in part by promoting insulin secretion from β cells in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. In Vitro Vitamin K 3 Effect on Conjunctival Fibroblast Migration and Proliferation

    OpenAIRE

    Pinilla, I.; Izaguirre, L. B.; Gonzalvo, F. J.; Piazuelo, E.; Garcia-Gonzalez, M. A.; Sanchez-Cano, A. I.; Sopeña, F.

    2014-01-01

    Purpose. To evaluate the dose effect of vitamin K3 on wound healing mechanisms. Methods. Conjunctival fibroblasts were incubated for 24 hours. An artificial wound was made and the cells were incubated with fresh medium plus doses of vitamin K3 to be tested. Wound repair was monitored at 0, 18, 24, and 48 hours. Proliferation was measured in actively dividing cells by [3H]thymidine uptake. Six different groups were tested: group 1/no drugs added, group 2/ethanol 0.1%, group 3/vitamin K3 1 mg/L...

  15. Elliptic fibrations of maximal rank on a supersingular K3 surface

    International Nuclear Information System (INIS)

    Shioda, Tetsuji

    2013-01-01

    We study a class of elliptic K3 surfaces defined by an explicit Weierstrass equation to find elliptic fibrations of maximal rank on K3 surface in positive characteristic. In particular, we show that the supersingular K3 surface of Artin invariant 1 (unique by Ogus) admits at least one elliptic fibration with maximal rank 20 in every characteristic p>7, p≠13, and further that the number, say N(p), of such elliptic fibrations (up to isomorphisms), is unbounded as p → ∞; in fact, we prove that lim p→∞ N(p)/p 2 ≥(1/12) 2 .

  16. Zvýšení ročního využití parního práškového kotle K5 ve ŽĎAS, a. s

    OpenAIRE

    Kubiš, David

    2017-01-01

    Tato diplomová práce se zabývá vyšším využitím kotle K5 v teplárně ŽĎAS, a.s. v přechodném období, kdy vlivem snížených odběrů dochází k přehřívání zpáteční větve horkovodu a je nutnost přejíždět na jiný kotel. Cílem práce je omezit přejíždění z kotle K5 na kotel K3 a zvýšit jeho časové využití v přechodném období pomocí ekonomicky únosného technického řešení. Na začátku práce je popsána teplárna ŽĎAS, a.s. a její vybavení. Následují čtyři metody výpočtů zvýšení ročního využití kotle K5. A to...

  17. SRNA-2K5, Proton Transport Using 3-D by Monte Carlo Techniques

    International Nuclear Information System (INIS)

    Ilic, Radovan D.

    2005-01-01

    1 - Description of program or function: SRNA-2K5 performs Monte Carlo transport simulation of proton in 3D source and 3D geometry of arbitrary materials. The proton transport based on condensed history model, and on model of compound nuclei decays that creates in nonelastic nuclear interaction by proton absorption. 2 - Methods: The SRNA-2K5 package is developed for time independent simulation of proton transport by Monte Carlo techniques for numerical experiments in complex geometry, using PENGEOM from PENELOPE with different material compositions, and arbitrary spectrum of proton generated from the 3D source. This package developed for 3D proton dose distribution in proton therapy and dosimetry, and it was based on the theory of multiple scattering. The compound nuclei decay was simulated by our and Russian MSDM models using ICRU 49 and ICRU 63 data. If protons trajectory is divided on great number of steps, protons passage can be simulated according to Berger's Condensed Random Walk model. Conditions of angular distribution and fluctuation of energy loss determinate step length. Physical picture of these processes is described by stopping power, Moliere's angular distribution, Vavilov's distribution with Sulek's correction per all electron orbits, and Chadwick's cross sections for nonelastic nuclear interactions, obtained by his GNASH code. According to physical picture of protons passage and with probabilities of protons transition from previous to next stage, which is prepared by SRNADAT program, simulation of protons transport in all SRNA codes runs according to usual Monte Carlo scheme: (i) proton from the spectrum prepared for random choice of energy, position and space angle is emitted from the source; (ii) proton is loosing average energy on the step; (iii) on that step, proton experience a great number of collisions, and it changes direction of movement randomly chosen from angular distribution; (iv) random fluctuation is added to average energy loss; (v

  18. Corrosion of K-3 glass-contact refractory in sodium-rich aluminosilicate melts

    International Nuclear Information System (INIS)

    Lu, X.D.; Gan, H.; Buechele, A.C.; Pegg, I.L.

    1999-01-01

    The corrosion of the glass-contact refractory Monofrax K-3 in two sodium-rich aluminosilicate melts has been studied at 1,208 and 1,283 C using a modified ASTM procedure with constant agitation of the melt by air bubbling. The results for the monolithic refractory indicate a fast initial stage involving phase dissolution and transformation and a later passivated stage in which the surface of the refractory has been substantially modified. The composition of the stable spinel phase in the altered layer on monolithic coupons of K-3 is almost identical to the equilibrium composition bracketed by the dissolution of powdered K-3 into under-saturated melts on the other. The temperature and melt shear viscosity were found to have significant effects on the rates of K-3 dissolution and transformation

  19. Structure of stable degeneration of K3 surfaces into pairs of rational elliptic surfaces

    OpenAIRE

    Kimura, Yusuke

    2018-01-01

    F-theory/heterotic duality is formulated in the stable degeneration limit of a K3 fibration on the F-theory side. In this note, we analyze the structure of the stable degeneration limit. We discuss whether stable degeneration exists for pairs of rational elliptic surfaces. We demonstrate that, when two rational elliptic surfaces have an identical complex structure, stable degeneration always exists. We provide an equation that systematically describes the stable degeneration of a K3 surface i...

  20. Analysis of the Mitogen-activated protein kinase kinase 4 (MAP2K4) tumor suppressor gene in ovarian cancer

    International Nuclear Information System (INIS)

    Davis, Sally J; Choong, David YH; Ramakrishna, Manasa; Ryland, Georgina L; Campbell, Ian G; Gorringe, Kylie L

    2011-01-01

    MAP2K4 is a putative tumor and metastasis suppressor gene frequently found to be deleted in various cancer types. We aimed to conduct a comprehensive analysis of this gene to assess its involvement in ovarian cancer. We screened for mutations in MAP2K4 using High Resolution Melt analysis of 149 primary ovarian tumors and methylation at the promoter using Methylation-Specific Single-Stranded Conformation Polymorphism analysis of 39 tumors. We also considered the clinical impact of changes in MAP2K4 using publicly available expression and copy number array data. Finally, we used siRNA to measure the effect of reducing MAP2K4 expression in cell lines. In addition to 4 previously detected homozygous deletions, we identified a homozygous 16 bp truncating deletion and a heterozygous 4 bp deletion, each in one ovarian tumor. No promoter methylation was detected. The frequency of MAP2K4 homozygous inactivation was 5.6% overall, and 9.8% in high-grade serous cases. Hemizygous deletion of MAP2K4 was observed in 38% of samples. There were significant correlations of copy number and expression in three microarray data sets. There was a significant correlation between MAP2K4 expression and overall survival in one expression array data set, but this was not confirmed in an independent set. Treatment of JAM and HOSE6.3 cell lines with MAP2K4 siRNA showed some reduction in proliferation. MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort

  1. The collision cross sections for excitation energy transfer in Rb*(5P3/2)+K(4S1/2)→Rb(5S1/2)+K*(4PJ) processes

    International Nuclear Information System (INIS)

    Horvatic, V.; Vadla, C.; Movre, M.

    1993-01-01

    The collisional excitation transfer for the processes Rb * (5P 3/2 ) + K(4S 1/2 ) → Rb(5S 1/2 ) + K * (4P J ), J = 1/2, 3/2, was investigated using two-photon laser excitation techniques with a thermionic heat-pipe diode as a detector. The population densities of the K 4P J levels induced by collisions with excited Rb atoms as well as those produced by direct laser excitation of the potassium atoms were probed through the measurement of the thermionic signals generated due to the ionization of the potassium atoms emerging from the K(4P J ) → K(7S 1/2 ) excitation channel. (orig./WL)

  2. Measuring psychological distress in older Aboriginal and Torres Strait Islanders Australians: a comparison of the K-10 and K-5.

    Science.gov (United States)

    McNamara, Bridgette J; Banks, Emily; Gubhaju, Lina; Williamson, Anna; Joshy, Grace; Raphael, Beverley; Eades, Sandra J

    2014-12-01

    To assess the cross-cultural validity of two Kessler psychological distress scales (K-10 and K-5) by examining their measurement properties among older Aboriginal and Torres Strait Islanders and comparing them to those in non-Aboriginal individuals from NSW Australia. Self-reported questionnaire data from the 45 and Up Study for 1,631 Aboriginal and 231,774 non-Aboriginal people were used to examine the factor structure, convergent validity, internal consistency and levels of missing data of K-10 and K-5. We found excellent agreement in classification of distress of Aboriginal participants by K-10 and K-5 (weighted kappa=0.87), high internal consistency (Cronbach's alpha K-10: 0.93, K-5: 0.88), and factor structures consistent with those for the total Australian population. Convergent validity was evidenced by a strong graded relationship between the level of distress and the odds of: problems with daily activities due to emotional problems; current treatment for depression or anxiety; and poor quality of life. K-10 and K-5 scales are promising tools for measuring psychological distress among Aboriginal and Torres Strait Islanders aged 45 and over in research and clinical settings. © 2014 Public Health Association of Australia.

  3. Final report on the key comparison CCPR-K5: Spectral diffuse reflectance

    Science.gov (United States)

    Nadal, Maria; Eckerle, Kenneth L.; Early, Edward A.; Ohno, Yoshi

    2013-01-01

    The CCPR K5 key comparison on spectral diffuse reflectance was carried out in the framework of the CIPM Mutual Recognition Arrangement, by 13 national metrology institutes (MMIs) as participants. The participants were CSIR-NML (South Africa), HUT (Finland), IFA-CSIC (Spain), KRISS (Republic of Korea), MSL (New Zealand), NIM (China), NIST (United States of America), NMIJ (Japan), NPL (United Kingdom), NRC (Canada), OMH (Hungary), PTB (Germany) and VNIIOFI (Russia Federation). NIST (USA) piloted the comparison. The aim of this comparison was to check the agreement of measurement of the spectral diffuse reflectance among participants, using the measurement geometry of d/0 or 0/d in the wavelength range of 360 nm to 820 nm at 20 nm increment. The comparison was a star type comparison with the samples provided by the pilot laboratory and with the measurement sequence: Pilot-Participant-Pilot. Spectralon and matte white ceramic tiles were used as the transfer standards. Each participant received three of each type of sample and at least one sample of each type was measured three times on three separate days, and the other two samples were measured once. The report presents the description of the measurement facilities, procedures and uncertainties of all the participants as well as the results of the comparison. Measurement results from the participants and their associated uncertainties were analyzed in accordance with the Guidelines for CCPR Key Comparison Report Preparation, using weighted mean with cut-off. For the calculation of the Key Comparison Reference Value (KCRV), as agreed by the participants, the data of both samples were used for the 460 nm to 820 nm region and only the data of the Spectralon samples were used in the spectral region of 360 nm to 440 nm. The unilateral degrees of equivalence (DoE) calculated for each participant are mostly consistent within the uncertainty (k = 2) of the DoE. This international comparison of spectral diffuse reflectance

  4. DNA replication origin function is promoted by H3K4 di-methylation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Rizzardi, Lindsay F; Dorn, Elizabeth S; Strahl, Brian D; Cook, Jeanette Gowen

    2012-10-01

    DNA replication is a highly regulated process that is initiated from replication origins, but the elements of chromatin structure that contribute to origin activity have not been fully elucidated. To identify histone post-translational modifications important for DNA replication, we initiated a genetic screen to identify interactions between genes encoding chromatin-modifying enzymes and those encoding proteins required for origin function in the budding yeast Saccharomyces cerevisiae. We found that enzymes required for histone H3K4 methylation, both the histone methyltransferase Set1 and the E3 ubiquitin ligase Bre1, are required for robust growth of several hypomorphic replication mutants, including cdc6-1. Consistent with a role for these enzymes in DNA replication, we found that both Set1 and Bre1 are required for efficient minichromosome maintenance. These phenotypes are recapitulated in yeast strains bearing mutations in the histone substrates (H3K4 and H2BK123). Set1 functions as part of the COMPASS complex to mono-, di-, and tri-methylate H3K4. By analyzing strains lacking specific COMPASS complex members or containing H2B mutations that differentially affect H3K4 methylation states, we determined that these replication defects were due to loss of H3K4 di-methylation. Furthermore, histone H3K4 di-methylation is enriched at chromosomal origins. These data suggest that H3K4 di-methylation is necessary and sufficient for normal origin function. We propose that histone H3K4 di-methylation functions in concert with other histone post-translational modifications to support robust genome duplication.

  5. The COMPASS Family of Histone H3K4 Methylases: Mechanisms of Regulation in Development and Disease Pathogenesis

    Science.gov (United States)

    Shilatifard, Ali

    2014-01-01

    The Saccharomyces cerevisiae Set1/COMPASS was the first histone H3 lysine 4 (H3K4) methylase identified over ten years ago. Since then, it has been demonstrated that Set1/COMPASS and its enzymatic product, H3K4 methylation, is highly conserved across the evolutionary tree. Although there is only one COMPASS in yeast, human cells bear at least six COMPASS family members each capable of methylating H3K4 with non-redundant functions. In yeast, the monoubiquitination of histone H2B by Rad6/Bre1 is required for proper H3K4 and H3K79 trimethylations. This histone crosstalk and its machinery are also highly conserved from yeast to human. In this review, the process of histone H2B monoubiquitination-dependent and independent histone H3K4 methylation as a mark of active transcription, enhancer signatures, and developmentally poised genes will be discussed. The misregulation of histone H2B monoubiquitination and H3K4 methylation results in the pathogenesis of human diseases including cancer. Recent findings in this regard will also be examined. PMID:22663077

  6. N=2 heterotic string compactifications on orbifolds of K3×T{sup 2}

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyaya, Aradhita; David, Justin R. [Centre for High Energy Physics, Indian Institute of Science,C.V. Raman Avenue, Bangalore 560012 (India)

    2017-01-10

    We study N=2 compactifications of E{sub 8}×E{sub 8} heterotic string theory on orbifolds of K3×T{sup 2} by g{sup ′} which acts as an ℤ{sub N} automorphism of K3 together with a 1/N shift on a circle of T{sup 2}. The orbifold action g{sup ′} corresponds to the 26 conjugacy classes of the Mathieu group M{sub 24}. We show that for the standard embedding the new supersymmetric index for these compactifications can always be decomposed into the elliptic genus of K3 twisted by g{sup ′}. The difference in one-loop corrections to the gauge couplings are captured by automorphic forms obtained by the theta lifts of the elliptic genus of K3 twisted by g{sup ′}. We work out in detail the case for which g{sup ′} belongs to the equivalence class 2B. We then investigate all the non-standard embeddings for K3 realized as a T{sup 4}/ℤ{sub ν} orbifold with ν=2,4 and g{sup ′} the 2A involution. We show that for non-standard embeddings the new supersymmetric index as well as the difference in one-loop corrections to the gauge couplings are completely characterized by the instanton numbers of the embeddings together with the difference in number of hypermultiplets and vector multiplets in the spectrum.

  7. Subcutaneous injection of thallium-201 chloride and gallium-67 citrate at acupuncture point K-3

    International Nuclear Information System (INIS)

    Johg, Shiang-Bin; Wu, Chung-Chieng; Chen, Ming-Feng; Wu, Sheng-Nan

    1992-01-01

    Subcutaneous (SC) injection of 99m Tc pertechnetate ( 99m Tc) at acupuncture points K-3 is a new method of lower-limb radionuclide venography. To investigate the mechanism of absorption of 99m Tc from SC injected sites into vascular system, various radioisotopes such as 201 Tl chloride ( 201 Tl) and 67 Ga citrate ( 67 Ga) were SC injected at K-3 points in animal and human-beings experiments. It was found that 99m Tc and 201 Tl were absorbed rapidly from K-3 points through venous system and into whole body soft tissue. However, 67 Ga with a larger effective ionic radius than 201 Tl was not absorbed throughout the observation of 5 minutes. Furthermore, intravenous administration of digitalis, a Na + -K + pump blocker, did not inhibit the absorption of 99m Tc and 201 Tl after SC injection at K-3 points. These results suggest that absorption of radionuclides on SC injection at K-3 points is mainly through the passive pathway of diffusion rather than the active transport, and the effective ionic radius may be a major factor influencing the absorption rate of the radionuclides. (author)

  8. Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases.

    Science.gov (United States)

    Alam, Parvez; Chaturvedi, Sumit Kumar; Siddiqi, Mohammad Khursheed; Rajpoot, Ravi Kant; Ajmal, Mohd Rehan; Zaman, Masihuz; Khan, Rizwan Hasan

    2016-05-27

    Protein misfolding and aggregation have been associated with several human diseases such as Alzheimer's, Parkinson's and familial amyloid polyneuropathy etc. In this study, anti-fibrillation activity of vitamin k3 and its effect on the kinetics of amyloid formation of hen egg white lysozyme (HEWL) and Aβ-42 peptide were investigated. Here, in combination with Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), transmission electron microscopy and cell cytotoxicity assay, we demonstrated that vitamin k3 significantly inhibits fibril formation as well as the inhibitory effect is dose dependent manner. Our experimental studies inferred that vitamin k3 exert its neuro protective effect against amyloid induced cytotoxicity through concerted pathway, modifying the aggregation formation towards formation of nontoxic aggregates. Molecular docking demonstrated that vitamin k3 mediated inhibition of HEWL and Aβ-42 fibrillogenesis may be initiated by interacting with proteolytic resistant and aggregation prone regions respectively. This work would provide an insight into the mechanism of protein aggregation inhibition by vitamin k3; pave the way for discovery of other small molecules that may exert similar effect against amyloid formation and its associated neurodegenerative diseases.

  9. Stimulation of ceramide formation and suicidal erythrocyte death by vitamin K(3) (menadione).

    Science.gov (United States)

    Qadri, Syed M; Eberhard, Matthias; Mahmud, Hasan; Föller, Michael; Lang, Florian

    2009-11-25

    Vitamin K(3) is an essential micronutrient required for the activation of coagulation factors and thus hemostasis. Administration of vitamin K(3) analogues may cause anemia, which at least in theory could be due to stimulation of suicidal erythrocyte death or eryptosis characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane leading to exposure of phosphatidylserine at the erythrocyte surface. Eryptosis is triggered by an increase in the cytosolic Ca(2+) activity, by ceramide and by energy depletion (decrease of cytosolic ATP). The present experiments explored, whether vitamin K(3) may influence eryptosis. Hemolysis was estimated from the supernatant hemoglobin concentration, phosphatidylserine-exposing erythrocytes from annexin V-binding in fluorescence-activated cell sorter (FACS) analysis, erythrocyte volume from forward scatter in FACS analysis, ceramide formation from binding of fluorescent antibodies, and erythrocyte ATP content from a luciferin-luciferase assay. As a result, vitamin K(3) (> or =1microM) caused lysis of an only small fraction of erythrocytes, but significantly increased ceramide formation, significantly increased the percentage of annexin V-binding erythrocytes, significantly decreased forward scatter and, at higher concentrations, significantly decreased the cellular ATP content. In conclusion, vitamin K(3) stimulates suicidal erythrocyte death, an effect at least partially due to ceramide formation and ATP depletion.

  10. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia.

    Science.gov (United States)

    Cao, Fang; Townsend, Elizabeth C; Karatas, Hacer; Xu, Jing; Li, Li; Lee, Shirley; Liu, Liu; Chen, Yong; Ouillette, Peter; Zhu, Jidong; Hess, Jay L; Atadja, Peter; Lei, Ming; Qin, Zhaohui S; Malek, Sami; Wang, Shaomeng; Dou, Yali

    2014-01-23

    Here we report a comprehensive characterization of our recently developed inhibitor MM-401 that targets the MLL1 H3K4 methyltransferase activity. MM-401 is able to specifically inhibit MLL1 activity by blocking MLL1-WDR5 interaction and thus the complex assembly. This targeting strategy does not affect other mixed-lineage leukemia (MLL) family histone methyltransferases (HMTs), revealing a unique regulatory feature for the MLL1 complex. Using MM-401 and its enantiomer control MM-NC-401, we show that inhibiting MLL1 methyltransferase activity specifically blocks proliferation of MLL cells by inducing cell-cycle arrest, apoptosis, and myeloid differentiation without general toxicity to normal bone marrow cells or non-MLL cells. More importantly, transcriptome analyses show that MM-401 induces changes in gene expression similar to those of MLL1 deletion, supporting a predominant role of MLL1 activity in regulating MLL1-dependent leukemia transcription program. We envision broad applications for MM-401 in basic and translational research. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. K 4R - Knowledge to the Power of RESTful, Resourceful and Reactive Rules

    Science.gov (United States)

    Amador, Ricardo

    The Web of today clearly answers questions of the form "What is the representation of ...?". The Semantic Web (SW) of tomorrow aims at answering questions of the form "What is the meaning of ...?". It is our stance that in order to realize the full potential of the original concept proposed by Tim Berners-Lee et al. (in Scientific American, May 2001), the SW must also answer, in a meaningful way, questions of a dynamic and active nature, like "What to do if ...?" or "What to do when ...?". Moreover, SW questions of the form "What to do ...?" must be expressed and answered in a declarative, compositional and language agnostic way. It is our (hypo)thesis that formally established concepts, viz. the Web's REST architectural style, declarative SW representation of resources based on Description Logics (e.g., OWL-DL), and Reactive Rules (e.g., "on Event if Condition do Action" -ECA- rules), provide the proper theoretical foundations to achieve this goal. This paper describes our current research proposal, K 4R (pronounced, with an Italian flavor, "Che fare?"), towards achieving a declarative model for expressing (re)active behavior in and for the SW.

  12. Inhibitory effects of vitamin K3 on DNA polymerase and angiogenesis.

    Science.gov (United States)

    Matsubara, Kiminori; Kayashima, Tomoko; Mori, Masaharu; Yoshida, Hiromi; Mizushina, Yoshiyuki

    2008-09-01

    Vitamins play essential roles in cellular reactions and maintain human health. Recent studies have revealed that some vitamins including D3, B6 and K2 and their derivatives have an anti-cancer effect. As a mechanism, their inhibitory effect on cancer-related angiogenesis has been demonstrated. Vitamin K2 (menaquinones) has an anti-cancer effect in particular for hepatic cancer and inhibits angiogenesis. In the current study, we demonstrated that sole vitamin K3 (menadione) selectively inhibits the in vitro activity of eukaryotic DNA polymerase gamma, which is a mitochondrial DNA polymerase, and suppresses angiogenesis in a rat aortic ring model. The anti-angiogenic effect of vitamin K3 has been shown in angiogenesis models using human umbilical vein endothelial cells (HUVECs) with regard to HUVEC growth, tube formation on reconstituted basement membrane and chemotaxis. These results suggest that vitamin K3 may be a potential anti-cancer agent like vitamin K2.

  13. K2-EDTA and K3-EDTA Greiner Tubes for HbA1c Measurement.

    Science.gov (United States)

    Vrtaric, Alen; Filipi, Petra; Hemar, Marina; Nikolac, Nora; Simundic, Ana-Maria

    2016-02-01

    To determine whether K2-ethylenediaminetetraacetic acid (EDTA) and K3-EDTA Greiner tubes could be used interchangeably for glycosylated hemoglobin, type A1C (HbA1c) measurement via the Abbott Laboratories ARCHITECT chemiluminescent microparticle HbA1c assay on the ARCHITECT i2000SR immunoanalyzer at our university hospital. We drew blood from a total of 45 outpatients into plastic Greiner Vacuette tubes, some of which were lined with K2-EDTA and others with K3-EDTA anticoagulant. Data are presented as median and interquartile range values. We used the Wilcoxon test and Passing-Bablok regression for tube comparison. For K2-EDTA tubes median HbA1c concentration was 54 mmol/mol (41 to 71 mmol/mol) and for K3-EDTA tubes 56 mmol/mol (43 to 69 mmol/mol). There was no statistically significant difference between K2-EDTA and K3-EDTA (bias= -1.29 mmol/mol; P = 0.24). Passing-Bablok regression showed that there is no constant and proportional error: y = -0.23 (95% CI[-3.52 to 0.69]) + 1.00( 95% CI[0.98 to 1.06]) x. In this study, we provide evidence for the lack of any clinically and statistically significant bias between K2-EDTA and K3-EDTA HbA1c measurements. Thus, Greiner tubes lined with K2-EDTA and those lined with K3-EDTA can safely be used interchangeably to measure HbA1c via the Abbott Laboratories ARCHITECT assay. © American Society for Clinical Pathology, 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Moving the School and Dancing Education: Case Study Research of K-5 Students' Experiences in a Dance Residency

    Science.gov (United States)

    Leonard, Alison E.

    2012-01-01

    This dissertation chronicles the qualitative case study of a dance artist-in-residence at a diverse and inclusive K-5 school in an urban district, integrating science, social studies, physical education, music, and visual arts school curriculum and culminating in two public performances. This study focused on how students made meaning through this…

  15. Comparative Analyses of H3K4 and H3K27 Trimethylations Between the Mouse Cerebrum and Testis

    KAUST Repository

    Cui, Peng

    2012-06-08

    The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. However, the bivalent domains tend towards a “winner-takes-all” approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a “winner-takes-all” principle to regulate gene expression.

  16. Subcutaneous injection of 99mTc pertechnetate at acupuncture points K-3 and B-60

    International Nuclear Information System (INIS)

    Wu Chung-Chieng; Jong Shiang-Bin; Lin Chun-Ching; Chen Min-Fen; Chen Jong-Rern; Chung Chieng.

    1990-01-01

    The acupuncture points are known to be morphologically related to the nerves and vessels. Yet the physiological role of blood vessels in the formation of acupuncture points remains unknown. With subcutaneous injection of 99m Tc pertechnetate at the acupuncture points K-3 and B-60 and with intra-acupuncture point injection of 99m Tc pertechnetate at K-3 and B-60, a lower-limb venography like what was obtained by intravenous injection of 99m Tc macroaggregated albumin was demonstrated in the present study. It seems that some acupuncture points do play a role in drainage of tissue fluid from soft tissue into the veins. (author)

  17. Investigation of the thermodynamic properties of the binary system vitamin K3/carbon dioxide

    OpenAIRE

    Trupej Nina; Knez-Hrnčič Maša; Škerget Mojca; Knez Željko

    2017-01-01

    The binary system of vitamin K3 and CO2 was investigated at temperatures of 40, 60 and 80 °C up to a pressure of 40 MPa. Solubility was measured by a static-analytic method. Partial molar volumes were determined by a method involving a vibrating tube densimeter. The solubility of vitamin K3 in CO2 is found as a function of pressure and temperature. The highest solubility (31.16×10-4 mol∙mol-1) was attained at a pressure of 25.40 MPa at temperature of 40°C. However, at temperature of 60°C and ...

  18. Effect of stearic acid on the properties of metronidazole/methocel K4M floating matrices

    Directory of Open Access Journals (Sweden)

    Belem Lara-Hernández

    2009-09-01

    Full Text Available The properties of metronidazole/Methocel K4M sustained release floating tablets have been studied varying the proportion of the lubricant, stearic acid, on formulations with and without sodium bicarbonate. The variables studied include technological properties of the tablets such as tablet hardness and ejection pressure, the drug release profile, the hydration kinetics and the floating behaviour. The presence of stearic acid and sodium bicarbonate improves the floating behaviour for more than 8 hours. The hydration volume, the tablet hardness and the ejection pressure decrease as the stearic acid content increases and the polymer content decreases. Drug dissolution increases with increasing proportions of stearic acid and decreasing proportions of the polymer in the tablets. The presence of sodium bicarbonate extends the differences in dissolution produced by stearic acid. These results are attributed to decreasing matrices coherence with an increasing quantity of stearic acid and a reducing polymer proportion. The carbon dioxide bubbles produced by sodium bicarbonate expand the matrices facilitating the dissolution, although their presence obstructs also the diffusion path through the hydrated gel layer.Estudaram-se as propriedades de comprimidos flutuantes de metronidazol/Methocel K4M de liberação controlada, variando-se a proporção do lubrificante, ácido esteárico, nas formulações com e sem bicarbonato de sódio. As variáveis estudadas incluem propriedades tecnológicas dos comprimidos, tais como dureza, pressão de ejeção, perfil de liberação do fármaco, cinética de hidratação e comportamento de flutuação. A presença de ácido esteárico e do bicarbonato de sódio melhora o comportamento de flutuação para mais de 8 horas. O volume de hidratação, a dureza e a pressão de ejeção do comprimido decrescem à medida que o conteúdo de ácido esteárico e de polímero diminui. A dissolução do fármaco aumenta com o

  19. αVβ3 Integrin-Targeted Radionuclide Therapy with 64Cu-cyclam-RAFT-c(-RGDfK-)4.

    Science.gov (United States)

    Jin, Zhao-Hui; Furukawa, Takako; Degardin, Mélissa; Sugyo, Aya; Tsuji, Atsushi B; Yamasaki, Tomoteru; Kawamura, Kazunori; Fujibayashi, Yasuhisa; Zhang, Ming-Rong; Boturyn, Didier; Dumy, Pascal; Saga, Tsuneo

    2016-09-01

    The transmembrane cell adhesion receptor αVβ3 integrin (αVβ3) has been identified as an important molecular target for cancer imaging and therapy. We have developed a tetrameric cyclic RGD (Arg-Gly-Asp) peptide-based radiotracer (64)Cu-cyclam-RAFT-c(-RGDfK-)4, which successfully captured αVβ3-positive tumors and angiogenesis by PET. Here, we subsequently evaluated its therapeutic potential and side effects using an established αVβ3-positive tumor mouse model. Mice with subcutaneous U87MG glioblastoma xenografts received single administrations of 37 and 74 MBq of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 (37 MBq/nmol), peptide control, or vehicle solution and underwent tumor growth evaluation. Side effects were assessed in tumor-bearing and tumor-free mice in terms of body weight, routine hematology, and hepatorenal functions. Biodistribution of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 with ascending peptide doses (0.25-10 nmol) and with the therapeutic dose of 2 nmol were determined at 3 hours and at various time points (2 minutes-24 hours) postinjection, respectively, based on which radiation-absorbed doses were estimated. The results revealed that (64)Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently slowed down the tumor growth. The mean tumor doses were 1.28 and 1.81 Gy from 37 and 74 MBq of (64)Cu-cyclam-RAFT-c(-RGDfK-)4, respectively. Peptide dose study showed that the tumor uptake of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently decreased at doses ≥1 nmol, indicating a saturation of αVβ3 with the administered therapeutic doses (1 and 2 nmol). Combined analysis of the data from tumor-bearing and tumor-free mice revealed no significant toxicity caused by 37-74 MBq of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 Our study demonstrates the therapeutic efficacy and safety of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 for αVβ3-targeted radionuclide therapy. (64)Cu-cyclam-RAFT-c(-RGDfK-)4 would be a promising theranostic drug for cancer imaging and therapy. Mol Cancer Ther; 15(9); 2076-85. ©2016 AACR

  20. Over-expression of histone H3K4 demethylase gene JMJ15 enhances salt tolerance in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yuan eShen

    2014-06-01

    Full Text Available Histone H3 lysine 4 trimethylation (H3K4me3 has been shown to be involved in stress-responsive gene expression and gene priming in plants. However, the role of H3K4me3 resetting in the processes is not clear. In this work we studied the expression and function of Arabidopsis H3K4 demethylase gene JMJ15. We show that the expression of JMJ15 was relatively low and was limited to a number of tissues during vegetative growth but was higher in young floral organs. Over-expression of the gene in gain-of-function mutants reduced the plant height with accumulation of lignin in stems, while the loss-of-function mutation did not produce any visible phenotype. The gain-of-function mutants showed enhanced salt tolerance, whereas the loss-of-function mutant was more sensitive to salt compared to the wild type. Transcriptomic analysis revealed that over-expression of JMJ15 down-regulated many genes which are preferentially marked by H3K4me3 and H3K4me2. Many of the down-regulated genes encode transcription regulators involved in stress responses. The data suggest that increased JMJ15 levels may regulate the gene expression program that enhances stress tolerance.

  1. Synthesis and Absolute Configuration of Enantiomerically Pure Vitamin K3 2,3-Epoxide

    NARCIS (Netherlands)

    Snatzke, Günther; Wijnberg, Hans; Feringa, Bernard; Marsman, Bea G.; Greydanus, Ben; Pluim, Henk

    1980-01-01

    The 2,3-epoxide of vitamin K3 (menadione, 1) has been prepared in enantiomerically pure form, and the absolute configuration has been deduced from the CD spectrum. The compound with the negative Cotton effect between 340 and 400 nm has the 2R,3S configuration.

  2. Investigation of the thermodynamic properties of the binary system vitamin K3/carbon dioxide

    Directory of Open Access Journals (Sweden)

    Trupej Nina

    2017-01-01

    Full Text Available The binary system of vitamin K3 and CO2 was investigated at temperatures of 40, 60 and 80 °C up to a pressure of 40 MPa. Solubility was measured by a static-analytic method. Partial molar volumes were determined by a method involving a vibrating tube densimeter. The solubility of vitamin K3 in CO2 is found as a function of pressure and temperature. The highest solubility (31.16×10-4 mol∙mol-1 was attained at a pressure of 25.40 MPa at temperature of 40°C. However, at temperature of 60°C and a pressure of 24.02 MPa, the solubility was 18.79×10-4 mol∙mol-1. Solubility was lower at a temperature of 80°C and a pressure of 22.06 MPa (6.48×10-4 mol∙mol-1. The partial molar volumes are negative and the dissolved vitamin K3 has a minor impact on the density of the solution of K3 in CO2 compared to the density of the pure CO2.

  3. Vitamin K3 attenuates cerulein-induced acute pancreatitis through inhibition of the autophagic pathway.

    Science.gov (United States)

    Chinzei, Ryo; Masuda, Atsuhiro; Nishiumi, Shin; Nishida, Masayuki; Onoyama, Mitsuko; Sanuki, Tsuyoshi; Fujita, Tsuyoshi; Moritoh, Satoshi; Itoh, Tomoo; Kutsumi, Hiromu; Mizuno, Shigeto; Azuma, Takeshi; Yoshida, Masaru

    2011-01-01

    The discovery of novel and effective treatment methods would be of great help to patients with acute pancreatitis. The aims of this study were to determine the inhibitory effects of vitamin K3 (VK3) against cerulein-induced acute pancreatitis in mice and to examine the mechanisms behind these effects. Acute pancreatitis in mice was induced by intraperitoneal injection of cerulein 6 times at hourly intervals. Vitamin K3 was administered once before the first injection of cerulein or twice before and after the first injection of cerulein. The degrees of inflammation and autophagy in the pancreatic tissue were estimated by histological examination, measurement of enzyme activity, confocal microscopy, and Western blotting. The inhibitory effects of VK3 against rapamycin-induced autophagy were also examined using HeLa cells stably expressing green fluorescent protein LC3. Cerulein-induced acute pancreatitis was markedly attenuated by the administration of VK3. In addition, VK3 led to the inhibition of cerulein-evoked autophagic changes and colocalization of autophagosomes and lysosomes in the pancreatic tissue. Vitamin K3 also reduced rapamycin-induced autophagy in HeLa/green fluorescent protein LC3 cells. Our data suggest that the administration of VK3 reduces pancreatic inflammation in acute pancreatitis through inhibition of the autophagic pathway. Vitamin K3 may be an effective therapeutic strategy against acute pancreatitis.

  4. BPS open strings and A-D-E-singularities in F-theory on K3

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Hartong, Jelle

    We improve on a recently constructed graphical representation of the supergravity 7-brane solution and apply this refined representation to re-study the open string description of the A-D-E-singularities in F-theory on K3. A noteworthy feature of the graphical representation is that it provides the

  5. PreK-3rd: What Is the Price Tag? Policy to Action Brief. No. 2

    Science.gov (United States)

    Shore, Rima

    2009-01-01

    In an era of intense fiscal pressures, educators are focusing on those investments most likely to lift student achievement. They are also trying to make more strategic use of existing resources. To achieve these goals, a growing number of policymakers are considering integrated PreK-3rd approaches. Increasingly, they are recognizing that the first…

  6. Have Recommended Book Lists Changed to Reflect Current Expectations for Informational Text in K-3 Classrooms?

    Science.gov (United States)

    Dreher, Mariam Jean; Kletzien, Sharon B.

    2016-01-01

    Despite both longstanding and recent calls for more informational text in K-3 classrooms, research indicates that narrative text remains in the majority for read alouds, classroom libraries, and instruction, thus limiting children's opportunity to experience the demands of expository text. Because national associations' recommended book lists are…

  7. A Bibliography of English as a Second Language Materials: Grades K-3.

    Science.gov (United States)

    National Clearinghouse for Bilingual Education, Arlington, VA.

    This annotated bibliography of English as a second language (ESL) materials for grades K-3 is divided into four parts. The first part, ESL texts, lists a number of series or single texts that are designed to teach the spoken language and reading to the elementary school child. The second part is a list of readers that, although were mostly…

  8. Evolutionary Adaptation of Kluyveromyces marxianus NIRE-K3 for Enhanced Xylose Utilization

    International Nuclear Information System (INIS)

    Sharma, Nilesh Kumar; Behera, Shuvashish; Arora, Richa; Kumar, Sachin

    2017-01-01

    The evolutionary adaptation was approached on the thermotolerant yeast Kluyveromyces marxianus NIRE-K3 at 45°C on xylose as a sole source of carbon for enhancement of xylose uptake. After 60 cycles, evolved strain K. marxianus NIRE-K3.1 showed comparatively 3.75- and 3.0-fold higher specific growth and xylose uptake rates, respectively, than that of native strain. Moreover, the short lag phase was also observed on adapted strain. During batch fermentation with xylose concentration of 30 g l −1 , K. marxianus NIRE-K3.1 could utilize about 96% of xylose in 72 h and produced 4.67 and 15.7 g l −1 of ethanol and xylitol, respectively, which were 9.72- and 4.63-fold higher than that of native strain. Similarly, specific sugar consumption rate, xylitol, and ethanol yields were 5.07-, 1.15-, and 2.44-fold higher as compared to the native strain, respectively. The results obtained after evolutionary adaptation of K. marxianus NIRE-K3 show the significant improvement in the xylose utilization, ethanol and xylitol yields, and productivities. By understanding the results obtained, the significance of evolutionary adaptation has been rationalized, since the adapted culture could be more stable and could enhance the productivity.

  9. Evolutionary Adaptation of Kluyveromyces marxianus NIRE-K3 for Enhanced Xylose Utilization

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Nilesh Kumar [Biochemical Conversion Division, Sardar Swaran Singh National Institute of Bio-Energy, Kapurthala (India); I. K. Gujral Punjab Technical University, Kapurthala (India); Behera, Shuvashish; Arora, Richa; Kumar, Sachin, E-mail: sachin.biotech@gmail.com [Biochemical Conversion Division, Sardar Swaran Singh National Institute of Bio-Energy, Kapurthala (India)

    2017-12-12

    The evolutionary adaptation was approached on the thermotolerant yeast Kluyveromyces marxianus NIRE-K3 at 45°C on xylose as a sole source of carbon for enhancement of xylose uptake. After 60 cycles, evolved strain K. marxianus NIRE-K3.1 showed comparatively 3.75- and 3.0-fold higher specific growth and xylose uptake rates, respectively, than that of native strain. Moreover, the short lag phase was also observed on adapted strain. During batch fermentation with xylose concentration of 30 g l{sup −1}, K. marxianus NIRE-K3.1 could utilize about 96% of xylose in 72 h and produced 4.67 and 15.7 g l{sup −1} of ethanol and xylitol, respectively, which were 9.72- and 4.63-fold higher than that of native strain. Similarly, specific sugar consumption rate, xylitol, and ethanol yields were 5.07-, 1.15-, and 2.44-fold higher as compared to the native strain, respectively. The results obtained after evolutionary adaptation of K. marxianus NIRE-K3 show the significant improvement in the xylose utilization, ethanol and xylitol yields, and productivities. By understanding the results obtained, the significance of evolutionary adaptation has been rationalized, since the adapted culture could be more stable and could enhance the productivity.

  10. Exploring K-3 Teachers' Implementation of Comprehension Strategy Instruction (CSI) Using Expectancy-Value Theory

    Science.gov (United States)

    Foley, Laura S.

    2011-01-01

    This research investigated factors that influence the implementation levels of evidence-based comprehension strategy instruction (CSI) among K-3 teachers. An explanatory design was chosen to gather and probe the data. Quantitative data were gathered via a mailed survey distributed through a representative sample of the 40 school districts (through…

  11. PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

    DEFF Research Database (Denmark)

    Chung, Ho-Ryun; Xu, Chao; Fuchs, Alisa

    2016-01-01

    and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA Pol......II. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA PolII S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue...... that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes....

  12. Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition

    DEFF Research Database (Denmark)

    Dahl, John Arne; Jung, Inkyung; Aanes, Håvard

    2016-01-01

    device that is not readily available. We developed a micro-scale chromatin immunoprecipitation and sequencing (μChIP-seq) method, which we used to profile genome-wide histone H3 lysine methylation (H3K4me3) and acetylation (H3K27ac) in mouse immature and metaphase II oocytes and in 2-cell and 8-cell....... Active removal of broad H3K4me3 domains by the lysine demethylases KDM5A and KDM5B is required for normal zygotic genome activation and is essential for early embryo development. Our results provide insight into the onset of the developmental program in mouse embryos and demonstrate a role for broad H3K4...

  13. Inhibition of the development of metastases by dietary vitamin C:K3 combination.

    Science.gov (United States)

    Taper, Henryk S; Jamison, James M; Gilloteaux, Jacques; Summers, Jack L; Calderon, Pedro Buc

    2004-07-09

    The tumor growth-inhibiting and chemo-potentiating effects of vitamin C and K(3)combinations have been demonstrated both in vitro and in vivo. The purpose of this study was to investigate the influence of orally administered vitamin C and K(3) on the metastasis of mouse liver tumor (T.L.T.) cells implanted in C3H mice. Adult male C3H mice were given water containing vitamin C and K3 (15 g/0.15 g dissolved in 1000 ml) beginning 2 weeks before tumor transplantation until the end of the experiment. T.L.T. cells (106) were implanted intramuscularly in the right thigh of mice. All mice were sacrificed 42 days after tumor transplantation. Primary tumor, lungs, lymph nodes and other organs or tissues suspected of harboring metastases were macroscopically examined. Samples of primary tumors, their local lymph nodes, lungs and main organs such as liver, kidneys, spleen were taken for histological examination. Forty-two percent of control mice exhibited lung metastases and 27% possessed metastases in local lymph nodes whereas 24% of vitamin-treated mice exhibited lung metastases and 10% possessed local lymph nodes metastases. The total number of lung metastases was 19 in control group and 10 in vitamin C and K(3)-treated mice. Histopathological examination of the metastatic tumors from the vitamin-treated mice revealed the presence of many tumor cells undergoing autoschizic cell death. These results demonstrate that oral vitamin C and K(3) significantly inhibited the metastases of T.L.T. tumors in C3H mice. At least a portion of this inhibition was due to tumor cell death by autoschizis.

  14. Crossed molecular beam-tunable laser determination of velocity dependence of intramultiplet mixing: K(4p2P1/2)+He →K(4p2P3/2)+He

    International Nuclear Information System (INIS)

    Anderson, R.W.; Goddard, T.P.; Parravano, C.; Warner, J.

    1976-01-01

    The velocity dependence of intramultiplet mixing, K(4p 2 P 1 / 2 ) +He→K(4p 2 P 3 / 2 )+He, has been measured over the relative velocity range v=1.3--3.4 km/sec. The cross section appears to fit a linear function Q (v) =A (v-v 0 ), where a=6.3 x 10 -4 A 2 and v 0 = 7.9 x 10 4 cm/sec. The value of A is obtained by normalization to the literature thermal average cross section. The intramultiplet mixing theory of Nikitin is modified to yield Q (v) for the process. The modified theory correctly exhibits detailed balancing, and it is normalized to provide a very good fit to the observed Q (v). The magnitude of the normalization factor, however, is larger than that predicted from recent pseudopotential calculations of the excited state potentials. The temperature dependence of intramultiplet mixing is predicted. The use of laser polarization to determine the m/subj/ dependence of the process K(4p 2 P 3 / 2 +He→K(4p 2 P 1 / 2 )+He and other collision processes of excited 2 P 3 / 2 states is examined

  15. K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation

    DEFF Research Database (Denmark)

    Boecker, Werner; Stenman, Goeran; Loening, Thomas

    2013-01-01

    different cell lineages and define their cellular hierarchy in tumors with myoepithelial differentiation. isTILT analysis of a series of 28 breast, salivary, and lacrimal gland tumors, including pleomorphic adenomas (n=8), epithelial-myoepithelial tumors (n=9), and adenoid cystic carcinomas (n=11) revealed...... heterologeous cell differentiations such as squamous and mesenchymal progenies. p63 was co-expressed with K5/K14 in basal-like progenitor cells, myoepithelial, and squamous cells but not in glandular cells. Our results show that the corresponding counterpart tumors of breast and salivary/lacrimal glands have....... For that reason, we performed an in situ triple immunofluorescence lineage/differentiation tracing (isTILT) and qRT-PCR study of basal (K5/K14), glandular (K7/K8/18), and epidermal-specific squamous (K10) keratins, p63, and smooth muscle actin (SMA; myoepithelial marker) with the aim to construct and trace...

  16. Transport mean free path in K5Bi1-xNdx(MoO4)4 laser crystal powders

    International Nuclear Information System (INIS)

    Illarramendi, M A; Aramburu, I; Fernandez, J; Balda, R; Al-Saleh, M

    2007-01-01

    In this work, we calculate in two different ways the transport mean free paths in K 5 Bi 1-x Nd x (MoO 4 ) 4 (x = 0.05, 0.2, 1) laser crystal powders by using the diffuse spectral reflectance and transmittance of the powders and the absorption coefficient of the crystal materials. The theoretical calculations have been made by assuming a diffusive propagation of light in these materials. Similar results have been obtained from both methods

  17. Draft Genome Sequence of Halomonas elongata Strain K4, an Endophytic Growth-Promoting Bacterium Enhancing Salinity Tolerance In Planta

    KAUST Repository

    Lafi, Feras Fawzi

    2016-11-04

    Halomonas elongata strain K4 is an endophytic bacterial strain that was isolated from roots of Cyperus conglomeratus collected at the Red Sea coast in Thuwal, Saudi Arabia. Here, we present a draft genome sequence of this strain, highlighting a number of pathways involved in plant growth promotion under salt stress.

  18. Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin.

    Science.gov (United States)

    Li, Sisi; Yen, Linda; Pastor, William A; Johnston, Jonathan B; Du, Jiamu; Shew, Colin J; Liu, Wanlu; Ho, Jamie; Stender, Bryan; Clark, Amander T; Burlingame, Alma L; Daxinger, Lucia; Patel, Dinshaw J; Jacobsen, Steven E

    2016-08-30

    Microrchidia (MORC) proteins are GHKL (gyrase, heat-shock protein 90, histidine kinase, MutL) ATPases that function in gene regulation in multiple organisms. Animal MORCs also contain CW-type zinc finger domains, which are known to bind to modified histones. We solved the crystal structure of the murine MORC3 ATPase-CW domain bound to the nucleotide analog AMPPNP (phosphoaminophosphonic acid-adenylate ester) and in complex with a trimethylated histone H3 lysine 4 (H3K4) peptide (H3K4me3). We observed that the MORC3 N-terminal ATPase domain forms a dimer when bound to AMPPNP. We used native mass spectrometry to show that dimerization is ATP-dependent, and that dimer formation is enhanced in the presence of nonhydrolyzable ATP analogs. The CW domain uses an aromatic cage to bind trimethylated Lys4 and forms extensive hydrogen bonds with the H3 tail. We found that MORC3 localizes to promoters marked by H3K4me3 throughout the genome, consistent with its binding to H3K4me3 in vitro. Our work sheds light on aspects of the molecular dynamics and function of MORC3.

  19. Draft Genome Sequence of Halomonas elongata Strain K4, an Endophytic Growth-Promoting Bacterium Enhancing Salinity Tolerance In Planta

    KAUST Repository

    Lafi, Feras Fawzi; Ramirez Prado, Juan Sebastian; Alam, Intikhab; Bajic, Vladimir B.; Hirt, Heribert; Saad, Maged

    2016-01-01

    Halomonas elongata strain K4 is an endophytic bacterial strain that was isolated from roots of Cyperus conglomeratus collected at the Red Sea coast in Thuwal, Saudi Arabia. Here, we present a draft genome sequence of this strain, highlighting a number of pathways involved in plant growth promotion under salt stress.

  20. An efficient solvent-free synthesis of imidazolines and benzimidazoles using K 4[Fe(CN 6] catalysis

    Directory of Open Access Journals (Sweden)

    Kabeer A. Shaikh

    2012-01-01

    Full Text Available Imidazolines and Benzimidazoles have been efficiently synthesized in high yields by treatment of 1,2-diamine with aldehydes using the metal co-ordinate complex K 4[Fe(CN 6] as a catalysis. The method was carried out under solvent free condition via oxidation of carbon-nitrogen bond. The process is green, mild and inexpensive.

  1. Homologous overexpression of RfaH in E. coli K4 improves the production of chondroitin-like capsular polysaccharide.

    Science.gov (United States)

    Cimini, Donatella; De Rosa, Mario; Carlino, Elisabetta; Ruggiero, Alessandro; Schiraldi, Chiara

    2013-05-09

    Glycosaminoglycans, such as hyaluronic acid, heparin, and chondroitin sulfate, are among the top ranked products in industrial biotechnology for biomedical applications, with a growing world market of billion dollars per year. Recently a remarkable progress has been made in the development of tailor-made strains as sources for the manufacturing of such products. The genetic modification of E. coli K4, a natural producer of chondroitin sulfate precursor, is challenging considering the lack of detailed information on its genome, as well as its mobilome. Chondroitin sulfate is currently used as nutraceutical for the treatment of osteoarthritis, and several new therapeutic applications, spanning from the development of skin substitutes to live attenuated vaccines, are under evaluation. E. coli K4 was used as host for the overexpression of RfaH, a positive regulator that controls expression of the polysaccharide biosynthesis genes and other genes necessary for the virulence of E. coli K4. Various engineering strategies were compared to investigate different types of expression systems (plasmid vs integrative cassettes) and integration sites (genome vs endogenous mobile element). All strains analysed in shake flasks on different media showed a capsular polysaccharide production improved by 40 to 140%, compared to the wild type, with respect to the final product titer. A DO-stat fed-batch process on the 2L scale was also developed for the best performing integrative strain, EcK4r3, yielding 5.3 g ∙ L(-1) of K4 polysaccharide. The effect of rfaH overexpression in EcK4r3 affected the production of lipopolysaccharide and the expression of genes involved in the polysaccharide biosynthesis pathway (kfoC and kfoA), as expected. An alteration of cellular metabolism was revealed by changes of intracellular pools of UDP-sugars which are used as precursors for polysaccharide biosynthesis. The present study describes the identification of a gene target and the application of a

  2. Subcutaneous injection of sup 99m Tc pertechnetate at acupuncture points K-3 and B-60

    Energy Technology Data Exchange (ETDEWEB)

    Wu Chung-Chieng; Jong Shiang-Bin; Lin Chun-Ching; Chen Min-Fen; Chen Jong-Rern (Kaohsiung Medical Coll., Taiwan (China)); Chung Chieng

    1990-06-01

    The acupuncture points are known to be morphologically related to the nerves and vessels. Yet the physiological role of blood vessels in the formation of acupuncture points remains unknown. With subcutaneous injection of {sup 99m}Tc pertechnetate at the acupuncture points K-3 and B-60 and with intra-acupuncture point injection of {sup 99m}Tc pertechnetate at K-3 and B-60, a lower-limb venography like what was obtained by intravenous injection of {sup 99m}Tc macroaggregated albumin was demonstrated in the present study. It seems that some acupuncture points do play a role in drainage of tissue fluid from soft tissue into the veins. (author).

  3. Low-temperature synthesis and structural properties of ferroelectric K 3WO 3F 3 elpasolite

    Science.gov (United States)

    Atuchin, V. V.; Gavrilova, T. A.; Kesler, V. G.; Molokeev, M. S.; Aleksandrov, K. S.

    2010-06-01

    Low-temperature ferroelectric G2 polymorph of K 3WO 3F 3 has been prepared by chemical synthesis. Structural and chemical properties of the final product have been evaluated with X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Structure parameters of G2-K 3WO 3F 3 are refined by the Rietveld method from XRD data measured at room temperature (space group Cm, Z = 2, a = 8.7350(3) Å, b = 8.6808(5) Å, c = 6.1581(3) Å, β = 135.124(3) Å, V = 329.46(3) Å 3; RB = 2.47%). Partial ordering of oxygen and fluorine atoms has been found over anion positions. Mechanism of ferroelectric phase transition in A 2BMO 3F 3 oxyfluorides is discussed.

  4. The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma.

    Science.gov (United States)

    von Gruenigen, Vivian E; Jamison, James M; Gilloteaux, Jacques; Lorimer, Heather E; Summers, Marcia; Pollard, Robert R; Gwin, Carley A; Summers, Jack L

    2003-01-01

    The objective was to evaluate the cytotoxic effect and mechanism of action of vitamins C (VC) and K3 (VK3) on ovarian carcinoma. Cytotoxicity assays were performed on ovarian cancer cell lines with VC, VK3 or a VC/VK3 combination. FIC index was employed to evaluate synergism. Flow cytometry was accomplished at 90% cytotoxic doses. Light, transmission electron microscopy and DNA isolation were performed. Antitumor activity was exhibited by both VC, VK3 and VC/VK3. VC/VK3 demonstrated synergistic activity. VC/VK3 may induce a G1 block in the cell cycle. Combined vitamin treatment resulted in cells that maintain apparently intact nuclei while extruding pieces of organelle-free cytoplasm. Degradation of chromosomal DNA was observed. Cell death (autoschizis) displayed characteristics of both apoptosis and necrosis. The cytotoxic effects observed may enable vitamins C and K3 to play an adjuvant role in the treatment of ovarian cancer.

  5. Synchrotron radiation photoemission spectrum study on K3C60 film

    Institute of Scientific and Technical Information of China (English)

    李宏年; 徐亚伯; 鲍世宁; 李海洋; 何丕模; 钱海杰; 刘风琴; 奎热西·易卜拉欣

    2000-01-01

    K3C60 single crystal film was prepared on the cleaved (111) surface of C60 single crystal. Synchrotron radiation angle-resolved photoemission spectra were measured at normal emission with sample temperature at - 150K. Up to four subpeaks of LUMO-derived band were observed. These sub-peaks exhibit distinct energy dispersions which resemble in general the theoretical ones calculated for K3C60 at low temperature with the so-called one-dimensional disordered structure. But there is large deviation of experimental sub-band intervals from the theoretical values. This result is meaningful for the studies of the physical properties of alkali-doped C60 solids, e.g. the mechanism for superconductivity.

  6. Structure analysis of K3H(SO4)2 by neutron powder diffraction

    International Nuclear Information System (INIS)

    Murakami, Satoshi; Kuroiwa, Yoshihiro; Noda, Yukio; Nakai, Yusuke; Kamiyama, Takashi; Asano, Hajime.

    1993-01-01

    Neutron powder diffraction experiments of K 3 H(SO 4 ) 2 were carried out at KENS-HRP station in order to obtain the positional parameters of hydrogen nuclei. The data was taken at six different temperatures from room temperature to 20K. Even though K 3 H(SO 4 ) 2 contained a hydrogen atom, the structural analysis was successfully performed by using a program RIETAN. Concerning the hydrogen position, four different models give almost the same R-factor so that the state of the hydrogen nucleus is not uniquely determined. The result based on the assumption that a hydrogen nucleus occupies two sites shows that the distance of split hydrogen nuclei is shorter than the distance of hydrogen electron clouds. This result suggests that a large polarizability exists in a hydrogen atom. (author)

  7. Boundary Fixed Points, Enhanced Gauge Symmetry and Singular Bundles on K3

    CERN Document Server

    Fuchs, J; Lerche, Wolfgang; Lütken, C A; Schweigert, C; Walcher, J

    2001-01-01

    We investigate certain fixed points in the boundary conformal field theory representation of type IIA D-branes on Gepner points of K3. They correspond geometrically to degenerate brane configurations, and physically lead to enhanced gauge symmetries on the world-volume. Non-abelian gauge groups arise if the stabilizer group of the fixed points is realized projectively, which is similar to D-branes on orbifolds with discrete torsion. Moreover, the fixed point boundary states can be resolved into several irreducible components. These correspond to bound states at threshold and can be viewed as (non-locally free) sub-sheaves of semi-stable sheaves. Thus, the BCFT fixed points appear to carry two-fold geometrical information: on the one hand they probe the boundary of the instanton moduli space on K3, on the other hand they probe discrete torsion in D-geometry.

  8. On algebraic cycles on a fibre product of families of K3-surfaces

    International Nuclear Information System (INIS)

    Nikol'skaya, Ol'ga V

    2013-01-01

    We prove the Hodge conjecture and the standard conjecture of Lefschetz type for fibre squares of smooth projective non-isotrivial families of K3-surfaces over a smooth projective curve under the assumption that the rank of the lattice of transcendental cycles on a generic geometric fibre of the family is an odd prime. We prove the Hodge conjecture for a fibre product of two non-isotrivial families of K3-surfaces (possibly with degenerations) under the condition that, for every point of the curve, at least one family has non-singular fibre over this point, and the rank of the lattice of transcendental cycles on a generic geometric fibre of one family is odd and not equal to the corresponding rank for the other.

  9. Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases

    OpenAIRE

    Parvez Alam; Sumit Kumar Chaturvedi; Mohammad Khursheed Siddiqi; Ravi Kant Rajpoot; Mohd Rehan Ajmal; Masihuz Zaman; Rizwan Hasan Khan

    2016-01-01

    Protein misfolding and aggregation have been associated with several human diseases such as Alzheimer?s, Parkinson?s and familial amyloid polyneuropathy etc. In this study, anti-fibrillation activity of vitamin k3 and its effect on the kinetics of amyloid formation of hen egg white lysozyme (HEWL) and A?-42 peptide were investigated. Here, in combination with Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), transmission electron microscopy and cell cytotoxicity assay, we demons...

  10. Synthesis, characterization and serum albumin binding studies of vitamin K3 derivatives.

    Science.gov (United States)

    Suganthi, Murugesan; Elango, Kuppanagounder P

    2017-01-01

    Synthesis, characterization and bovine serum albumin (BSA) binding properties of three derivatives of vitamin K3 have been described. Results of UV-Vis and fluorescence spectra indicate complexation between BSA and the ligands with conformational changes in protein, which is strongly supported by synchronous and three dimensional fluorescence studies. Addition of the ligands quenches the fluorescence of BSA which is accompanied by reduction in quantum yield (Ф) from 0.1010 to 0.0775-0.0986 range. Thermodynamic investigations reveal that hydrophobic interaction is the major binding force in the spontaneous binding of these ligands with BSA. The binding constants obtained depend on the substituent present in the quinone ring, which correlates linearly with the Taft's field substituent constant (σ F ). The results show that compound with strong electron withdrawing nitro-group forms relatively stronger complex with BSA than amino and thioglycolate substituted ones. Circular dichroism studies show that the α-helical content of the protein, upon complexation with the ligands, decreases in the case of amino and nitro substituted vitamin K3 while increases in thioglycolate substituted compound. Molecular docking studies indicated that the vitamin K3 derivatives are surrounded by hydrophobic residues of the BSA molecule, which is in good agreement with the results of fluorescence spectral and thermodynamic studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The monodromy property for K3 surfaces allowing a triple-point-free model

    DEFF Research Database (Denmark)

    Jaspers, Annelies Kristien J

    2017-01-01

    The aim of this thesis is to study under which conditions K3 surfaces allowing a triple-point-free model satisfy the monodromy property. This property is a quantitative relation between the geometry of the degeneration of a Calabi-Yau variety X and the monodromy action on the cohomology of...... X: a Calabi- Yau variety X satisfies the monodromy property if poles of the motivic zeta function ZX,ω(T) induce monodromy eigenvalues on the cohomology of X. Let k be an algebraically closed field of characteristic 0, and set K = k((t)). In this thesis, we focus on K3 surfaces over K allowing a triple-point...... is very precise, which allows to use a combination of geometrical and combinatorial techniques to check the monodromy property in practice. The first main result is an explicit computation of the poles of ZX,ω(T) for a K3 surface X allowing a triple-point-free model and a volume form ! on X. We show that...

  12. KEY COMPARISON: Report on the Regional Comparison COOMET.AUV.A-K3

    Science.gov (United States)

    Barrera-Figueroa, Salvador; Nielsen, Lars; Rasmussen, Knud

    2007-01-01

    COOMET.AUV.A-K3 is a Regional Comparison that supplements the Key Comparison CCAUV.A-K3 organized by the CCAUV. The participating NMIs are GUM (Poland), INM (Romania), VNIIFTRI (Russia) and DP-NDI 'Systema' (Ukraine). The role of Pilot laboratory was undertaken by DPLADFM (Denmark). The measurements took place between May 2005 and February 2006. The time schedule was organized in a single star configuration. Initially, two LS2aP microphones were circulated. However, a sudden change of sensitivity of one of them forced the inclusion of an additional microphone. Nevertheless, the analysis was performed on all microphones involved. This report includes the measurement results from the participants, information about their calibration methods, and the analysis leading to the assignation of degrees of equivalence and the link to the CCAUV.A-K3. Main text. To reach the main text of this paper, click on Final Report. The final report has been peer-reviewed and approved for publication by the CCAUV, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  13. Microscopic Aspects of Autoschizic Cell Death in Human Ovarian Carcinoma (2774) Cells Following Vitamin C, Vitamin K3 or Vitamin C:K3 Treatment

    Science.gov (United States)

    Gilloteaux, Jacques; Jamison, James M.; Arnold, David; Taper, Henryk S.; von Gruenigen, Vivian E.; Summers, Jack L.

    2003-08-01

    Human ovarian carcinoma cells (MDAH 2774) were treated with sodium ascorbate (VC), menadione (VK3), or with a VC:VK3 combination for 1 h and then studied using light microscopy (LM) and scanning (SEM) and transmission electron (TEM) microscopy. Plasma membrane damage (blisters and blebs, hairy aspect) results from vitamin C (VC) treatment, while cytoskeletal damage and self-morsellation are caused by vitamin K3 (VK3) treatment. VC:VK3-treated cells exhibit exacerbated injuries characteristic of both VC and VK3 treatment as well as a significant decrease in cell diameters from 20 35 [mu]m for control cells to 7 12 [mu]m for VC:VK3 treatment. Moreover, after a 1-h exposure to the vitamin combination, autoschizis (43%), apoptosis (3%), and oncosis (1.9%) are observed at the percentages indicated. All cellular changes associated with autoschizis observed with SEM were confirmed by LM and TEM observations and are consistent with cell death by autoschizis: decrease in cell size, cytoplasmic self-excisions, degradation of the nucleus and nucleolus without formation of apoptotic bodies and, ultimately, karyorrhexis and karyolysis. These results also suggest that the vitamin combination may find clinical use in the treatment of ovarian cancer.

  14. Toric K3-fibred Calabi-Yau manifolds with del Pezzo divisors for string compactifications

    Energy Technology Data Exchange (ETDEWEB)

    Cicoli, Michele [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Mayrhofer, Christoph [Heidelberg Univ. (Germany). Inst. fuer Theoretische Physik; Kreuzer, Maximilian

    2011-06-15

    We analyse several explicit toric examples of compact K3-fibred Calabi-Yau three-folds which can be used for the study of string dualities and are crucial ingredients for the construction of LARGE Volume type IIB vacua with promising applications to cosmology and particle phenomenology. In order to build a phenomenologically viable model, on top of the two moduli corresponding to the base and the K3 fibre, we demand also the existence of two additional rigid divisors: the first supporting the non-perturbative effects needed to achieve moduli stabilisation, and the second allowing the presence of chiral matter on wrapped D-branes. We clarify the topology of these rigid divisors by discussing the interplay between a diagonal structure of the Calabi-Yau volume and D-terms. Del Pezzo divisors appearing in the volume form in a completely diagonal way are natural candidates for supporting non-perturbative effects and for quiver constructions, while 'non-diagonal' del Pezzo and rigid but not del Pezzo divisors are particularly interesting for model building in the geometric regime. Searching through the existing list of four dimensional reflexive lattice polytopes, we find 158 examples admitting a Calabi-Yau hypersurface which is a K3 fibration with four Kaehler moduli where at least one of them is a 'diagonal' del Pezzo. We work out explicitly the topological details of a few examples showing how, in the case of simplicial polytopes, all the del Pezzo divisors are 'diagonal', while 'non-diagonal' ones appear only in the case of non-simplicial polytopes. A companion paper will use these results in the study of moduli stabilisation for globally consistent explicit Calabi-Yau compactifications with the local presence of chirality. (orig.)

  15. Toric K3-fibred Calabi-Yau manifolds with del Pezzo divisors for string compactifications

    International Nuclear Information System (INIS)

    Cicoli, Michele; Mayrhofer, Christoph; Kreuzer, Maximilian

    2011-06-01

    We analyse several explicit toric examples of compact K3-fibred Calabi-Yau three-folds which can be used for the study of string dualities and are crucial ingredients for the construction of LARGE Volume type IIB vacua with promising applications to cosmology and particle phenomenology. In order to build a phenomenologically viable model, on top of the two moduli corresponding to the base and the K3 fibre, we demand also the existence of two additional rigid divisors: the first supporting the non-perturbative effects needed to achieve moduli stabilisation, and the second allowing the presence of chiral matter on wrapped D-branes. We clarify the topology of these rigid divisors by discussing the interplay between a diagonal structure of the Calabi-Yau volume and D-terms. Del Pezzo divisors appearing in the volume form in a completely diagonal way are natural candidates for supporting non-perturbative effects and for quiver constructions, while 'non-diagonal' del Pezzo and rigid but not del Pezzo divisors are particularly interesting for model building in the geometric regime. Searching through the existing list of four dimensional reflexive lattice polytopes, we find 158 examples admitting a Calabi-Yau hypersurface which is a K3 fibration with four Kaehler moduli where at least one of them is a 'diagonal' del Pezzo. We work out explicitly the topological details of a few examples showing how, in the case of simplicial polytopes, all the del Pezzo divisors are 'diagonal', while 'non-diagonal' ones appear only in the case of non-simplicial polytopes. A companion paper will use these results in the study of moduli stabilisation for globally consistent explicit Calabi-Yau compactifications with the local presence of chirality. (orig.)

  16. Wear of K3 and ProTaper files after simulated clinical use in curved canals

    Directory of Open Access Journals (Sweden)

    Patrícia de Almeida Rodrigues Silva e Souza

    2009-01-01

    Full Text Available Objective: To assess wear, after simulated clinical use of K3 (SybronEndo, Orange, CA, EUA and ProTaper files (Dentsply-Maillefer, Tulsa, Oklahoma, EUA in 46 mesiovestibular roots of human maxillary first molars, recently extracted and with mean angulation of 40°.Methods: The teeth were divided as follows: a K3 (SybronEndo, Orange, CA, EUA (with radial bands and b ProTaper (Dentsply-Maillefer, Tulsa, Oklahoma, EUA (without radial bands. The files were assessed by scanning electronic microscopy before first use to visualize fabrication defects, and after 7 and 13 cycles of debridement in the canals. Debridement with files K3 (SybronEndo, Orange, CA, EUA and ProTaper (Dentsply-Maillefer, Tulsa, Oklahoma, EUA was performed in accordance with the manufacturers’ recommendations. The criteria for wear assessment were: defects (stretching, shortening/spiral inversion, presence of craters, oblique cracks and fracture. After assessment by SEM and before they were used, metal barbs on the crest of the spirals and oblique scratches due to the machining process were found in all the files.Results: In the K3 system (SybronEndo, Orange, CA, USA, after being used seven times, all the instruments showed cutting angle defects,and 25/08 and 25/10 had oblique cracks in the body of the active part leading to ductile fracture after being used for the eighth time. In the ProTaper system (Dentsply-Maillefer, Tulsa, Oklahoma, USA, after being used seven times, in addition to cutting angle defects, the files also presented cracks, and ruptile fracture occurred in F3 during use for the thirteenth time. At the end of preparation, craters were seen along the active part of the files.Conclusion: In the final analysis, it was seen that the system are equivalent with regard to the defects found, irrespective of the active part design,being proportional to the number of cycles of use, and these defects could act as points of greater fragility, favoring fracture.

  17. [Vitamin K3-induced activation of molecular oxygen in glioma cells].

    Science.gov (United States)

    Krylova, N G; Kulagova, T A; Semenkova, G N; Cherenkevich, S N

    2009-01-01

    It has been shown by the method of fluorescent analysis that the rate of hydrogen peroxide generation in human U251 glioma cells under the effect of lipophilic (menadione) or hydrophilic (vikasol) analogues of vitamin K3 was different. Analyzing experimental data we can conclude that menadione underwent one- and two-electron reduction by intracellular reductases in glioma cells. Reduced forms of menadione interact with molecular oxygen leading to reactive oxygen species (ROS) generation. The theoretical model of ROS generation including two competitive processes of one- and two-electron reduction of menadione has been proposed. Rate constants of ROS generation mediated by one-electron reduction process have been estimated.

  18. ESR studies of electron irradiated K3Ir(CN)6 in KCl single crystals

    International Nuclear Information System (INIS)

    Vugman, N.V.; Pinhal, N.M.

    1983-01-01

    ESR studies of KCl single crystals doped with small amounts of K 3 Ir(CN) 6 and submitted to a prolongued 2 MeV electron irradiation at room temperature reveal the presence of the [IR(CN) 5 Cl] 4- and [Ir(CN) 4 Cl 2 ] 4- new molecular species. Ligand spin densities and ligand field parameters are calculated from the experimental hyperfine and superhyperfine interactions and compared to previous data on the [Ir(CN) 5 ] 4- species. (Author) [pt

  19. Study of charge transfer complexes of menadione (vitamin K 3) with a series of anilines

    Science.gov (United States)

    Pal, Purnendu; Saha, Avijit; Mukherjee, Asok K.; Mukherjee, Dulal C.

    2004-01-01

    Menadione (vitamin K 3) has been shown to form charge transfer complexes with N, N-dimethyl aniline, N, N-dimethyl p-toluidine and N, N-dimethyl m-toluidine in CCl 4 medium. The CT transition energies are well correlated with the ionisation potentials of the anilines. The formation constants of the complexes have been determined at a number of temperatures from which the enthalpies and entropies of formation have been obtained. The formation constants exhibit a very good linear free energy relationship (Hammett) at all the temperatures studied.

  20. Peningkatan Motivasi Belajar Kimia Siswa Sekolah Menengah Menggunakan Metode Koligatif Kemas Kreatif (K3

    Directory of Open Access Journals (Sweden)

    Suci Rizki Nurul Aeni

    2016-01-01

    Full Text Available Abstract: This research is classroom action research at XII class of Madrasah Aliyah YAPIKA. The subject matter  properties of Colligative Solution conducted with K3 method (Koligatif Kemas Kreatif to improve student’s learning motivation. Research has been conducted with the repetition of three times so that the study be completed for three years. Three phase of learning are preparation, implementation and evaluation. Preparation phase is done by teachers and students at home. The teacher is preparing the learning media there are games rules, cardboard spacecraft, question cards,  stopwatch, and a dice. Students learn the material properties of koligatif independently learning by themself using  the student hand book. Implementation of the learning is done through a number of methods, there are the story method, discussions and cooperative teamwork through creative games. The evaluation was direct observation methods. The observation sheets assessing of cognitive and affective aspects of students. Based on the results of observation showed that students can impact the content, focus attention and participate active in learning, supported by innovations that have been implemented.Keywords: Colligative properties, K3, MotivationAbstrak: Penelitian ini adalah penelitian tindakan kelas di Madrasah Aliyah YAPIKA Kurnia kelas XII yang mengkaji materi Sifat Koligatif Larutan melalui metode pembelajaran K3 (Koligatif Kemas Kreatif, sebagai cara untuk meningkatkan motivasi belajar siswa. Penelitian telah dilakukan dengan pengulangan sebanyak tiga kali. Pembelajaran yang ditempuh berupa tahap persiapan, pelaksanaan dan evaluasi. Tahap persiapan dilakukan oleh guru dan siswa di rumah. Guru mempersiapkan media pembelajaran berupa petunjuk games, karton wahana, question card, stopwatch, dan dadu. Siswa mempelajari materi sifat koligatif secara mandiri dengan cara belajar melalui buku pegangan siswa. Pelaksanaan

  1. Self-broadening and shifting of the Li(2s-2p) and K(4s-4p) line cores

    International Nuclear Information System (INIS)

    Reggami, L.; Bouledroua, M.; Allouche, A.R.; Aubert-Frecon, M.

    2009-01-01

    The aim of this work is to determine quantum mechanically the width Γ and the shift Δ of the lithium Li(2p→2s) and potassium K(4p→4s) resonance lines when these atoms are evolving in their parent gases. The interaction potentials along which the atoms Li(2p)+Li(2s) and K(4p)+K(4s) approach each other are constructed from reliable data. The radial wave equation is then solved numerically by using these potentials to compute the elastic phase shifts. By adopting the simplified Baranger model for the pressure broadening, which assumes the impact approximation, the cross sections effective in linewidth and lineshift are analyzed. The analysis leads in particular to the determination of the width and shift rates and the computations show that these rates have constant values and, mainly, do not depend on temperature. An approximate method is further applied to the calculations of the cross sections. The results reveal the influence of the long-range -C 3 /R 3 interactions and confirm the universality of the obtained formulas of Γ and Δ

  2. Exploration on anion ordering, optical properties and electronic structure in K3WO3F3 elpasolite

    International Nuclear Information System (INIS)

    Atuchin, V.V.; Isaenko, L.I.; Kesler, V.G.; Lin, Z.S.; Molokeev, M.S.; Yelisseyev, A.P.; Zhurkov, S.A.

    2012-01-01

    Room-temperature modification of potassium oxyfluorotungstate, G2-K 3 WO 3 F 3 , has been prepared by low-temperature chemical route and single crystal growth. Wide optical transparency range of 0.3–9.4 μm and forbidden band gap E g =4.32 eV have been obtained for G2-K 3 WO 3 F 3 crystal. Meanwhile, its electronic structure has been calculated with the first-principles calculations. The good agreement between the theorectical and experimental results have been achieved. Furthermore, G2-K 3 WO 3 F 3 is predicted to possess the relatively large nonlinear optical coefficients. - Graphical abstract: Using the cm-size K 3 WO 3 F 3 crystal (left upper), the transmission spectrum (right upper) and XPS valence electronic states (left lower) were measured, agreed with the ab initio results (right lower). Highlights: ► The cm-size G2-K 3 WO 3 F 3 single crystals are obtained. ► Optical absorption edge and transmission range are defined for G2-K 3 WO 3 F 3 crystal. ► Crystal structures of all known K 3 WO 3 F 3 polymorph modifications are determined. ► Experimental electronic structure is consistent with the first-principles result. ► G2-K 3 WO 3 F 3 is predicted as a crystal with large NLO coefficients.

  3. Deformation and fracture of K3 rotary nickel-titanium endodontic instruments after clinical use.

    Science.gov (United States)

    Shen, S M; Deng, M; Wang, P P; Chen, X M; Zheng, L W; Li, H L

    2016-11-01

    The aim was to evaluate the incidence and type of defects that occurred with K3 rotary nickel-titanium instruments during routine clinical use. A total of 2397 K3 (G-PACKS, SybronEndo, West Collins, Orange, CA, USA) instruments were collected from a graduate endodontic clinic over 21 months. All the instruments were limited to a maximum use of 30 canal preparations. The collected instruments were measured by a digital caliper to determine whether any fractures had occurred and then were visually inspected for deformation and fracture under a stereomicroscope. The surfaces of fractured instruments were further evaluated under a scanning electron microscope. Data were analysed using chi-square test and Kruskal-Wallis test. The incidence of instrument defect was 5.63%, consisting of 3.59% fractures and 2.05% deformations. The defect rates of 0.04 and 0.06 files were statistically higher than the other taper groups (P  0.05). For the fractured instruments, 63.95% failed from flexural fatigue, whilst 36.05% failed from torsion. Flexural fracture was the major mode of fracture for instruments with larger taper. A routine check for instrument integrity particularly for 0.04 and 0.06 files at high magnification is recommended after each clinical use. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  4. Comparison of fracture and deformation in the rotary endodontic instruments: Protaper versus K-3 system.

    Science.gov (United States)

    Nagi, Sana Ehsen; Khan, Farhan Raza; Rahman, Munawar

    2016-03-01

    This experimental study was done on extracted human teeth to compare the fracture and deformation of the two rotary endodontic files system namely K-3 and Protapers. It was conducted at the dental clinics of the Aga Khan University Hospital, Karachi, A log of file deformation or fracture during root canal preparation was kept. The location of fracture was noted along with the identity of the canal in which fracture took place. The fracture in the two rotary systems was compared. SPSS 20 was used for data analysis. Of the 172(80.4%) teeth possessing more than 15 degrees of curvature, fracture occurred in 7(4.1%) cases and deformation in 10(5.8%). Of the 42(19.6%) teeth possessing less than 15 degrees of curvature, fracture occurred in none of them while deformation was seen in 1(2.4%). There was no difference in K-3 and Protaper files with respect to file deformation and fracture. Most of the fractures occurred in mesiobuccal canals of maxillary molars, n=3(21.4%). The likelihood of file fracture increased 5.65-fold when the same file was used more than 3 times. Irrespective of the rotary system, apical third of the root canal space was the most common site for file fracture.

  5. Luminescence and color center distributions in K3YB6O12:Ce3+ phosphor

    International Nuclear Information System (INIS)

    Yang, Li; Wan, Yingpeng; Weng, Honggen; Huang, Yanlin; Chen, Cuili; Seo, Hyo Jin

    2016-01-01

    Polycrystalline Ce 3+ -doped K 3 YB 6 O 12 (1–14 mol%) phosphors were prepared by facile chemical sol–gel synthesis. The phase formation of the phosphors was confirmed by x-ray powder diffraction (XRD) analysis. The photoluminescence excitation spectra (PLE), emission spectra (PL) and the luminescence decay curves were tested. Under the near-UV light, the phosphors present the emission from blue color to yellowish green due to the allowed 4 f  –5 d transitions of Ce 3+ ions. The absolute quantum efficiency (QE) of K 3 YB 6 O 12 :Ce 3+ can reach 53% under the excitation of near-UV light. The luminescence thermal quenching of the phosphor was investigated by the temperature-dependent spectra. The crystallographic site of Ce 3+ ions in the lattice was identified and discussed on the basis of luminescence characteristics and structural data. There is only one isolated Ce 3+ center occupying the Y(II) sites in the lightly doped samples presenting a typical doublet emission profile. While the Ce 3+ multi-centers could be created with the enhancement of the doping levels, which could induce the distinct red-shift of the spectra due to the dipole–dipole interactions. The result in this work could be useful for the further investigation of other rare earth ions in this host. (paper)

  6. Structure of ferroelastic K3H(SeO4)2

    International Nuclear Information System (INIS)

    Ichikawa, M.; Sato, S.; Komukae, M.; Osaka, T.

    1992-01-01

    Tripotassium hydrogenbis(selenate), K 3 H(SeO 4 ) 2 , M r = 404.2, monoclinic, A2/a, a = 10.1291 (8), b = 5.9038 (5), c = 14.961 (1) A, β = 103.640 (8) 0 , V = 869.5 (1) A 3 , Z = 4, D x = 3.086 Mg m -3 , λ(Mo Kα) = 0.71073 A, μ = 9.86 mm -1 , F(000) = 760, T = 299 K, R(F) = 0.0294 for 1670 unique reflections. K 3 H(SeO 4 ) 2 is isomorphous with most M 3 H(XO 4 ) 2 -type crystals (M=K,Rb and Cs; Cs; X = S and Se); two SeO 4 groups are connected by a crystallographically symmetric hydrogen bond into a dimer. The bond distances and angles in the SeO 4 group are similar to those in Rb 3 H(SeO 4 ) 2 and Rb 3 D(SeO 4 ) 2 . The hydrogen-bond length, 2.524 (5) A, is the shortest among the members of the M 3 H(SeO 4 ) 2 family exhibiting the low-temperature phase transition. (orig.)

  7. Extraction of Biomolecules Using Phosphonium-Based Ionic Liquids + K3PO4 Aqueous Biphasic Systems

    Science.gov (United States)

    Louros, Cláudia L. S.; Cláudio, Ana Filipa M.; Neves, Catarina M. S. S.; Freire, Mara G.; Marrucho, Isabel M.; Pauly, Jérôme; Coutinho, João A. P.

    2010-01-01

    Aqueous biphasic systems (ABS) provide an alternative and efficient approach for the extraction, recovery and purification of biomolecules through their partitioning between two liquid aqueous phases. In this work, the ability of hydrophilic phosphonium-based ionic liquids (ILs) to form ABS with aqueous K3PO4 solutions was evaluated for the first time. Ternary phase diagrams, and respective tie-lines and tie-lines length, formed by distinct phosphonium-based ILs, water, and K3PO4 at 298 K, were measured and are reported. The studied phosphonium-based ILs have shown to be more effective in promoting ABS compared to the imidazolium-based counterparts with similar anions. Moreover, the extractive capability of such systems was assessed for distinct biomolecules (including amino acids, food colourants and alkaloids). Densities and viscosities of both aqueous phases, at the mass fraction compositions used for the biomolecules extraction, were also determined. The evaluated IL-based ABS have been shown to be prospective extraction media, particularly for hydrophobic biomolecules, with several advantages over conventional polymer-inorganic salt ABS. PMID:20480041

  8. Development of a K3A robot for deployment in radioactive environments

    International Nuclear Information System (INIS)

    Sias, F.R. Jr.

    1996-01-01

    Radioactive materials make up a significant part of the hazardous-material inventory of the United States Department of Energy. Much of the radioactive material will be inspected or handled by robotic systems that contain electronic circuits that may be damaged by gamma radiation and other particles emitted from radioactive material. To use a mobile robot in the vicinity of high-level gamma radiation requires a special design. Since materials and electronic circuits can withstand some radiation without failure, the simplest approach would be simply to use an unmodified commercial mobile robot in the radioactive environment but remove it before failure occurs. Unpowered backup is another method of extending system lifetime in an ionizing radiation environment. When the primary system fails or degrades sufficiently, the backup system can be switched in to maintain system operation. By careful design and production-lot testing, systems can be designed to meet moderate doses of radiation; however, randomly-selected off- the-shelf commercial parts cannot be guaranteed to meet a specified total-dose tolerance. We can define the Basic Radiation-Hardened System to be a teleoperated K3A transport capable of deploying a radiation-hardened video camera for initial entry and inspection applications. The electronics in the K3A mobile base has three essential modules: MA-2 Motor Amplifier Circuit, DC-I Drive Control Computer, and DC/DC Converter for powering the electronics. Design of the system will be discussed

  9. Enhancer-associated H3K4 monomethylation by trithorax-related, the drosophila homolog of mammalian MLL3/MLL4

    NARCIS (Netherlands)

    H.-M. Herz (Hans-Martin); M. Mohan (Man); A.S. Garruss (Alexander); K. Liang (Kaiwei); Y.-H. Takahashi (Yoh-hei); K. Mickey (Kristen); O. Voets (Olaf); C.P. Verrijzer (Peter); A. Shilatifard (Ali)

    2012-01-01

    textabstractMonomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are

  10. Dynamic variation of histone H3 trimethyl Lys4 (H3K4me3) and heterochromatin protein 1 (HP1) with employment length in nickel smelting workers.

    Science.gov (United States)

    Zhao, Yanhong; Cheng, Ning; Dai, Min; Pu, Hongquan; Zheng, Tongzhang; Li, Haiyan; He, Jie; Bai, Yana

    2017-07-01

    To investigate the dynamic variation in H3K4me3 and HP1 with employment length in nickel smelting workers. Blood samples were collected from 140 nickel smelting workers and 140 age-matched office workers to test for H3K4me3, and HP1 levels. H3K4me3 was statistically significantly different (p exposure to nickel can induce oxidative damage, and increase H3K4me3 expression and inhibit HP1 expression.

  11. Inter-RMO Key Comparison EUROMET.L-K5.2004: Calibration of a step gauge

    DEFF Research Database (Denmark)

    Prieto, Emilio; Brown, Nicholas; Lassila, Antti

    2012-01-01

    The results of the inter-RMO key comparison EUROMET.L-K5.2004 on the calibration of a step gauge are reported. Eighteen National Metrology Institutes and one Designated Institute from four different metrological regions all over the world participated in this comparison which lasted three years...... value. Due to the significant instability of the step it was also considered an artefact uncertainty. The reported uncertainties ranged from 0.045 µm to 1.2 µm (k = 1). The uncertainty of the artefact ranged from 0.018 µm (for the 20 mm face) to 0.176 µm (for the 400 mm face). The compatibility of all...... participants for measuring step gauges was demonstrated with the only exception of a participant showing very high systematic (both positive and negative) errors. Five participants communicated higher uncertainties than the corresponding approved CMCs. A set of Recommendations and Actions were agreed therefore...

  12. Report of the key-comparison of spectral diffuse reflectance (EURAMET.PR-K5) (Ref. 619)

    Science.gov (United States)

    Andor, György; Gál, Péter

    2018-01-01

    This report details the final results of the EURAMET comparison on regular spectral transmittance carried out between 2006 and 2016. The aim of this comparison was to check the agreement of measurement of the spectral diffuse reflectance among participants, using the measurement geometry of d/0 or 0/d in the wavelength range of 360 nm to 780 nm at 20 nm increment. We used a star type comparison: first the participants sent their samples to the pilot, than the pilot measured all the samples of the participants and sent them back. The participants measured the samples and sent them to the pilot for control measurement. Six standards were used as reference standards in order to maintain the scale during the comparison. These were three samples of BCR-406 opal glasses (BCR 30506; BCR 30303; BCR 30704), an MC20 Russian opal glass (MC 4777) and two samples made of pressed halon (polytetrafluoroethylene) powder (halon 2007A; halon 2007C). These six samples were designated as the Comparison reference standards. The diffuse reflectance was initially measured on the OMH (BFKH) absolute reflectometer. The link to the CCPR-K5 results was BFKH, and the check on BFKH was the PTB results who also participated in the CCPR-K5 comparison. The participants were GUM, INM, LNE, METAS, BFKH, PTB, SP. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCPR, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  13. Structural analysis of the core COMPASS family of histone H3K4 methylases from yeast to human.

    Science.gov (United States)

    Takahashi, Yoh-hei; Westfield, Gerwin H; Oleskie, Austin N; Trievel, Raymond C; Shilatifard, Ali; Skiniotis, Georgios

    2011-12-20

    Histone H3 lysine 4 (H3K4) methylation is catalyzed by the highly evolutionarily conserved multiprotein complex known as Set1/COMPASS or MLL/COMPASS-like complexes from yeast to human, respectively. Here we have reconstituted fully functional yeast Set1/COMPASS and human MLL/COMPASS-like complex in vitro and have identified the minimum subunit composition required for histone H3K4 methylation. These subunits include the methyltransferase C-terminal SET domain of Set1/MLL, Cps60/Ash2L, Cps50/RbBP5, Cps30/WDR5, and Cps25/Dpy30, which are all common components of the COMPASS family from yeast to human. Three-dimensional (3D) cryo-EM reconstructions of the core yeast complex, combined with immunolabeling and two-dimensional (2D) EM analysis of the individual subcomplexes reveal a Y-shaped architecture with Cps50 and Cps30 localizing on the top two adjacent lobes and Cps60-Cps25 forming the base at the bottom. EM analysis of the human complex reveals a striking similarity to its yeast counterpart, suggesting a common subunit organization. The SET domain of Set1 is located at the juncture of Cps50, Cps30, and the Cps60-Cps25 module, lining the walls of a central channel that may act as the platform for catalysis and regulative processing of various degrees of H3K4 methylation. This structural arrangement suggested that COMPASS family members function as exo-methylases, which we have confirmed by in vitro and in vivo studies.

  14. The Oryza sativa Regulator HDR1 Associates with the Kinase OsK4 to Control Photoperiodic Flowering.

    Directory of Open Access Journals (Sweden)

    Xuehui Sun

    2016-03-01

    Full Text Available Rice is a facultative short-day plant (SDP, and the regulatory pathways for flowering time are conserved, but functionally modified, in Arabidopsis and rice. Heading date 1 (Hd1, an ortholog of Arabidopsis CONSTANS (CO, is a key regulator that suppresses flowering under long-day conditions (LDs, but promotes flowering under short-day conditions (SDs by influencing the expression of the florigen gene Heading date 3a (Hd3a. Another key regulator, Early heading date 1 (Ehd1, is an evolutionarily unique gene with no orthologs in Arabidopsis, which acts as a flowering activator under both SD and LD by promoting the rice florigen genes Hd3a and RICE FLOWERING LOCUST 1 (RFT1. Here, we report the isolation and characterization of the flowering regulator Heading Date Repressor1 (HDR1 in rice. The hdr1 mutant exhibits an early flowering phenotype under natural LD in a paddy field in Beijing, China (39°54'N, 116°23'E, as well as under LD but not SD in a growth chamber, indicating that HDR1 may functionally regulate flowering time via the photoperiod-dependent pathway. HDR1 encodes a nuclear protein that is most active in leaves and floral organs and exhibits a typical diurnal expression pattern. We determined that HDR1 is a novel suppressor of flowering that upregulates Hd1 and downregulates Ehd1, leading to the downregulation of Hd3a and RFT1 under LDs. We have further identified an HDR1-interacting kinase, OsK4, another suppressor of rice flowering under LDs. OsK4 acts similarly to HDR1, suppressing flowering by upregulating Hd1 and downregulating Ehd1 under LDs, and OsK4 can phosphorylate HD1 with HDR1 presents. These results collectively reveal the transcriptional regulators of Hd1 for the day-length-dependent control of flowering time in rice.

  15. Morphed and moving: TNFα-driven motility promotes cell dissemination through MAP4K4-induced cytoskeleton remodeling

    Directory of Open Access Journals (Sweden)

    Min Ma

    2014-04-01

    Full Text Available Cell dissemination from an initial site of growth is a highly coordinated and controlled process that depends on cell motility. The mechanistic principles that orchestrate cell motility, namely cell shape control, traction and force generation, are highly conserved between cells of different origins. Correspondingly, the molecular mechanisms that regulate these critical aspects of migrating cells are likely functionally conserved too. Thus, cell motility deregulation of unrelated pathogenesis could be caused and maintained by similar mechanistic principles. One such motility deregulation disorder is the leukoproliferative cattle disease Tropical Theileriosis, which is caused by the intracellular, protozoan parasite Theileria annulata. T. annulata transforms its host cell and promotes the dissemination of parasite-infected cells throughout the body of the host. An analogous condition with a fundamentally different pathogenesis is metastatic cancer, where oncogenically transformed cells disseminate from the primary tumor to form distant metastases. Common to both diseases is the dissemination of motile cells from the original site. However, unlike metastatic cancer, host cell transformation by Theileria parasites can be reverted by drug treatment and cell signaling be analyzed under transformed and non-transformed conditions. We have used this reversible transformation model and investigated parasite control of host cell motile properties in the context of inflammatory signaling in Ma M. et al. [PLoS Pathog (2014 10: e1004003]. We found that parasite infection promotes the production of the inflammatory cytokine TNFα in the host macrophage. We demonstrated that increased TNFα triggers motile and invasive properties by enhancing actin cytoskeleton remodeling and cell motility through the ser/thr kinase MAP4K4. We concluded that inflammatory conditions resulting in increased TNFα could facilitate cell dissemination by activating the actin

  16. Theoretical investigation of the Omega(g,u)(+/-) states of K2 dissociating adiabatically up to K(4p 2P(3/2)) + K(4p 2P(3/2)).

    Science.gov (United States)

    Jraij, A; Allouche, A R; Magnier, S; Aubert-Frécon, M

    2009-06-28

    A theoretical investigation of the electronic structure of the K(2) molecule, including spin-orbit effects, has been performed. Potential energies have been calculated over a large range of R up to 75a(0) for the 88 Omega(g,u)(+/-) states dissociating adiabatically into the limits up to K(4p (2)P(3/2))+K(4p (2)P(3/2)). Equilibrium distances, transition energies, harmonic frequencies, as well as depths for wells and heights for barriers are reported for all of the bound Omega(g,u)(+/-) states. Present ab initio calculations are shown to be able to reproduce quite accurately the small structures (wells and barrier) displayed at very long-range (R>50a(0)) by the (2,3)1(u) and (2)0(g)(-) purely long-range states. As the present data could help experimentalists, we make available extensive tables of energy values versus internuclear distances in our database at the web address http://www-lasim.univ-lyon1.fr/spip.php?rubrique99.

  17. Study on vitamin K 3-cyclodextrin inclusion complex and analytical application

    Science.gov (United States)

    Zhenming, Dong; Xiuping, Liu; Guomei, Zhang; Shaomin, Shuang; Jinghao, Pan

    2003-07-01

    The inclusion interaction of the complexes between Vitamin K3 (VK3) and β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) were studied by using steady-state fluorescence measurements. The various factors affecting the inclusion process were examined in detail. The formation constants and inclusion stoichiometry for VK3-CDs were determined. The results showed that the inclusion ability of β-CD and its derivatives was the order: SBE-β-CD>HP-β-CD>β-CD. The related inclusion mechanism is proposed to explain the inclusion process. A method of determining VK3 was established with the linear range was 2.5×10-6-5.0×10-4 M, and was used to determine the VK3 tablets. The recoveries were in the range of 97.52-103.5%. The results were satisfactory.

  18. Effective action of heterotic compactification on K3 with non-trivial gauge bundles

    International Nuclear Information System (INIS)

    Schasny, Martin

    2012-10-01

    In this thesis we study the heterotic string compactified on K3 with non-trivial gauge bundles. We focus on two backgrounds, the well-known standard embedding and abelian line bundles. Using a Kaluza-Klein reduction, the six-dimensional effective action is computed up to terms of order α' 2 with special attention on the hypermultiplet sector. We compute the moduli dependent couplings of the matter fields and analyze the geometry of the hyperscalar sigma model. Moreover, we prove the consistency with six-dimensional supergravity and derive the appropriate D-term scalar potential. For the line bundle backgrounds we show that the gauge flux stabilizes some geometrical moduli and renders some abelian vector multiplets massive.

  19. Twining genera of (0,4) supersymmetric sigma models on K3

    International Nuclear Information System (INIS)

    Harrison, Sarah; Kachru, Shamit; Paquette, Natalie M.

    2014-01-01

    Conformal field theories with (0,4) worldsheet supersymmetry and K3 target can be used to compactify the E 8 ×E 8 heterotic string to six dimensions in a supersymmetric manner. The data specifying such a model includes an appropriate configuration of 24 gauge instantons in the E 8 ×E 8 gauge group to satisfy the constraints of anomaly cancellation. In this note, we compute twining genera — elliptic genera with appropriate insertions of discrete symmetry generators in the trace — for (0,4) theories with various instanton embeddings. We do this by constructing linear sigma models which flow to the desired conformal field theories, and using the techniques of localization. We present several examples of such twining genera which are consistent with a moonshine relating these (0,4) models to the finite simple sporadic group M 24

  20. Effective action of heterotic compactification on K3 with non-trivial gauge bundles

    Energy Technology Data Exchange (ETDEWEB)

    Schasny, Martin

    2012-10-15

    In this thesis we study the heterotic string compactified on K3 with non-trivial gauge bundles. We focus on two backgrounds, the well-known standard embedding and abelian line bundles. Using a Kaluza-Klein reduction, the six-dimensional effective action is computed up to terms of order {alpha}'{sup 2} with special attention on the hypermultiplet sector. We compute the moduli dependent couplings of the matter fields and analyze the geometry of the hyperscalar sigma model. Moreover, we prove the consistency with six-dimensional supergravity and derive the appropriate D-term scalar potential. For the line bundle backgrounds we show that the gauge flux stabilizes some geometrical moduli and renders some abelian vector multiplets massive.

  1. Cytotoxic activity of vitamins K1, K2 and K3 against human oral tumor cell lines.

    Science.gov (United States)

    Okayasu, H; Ishihara, M; Satoh, K; Sakagami, H

    2001-01-01

    Vitamin K1, K2 and K3 were compared for their cytotoxic activity, radical generation and O2- scavenging activity. Among these compounds, vitamin K3 showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), human promyelocytic leukemic cell line (HL-60) and human gingival fibroblast (HGF). Vitamin K3 induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 or HSG cells. The cytotoxic activity of vitamins K2 and K1 was one and two orders lower, respectively, than K3. Vitamin K2, but not vitamin K3, showed tumor-specific cytotoxic action. ESR spectroscopy showed that only vitamin K3 produced radical(s) under alkaline condition and most potently enhanced the radical intensity of sodium ascorbate and scavenged O2- (generated by hypoxanthine-xanthine oxidase reaction system); vitamin K2 was much less active whereas vitamin K1 was inactive. These data suggest that the cytotoxic activity of vitamin K3 is generated by radical-mediated oxidation mechanism and that this vitamin has two opposing actions (that is, antioxidant and prooxidant), depending on the experimental conditions.

  2. Vitamin K3 Induces the Expression of the Stenotrophomonas maltophilia SmeVWX Multidrug Efflux Pump.

    Science.gov (United States)

    Blanco, P; Corona, F; Sánchez, M B; Martínez, J L

    2017-05-01

    Stenotrophomonas maltophilia is an opportunistic pathogen with increasing prevalence, which is able to cause infections in immunocompromised patients or in those with a previous pathology. The treatment of the infections caused by this bacterium is often complicated due to the several intrinsic antibiotic resistance mechanisms that it presents. Multidrug efflux pumps are among the best-studied mechanisms of S. maltophilia antibiotic resistance. Some of these efflux pumps have a basal expression level but, in general, their expression is often low and only reaches high levels when the local regulator is mutated or bacteria are in the presence of an effector. In the current work, we have developed a yellow fluorescent protein (YFP)-based sensor with the aim to identify effectors able to trigger the expression of SmeVWX, an efflux pump that confers resistance to quinolones, chloramphenicol, and tetracycline when it is expressed at high levels. With this purpose in mind, we tested a variety of different compounds and analyzed the fluorescence signal given by the expression of YFP under the control of the smeVWX promoter. Among the tested compounds, vitamin K 3 , which is a compound belonging to the 2-methyl-1,4-naphthoquinone family, is produced by plants in defense against infection, and has increasing importance in human therapy, was able to induce the expression of the SmeVWX efflux pump. In addition, a decrease in the susceptibility of S. maltophilia to ofloxacin and chloramphenicol was observed in the presence of vitamin K 3 , in both wild-type and smeW -deficient strains. Copyright © 2017 American Society for Microbiology.

  3. MANAJEMEN RISIKO KESELAMATAN DAN KESEHATAN KERJA (K3 PADA PROYEK PEMBANGUNAN JAMBULUWUK HOTEL & RESORT PETITENGET

    Directory of Open Access Journals (Sweden)

    Anak Agung Bayu Dharma

    2017-01-01

    Full Text Available Abstract: Work accidents that occur on the construction project will be one of the causes of the disruption or cessation of activities of the project work. The construction sector is the highest contributor to work accidents and occupational illness in Bali. Rampant construction of temporary lodging facilities or hotels in Bali can be one of the contributors to accidents. This study aims to determine the potential hazard and any dominant risk contained in a hotel development process as well as provides preventive measures to reduce such risks. In this research, the method used was descriptive qualitative. The risk of Occupational Health and Safety (K3 was identified through JSA (Job Safety Analysis. Questionnaire survey was carried out to get feedback from the experts regarding the potential hazards identified. The dominant category of risk assessment that was rated by the concept of ALARP (As Low As Reasonably Practicable. The research identified 45 of dominant risks contained in the phase of work structures including 43 risks classified as high risk such as : exposed to maneuver heavy equipment and vehicles, heavy equipment rolled because the excavated area slid down/ subsided, cross rope of Tower Crane disconnected / entangled on the operation, the charge fell from Tower Crane and as many as two risks were classified as very high risk (extreme risk that is : exposed to maneuver mixer and swing Tower Crane over the edge area of the project. The risks tended to be sourced in the work environment factors and work equipment. In order to minimize the impact of K3 risks, it is necessary to conduct risk control, evaluation activities in a daily, weekly, monthly periodic, considering a safe distance hazard source from workers, setting working hours, scenario procedures of an emergency, as well as safe work through work instruction to remind the importance of working in a healthy and safe condition.

  4. Antitumor effects of vitamins K1, K2 and K3 on hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Hitomi, Misuzu; Yokoyama, Fumi; Kita, Yuko; Nonomura, Takako; Masaki, Tsutomu; Yoshiji, Hitoshi; Inoue, Hideyuki; Kinekawa, Fumihiko; Kurokohchi, Kazutaka; Uchida, Naohito; Watanabe, Seishiro; Kuriyama, Shigeki

    2005-03-01

    A number of studies have shown that various K vitamins, specifically vitamins K2 and K3, possess antitumor activity on various types of rodent- and human-derived neoplastic cell lines. In the present study, we examined the antitumor effects of vitamins K1, K2 and K3 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vitro and in vivo. Furthermore, we examined the mechanisms of antitumor actions of these vitamins in vitro and in vivo. Although vitamin K1 did not inhibit proliferation of PLC/PRF/5 cells at a 90-microM concentration (the highest tested), vitamins K2 and K3 suppressed proliferation of the cells at concentrations of 90 and 9 microM, respectively. By flow cytometric analysis, it was shown that not only vitamin K1, but also vitamin K2 did not induce apoptosis or cell cycle arrest on PLC/PRF/5 cells. In contrast, vitamin K3 induced G1 arrest, but not apoptosis on PLC/PRF/5 cells. Subsequent in vivo study using subcutaneous HCC-bearing athymic nude mice demonstrated that both vitamins K2 and K3 markedly suppressed the growth of HCC tumors to similar extent. Protein expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4), but not p16INK4a Cdk inhibitor in the tumor was significantly reduced by vitamin K2 or K3 treatment, indicating that vitamins K2 and K3 may induce G1 arrest of cell cycle on PLC/PRF/5 cells in vivo. Taken collectively, vitamins K2 and K3 were able to induce potent antitumor effects on HCC in vitro and in vivo, at least in part, by inducing G1 arrest of the cell cycle. The results indicate that vitamins K2 and K3 may be useful agents for the treatment of patients with HCC.

  5. Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation.

    Science.gov (United States)

    Scott, Gary K; Atsriku, Christian; Kaminker, Patrick; Held, Jason; Gibson, Brad; Baldwin, Michael A; Benz, Christopher C

    2005-09-01

    The vitamin K analog menadione (K3), capable of both redox cycling and arylating nucleophilic substrates by Michael addition, has been extensively studied as a model stress-inducing quinone in both cell culture and animal model systems. Exposure of keratin 8 (k-8) expressing human breast cancer cells (MCF7, T47D, SKBr3) to K3 (50-100 microM) induced rapid, sustained, and site-specific k-8 serine phosphorylation (pSer73) dependent on signaling by a single mitogen activated protein kinase (MAPK) pathway, MEK1/2. Normal nuclear morphology and k-8 immunofluorescence coupled with the lack of DNA laddering or other features of apoptosis indicated that K3-induced cytotoxicity, evident within 4 h of treatment and delayed but not prevented by MEK1/2 inhibition, was due to a form of stress-activated cell death known as oncosis. Independent of MAPK signaling was the progressive appearance of K3-induced cellular fluorescence, principally nuclear in origin and suggested by in vitro fluorimetry to have been caused by K3 thiol arylation. Imaging by UV transillumination of protein gels containing nuclear extracts from K3-treated cells revealed a prominent 17-kDa band shown to be histone H3 by immunoblotting and mass spectrometry (MS). K3 arylation of histones in vitro followed by electrospray ionization-tandem MS analyses identified the unique Cys110 residue within H3, exposed only in the open chromatin of transcriptionally active genes, as a K3 arylation target. These findings delineate new pathways associated with K3-induced stress and suggest a potentially novel role for H3 Cys110 as a nuclear stress sensor.

  6. The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1

    DEFF Research Database (Denmark)

    Mariani, Luca; Lussi, Yvonne C.; Vandamme, Julien

    2016-01-01

    . Here, we show that RBR-2, the sole homolog of the KDM5 family of H3K4me3/2 demethylases in Caenorhabditis elegans, ensures correct axon guidance by controlling the expression of the actin regulator wsp-1. Loss of rbr-2 results in increased levels of H3K4me3 at the transcriptional start site of wsp-1...

  7. Differential cross sections of fine-structure transitions in K(4P)-He and -Ar collisions

    International Nuclear Information System (INIS)

    Mestdagh, J.M.; de Pujo, P.; Pascale, J.; Cuvellier, J.; Berlande, J.

    1987-01-01

    Differential cross sections for the transition K(4P/sub 3/2/→4P/sub 1/2/) induced by He and Ar have been studied both experimentally and theoretically. Calculations were performed using a full quantal close-coupling formalism. The angular distribution of the scattered atoms is measured by Doppler shift (ADDS method). The comparison with the theoretical calculations is performed on the basis of thorough kinematic analysis. In addition, the polarization effects corresponding to the experimental conditions are taken into account carefully. This allows one to test the accuracy of various interaction potentials available for the K-He and -Ar systems. The most interesting result concerns the K-He l-dependent pseudopotentials, which are found accurate to a sufficiently high level to allow good predictions of the observed differential cross-section patterns. In particular the positions and amplitudes of the cross-section oscillations at large center-of-mass scattering angles are well reproduced. The results for Ar show that the K-Ar potentials must be improved. Finally, taking the K(4P)-He fine-structure transition as an example, it has been shown how polarization effects may be used in ADDS measurements to obtain information on the dynamics of the collision process

  8. K4MR METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  9. K4BM METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  10. Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole

    2017-01-01

    PURPOSE: Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated...... the effect of a vitamin K3 cream on cetuximab-induced rash. MATERIALS AND METHODS: Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream...... stained for EGFR and pEGFR. RESULTS: Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed...

  11. Pengaruh kesehatan dan keselamatan kerja (K3, dan insentif terhadap motivasi serta kinerja karyawan pada bagian produksi

    Directory of Open Access Journals (Sweden)

    Anthony Frans

    2015-10-01

    Full Text Available The human factor is an important factor in implementing vision, mission in achieving company target. Human resources aspect need to get more attention from the company. Example of consideration that was given by the company is the provision of Occupational Health and Safety (K3 to the employees. This research examines a hypothesis, known as explanatory research. The research purpose are to explaining and analyzing the effect of work safety to work motivation; effect of work health to work motivation; understanding and analyzing the effect of incentive to employee performance; and explaining and analyzing the effect of motivation to employee performance in CV. Intan Mandiri Pratam, Kupang. In this research, work motivation was set as intervening variable. Direct impact between (K3 and incentive to employee are higher compare to K3 and incentive to motivation as variable. This research found that K3 and incentive are more impactful to worker compare to motivation as variable.

  12. Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize Polycomb silencing

    Science.gov (United States)

    Tie, Feng; Banerjee, Rakhee; Saiakhova, Alina R.; Howard, Benny; Monteith, Kelsey E.; Scacheri, Peter C.; Cosgrove, Michael S.; Harte, Peter J.

    2014-01-01

    Trithorax (TRX) antagonizes epigenetic silencing by Polycomb group (PcG) proteins, stimulates enhancer-dependent transcription, and establishes a ‘cellular memory’ of active transcription of PcG-regulated genes. The mechanisms underlying these TRX functions remain largely unknown, but are presumed to involve its histone H3K4 methyltransferase activity. We report that the SET domains of TRX and TRX-related (TRR) have robust histone H3K4 monomethyltransferase activity in vitro and that Tyr3701 of TRX and Tyr2404 of TRR prevent them from being trimethyltransferases. The trxZ11 missense mutation (G3601S), which abolishes H3K4 methyltransferase activity in vitro, reduces the H3K4me1 but not the H3K4me3 level in vivo. trxZ11 also suppresses the impaired silencing phenotypes of the Pc3 mutant, suggesting that H3K4me1 is involved in antagonizing Polycomb silencing. Polycomb silencing is also antagonized by TRX-dependent H3K27 acetylation by CREB-binding protein (CBP). We show that perturbation of Polycomb silencing by TRX overexpression requires CBP. We also show that TRX and TRR are each physically associated with CBP in vivo, that TRX binds directly to the CBP KIX domain, and that the chromatin binding patterns of TRX and TRR are highly correlated with CBP and H3K4me1 genome-wide. In vitro acetylation of H3K27 by CBP is enhanced on K4me1-containing H3 substrates, and independently altering the H3K4me1 level in vivo, via the H3K4 demethylase LSD1, produces concordant changes in H3K27ac. These data indicate that the catalytic activities of TRX and CBP are physically coupled and suggest that both activities play roles in antagonizing Polycomb silencing, stimulating enhancer activity and cellular memory. PMID:24550119

  13. PRX1 knockdown potentiates vitamin K3 toxicity in cancer cells: a potential new therapeutic perspective for an old drug.

    Science.gov (United States)

    He, Tiantian; Hatem, Elie; Vernis, Laurence; Lei, Ming; Huang, Meng-Er

    2015-12-21

    Many promising anticancer molecules are abandoned during the course from bench to bedside due to lack of clear-cut efficiency and/or severe side effects. Vitamin K3 (vitK3) is a synthetic naphthoquinone exhibiting significant in vitro and in vivo anticancer activity against multiple human cancers, and has therapeutic potential when combined with other anticancer molecules. The major mechanism for the anticancer activity of vitK3 is the generation of cytotoxic reactive oxygen species (ROS). We thus reasoned that a rational redox modulation of cancer cells could enhance vitK3 anticancer efficiency. Cancer cell lines with peroxiredoxin 1 (PRX1) gene transiently or stably knocked-down and corresponding controls were exposed to vitK3 as well as a set of anticancer molecules, including vinblastine, taxol, doxorubicin, daunorubicin, actinomycin D and 5-fluorouracil. Cytotoxic effects and cell death events were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based assay, cell clonogenic assay, measurement of mitochondrial membrane potential and annexin V/propidium iodide double staining. Global ROS accumulation and compartment-specific H2O2 generation were determined respectively by a redox-sensitive chemical probe and H2O2-sensitive sensor HyPer. Oxidation of endogenous antioxidant proteins including TRX1, TRX2 and PRX3 was monitored by redox western blot. We observed that the PRX1 knockdown in HeLa and A549 cells conferred enhanced sensitivity to vitK3, reducing substantially the necessary doses to kill cancer cells. The same conditions (combination of vitK3 and PRX1 knockdown) caused little cytotoxicity in non-cancerous cells, suggesting a cancer-cell-selective property. Increased ROS accumulation had a crucial role in vitK3-induced cell death in PRX1 knockdown cells. The use of H2O2-specific sensors HyPer revealed that vitK3 lead to immediate accumulation of H2O2 in the cytosol, nucleus, and mitochondrial matrix. PRX1 silencing

  14. Tuning the redox potential of vitamin K3 derivatives by oxidative functionalization using a Ag(i)/GO catalyst.

    Science.gov (United States)

    El-Hout, S I; Suzuki, H; El-Sheikh, S M; Hassan, H M A; Harraz, F A; Ibrahim, I A; El-Sharkawy, E A; Tsujimura, S; Holzinger, M; Nishina, Y

    2017-08-03

    We propose herein initial results to develop optimum redox mediators by the combination of computational simulation and catalytic functionalization of the core structure of vitamin K 3 . We aim to correlate the calculated energy value of the LUMO of different vitamin K 3 derivatives with their actual redox potential. For this, we optimized the catalytic alkylation of 1,4-naphthoquinones with a designed Ag(i)/GO catalyst and synthesized a series of molecules.

  15. Photoluminescence and thermoluminescence properties of Tb3+ doped K3Gd(PO4)2 nanophosphor

    International Nuclear Information System (INIS)

    Gupta, Palvi; Bedyal, A.K.; Kumar, Vinay; Khajuria, Y.; Lochab, S.P.; Pitale, S.S.; Ntwaeaborwa, O.M.; Swart, H.C.

    2014-01-01

    Energy level diagram of Tb 3+ ion in the K 3 Gd(PO 4 ) 2 host lattice. - Highlights: • First time, a detailed TL and PL study on undoped and Tb 3+ doped K 3 Gd(PO 4 ) 2 nanophosphor. • Combustion method was employed to synthesize the Tb 3+ doped K 3 Gd(PO 4 ) 2 nanophosphor. • Mechanism of excitation and emission in undoped and Tb 3+ doped K 3 Gd(PO 4 ) 2 nanophosphor was given. - Abstract: Tb 3+ doped nanoparticulate K 3 Gd(PO 4 ) 2 phosphor was prepared by combustion method using urea as a fuel. The structure, optical and luminescent properties of the phosphor were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), diffuse reflectance spectroscopy (DRS), photoluminescence spectroscopy (PL), and thermoluminescence (TL) spectroscopy. In undoped K 3 Gd(PO 4 ) 2 , the excitation and emission peaks at 273 nm and 323 nm belongs to the 8 S 7/2 → 6 I J(J=7/2) and 6 P J(J=7/2) → 8 S 7/2 transitions of Gd 3+ while green emission was observed in the Tb 3+ doped K 3 Gd(PO 4 ) 2 . TL study was carried out after exposing the samples to γ-radiations (0.1–5 kGy) in the K 3 Gd(PO 4 ) 2 :Tb 3+ (1.5 mol%). The calculated kinetic parameters were compared with different methods. The band gap of the phosphor was estimated as 5.80 eV. The green shade of the Tb 3+ ion with the CIE coordinates (x, y) as (0.29, 0.54) was in good agreement with the well known green phosphors

  16. Direct and indirect methods for the determination of vitamin K3 using differential pulse polarography and application to pharmaceuticals.

    Science.gov (United States)

    Somer, Güler; Doğan, Mehmet

    2008-11-01

    Two methods for the determination of vitamin K(3) have been developed. Vitamin K(3) in its oxidized form is determined by direct and indirect methods. Its standard solution was prepared by the indirect method using Ti(III) as reducing agent. For this purpose vitamin K(3) (menadion) in a clinical injection solution, which is in its hydroquinone form in the presence of sulfite, is oxidized with oxygen. In 0.2 M HAc and 0.02 M HCl electrolyte vitamin K(3) and Ti(IV) have reduction peaks at -0.58 V at -0.82 V respectively. The reaction between Ti(III) and vitamin takes place quantitatively in a medium of 0.2 M HAc and 0.002 M HCl. After the reduction, the reaction product Ti(IV) is followed from its polarographic peak at about -0.82 V. The most important result in this work is that, with this method vitamin K(3) can be standardized and after standardization this solution can be used for the direct determination in routine analysis with a very simple and fast method, using only the peak at -0.71 V in 0.2 M HAc medium. Both direct and indirect methods have been used for the determination of Vitamin K(3) in a clinical injection solution. The limit of quantification (LOQ) was 1.5x10(-6) M and in both methods the detection limit found was 7x10(-7) M.

  17. Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash.

    Science.gov (United States)

    Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole; Overgaard, Jens; Pfeiffer, Per

    2017-07-01

    Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated the effect of a vitamin K3 cream on cetuximab-induced rash. Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m 2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream and placebo were applied twice daily on two separate areas of the skin of minimum 10 × 10 cm for up to 2 months. Papulopustular eruptions were evaluated clinically and monitored by clinical photos. Skin biopsies, from ten patients taken before and after 1 month of treatment from each treatment area, were stained for EGFR and pEGFR. Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed in the skin of the vitamin K3-treated area compared to the placebo area. The present data do not support any clinical or immunohistochemical benefit of using vitamin K3 cream for cetuximab-induced rash.

  18. Collecting the Missing Piece of the Puzzle: The Wind Temperatures of Arcturus (K2 III) and Aldeberan (K5 III)

    Science.gov (United States)

    Harper, Graham

    2017-08-01

    Unravelling the poorly understood processes that drive mass loss from red giant stars requires that we empirically constrain the intimately coupled momentum and energy balance. Hubble high spectral resolution observations of wind scattered line profiles, from neutral and singly ionized species, have provided measures of wind acceleration, turbulence, terminal speeds, and mass-loss rates. These wind properties inform us about the force-momentum balance, however, the spectra have not yielded measures of the much needed wind temperatures, which constrain the energy balance.We proposed to remedy this omission with STIS E140H observations of the Si III 1206 Ang. resonance emission line for two of the best studied red giants: Arcturus (alpha Boo: K2 III) and Aldebaran (alpha Tau: K5 III), both of which have detailed semi-empirical wind velocity models. The relative optical depths of wind scattered absorption in Si III 1206 Ang., O I 1303 Ang. triplet., C II 1335 Ang., and existing Mg II h & k and Fe II profiles give the wind temperatures through the thermally controlled ionization balance. The new temperature constraints will be used to test existing semi-empirical models by comparision with multi-frequency JVLA radio fluxes, and also to constrain the flux-tube geometry and wave energy spectrum of magnetic wave-driven winds.

  19. The first naphthosemiquinone complex of K+ with vitamin K3 analog: Experiment and density functional theory

    Science.gov (United States)

    Kathawate, Laxmi; Gejji, Shridhar P.; Yeole, Sachin D.; Verma, Prakash L.; Puranik, Vedavati G.; Salunke-Gawali, Sunita

    2015-05-01

    Synthesis and characterization of potassium complex of 2-hydroxy-3-methyl-1,4-naphthoquinone (phthiocol), the vitamin K3 analog, has been carried out using FT-IR, UV-Vis, 1H and 13C NMR, EPR, cyclic voltammetry and single crystal X-ray diffraction experiments combined with the density functional theory. It has been observed that naphthosemiquinone binds to two K+ ions extending the polymeric chain through bridging oxygens O(2) and O(3). The crystal network possesses hydrogen bonding interactions from coordinated water molecules showing water channels along the c-axis. 13C NMR spectra revealed that the complexation of phthiocol with potassium ion engenders deshielding of C(2) signals, which appear at δ = ∼14.6 ppm whereas those of C(3) exhibit up-field signals near δ ∼ 6.9 ppm. These inferences are supported by the M06-2x based density functional theory. Electrochemical experiments further suggest that reduction of naphthosemiquinone results in only a cathodic peak from catechol. A triplet state arising from interactions between neighboring phthiocol anion lead to a half field signal at g = 4.1 in the polycrystalline X-band EPR spectra at 133 K.

  20. Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication.

    Science.gov (United States)

    Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

    2015-10-01

    Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting oxidative stress and inflammation.

    Science.gov (United States)

    Gupta, Amit Chand; Mohanty, Shilpa; Saxena, Archana; Maurya, Anil Kumar; Bawankule, Dnyaneshwar U

    2018-03-22

    Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter's 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.

  2. Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner.

    Science.gov (United States)

    Checker, Rahul; Sharma, Deepak; Sandur, Santosh K; Khan, Nazir M; Patwardhan, Raghavendra S; Kohli, Vineet; Sainis, Krishna B

    2011-08-01

    Recent investigations suggest that cellular redox status may play a key role in the regulation of several immune functions. Treatment of lymphocytes with vitamin K3 (menadione) resulted in a significant decrease in cellular GSH/GSSG ratio and concomitant increase in the ROS levels. It also suppressed Concanavalin A (Con A)-induced proliferation and cytokine production in lymphocytes and CD4 + T cells in vitro. Immunosuppressive effects of menadione were abrogated only by thiol containing antioxidants. Mass spectrometric analysis showed that menadione directly interacted with thiol antioxidant GSH. Menadione completely suppressed Con A-induced activation of ERK, JNK and NF-κB in lymphocytes. It also significantly decreased the homeostasis driven proliferation of syngeneic CD4 + T cells. Further, menadione significantly delayed graft-vs-host disease morbidity and mortality in mice. Menadione suppressed phytohemagglutinin-induced cytokine production in human peripheral blood mononuclear cells. These results reveal that cellular redox perturbation by menadione is responsible for significant suppression of lymphocyte responses.

  3. Menadione (Vitamin K3) decreases melanin synthesis through ERK activation in Mel-Ab cells.

    Science.gov (United States)

    Kim, Eun-Hyun; Kim, Myo-Kyoung; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Park, Kyoung-Chan; Kim, Dong-Seok

    2013-10-15

    Menadione is a synthetic vitamin K3 derivative. Here, we examined the effects of menadione on melanogenesis and its related signaling pathways. Our results showed that melanin content was significantly reduced after menadione treatment in a dose-dependent manner. However, menadione treatment did not reduce tyrosinase activity directly. Wnt signaling is known to play a major role in the control of melanin synthesis. Thus, we tested the effects of menadione treatment on GSK3β and β-catenin signaling, but found that menadione did not influence either of these signaling pathways. We also investigated changes in the phosphorylation of ERK, which is related to melanin regulation. These results indicated that menadione treatment led to the phosphorylation of ERK. Additionally, menadione treatment reduced both MITF and tyrosinase protein levels. Treatment with PD98059, a specific ERK pathway inhibitor, restored menadione-induced melanin reduction and also prevented MITF and tyrosinase downregulation by menadione. These results suggest that the hypopigmentary action of menadione is due to MITF and tyrosinase downregulation by ERK activation. © 2013 Elsevier B.V. All rights reserved.

  4. Vitamin K3 triggers human leukemia cell death through hydrogen peroxide generation and histone hyperacetylation.

    Science.gov (United States)

    Lin, Changjun; Kang, Jiuhong; Zheng, Rongliang

    2005-10-01

    Vitamin K3 (VK3) is a well-known anticancer agent, but its mechanism remains elusive. In the present study, VK3 was found to simultaneously induce cell death, reactive oxygen species (ROS) generation, including superoxide anion (O2*-) and hydrogen peroxide (H2O2) generation, and histone hyperacetylation in human leukemia HL-60 cells in a concentration- and time-dependent manner. Catalase (CAT), an antioxidant enzyme that specifically scavenges H2O2, could significantly diminish both histone acetylation increase and cell death caused by VK3, whereas superoxide dismutase (SOD), an enzyme that specifically eliminates O2*-, showed no effect on both of these, leading to the conclusion that H2O2 generation, but not O2*- generation, contributes to VK3-induced histone hyperacetylation and cell death. This conclusion was confirmed by the finding that enhancement of VK3-induced H2O2 generation by vitamin C (VC) could significantly promote both the histone hyperacetylation and cell death. Further studies suggested that histone hyperacetylation played an important role in VK3-induced cell death, since sodium butyrate, a histone deacetylase (HDAC) inhibitor, showed no effect on ROS generation, but obviously potentiated VK3-induced histone hyperacetylation and cell death. Collectively, these results demonstrate a novel mechanism for the anticancer activity of VK3, i.e., VK3 induced tumor cell death through H2O2 generation, which then further induced histone hyperacetylation.

  5. K(3)TaF(8) from laboratory X-ray powder data.

    Science.gov (United States)

    Smrcok, Lubomír; Cerný, Radovan; Boca, Miroslav; Macková, Iveta; Kubíková, Blanka

    2010-02-01

    The crystal structure of tripotassium octafluoridotantalate, K(3)TaF(8), determined from laboratory powder diffraction data by the simulated annealing method and refined by total energy minimization in the solid state, is built from discrete potassium cations, fluoride anions and monocapped trigonal-prismatic [TaF(7)](2-) ions. All six atoms in the asymmetric unit are in special positions of the P6(3)mc space group: the Ta and one F atom in the 2b (3m) sites, the K and two F atoms in the 6c (m) sites, and one F atom in the 2a (3m) site. The structure consists of face-sharing K(6) octahedra with a fluoride anion at the center of each octahedron, forming chains of composition [FK(3)](2+) running along [001] with isolated [TaF(7)](2-) trigonal prisms in between. The structure of the title compound is different from the reported structure of Na(3)TaF(8) and represents a new structure type.

  6. Genetic ablation of the GluK4 kainate receptor subunit causes anxiolytic and antidepressant-like behavior in mice.

    Science.gov (United States)

    Catches, Justin S; Xu, Jian; Contractor, Anis

    2012-03-17

    There is a clear link between dysregulation of glutamatergic signaling and mood disorders. Genetic variants in the glutamate receptor gene GRIK4, which encodes the kainate receptor subunit GluK4, alter the susceptibility for depression, bipolar disorder and schizophrenia. Here we demonstrate that Grik4(-/-) mice have reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, Grik4(-/-) mice spent significantly more time exploring the open areas of the maze. In anxiogenic tests of marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim test, a test of learned helplessness that is used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting that Grik4 ablation has an antidepressant-like effect. Finally, in the sucrose preference test, a test for anhedonia in rodents, Grik4(-/-) mice demonstrated increased sucrose preference. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs are known to modulate synaptic plasticity. We tested whether Grik4 ablation had effects on mossy fiber (MF) plasticity and found there to be a significant impairment in LTP likely through a loss of KAR modulation of excitability of the presynaptic MF axons. These studies demonstrate a clear anxiolytic and antidepressant phenotype associated with ablation of Grik4 and a parallel disruption in hippocampal plasticity, providing support for the importance of this receptor subunit in mood disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation

    Science.gov (United States)

    Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

    2010-01-01

    Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-α-evoked translocation of nuclear factor (NF)-κB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB and production of TNF-α in mouse macrophage RAW264·7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-α level and inhibited the LPS-evoked nuclear translocation of NF-κB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS. PMID:20030669

  8. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation.

    Science.gov (United States)

    Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

    2010-05-01

    Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.

  9. Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Jan, Yi-Hua [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Richardson, Jason R., E-mail: jricha3@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Baker, Angela A. [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Mishin, Vladimir [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Health Science, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2015-10-01

    Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40 mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. - Highlights: • Menadione redox cycles with cytochrome P450 reductase and generates reactive oxygen species. • Redox cycling inhibits cytochrome P450-mediated parathion metabolism. • Short term administration of menadione inhibits parathion toxicity by inhibiting paraoxon formation.

  10. The phosphatase inhibitor menadione (vitamin K3) protects cells from EGFR inhibition by erlotinib and cetuximab.

    Science.gov (United States)

    Perez-Soler, Roman; Zou, Yiyu; Li, Tianhong; Ling, Yi He

    2011-11-01

    Skin toxicity is the main side effect of epidermal growth factor receptor (EGFR) inhibitors, often leading to dose reduction or discontinuation. We hypothesized that phosphatase inhibition in the skin keratinocytes may prevent receptor dephosphorylation caused by EGFR inhibitors and be used as a new potential strategy for the prevention or treatment of this side effect. Menadione (Vitamin K3) was used as the prototype compound to test our hypothesis. HaCat human skin keratinocyte cells and A431 human squamous carcinoma cells were used. EGFR inhibition was measured by Western blotting and immunofluorescence. Phosphatase inhibition and reactive oxygen species (ROS) generation were measured by standard ELISA and fluorescence assays. Menadione caused significant and reversible EGFR activation in a dose-dependent manner starting at nontoxic concentrations. EGFR activation by menadione was associated with reversible protein tyrosine phosphatase inhibition, which seemed to be mediated by ROS generation as exposure to antioxidants prevented both menadione-induced ROS generation and phosphatase inhibition. Short-term coincubation of cells with nontoxic concentrations of menadione and the EGFR inhibitors erlotinib or cetuximab prevented EGFR dephosphorylation. Seventy-two-hour coincubation of cells with the highest nontoxic concentration of menadione and erlotinib provided for a fourfold cell growth inhibitory protection in HaCat human keratinocyte cells. Menadione at nontoxic concentrations causes EGFR activation and prevents EGFR dephosphorylation by erlotinib and cetuximab. This effect seems to be mediated by ROS generation and secondary phosphatase inhibition. Mild oxidative stress in skin keratinocytes by topical menadione may protect the skin from the toxicity secondary to EGFR inhibitors without causing cytotoxicity. ©2011 AACR

  11. Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication

    International Nuclear Information System (INIS)

    Jan, Yi-Hua; Richardson, Jason R.; Baker, Angela A.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2015-01-01

    Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40 mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. - Highlights: • Menadione redox cycles with cytochrome P450 reductase and generates reactive oxygen species. • Redox cycling inhibits cytochrome P450-mediated parathion metabolism. • Short term administration of menadione inhibits parathion toxicity by inhibiting paraoxon formation.

  12. Interaction Mode between Inclusion Complex of Vitamin K3 with γ- Cyclodextrin and Herring-Sperm DNA.

    Science.gov (United States)

    Tang, Yan; Cai, Li; Xue, Kang; Wang, Chunling; Xiong, Xiaoli

    2016-05-03

    Methods including spectroscopy, electronic chemistry and thermodynamics were used to study the inclusion effect between γ-cyclodextrin (CD) and vitamin K3(K3), as well as the interaction mode between herring-sperm DNA (hsDNA) and γ-CD-K3 inclusion complex. The results from ultraviolet spectroscopic method indicated that VK3 and γ-CD formed 1:1 inclusion complex, with the inclusion constant Kf = 1.02 × 10(4) L/mol, which is based on Benesi-Hildebrand's viewpoint. The outcomes from the probe method and Scatchard methods suggested that the interaction mode between γ-CD-K3 and DNA was a mixture mode, which included intercalation and electrostatic binding effects. The binding constants were K (θ)25°C = 2.16 × 10(4) L/mol, and K(θ)37°C = 1.06 × 10(4) L/mol. The thermodynamic functions of the interaction between γ-CD-K3 and DNA were ΔrHm(θ) = -2.74 × 10(4) J/mol, ΔrSm(θ) = 174.74 J·mol(-1)K(-1), therefore, both ΔrHm(θ) (enthalpy) and ΔrSm(θ) (entropy) worked as driven forces in this action.

  13. Inhibition of B16-BL6 melanoma lung colonies by semisynthetic sulfaminoheparosan sulfates from E. coli K5 polysaccharide.

    Science.gov (United States)

    Poggi, Andreina; Rossi, Cosmo; Casella, Nicola; Bruno, Cristiana; Sturiale, Luisella; Dossi, Carla; Naggi, Annamaria

    2002-08-01

    Heparin (H), heparan sulfate (HS), and related glycosaminoglycans can inhibit cancer cell invasion, possibly due to their ability to interact with vascular growth factors, adhesion molecules, endoglycosidases, and signaling proteins, in addition to the well-known effects on the clotting system. We evaluated the antitumor activity of a series of semisynthetic sulfaminoheparosan sulfates (SAHSs) with different degree and distribution of sulfates, obtained by chemical modifications of the E. coli K5 polysaccharide, namely type A, B, and C compounds. B16-BL6 melanoma cells (10 5 cells/mouse) were injected intravenously (i.v.) in a lateral tail vein of C57BL6 mice at a dose of 0.5 mg/ mouse together with test compounds. Tumor lung nodules were significantly reduced as compared with controls only by H (95.5 +/- 1.0% inhibition), SAHS-2 (84.2 +/- 5.0% inhibition), and SAHS-4 (91.1 +/- 4.2% inhibition), among compounds tested. SAHS-2 and SAHS-4 are type B compounds, with a sulfate/carboxylate ratio similar to that of H. A typical mammalian HS showed only 54.8% inhibition. Supersulfated low-molecular-weight heparin and heparan sulfate (ssLMWH and ssLMWHS) showed an activity similar to that of unfractionated compounds. H and SAHS-4 inhibited dose dependently B16-BL6 lung colonies, with IC-50 values of 0.05 and 0.1 mg/mouse, respectively. The relationship with ex vivo anticoagulant potency was evaluated by activated partial thromboplastin time (aPTT) on mouse plasma at different time intervals after i.v. injection (0.1 to 0.5 mg/mouse) of the compound. H showed a dose-dependent anticoagulant activity lasting up to 2 hours, whereas SAHS-4 showed a potent anticoagulant effect only at a dose of 0.5 mg/mouse. Accordingly, H but not SAHS-4 consistently inhibited B16-BL6 lung colonies when given 1 hour before tumor cells. SAHS-4 derivatives, with different size and/or affinity depleted of AT binding sites, showed an inhibitory effect on B16-BL6 melanoma similar to that of SAHS-4

  14. Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

    Science.gov (United States)

    Herz, Hans-Martin; Mohan, Man; Garruss, Alexander S; Liang, Kaiwei; Takahashi, Yoh-Hei; Mickey, Kristen; Voets, Olaf; Verrijzer, C Peter; Shilatifard, Ali

    2012-12-01

    Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.

  15. Antiparasitic activity of menadione (vitamin K3) against Schistosoma mansoni in BABL/c mice.

    Science.gov (United States)

    Kapadia, Govind J; Soares, Ingrid A O; Rao, G Subba; Badoco, Fernanda R; Furtado, Ricardo A; Correa, Mariana B; Tavares, Denise C; Cunha, Wilson R; Magalhães, Lizandra G

    2017-03-01

    Schistosomiasis is one of the neglected tropical diseases affecting nearly quarter of a billion people in economically challenged tropical and subtropical countries of the world. Praziquantel (PZQ) is the only drug currently available to treat this parasitic disease in spite being ineffective against juvenile worms and concerns about developing resistance to treat reinfections. Our earlier in vitro viability studies demonstrated significant antiparasitic activity of menadione (MEN) (vitamin K 3 ) against Schistosoma mansoni adult worms. To gain insight into plausible mechanism of antischistosomal activity of MEN, its effect on superoxide anion levels in adult worms were studied in vitro which showed significant increases in both female and male worms. Further confirmation of the deleterious morphological changes in their teguments and organelles were obtained by ultrastructural analysis. Genotoxic and cytotoxic studies in male Swiss mice indicated that MEN was well tolerated at the oral dose of 500mg/kg using the criteria of MNPCE frequency and PCE/RBC ratio in the bone marrow of infected animals. The in vivo antiparasitic activity of MEN was conducted in female BALB/c mice infected with S. mansoni and significant reductions (P<0.001) in total worm burden were observed at single oral doses of 40 and 400mg/kg (48.57 and 61.90%, respectively). Additionally, MEN significantly reduced (P<0.001) the number of eggs in the liver of infected mice by 53.57 and 58.76%, respectively. Similarly, histological analysis of the livers showed a significant reduction (P<0.001) in the diameter of the granulomas. Since MEN is already in use globally as an over-the-counter drug for a variety of common ailments and a dietary supplement with a safety record in par with similar products when used in recommended doses, the above antiparasitic results which compare reasonably well with PZQ, make a compelling case for considering MEN to treat S. mansoni infection in humans. Copyright © 2016

  16. Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib.

    Science.gov (United States)

    Ivanova, Donika; Zhelev, Zhivko; Lazarova, Dessislava; Getsov, Plamen; Bakalova, Rumiana; Aoki, Ichio

    2018-03-01

    Recent studies provided convincing evidence for the anticancer activity of combined application of vitamin C and pro-vitamin K3 (menadione). The molecular pathways underlying this process are still not well established. The present study aimed to investigate the effect of the combination of vitamin C plus pro-vitamin K3 on the redox status of leukemia and normal lymphocytes, as well as their sensitizing effect for a variety of anticancer drugs. Cytotoxicity of the substances was analyzed by trypan blue staining and automated counting of live and dead cells. Apoptosis was analyzed by fluorescein isothiocyanate-annexin V test. Oxidative stress was evaluated by the intracellular levels of reactive oxygen and nitrogen species and protein-carbonyl products. Combined administration of 300 μM vitamin C plus 3 μM pro-vitamin K3 reduced the viability of leukemia lymphocytes by ~20%, but did not influence the viability of normal lymphocytes. All combinations of anticancer drug plus vitamins C and K3 were characterized by synergistic cytotoxicity towards Jurkat cells, compared to cells treated with drug alone for 24 h. In the case of barasertib and everolimus, this synergistic cytotoxicity increased within 72 hours. It was accompanied by strong induction of apoptosis, but a reduction of level of hydroperoxides and moderately increased protein-carbonyl products in leukemia cells. Leukemia lymphocytes were more sensitive to combined administration of anticancer drug (everolimus or barasertib) plus vitamins C and K3, compared to normal lymphocytes. The combination of vitamin C plus K3 seems to be a powerful redox system that could specifically influence redox homeostasis of leukemia cells and sensitize them to conventional chemotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Characterization of Camptothecin-induced Genomic Changes in the Camptothecin-resistant T-ALL-derived Cell Line CPT-K5

    DEFF Research Database (Denmark)

    Kjeldsen, Eigil; Nielsen, Christine J F; Roy, Amit

    2018-01-01

    -K5 and its parental cell line. We identified copy number alterations affecting genes important for maintaining genome integrity and reducing CPT-induced DNA damage. We show for the first time that short tandem repeats are targets for TOP1 cleavage, that can be differentially stimulated by CPT.......Acquisition of resistance to topoisomerase I (TOP1)-targeting camptothecin (CPT) derivatives is a major clinical problem. Little is known about the underlying chromosomal and genomic mechanisms. We characterized the CPT-K5 cell line expressing mutant CPT-resistant TOP1 and its parental T......-cell derived acute lymphoblastic leukemia CPT-sensitive RPMI-8402 cell line by karyotyping and molecular genetic methods, including subtractive oligo-based array comparative genomic hybridization (soaCGH) analysis. Karyotyping revealed that CPT-K5 cells had acquired additional structural aberrations...

  18. H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells.

    Science.gov (United States)

    Fernández, Agustín F; Bayón, Gustavo F; Urdinguio, Rocío G; Toraño, Estela G; García, María G; Carella, Antonella; Petrus-Reurer, Sandra; Ferrero, Cecilia; Martinez-Camblor, Pablo; Cubillo, Isabel; García-Castro, Javier; Delgado-Calle, Jesús; Pérez-Campo, Flor M; Riancho, José A; Bueno, Clara; Menéndez, Pablo; Mentink, Anouk; Mareschi, Katia; Claire, Fabian; Fagnani, Corrado; Medda, Emanuela; Toccaceli, Virgilia; Brescianini, Sonia; Moran, Sebastián; Esteller, Manel; Stolzing, Alexandra; de Boer, Jan; Nisticò, Lorenza; Stazi, Maria A; Fraga, Mario F

    2015-01-01

    In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors. © 2015 Fernández et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Mutations in Mll2, an H3K4 Methyltransferase, Result in Insulin Resistance and Impaired Glucose Tolerance in Mice

    Science.gov (United States)

    Schröter, David; Matthews, Helen C.; Bogani, Debora; Moir, Lee; Long, Anna; Church, Christopher; Hugill, Alison; Anstee, Quentin M.; Goldin, Rob; Thursz, Mark; Hollfelder, Florian; Cox, Roger D.

    2013-01-01

    We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7) gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes) died during embryonic development at 9.5–14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level. PMID:23826075

  20. Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice.

    Directory of Open Access Journals (Sweden)

    Michelle Goldsworthy

    Full Text Available We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7 gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes died during embryonic development at 9.5-14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level.

  1. On the Vertex-Distinguishing Proper Edge-coloring of K3,4 ∨ Kt%图K3,4∨Kt的点可区别正常边染色

    Institute of Scientific and Technical Information of China (English)

    魏甲静; 王治文; 陈祥恩

    2012-01-01

    Let f be a proper edge coloring of G. For each x ∈ V(G), let S(x) denote the set of all colors of the edges incident with x. If (A) u, v∈ V(G), u ≠ v, we have S(u)≠ S(v), then f is called a vertex distinguishing proper edge coloring of G. The minimum number k for which there exists a vertex distinguishing proper edge coloring of G using k colors is called the vertex distinguishing proper edge chromatic number of G and denoted by x's(G). In this paper, we discuss vertex-distinguishing proper edge colorings of K3,4∨Kt. By using symmetry of regular polygons to construct coloring and methods of combinatorial analysis, we showed that for t is even with t ≥ 2 or t is odd with 3 ≤ t ≤ 25, we have x's(K3,4 ∨ Kt) =t+7; for t is odd with t ≥ 27, we have X's(K3,4∨Kt)=t+8.%设f是图G的一个正常边染色.对任意x∈V(G),令S(x)表示与点x相关联的边的颜色所构成的集合.若对任意u,v∈V(G),u≠v,有S(u)≠S(v),则称f是图G的一个点可区别正常边染色.对一个图G进行点可区别正常边染色所需的最少的颜色的数目称为G的点可区别正常边色数,记为x's(G).讨论了图K3,4 ∨Kt的点可区别正常边染色及其色数,利用正多边形的对称性构造染色以及组合分析的方法,确定了图K3,4 ∨Kt的点可区别正常边色数,得到了当t是大于等于2的偶数以及t是奇数且3≤t≤25时,x's(K3,4 ∨Kt)=t+7;当t是奇数且t≥27时,x's(K3,4∨Kt)=t+8.

  2. Evidence of a massive planet candidate orbiting the young active K5V star BD+20 1790

    Science.gov (United States)

    Hernán-Obispo, M.; Gálvez-Ortiz, M. C.; Anglada-Escudé, G.; Kane, S. R.; Barnes, J. R.; de Castro, E.; Cornide, M.

    2010-03-01

    Context. BD+20 1790 is a young active, metal-rich, late-type K5Ve star. We have undertaken a study of stellar activity and kinematics for this star over the past few years. Previous results show a high level of stellar activity, with the presence of prominence-like structures, spots on the surface, and strong flare events, despite the moderate rotational velocity of the star. In addition, radial velocity variations with a semi-amplitude of up to 1 km s-1 were detected. Aims: We investigate the nature of these radial velocity variations, in order to determine whether they are due to stellar activity or the reflex motion of the star induced by a companion. Methods: We have analysed high-resolution echelle spectra by measuring stellar activity indicators and computing radial velocity (RV) and bisector velocity spans. Two-band photometry was also obtained to produce the light curve and determine the photometric period. Results: Based upon the analysis of the bisector velocity span, as well as spectroscopic indices of chromospheric indicators, Ca ii H & K, Hα, and taking the photometric analysis into account, we report that the best explanation for the RV variation is the presence of a substellar companion. The Keplerian fit of the RV data yields a solution for a close-in massive planet with an orbital period of 7.78 days. The presence of the close-in massive planet could also be an interpretation for the high level of stellar activity detected. Since the RV data are not part of a planet search programme, we can consider our results as a serendipitous evidence of a planetary companion. To date, this is the youngest main sequence star for which a planetary candidate has been reported. Based on observations collected at the German-Spanish Astronomical Center, Calar Alto, jointly operated by the Max-Planck-Institut für Astronomie Heidelberg and the Instituto de Astrofísica de Andalucía (CSIC). Based on observations made with the Italian Telescopio Nazionale Galileo

  3. THE CCAUV.A-K3 KEY COMPARISON OF PRESSURE RECIPROCITY CALIBRATION OF LS2P MICROPHONES: RESULTS AND ANALYSIS

    DEFF Research Database (Denmark)

    Cutanda Henríquez, Vicente; Rasmussen, Knud; Nielsen, Lars

    2006-01-01

    The CCAUV.A-K3 Key Comparison has involved 15 countries organized in two loops with two common laboratories, CENAM and DPLA. The measurements took place in 2003. This is the first CCAUV key comparison organized with more than one loop, and therefore the analysis of the results required a more ela...

  4. K3[Fe(CN)6].3H2O supported on silica gel: An efficient and selective ...

    Indian Academy of Sciences (India)

    Department of Chemistry, Payame Noor University, 19395-4697 Tehran, I. R. of IRAN e-mail: ... K3[Fe(CN)6].3H2O, Silica gel; oxime; aldehyde; ketone. 1. Introduction .... ysis, hydrogenation, etc., using organic and inorganic reagents. Besides ...

  5. Selective synthesis of vitamin K3 over mesoporous NbSBA-15 catalysts synthesized by an efficient hydrothermal method.

    Science.gov (United States)

    Selvaraj, M; Park, D-W; Kim, I; Kawi, S; Ha, C S

    2012-08-28

    Well hexagonally ordered NbSBA-15 catalysts synthesized by an efficient hydrothermal method were used, for the first time, for the selective synthesis of vitamin K(3) by liquid-phase oxidation of 2-methyl-1-naphthol (2MN1-OH) under various reaction conditions. The recyclable NbSBA-15 catalysts were also reused to find their catalytic activities. To investigate the leaching of non-framework niobium species on the surface of silica networks, the results of original and recyclable NbSBA-15 catalysts were correlated and compared. To find an optimum condition for the selective synthesis of vitamin K(3), the washed NbSBA-15(2.2pH) was extensively used in this reaction with various reaction parameters such as temperature, time and ratios of reactant (2M1N-OH to H(2)O(2)), and the obtained results were also demonstrated. Additionally, the liquid-phase oxidation of 2M1N-OH was carried out with different solvents to find the best solvent with a good catalytic activity. Based on the all catalytic studies, the vitamin K(3) selectivity (97.3%) is higher in NbSBA-15(2.2pH) than that of other NbSBA-15 catalysts, and the NbSBA-15(2.2pH) is found to be a highly active and eco-friendly heterogeneous catalyst for the selective synthesis of vitamin K(3).

  6. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum

    NARCIS (Netherlands)

    Fülöp, Krisztina; Jiang, Qiujie; van de Wetering, Koen; Pomozi, Viola; Szabó, Pál T.; Arányi, Tamás; Sarkadi, Balázs; Borst, Piet; Uitto, Jouni; Váradi, András

    2011-01-01

    Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been

  7. Effects of dietary particulate limestone, vitamin K3 and fluoride and photostimulation on skeletal morphology and osteoporosis in laying hens.

    Science.gov (United States)

    Fleming, R H; McCormack, H A; McTeir, L; Whitehead, C C

    2003-12-01

    1. Female chicks of a White Leghorn strain were fed three different diets from one day old: control, additional vitamin K3 (10 mg/kg), and a diet containing a combination of additional vitamin K3, sodium fluoride (10 mg/kg) and limestone in particulate rather than powdered form. At 16 weeks photoperiod was increased for half the birds from 8:16 L:D to 16:8 L:D immediately or by one hour per week to the same ultimate photoperiod for the other half. 2. Age at first egg was lower by 4.0 d for birds on the fast lighting regime but there were no overall effects of lighting on bone quality at either 25 or 70 weeks. 3. Additional vitamin K3 resulted in higher proximal tarsometatarsus cancellous bone volumes at 15 weeks and throughout the laying period compared with controls. Plasma osteocalcin concentrations were unaffected by vitamin K3 supplementation during growth. 4. The combination diet resulted in beneficial responses of 12 to 20% in most bone characteristics in hens at 70 weeks. The magnitude of these effects was similar to a previous study involving a particulate calcium source alone (Fleming et al., Poultry Science, 39: 434-440, 1998b). We conclude that the beneficial effects of the combined treatment over the lifetime of the hens were attributable mainly to the presence in the diet of a calcium source in particulate form.

  8. Examining Change in K-3 Teachers' Mathematical Knowledge, Attitudes, and Beliefs: The Case of Primarily Math

    Science.gov (United States)

    Kutaka, T. S.; Ren, L.; Smith, W. M.; Beattie, H. L.; Edwards, C. P.; Green, J. L.; Chernyavskiy, P.; Stroup, W.; Heaton, R. M.; Lewis, W. J.

    2018-01-01

    This study examines the impact of the Primarily Math Elementary Mathematics Specialist program on K-3 teachers' mathematical content knowledge for teaching, attitudes toward learning mathematics, and beliefs about mathematics teaching and learning. Three cohorts of teachers participating in the program were compared to a similar group of…

  9. The Impact of a "Framework"-Aligned Science Professional Development Program on Literacy and Mathematics Achievement of K-3 Students

    Science.gov (United States)

    Paprzycki, Peter; Tuttle, Nicole; Czerniak, Charlene M.; Molitor, Scott; Kadervaek, Joan; Mendenhall, Robert

    2017-01-01

    This study investigates the effect of a Framework-aligned professional development program at the PreK-3 level. The NSF funded program integrated science with literacy and mathematics learning and provided teacher professional development, along with materials and programming for parents to encourage science investigations and discourse around…

  10. Quantum-chemical calculations and electron diffraction study of the equilibrium molecular structure of vitamin K3

    Science.gov (United States)

    Khaikin, L. S.; Tikhonov, D. S.; Grikina, O. E.; Rykov, A. N.; Stepanov, N. F.

    2014-05-01

    The equilibrium molecular structure of 2-methyl-1,4-naphthoquinone (vitamin K3) having C s symmetry is experimentally characterized for the first time by means of gas-phase electron diffraction using quantum-chemical calculations and data on the vibrational spectra of related compounds.

  11. Happy 50th Birthday Smokey Bear! A Learning Kit about Forests and Fire Safety for Grades K-3.

    Science.gov (United States)

    Hall, Meryl

    For over 50 years, the primary goal of Smokey Bear has been to introduce the forest fire prevention message to young children. This learning kit provides the K-3 teacher with activities and resources to help students learn about Smokey Bear and fire safety, about forests as habitats, and about what they can do to protect forests. Students are…

  12. Exploring PHD fingers and H3K4me0 interactions with molecular dynamics simulations and binding free energy calculations: AIRE-PHD1, a comparative study.

    Directory of Open Access Journals (Sweden)

    Dimitrios Spiliotopoulos

    Full Text Available PHD fingers represent one of the largest families of epigenetic readers capable of decoding post-translationally modified or unmodified histone H3 tails. Because of their direct involvement in human pathologies they are increasingly considered as a potential therapeutic target. Several PHD/histone-peptide structures have been determined, however relatively little information is available on their dynamics. Studies aiming to characterize the dynamic and energetic determinants driving histone peptide recognition by epigenetic readers would strongly benefit from computational studies. Herein we focus on the dynamic and energetic characterization of the PHD finger subclass specialized in the recognition of histone H3 peptides unmodified in position K4 (H3K4me0. As a case study we focused on the first PHD finger of autoimmune regulator protein (AIRE-PHD1 in complex with H3K4me0. PCA analysis of the covariance matrix of free AIRE-PHD1 highlights the presence of a "flapping" movement, which is blocked in an open conformation upon binding to H3K4me0. Moreover, binding free energy calculations obtained through Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA methodology are in good qualitative agreement with experiments and allow dissection of the energetic terms associated with native and alanine mutants of AIRE-PHD1/H3K4me0 complexes. MM/PBSA calculations have also been applied to the energetic analysis of other PHD fingers recognizing H3K4me0. In this case we observe excellent correlation between computed and experimental binding free energies. Overall calculations show that H3K4me0 recognition by PHD fingers relies on compensation of the electrostatic and polar solvation energy terms and is stabilized by non-polar interactions.

  13. High cell density cultivation of Escherichia coli K4 in a microfiltration bioreactor: a step towards improvement of chondroitin precursor production

    Directory of Open Access Journals (Sweden)

    De Rosa Mario

    2011-02-01

    Full Text Available Abstract Background The bacteria Escherichia coli K4 produces a capsular polysaccharide (K4 CPS whose backbone is similar to the non sulphated chondroitin chain. The chondroitin sulphate is one of the major components of the extra-cellular matrix of the vertebrate connective tissues and a high value molecule, widely employed as active principle in the treatment of osteoarthritis. It is usually obtained by extraction from animal tissues, but the risk of virus contaminations, as well as the scarceness of raw material, makes this productive process unsafe and unable to satisfy the growing market demand. In previous studies a new biotechnological process to produce chondroitin from Escherichia coli K4 capsular polysaccharide was investigated and a 1.4 g·L-1 K4 CPS concentration was reached using fed-batch fermentation techniques. In this work, on the trail of these results, we exploited new fermentation strategies to further improve the capsular polysaccharide production. Results The inhibitory effect of acetate on the bacterial cells growth and K4 CPS production was studied in shake flask conditions, while a new approach, that combined the optimization of the feeding profiles, the improvement of aeration conditions and the use of a microfiltration bioreactor, was investigated in three different types of fermentation processes. High polysaccharide concentrations (4.73 ± 0.2 g·L-1, with corresponding average yields (0.13 ± 0.006 gK4 CPS·gcdw-1, were obtained; the increase of K4 CPS titre, compared to batch and fed-batch results, was of 16-fold and 3.3-fold respectively, while average yield was almost 3.5 and 1.4 fold higher. Conclusion The increase of capsular polysaccharide titre confirmed the validity of the proposed fermentation strategy and opened the way to the use of the microfiltration bioreactor for the biotechnological production of chondroitin.

  14. Effect of the sterilization on the cutting efficiency of ProTaper® and K3® endodontic instruments

    Directory of Open Access Journals (Sweden)

    Alex Niederauer Becker

    2009-12-01

    Full Text Available Objective: This objective of this study was to evaluate the effect of sterilization on the cutting efficiency of rotary endodontic instruments, ProTaper® (Dentsply Maillefer Instruments S.A., Ballaigues, Suíça and K3® (Sybron/Kerr, Orange, CA, USA, by the time X weighing method. Method: For this purpose, 60 simulated canals and 66 instruments were used (36 of the ProTaper® system, (Dentsply Maillefer Instruments S.A., Ballaigues, Switzerland and 30 of the K3® system (Sybron/Kerr, Orange, CA, USA. The rotary instruments were divided into four experimental groups. The instruments in Group A (K3®, Sybron/Kerr, Orange, CA, USA and Group B (ProTaper®, Dentsply Maillefer Instruments S.A., Ballaigues, Switzerland, were subjected to a process of cleaning and sterilization. Whereas the instruments in Group C (K3®, Sybron/Kerr, Orange, CA, USA and Group D (ProTaper®, Dentsply Maillefer Instruments S.A., Ballaigues, Switzerland, were subjected to the cleanness process only, and were not sterilized. Results: As regards analysis of the results, the Student’s-t test was used, by which it was verified that the instruments in Group had greater cutting efficiency in comparison with those in Group B. Similarly the instruments in Group C had greater cutting efficiency in comparison with those in Group D, nevertheless, there was no statistically significant difference. Moreover, as regards the number times of use, there was also no statistically significant difference between the experimental groups. However in all the groups there was a decrease in the cutting efficiency with an increasing number of times of use. Conclusion: Thus, the cutting efficiency of rotary endodontic instruments K3® (Sybron/Kerr, Orange, CA, USA and ProTaper® (Dentsply Maillefer Instruments S.A., Ballaigues, Suição was not statistically affected after the use of 6 autoclave sterilization cycles.

  15. Modeling Math Growth Trajectory--An Application of Conventional Growth Curve Model and Growth Mixture Model to ECLS K-5 Data

    Science.gov (United States)

    Lu, Yi

    2016-01-01

    To model students' math growth trajectory, three conventional growth curve models and three growth mixture models are applied to the Early Childhood Longitudinal Study Kindergarten-Fifth grade (ECLS K-5) dataset in this study. The results of conventional growth curve model show gender differences on math IRT scores. When holding socio-economic…

  16. Cancer stemness and metastatic potential of the novel tumor cell line K3: an inner mutated cell of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Qian, Hui; Ding, Xiaoqing; Zhang, Jiao; Mao, Fei; Sun, Zixuan; Jia, Haoyuan; Yin, Lei; Wang, Mei; Zhang, Xu; Zhang, Bin; Yan, Yongmin; Zhu, Wei; Xu, Wenrong

    2017-06-13

    Mesenchymal stem cells (MSCs) transplantation has been used for therapeutic applications in various diseases. Here we report MSCs can malignantly transform in vivo. The novel neoplasm was found on the tail of female rat after injection with male rat bone marrow-derived MSCs (rBM-MSCs) and the new tumor cell line, K3, was isolated from the neoplasm. The K3 cells expressed surface antigens and pluripotent genes similar to those of rBM-MSCs and presented tumor cell features. Moreover, the K3 cells contained side population cells (SP) like cancer stem cells (CSCs), which might contribute to K3 heterogeneity and tumorigenic capacity. To investigate the metastatic potential of K3 cells, we established the nude mouse models of liver and lung metastases and isolated the corresponding metastatic cell lines K3-F4 and K3-B6. Both K3-F4 and K3-B6 cell lines with higher metastatic potential acquired more mesenchymal and stemness-related features. Epithelial-mesenchymal transition is a potential mechanism of K3-F4 and K3-B6 formation.

  17. Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation.

    Science.gov (United States)

    Grandy, Rodrigo A; Whitfield, Troy W; Wu, Hai; Fitzgerald, Mark P; VanOudenhove, Jennifer J; Zaidi, Sayyed K; Montecino, Martin A; Lian, Jane B; van Wijnen, André J; Stein, Janet L; Stein, Gary S

    2016-02-15

    Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotency. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Noninvasive k3 estimation method for slow dissociation PET ligands: application to [11C]Pittsburgh compound B.

    Science.gov (United States)

    Sato, Koichi; Fukushi, Kiyoshi; Shinotoh, Hitoshi; Shimada, Hitoshi; Hirano, Shigeki; Tanaka, Noriko; Suhara, Tetsuya; Irie, Toshiaki; Ito, Hiroshi

    2013-11-16

    Recently, we reported an information density theory and an analysis of three-parameter plus shorter scan than conventional method (3P+) for the amyloid-binding ligand [11C]Pittsburgh compound B (PIB) as an example of a non-highly reversible positron emission tomography (PET) ligand. This article describes an extension of 3P + analysis to noninvasive '3P++' analysis (3P + plus use of a reference tissue for input function). In 3P++ analysis for [11C]PIB, the cerebellum was used as a reference tissue (negligible specific binding). Fifteen healthy subjects (NC) and fifteen Alzheimer's disease (AD) patients participated. The k3 (index of receptor density) values were estimated with 40-min PET data and three-parameter reference tissue model and were compared with that in 40-min 3P + analysis as well as standard 90-min four-parameter (4P) analysis with arterial input function. Simulation studies were performed to explain k3 biases observed in 3P++ analysis. Good model fits of 40-min PET data were observed in both reference and target regions-of-interest (ROIs). High linear intra-subject (inter-15 ROI) correlations of k3 between 3P++ (Y-axis) and 3P + (X-axis) analyses were shown in one NC (r2 = 0.972 and slope = 0.845) and in one AD (r2 = 0.982, slope = 0.655), whereas inter-subject k3 correlations in a target region (left lateral temporal cortex) from 30 subjects (15 NC + 15 AD) were somewhat lower (r2 = 0.739 and slope = 0.461). Similar results were shown between 3P++ and 4P analyses: r2 = 0.953 for intra-subject k3 in NC, r2 = 0.907 for that in AD and r2 = 0.711 for inter-30 subject k3. Simulation studies showed that such lower inter-subject k3 correlations and significant negative k3 biases were not due to unstableness of 3P++ analysis but rather to inter-subject variation of both k2 (index of brain-to-blood transport) and k3 (not completely negligible) in the reference region. In [11C]PIB, the applicability of 3

  19. The Demethylase JMJD2C Localizes to H3K4me3 Positive Transcription Start Sites and Is Dispensable for Embryonic Development

    DEFF Research Database (Denmark)

    Pedersen, Marianne Terndrup; Agger, Karl; Laugesen, Anne

    2014-01-01

    cell (ESC) self-renewal and embryonic development. Moreover, we report that JMJD2C localizes to H3K4me3 positive transcription start sites in both primary cells and in the human carcinoma KYSE150 cell line, containing an amplification of the JMJD2C locus. Binding is dependent on the double Tudor domain...... expression of a subset of target genes involved in cell cycle progression. Taken together, we show that JMJD2C is targeted to H3K4me3 positive transcription start sites, where it can contribute to transcriptional regulation, and report that the putative oncogene, JMJD2C, is not generally required...

  20. Neutron scattering studies of K3H(SO4)2 and K3D(SO4)2: the particle-in-a-box model for the quantum phase transition.

    Science.gov (United States)

    Fillaux, François; Cousson, Alain

    2012-08-21

    In the crystal of K(3)H(SO(4))(2) or K(3)D(SO(4))(2), dimers SO(4)···H···SO(4) or SO(4)···D···SO(4) are linked by strong centrosymmetric hydrogen or deuterium bonds whose O···O length is ≈2.50 Å. We address two open questions. (i) Are H or D sites split or not? (ii) Is there any structural counterpart to the phase transition observed for K(3)D(SO(4))(2) at T(c) ≈ 85.5 K, which does not exist for K(3)H(SO(4))(2)? Neutron diffraction by single-crystals at cryogenic or room temperature reveals no structural transition and no resolvable splitting of H or D sites. However, the width of the probability densities suggest unresolved splitting of the wavefunctions suggesting rigid entities H(L1/2)-H(R1/2) or D(L1/2)-D(R1/2) whose separation lengths are l(H) ≈ 0.16 Å or l(D) ≈ 0.25 Å. The vibrational eigenstates for the center of mass of H(L1/2)-H(R1/2) revealed by inelastic neutron scattering are amenable to a square-well and we suppose the same potential holds for D(L1/2)-D(R1/2). In order to explain dielectric and calorimetric measurements of mixed crystals K(3)D((1-ρ))H(ρ)(SO(4))(2) (0 ≤ ρ ≤ 1), we replace the classical notion of order-disorder by the quantum notion of discernible (e.g., D(L1/2)-D(R1/2)) or indiscernible (e.g., H(L1/2)-H(R1/2)) components depending on the separation length of the split wavefunction. The discernible-indiscernible isostructural transition at finite temperatures is induced by a thermal pure quantum state or at 0 K by ρ.

  1. X-ray diffraction studies on K3Gd5 (PO4) 6 between 20K to 1073 K

    International Nuclear Information System (INIS)

    Bevara, Samatha; Achary, S.N.; Tyagi, A.K.; Sinha, A.K.; Sastry, P.U.

    2016-01-01

    Complex inorganic phosphates have been of interest due to their diversified crystal chemistry depending on composition, preparation condition as well as external parameters like temperature and pressure. In addition varieties of complex phosphates have been considered as potential host matrices for immobilization of radioactive elements as well as for selective separation of ions from high level nuclear waste or heavy metal ion pollutants from environment. Temperature and/or pressure induced structural variations are often noticed in such type complex phosphates. In K 2 O-Gd 2 O 3 -P 2 O 5 , a novel complex phosphate with K 3 Gd 5 (PO 4 ) 6 has been reported recently. In order to study the effect of temperature on crystal structure of K 3 Gd 5 (PO 4 ) 6 variable temperature XRD studies between 20 K to 1073 K were carried out and the results are presented herein

  2. Effects of gamma radiation and menadione (vit. K3) on dissolution and dimerization of δ-tocopherol

    International Nuclear Information System (INIS)

    Kupczyk, B.; Gogolewski, M.

    1997-01-01

    Effect of ionizing radiation and menadione (vit. K 3 ) on dissolution and dimerization of δ-tocopherol was studied. Mixture of δ-tocopherol and menadione (vit. K 3 ) dissolved in benzene, ethanol or used in substantia were irradiated at 2.5, 5, 10, 20 kGy dose using Co-60 as a radiation source. Dissolution of δ-tocopherol in substantia was lower then disintegration of δ-tocopherol dissolved in benzene or in ethanol. However, we did not observe any significant difference between dissolution of δ-tocopherol in both studied solvents. The number of formed dimers of δ-tocopherol were different for all three cases tested. The quantities of δ-tocopherol dimers were dependent on radiation dose. (author)

  3. Azide derivatized anticancer agents of Vitamin K 3: X-ray structural, DSC, resonance spectral and API studies

    Science.gov (United States)

    Badave, Kirti; Patil, Yogesh; Gonnade, Rajesh; Srinivas, Darbha; Dasgupta, Rajan; Khan, Ayesha; Rane, Sandhya

    2011-12-01

    Compound 1 [1-imino (acetyl hydrazino)-Vitamin K 3], displays valence tautomerically related electronic isomers as Form I and Form II. Form I exhibits 2D packing fragment with 1D ribbon chains of N-H⋯O hydrogen bonds and shows EPR silent features. While Form II is EPR active and exhibits biradical nature with double quantum transitions at g = 2.0040. 1H NMR of compound 2, [1-imino (hydrazino carboxylate)-Vitamin K 3] and Form II exhibit π delocalization via resonance assisted H-bonding [RAHB] effect compared to Form I. Molecular interactions in Form I and II are visualized by DSC. The electronic structures of compounds 1 and 2 have been correlated to their API values by measuring anticancer activities, mitochondrial potentials and DNA shearing patterns. Form II and compound 2 indicate mitochondria mediated apoptosis (˜75% cell death) while Form I causes 35% cell death.

  4. Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics?

    OpenAIRE

    Mannello, Ferdinando; Gazzanelli, Giancarlo

    2001-01-01

    Since its identification, much information has been obtained about prostate-specific antigen (PSA, or human glandular kallikrein 3 [hK3]), a kallikrein-like serine protease that is the most valuable tumour marker for the screening, diagnosis and management of human prostate carcinoma. Recently, it has become widely accepted that PSA is also present in many nonprostatic sources, casting doubts about the specificity of its tissue expression. Here we summarize the findings on the biomolecular ex...

  5. Therapeutic role of calcium and vitamin K3 in chemically induced hepatocarcinogenesis - new tools for cancer treatment.

    Science.gov (United States)

    Anwar, Firoz; Khan, Ruqaiyah; Sachan, Richa; Kazmi, Imran; Rawat, Alisha; Sabih, Abdullah; Singh, Rajbala; Afzal, Muhammad; Ahmad, Aftab; Al-Orab, Abdulaziz S; Al-Abbasi, F A; Bhatt, Prakash Chandra; Kumar, Vikas

    2018-04-17

    HCC has been reported to be immensely occurring carcinoma worldwide. Recent days the mortality occurred due to liver cancer has also been found to be increased at an alarming speed affecting mostly the young patients. The aim of the current study was to decipher the role of calcium and vitamin K3 in the treatment of chemically induced hepatocarcinogenesis in the male Wistar rats. Liver cancer was induced via a subnecrogenic dose of 160 mg/kg body weight, diethylnitrosamine (DENA) when associated with fasting/refeeding in male Wistar rats. It elevated the serum glutamate oxaloacetate (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, total cholesterol (CH), triglycerides (TG), alfa-fetoprotein (AFP) and reduced high-density lipoprotein (HDL). Histopathological examination of liver tissue showed marked carcinogenicity of the chemical carcinogen. Food, water intake and animal weights were also assessed, respectively. The animals exposed to DENA showed a significant decrease in the body weight. The elevated levels of serum SGOT, SGPT, ALP, AFP, TC and TG were restored by administration of calcium and Vit K (ad libitum) combination at higher dose than the normal dietary requirement (3 mg/kg) daily for 12 weeks p.o. Physiological and biochemical analysis showed the beneficial effects of calcium and vitamin K3 combination in the animals exposed to DENA. The results deciphered the beneficial effects of calcium and vitamin K3 in combination.

  6. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum.

    Science.gov (United States)

    Fülöp, Krisztina; Jiang, Qiujie; Wetering, Koen V D; Pomozi, Viola; Szabó, Pál T; Arányi, Tamás; Sarkadi, Balázs; Borst, Piet; Uitto, Jouni; Váradi, András

    2011-11-25

    Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery. This activity is missing in pseudoxanthoma elasticum, a genetic disorder caused by mutations in ABCC6 characterized by abnormal soft tissue mineralization. Here we examined the efflux of the glutathione conjugate of vitamin K3 (VK3GS) from the liver in wild type and Abcc6(-/-) mice, and in transport assays in vitro. We found in liver perfusion experiments that VK3GS is secreted into the inferior vena cava, but we observed no significant difference between wild type and Abcc6(-/-) animals. We overexpressed the human ABCC6 transporter in Sf9 insect and MDCKII cells and assayed its vitamin K3-conjugate transport activity in vitro. We found no measurable transport of VK3GS by ABCC6, whereas ABCC1 transported this compound at high rate in these assays. These results show that VK3GS is not the essential metabolite transported by ABCC6 from the liver and preventing the symptoms of pseudoxanthoma elasticum. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Ultrastable, high efficiency picosecond green light generation using K3B6O10Br series nonlinear optical crystals

    Science.gov (United States)

    Hou, Z. Y.; Xia, M. J.; Wang, L. R.; Xu, B.; Yan, D. X.; Meng, L. P.; Liu, L. J.; Xu, D. G.; Zhang, L.; Wang, X. Y.; Li, R. K.; Chen, C. T.

    2017-09-01

    Two perovskite-structure K3B6O10Br1-x Cl x (x  =  0 and 0.5) series nonlinear optical crystals were thoroughly investigated for their picosecond 532 nm laser pulses abilities and high power outputs were achieved via second harmonic generation (SHG) technique for the first time. SHG conversion efficiency of 57.3% with a 13.2 mm length K3B6O10Br (KBB) crystal was achieved using a laser source of pulse repetition rate of 10 Hz and pulse width of 25 ps, which is the highest conversion efficiency of ps visible laser based on KBB crystal. And by employing an 80 MHz, 10 ps fundamental laser beam, maximum power outputs of 12 W with K3B6O10Br0.5Cl0.5 (KBBC) and 11.86 W with KBB crystals were successfully demonstrated. Furthermore, the standard deviation jitters of the average power outputs are less than 0.6% and 1.17% by KBB and KBBC, respectively, showing ultrastable power stabilities favorable for practical applications. In addition, the other optical parameters including acceptance angle and temperature bandwidth were also investigated.

  8. An HST COS 'SNAPSHOT' spectrum of the K supergiant λ Vel (K4Ib-II)

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, Kenneth G. [NASA/GSFC Code 667, Greenbelt, MD 20771 (United States); Ayres, Thomas R. [University of Colorado, CASA, 389-UCB, Boulder, CO 80309 (United States); Harper, Graham M. [School of Physics, Trinity College, Dublin 2 (Ireland); Kober, Gladys; Nielsen, Krister E.; Wahlgren, Glenn M., E-mail: Kenneth.G.Carpenter@nasa.gov [Deptartment of Physics, Catholic University of America, Washington, DC 20064 (United States)

    2014-10-10

    We present a far-ultraviolet spectrum of the K4 Ib-II supergiant λ Vel obtained with the Hubble Space Telescope's Cosmic Origins Spectrograph (COS) as a part of the SNAPshot program 'SNAPing coronal iron' (GO 11687). The observation covers a wavelength region (1326-1467 Å) not previously recorded for λ Vel at a spectral resolving power of R ∼ 20,000 and displays strong emission and absorption features, superposed on a bright chromospheric continuum. Fluorescent excitation is responsible for much of the observed emission, mainly powered by strong H I Lyα and the O I (UV 2) triplet emission near λ1304. The molecular CO and H{sub 2} fluorescences are weaker than in the early-K giant α Boo while the Fe II and Cr II lines, also pumped by H I Lyα, are stronger in λ Vel. This pattern of relative line strengths between the two stars is explained by the lower iron-group element abundance in α Boo, which weakens that star's Fe II and Cr II emission without reducing the molecular fluorescences. The λ Vel spectrum shows fluorescent Fe II, Cr II, and H{sub 2} emission similar to that observed in the M supergiant α Ori, but more numerous well-defined narrow emissions from CO. The additional CO emissions are visible in the spectrum of λ Vel since that star does not have the cool, opaque circumstellar shells that surround α Ori and produce broad circumstellar CO (A-X) band absorptions that hide those emissions in the cooler star. The presence of Si IV emission in λ Vel indicates a ∼8 × 10{sup 4} K plasma that is mixed into the cooler chromosphere. Evidence of the stellar wind is seen in the C II λλ1334,1335 lines and in the blueshifted Fe II and Ni II wind absorption lines. Line modeling using Sobolev with Exact Integration for the C II lines indicates a larger terminal velocity (∼45 versus ∼30 km s{sup –1}) and turbulence (∼27 versus <21 km s{sup –1}) with a more quickly accelerating wind (β = 0.35 versus 0.7) at the time of

  9. The Histone Demethylase Jarid1b Ensures Faithful Mouse Development by Protecting Developmental Genes from Aberrant H3K4me3

    DEFF Research Database (Denmark)

    Albert, Mareike; Schmitz, Sandra U; Kooistra, Susanne M

    2013-01-01

    of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development, and increased incidences of exencephaly. Moreover, in line...

  10. Cooperative redox-active additives of anthraquinone-2,7-disulphonate and K4Fe(CN)6 for enhanced performance of active carbon-based capacitors

    Science.gov (United States)

    Tian, Ying; Liu, Ming; Che, Ruxing; Xue, Rong; Huang, Liping

    2016-08-01

    Two redox additives of anthraquinone-2,7-disulphonate (AQDS) and K4Fe(CN)6 are introduced into the neutral medium of KNO3 for enhanced performance of active carbon-based (AC) capacitor. The Faradaic redox reactions of AQ/H2AQ and Fe(CN)63-/Fe(CN)64- are diffusion-controlled and occurred on the negative electrode and the positive electrode respectively and simultaneously, resulting in the enhancement of specific capacitance, power density and energy density of 240 F g-1, 527 W kg-1 and 26.3 Wh kg-1, respectively at a current density of 1.0 A g-1 for a symmetric AC capacitor in the electrolyte of 1 M KNO3-0.017 M K4Fe(CN)6-0.017 M AQDS. These values are much higher than those in the controls of either 1 M KNO3-0.017 M K4Fe(CN)6 or 1 M KNO3-0.017 M AQDS with only one pair of redox additives. These results demonstrate the cooperative K4Fe(CN)6 and AQDS for enhanced performance of AC capacitor, and thus provide an alternative approach for efficient capacitors.

  11. The naphthoquinones, vitamin K3 and its structural analog plumbagin, are substrates of the multidrug resistance-linked ABC drug transporter ABCG2

    OpenAIRE

    Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V.

    2007-01-01

    Vitamin K3 (Menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2 which are essential for blood clotting. The naturally occurring structural analog of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We, here, report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette (ABC) drug transporter, ABCG2. Vitamin K3 and plu...

  12. SseK3 Is a Salmonella Effector That Binds TRIM32 and Modulates the Host's NF-κB Signalling Activity.

    Directory of Open Access Journals (Sweden)

    Zhe Yang

    Full Text Available Salmonella Typhimurium employs an array of type III secretion system effectors that facilitate intracellular survival and replication during infection. The Salmonella effector SseK3 was originally identified due to amino acid sequence similarity with NleB; an effector secreted by EPEC/EHEC that possesses N-acetylglucoasmine (GlcNAc transferase activity and modifies death domain containing proteins to block extrinsic apoptosis. In this study, immunoprecipitation of SseK3 defined a novel molecular interaction between SseK3 and the host protein, TRIM32, an E3 ubiquitin ligase. The conserved DxD motif within SseK3, which is essential for the GlcNAc transferase activity of NleB, was required for TRIM32 binding and for the capacity of SseK3 to suppress TNF-stimulated activation of NF-κB pathway. However, we did not detect GlcNAc modification of TRIM32 by SseK3, nor did the SseK3-TRIM32 interaction impact on TRIM32 ubiquitination that is associated with its activation. In addition, lack of sseK3 in Salmonella had no effect on production of the NF-κB dependent cytokine, IL-8, in HeLa cells even though TRIM32 knockdown suppressed TNF-induced NF-κB activity. Ectopically expressed SseK3 partially co-localises with TRIM32 at the trans-Golgi network, but SseK3 is not recruited to Salmonella induced vacuoles or Salmonella induced filaments during Salmonella infection. Our study has identified a novel effector-host protein interaction and suggests that SseK3 may influence NF-κB activity. However, the lack of GlcNAc modification of TRIM32 suggests that SseK3 has further, as yet unidentified, host targets.

  13. The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo.

    Science.gov (United States)

    Powers, Natalie R; Parvanov, Emil D; Baker, Christopher L; Walker, Michael; Petkov, Petko M; Paigen, Kenneth

    2016-06-01

    In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination. PRDM9 binds to DNA at hotspots through its zinc finger domain and activates recombination by trimethylating histone H3K4 on adjacent nucleosomes through its PR/SET domain. Recently, the isolated PR/SET domain of PRDM9 was shown capable of also trimethylating H3K36 in vitro, raising the question of whether this reaction occurs in vivo during meiosis, and if so, what its function might be. Here, we show that full-length PRDM9 does trimethylate H3K36 in vivo in mouse spermatocytes. Levels of H3K4me3 and H3K36me3 are highly correlated at hotspots, but mutually exclusive elsewhere. In vitro, we find that although PRDM9 trimethylates H3K36 much more slowly than it does H3K4, PRDM9 is capable of placing both marks on the same histone molecules. In accord with these results, we also show that PRDM9 can trimethylate both K4 and K36 on the same nucleosomes in vivo, but the ratio of K4me3/K36me3 is much higher for the pair of nucleosomes adjacent to the PRDM9 binding site compared to the next pair further away. Importantly, H3K4me3/H3K36me3-double-positive nucleosomes occur only in regions of recombination: hotspots and the pseudoautosomal (PAR) region of the sex chromosomes. These double-positive nucleosomes are dramatically reduced when PRDM9 is absent, showing that this signature is PRDM9-dependent at hotspots; the residual double-positive nucleosomes most likely come from the PRDM9-independent PAR. These results, together with the fact that PRDM9 is the only known mammalian histone methyltransferase with both H3K4 and H3K36 trimethylation activity, suggest that trimethylation of H3K36 plays an important role in the recombination process. Given the known requirement of H3K36me3 for double strand break repair by homologous recombination in somatic cells, we

  14. Vitamin K3 inhibits mouse uterine contraction in vitro via interference with the calcium transfer and the potassium channels.

    Science.gov (United States)

    Zhang, Xian-Xia; Lu, Li-Min; Wang, Li

    2016-08-05

    Previous studies have demonstrated vitamin K3 had a great relief to smooth muscle spastic disorders, but no researches have yet pinpointed its possible anti-contractile activity in the uterus. Here, we evaluated the effect of vitamin K3 on myometrial contractility and explored the possible mechanisms of vitamin K3 action. Myograph apparatus were used to record the changes in contractility of isolated mouse uterine strips in a tissue bath. Uterine strips were exposed to vitamin K3 or vehicle. Vitamin K3 suppressed spontaneous contractions in a concentration dependent manner. It significantly decreased the contractile frequency induced by PGF2ɑ but not their amplitude (expect 58.0 μM). Prior incubation with vitamin K3 reduced the effectiveness of PGF2ɑ-induced contraction. The antispasmodic effect of vitamin K3 was also sensitive to potassium channel blockers, such as tetraethylammonium, 4-aminopyridine, iberiotoxin) but not to the nitric oxide related pathway blockers. High concentrations (29.0, 58.0 μM) of vitamin K3 weakened the Ca(2+) dose response and inhibited phase 1 contraction (intracellular stored calcium release). These dates suggest that vitamin K3 specifically suppresses myometrial contractility by affecting calcium and potassium channels; thus, this approach has potential therapy for uterine contractile activity related disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Quantitative evaluation of apical extrusion of intracanal bacteria using rotary ProTaper, K3XF, twisted and hand K-file system: An ex vivo study

    Directory of Open Access Journals (Sweden)

    Priyanka Ghogre

    2015-01-01

    Conclusions: Both the rotary and hand instrumentation systems extruded intracanal bacteria through the apical foramen. K3XF file system showed least bacterial extrusion amongst all instrumentation groups.

  16. Inhibition of Siah2 Ubiquitin Ligase by Vitamin K3 Attenuates Chronic Myeloid Leukemia Chemo-Resistance in Hypoxic Microenvironment.

    Science.gov (United States)

    Huang, Jixian; Lu, Ziyuan; Xiao, Yajuan; He, Bolin; Pan, Chengyun; Zhou, Xuan; Xu, Na; Liu, Xiaoli

    2018-02-05

    BACKGROUND A hypoxic microenvironment is associated with resistance to tyrosine kinase inhibitors (TKIs) and a poor prognosis in chronic myeloid leukemia (CML). The E3 ubiquitin ligase Siah2 plays a vital role in the regulation of hypoxia response, as well as in leukemogenesis. However, the role of Siah2 in CML resistance is unclear, and it is unknown whether vitaminK3 (a Siah2 inhibitor) can improve the chemo-sensitivity of CML cells in a hypoxic microenvironment. MATERIAL AND METHODS The expression of Siah2 was detected in CML patients (CML-CP and CML-BC), K562 cells, and K562-imatinib-resistant cells (K562-R cells). We measured the expression of PHD3, HIF-1α, and VEGF in both cell lines under normoxia and hypoxic conditions, and the degree of leukemic sensitivity to imatinib and VitaminK3 were evaluated. RESULTS Siah2 was overexpressed in CML-BC patients (n=9) as compared to CML-CP patients (n=13). Similarly, K562-imatinib-resistant cells (K562-R cells) showed a significantly higher expression of Siah2 as compared to K562 cells in a hypoxic microenvironment. Compared to normoxia, under hypoxic conditions, both cell lines had lower PHD3, higher HIF-1α, and higher VEGF expression. Additionally, Vitamin K3 (an inhibitor of Siah2) reversed these changes and promoted a higher degree of leukemic sensitivity to imatinib. CONCLUSIONS Our findings indicate that the Siah2-PHD3- HIF-1α-VEGF axis is an important hypoxic signaling pathway in a leukemic microenvironment. An inhibitor of Siah2, combined with TKIs, might be a promising therapy for relapsing and refractory CML patients.

  17. Generation of femtosecond laser pulses at 263 nm by K3B6O10Cl crysta*

    International Nuclear Information System (INIS)

    Zhang Ning-Hua; He Peng; Huang Hang-Dong; Zhu Jiang-Feng; Tian Wen-Long; Fang Shao-Bo; Teng Hao; Wei Zhi-Yi; Wu Hong-Ping; Pan Shi-Lie

    2017-01-01

    The third harmonic generation (THG) of a linear cavity Ti:sapphire regenerative amplifier by use of a K 3 B 6 O 10 Cl (KBOC) crystal is studied for the first time. Output power up to 5.9 mW is obtained at a central wavelength of 263 nm, corresponding to a conversion efficiency of 4.5% to the second harmonic power. Our results show a tremendous potential for nonlinear frequency conversion into the deep ultraviolet range with the new crystal and the output laser power can be further improved. (paper)

  18. Identification and quantitation of vitamins K1 and K3 in cosmetic products for facial skin protection.

    Science.gov (United States)

    De Orsi, D; Giannini, G; Gagliardi, L; Carpani, I; Tonelli, D

    2008-01-01

    A simple and rapid analytical method was developed for the determination of vitamins K1 and K3 in facial anti-rash creams. The procedure is based on an ultrasonic extraction of the cosmetic sample with dimethylacetamide, in the presence of an internal standard, followed by HPLC separation. HPLC was performed using a C18 column and spectrophotometric detection at 333 nm. A linear gradient elution was carried out starting with 50% acetonitrile-methanol (75:25 v/v) and water up to 100% acetonitrile-methanol for 5 min. Linearity was established over the concentration range from 0.2 to 1.0 mg/ml for vitamin K1 and from 0.02 to 0.1 mg/ml for vitamin K3, with LOD values of 100 ng and 20 ng injected, respectively. The accuracy was verified by spiking experiments on model cosmetic samples. The proposed method has been successfully applied for the analysis of commercial samples of creams.

  19. Absorption spectrometric and thermodynamic study of charge transfer complexes of menadione (Vitamin K3) with a series of phenols.

    Science.gov (United States)

    Pal, Purnendu; Bhattacharya, Sumanta; Mukherjee, Asok K; Mukherjee, Dulal C

    2005-03-01

    The electron donor-acceptor (EDA) interactions between menadione (i.e., 2-methyl-1,4-naphthoquinone, which is also called 'Vitamin K3') and a series of phenols (viz., phenol, resorcinol and p-quinol) have been studied in CCl4 medium. In all the cases, charge transfer (CT) bands have been located. The CT transition energies (h nu(CT)) of the complexes are found to change systematically with change in the number and position of the -OH groups in the aromatic ring of the phenol moiety. From the trends in the h nu(CT) values, the Hückel parameters (h(O) and k(C-O)) for the -OH group have been obtained. The CT transition energies are well correlated with the ionisation potentials of the phenols. From an analysis of this variation the electron affinity of Vitamin K3 has been found to be 2.28 eV. The stoichiometry of the complexes in each case has been found to be 1(menadione):2 (phenol). Formation constants of the complexes have been determined at four different temperatures from which the enthalpies and entropies of formation of the complexes have been estimated.

  20. ANALISIS FAKTOR KESEHATAN DAN KESELAMATAN KERJA (K3 YANG SIGNIFIKAN MEMPENGARUHI KECELAKAAN KERJA PADA PROYEK PEMBANGUNAN APARTEMENT STUDENT CASTLE

    Directory of Open Access Journals (Sweden)

    Saloni Waruwu

    2016-04-01

    Full Text Available Health and Safety (K3 is an effort to create a safe working atmosphere, comfortable and achieve the goal of maximum productivity. K3 is very important to be implemented in all areas of employment without exception building projects such as apartments, hotels, malls. However, to prevent any risk of workplace accidents is not as easy as turning the palm of the hand. Occupational accidents disebab by several factors, among others, occupational safety and health training (X1, the commitment of top management (X2, work environment (X3, awareness of workers (X4, regulations and safety and health procedures (X5, availability rambu- occupational health and safety signs (X6 in the workplace, and communication workers (X7. The most significant factor affecting the accidents are the top management commitment (X2 with a value of 36.4% koefien regression and awareness of workers (X4 of 30.1%. If both of these factors add up the total is 66.5%.

  1. Absorption spectrometric and thermodynamic study of charge transfer complexes of menadione (Vitamin K 3) with a series of phenols

    Science.gov (United States)

    Pal, Purnendu; Bhattacharya, Sumanta; Mukherjee, Asok K.; Mukherjee, Dulal C.

    2005-03-01

    The electron donor-acceptor (EDA) interactions between menadione (i.e., 2-methyl-1,4-naphthoquinone, which is also called 'Vitamin K 3') and a series of phenols (viz., phenol, resorcinol and p-quinol) have been studied in CCl 4 medium. In all the cases, charge transfer (CT) bands have been located. The CT transition energies ( hνCT) of the complexes are found to change systematically with change in the number and position of the -OH groups in the aromatic ring of the phenol moiety. From the trends in the hνCT values, the Hückel parameters ( hÖ and kC-Ö) for the -OH group have been obtained. The CT transition energies are well correlated with the ionisation potentials of the phenols. From an analysis of this variation the electron affinity of Vitamin K 3 has been found to be 2.28 eV. The stoichiometry of the complexes in each case has been found to be 1(menadione):2 (phenol). Formation constants of the complexes have been determined at four different temperatures from which the enthalpies and entropies of formation of the complexes have been estimated.

  2. Orthorhombic fulleride (CH3NH2)K3C60 close to Mott-Hubbard instability: Ab initio study

    Science.gov (United States)

    Potočnik, Anton; Manini, Nicola; Komelj, Matej; Tosatti, Erio; Arčon, Denis

    2012-08-01

    We study the electronic structure and magnetic interactions in methylamine-intercalated orthorhombic alkali-doped fullerene (CH3NH2)K3C60 within the density functional theory. As in the simpler ammonia intercalated compound (NH3)K3C60, the orthorhombic crystal-field anisotropy Δ lifts the t1u triple degeneracy at the Γ point and drives the system deep into the Mott-insulating phase. However, the computed Δ and conduction electron bandwidth W cannot alone account for the abnormally low experimental Néel temperature, TN=11 K, of the methylamine compound, compared to the much higher value TN=40 K of the ammonia one. Significant interactions between CH3NH2 and C603- are responsible for the stabilization of particular fullerene-cage distortions and the ensuing low-spin S=1/2 state. These interactions also seem to affect the magnetic properties, as interfullerene exchange interactions depend on the relative orientation of deformations of neighboring C603- molecules. For the ferro-orientational order of CH3NH2-K+ groups we find an apparent reduced dimensionality in magnetic exchange interactions, which may explain the suppressed Néel temperature. The disorder in exchange interactions caused by orientational disorder of CH3NH2-K+ groups could further contribute to this suppression.

  3. K3FU METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  4. K3MW METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  5. K3TH METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  6. KEY COMPARISON: Final report of comparison of the calibrations of hydrometers for liquid density determination between SIM laboratories: SIM.M.D-K4

    Science.gov (United States)

    Becerra, Luis Omar

    2009-01-01

    This SIM comparison on the calibration of high accuracy hydrometers was carried out within fourteen laboratories in the density range from 600 kg/m3 to 1300 kg/m3 in order to evaluate the degree of equivalence among participant laboratories. This key comparison anticipates the planned key comparison CCM.D-K4, and is intended to be linked with CCM.D-K4 when results are available. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  7. 2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety.

    Science.gov (United States)

    Dow, Robert L; Ammirati, Mark; Bagley, Scott W; Bhattacharya, Samit K; Buckbinder, Leonard; Cortes, Christian; El-Kattan, Ayman F; Ford, Kristen; Freeman, Gary B; Guimarães, Cristiano R W; Liu, Shenping; Niosi, Mark; Skoura, Athanasia; Tess, David

    2018-04-12

    Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a number of biological processes and/or diseases, including diabetes, cancer, inflammation, and angiogenesis. With a majority of the members of our lead series (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought design avenues that would eliminate this risk. One such approach arose from the observation that carboxylic acid-based intermediates employed in our discovery efforts retained high MAP4K4 inhibitory potency and were devoid of the TDI risk. The medicinal chemistry effort that led to the discovery of this central nervous system-impaired inhibitor together with its preclinical safety profile is described.

  8. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Lena Willkomm

    Full Text Available Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs. Lactate (La-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3 known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD vs. high intensity RE (HIT. Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  9. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Science.gov (United States)

    Willkomm, Lena; Gehlert, Sebastian; Jacko, Daniel; Schiffer, Thorsten; Bloch, Wilhelm

    2017-01-01

    Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs). Lactate (La)-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK) which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3) known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM) and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC) leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE) associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD) vs. high intensity RE (HIT). Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  10. Effect of follicular diameter, time of first cleavage and H3K4 methylation on embryo production rates of Bos indicus cattle

    Directory of Open Access Journals (Sweden)

    Paula Alvares Lunardelli

    2016-10-01

    Full Text Available This study aimed investigate the relationship between epigenetics, follicular diameter and cleavage speed, by evaluating the developmental potential and occurence of H3K4 monomethylation of early-, intermediate- and late-cleaving Bos indicus embryos from in vitro fertilized oocytes originating from follicles up to 2 mm in diameter or between 4 and 8 mm in diameter. Oocytes (n = 699 from small follicles (? 2 mm and 639 oocytes from large follicles (4-8 mm were punched from 1,982 Bos indicus’ slaughterhouse ovaries. After maturation and in vitro fertilization (IVF, the cultured embryos were separated into early (? 28 h post-IVF, intermediate (> 28 h and ? 34 h post-IVF and late (> 34 h and ? 54 h post-IVF cleavage groups. Blastocysts were subjected to an immunofluorescence assessment for H3K4me investigation. The blastocyst rate for large follicles (36.3% was higher than that for small follicles (22.9%, P < 0.05. In addition, blastocyst rates for early and intermediate cleavage groups (45.3% and 33.8%, respectively were higher than that for late cleavage group (13.5%, P < 0.05. The blastocysts from all groups displayed H3K4me staining by immunofluorescence, particularly intense in what seemed to be trophectoderm cells and weak or absent in cells seemingly from the inner cell mass. For the first time for indicus embryos, data from this study demonstrate that higher blastocyst embryo rates are obtained from embryos that cleave within 34 h after fertilization and from those produced from follicles of 4-8 mm in diameter, indicating a greater ability of these embryos to develop to the stage of embryonic preimplantation. This is the first article demonstrating the occurrence of H3K4me in cattle embryos; its presence in all the evaluated blastocysts suggests that this histone modification plays a key role in maintaining embryo viability at preimplantation stage.

  11. H3K27me3 and H3K4me3 chromatin environment at super-induced dehydration stress memory genes of Arabidopsis thaliana.

    Science.gov (United States)

    Liu, Ning; Fromm, Michael; Avramova, Zoya

    2014-03-01

    Pre-exposure to a stress may alter the plant's cellular, biochemical, and/or transcriptional responses during future encounters as a 'memory' from the previous stress. Genes increasing transcription in response to a first dehydration stress, but producing much higher transcript levels in a subsequent stress, represent the super-induced 'transcription memory' genes in Arabidopsis thaliana. The chromatin environment (histone H3 tri-methylations of Lys 4 and Lys 27, H3K4me3, and H3K27me3) studied at five dehydration stress memory genes revealed existence of distinct memory-response subclasses that responded differently to CLF deficiency and displayed different transcriptional activities during the watered recovery periods. Among the most important findings is the novel aspect of the H3K27me3 function observed at specific dehydration stress memory genes. In contrast to its well-known role as a chromatin repressive mechanism at developmentally regulated genes, H3K27me3 did not prevent transcription from the dehydration stress-responding genes. The high H3K27me3 levels present during transcriptionally inactive states did not interfere with the transition to active transcription and with H3K4me3 accumulation. H3K4me3 and H3K27me3 marks function independently and are not mutually exclusive at the dehydration stress-responding memory genes.

  12. Compounding of vitamin A, D3, E and K3 supplements for cystic fibrosis patients: formulation and stability study.

    Science.gov (United States)

    Huyghebaert, N; De Beer, J; Vervaet, C; Remon, J P

    2007-10-01

    Cystic fibrosis (CF) patients suffer from malabsorption of fat-soluble vitamins (A, D, E and K). These vitamins are available as water-dispersible (A, D(3) and E) or water-soluble grades (K(3)), which is favoured in CF patients as they fail to absorb oil-based products. The objective of this study was to determine stability of these raw materials after opening the original package and to develop a compounded formulation of acceptable quality, stability and taste, allowing flexible dose adaptation and being appropriate for administration to children and elderly people. The raw materials were stored after opening their original package for 8 months at 8 degrees C and room temperature (RT). Stability was assessed using a validated HPLC method after extraction of the vitamin from the cold water-soluble matrix (vitamin A acetate, D(3) and E) or using a spectrophotometrical method (vitamin K(3)). These materials were mixed with an appropriate lactose grade (lactose 80 m for vitamins A and D(3); lactose 90 m for vitamin E, lactose very fine powder for vitamin K(3)) and filled in hard gelatin capsules. Mass and content uniformity were determined and stability of the vitamins in the capsules was assessed after 2 months storage at 8 degrees C and RT. All raw materials showed good stability during storage in the opened original package for 8 months storage at 8 degrees C as well as RT (>95% of the initial content). The compounded formulations complied with the requirements of the European Pharmacopoeia for mass and content uniformity and can be stored for 2 months at 8 degrees C or RT while maintaining the vitamin content between 90% and 110%. As these fat-soluble vitamins are not commercially available on the Belgian market, compounded formulations are a valuable alternative for prophylactic administration of these vitamins to CF patients, i.e. a stable formulation, having an acceptable taste, allowing flexible dose adaptation and being appropriate for administration to

  13. Generation of femtosecond laser pulses at 396 nm in K3B6O10Cl crystal

    International Nuclear Information System (INIS)

    Zhang Ning-Hua; Huang Hang-Dong; Tian Wen-Long; Zhu Jiang-Feng; Teng Hao; Fang Shao-Bo; Wei Zhi-Yi; Wu Hong-Ping; Pan Shi-Lie

    2016-01-01

    K 3 B 6 O 10 Cl (KBOC), a new nonlinear optical crystal, shows potential advantages for the generation of deep ultraviolet (UV) light compared with other borate crystals. In this paper we study for the first time the second harmonic generation (SHG) of a femtosecond Ti:sapphire amplifier with this crystal. Laser power is obtained to be as high as 220 mW at the central wavelength of 396 nm with a 1-mm-long crystal, and the maximum SHG conversion efficiency reaches 39.3%. The typical pulse duration is 83 fs. The results show that second harmonic (SH) conversion efficiency has the room to be further improved and that the new nonlinear crystal is very suited to generate the high efficiency deep ultraviolet laser radiation below 266 nm. (paper)

  14. Stable, high power, high efficiency picosecond ultraviolet generation at 355 nm in K3B6O10 Br crystal

    Science.gov (United States)

    Hou, Z. Y.; Wang, L. R.; Xia, M. J.; Yan, D. X.; Zhang, Q. L.; Zhang, L.; Liu, L. J.; Xu, D. G.; Zhang, D. X.; Wang, X. Y.; Li, R. K.; Chen, C. T.

    2018-06-01

    We demonstrate a high efficiency and high power picosecond ultraviolet source at 355 nm with stable output by sum frequency generation from a Nd:YAG laser using a type-I critically phase matched K3B6O10 Br crystal as nonlinear optical material. Conversion efficiency as high as 30.8% was achieved using a 25 ps laser at 1064 nm operated at 10 Hz. Similar work is done by using a 35 W 10 ps laser at 1064 nm as the pump source with a repetition rate of 80 MHz, and the highest average output power obtained was up to 5.3 W. In addition, the power stability of the 355 nm output power measurement shows that the standard deviation fluctuations of the average power are ±0.69% and ±0.91% at 3.0 W and 3.5 W, respectively.

  15. Effect of K3PO4 addition as sintering inhibitor during calcination of Y2O3 nanoparticles

    Science.gov (United States)

    Soga, K.; Okumura, Y.; Tsuji, K.; Venkatachalam, N.

    2009-11-01

    Erbium-doped yttrium oxide nanoparticle is one of the most important for fluorescence bioimaging under near infrared excitation. Particle size of it below 100 nm is an important requirement for a cellular bioimaging. However, the synthesis with such small particles is difficult at the calcination temperature above 1200 °C due to the sintering and crystal growth of the particles. In this study, yttrium oxide nanoparticles with average size of 30 nm were successfully synthesized by using K3PO4 as a sintering inhibitor during the calcination. A single phase of cubic Y2O3 as the resultant material was confirmed by XRD, which was also confirmed to emit a bright upconversion emission under 980-nm excitation. Improvement of chemical durability due to the introduction of phosphate group on the surface of the Y2O3 particles is also reported.

  16. The effects of physical aging at elevated temperatures on the viscoelastic creep on IM7/K3B

    Science.gov (United States)

    Gates, Thomas S.; Feldman, Mark

    1994-01-01

    Physical aging at elevated temperature of the advanced composite IM7/K3B was investigated through the use of creep compliance tests. Testing consisted of short term isothermal, creep/recovery with the creep segments performed at constant load. The matrix dominated transverse tensile and in-plane shear behavior were measured at temperatures ranging from 200 to 230 C. Through the use of time based shifting procedures, the aging shift factors, shift rates and momentary master curve parameters were found at each temperature. These material parameters were used as input to a predictive methodology, which was based upon effective time theory and linear viscoelasticity combined with classical lamination theory. Long term creep compliance test data was compared to predictions to verify the method. The model was then used to predict the long term creep behavior for several general laminates.

  17. A Hiker's guide to K3. Aspects of N=(4,4) superconformal field theory with central charge c=6

    International Nuclear Information System (INIS)

    Nahm, W.; Wendland, K.

    2001-01-01

    We study the moduli space M of N=(4,4) superconformal field theories with central charge c=6. After a slight emendation of its global description we find the locations of various known models in the component of M associated to K3 surfaces. Among them are the Z 2 and Z 4 orbifold theories obtained from the torus component of M. Here, SO(4,4) triality is found to play a dominant role. We obtain the B-field values in direction of the exceptional divisors which arise from orbifolding. We prove T-duality for the Z 2 orbifolds and use it to derive the form of M purely within conformal field theory. For the Gepner model (2) 4 and some of its orbifolds we find the locations in M and prove isomorphisms to nonlinear σ models. In particular we prove that the Gepner model (2) 4 has a geometric interpretation with Fermat quartic target space. (orig.)

  18. Ortho-vanadates K3RE(VO4)2 (RE = La, Pr, Eu, Gd, Dy, Y) for near UV-converted phosphors

    International Nuclear Information System (INIS)

    Qin, Lin; Wei, Dong-Lei; Huang, Yanlin; Qin, Chuanxiang; Cai, Peiqing; Kim, Sun-Il; Seo, Hyo-Jin

    2014-01-01

    The orthovanadate poly-crystals K 3 RE(VO 4 ) 2 (RE = La, Pr, Eu, Gd, Dy, Y) were synthesized via the solid-state reaction route. The crystal phase formation was verified through X-ray diffraction (XRD) studies and was performed by structural refinements. The optical properties were also investigated in detail. K 3 RE(VO 4 ) 2 (RE = Eu, Dy, Gd, Pr, La, Y) phosphors present different luminescence behaviors: the profiles of excitation and emission spectra, the spectra shift, the luminescence decay lifetimes, the absolute quantum efficiency (QE), and the CIE color coordinates are very different. The luminescence of K 3 RE(VO 4 ) 2 (RE = La, Gd, Y, Pr) presents yellow or yellowish green color, while, K 3 Dy(VO 4 ) 2 and K 3 Eu(VO 4 ) 2 show white and red luminescence, respectively. This was discussed on the base of the different micro-structure, activator centers, and the charge transfer transitions from [VO 4 ] 3− groups in the lattices. K 3 Y(VO 4 ) 2 and K 3 Eu(VO 4 ) 2 show higher QE values of 47.0% and 45.0% at room temperature, respectively. All the phosphors have efficient absorption in the region of near-UV wavelengths or blue wavelength region. This can well match with the light from UV-LED (360–400 nm) or blue LED chips (450–480 nm) based on GaN semiconductor. K 3 RE(VO 4 ) 2 could be suggested to be a potential candidate to give further investigations for the application on near-UV excited white LEDs. - Graphical abstract: A series of orthovanadates K 3 RE(VO 4 ) 2 (RE = Eu, Dy, Gd, Pr, La, Y) have been developed to be new phosphors with rich luminescence colors; there are efficiency excitation in the near UV wavelength region. Compared with the reported vanadate phosphors K 3 R(VO 4 ) 2 has rich luminescence color, rich color, no concentration quenching, and comparable luminescence QE. - Highlights: • A new phosphor of non-doped of K 3 R(VO 4 ) 2 (R = Eu, Dy, Gd, Pr, La, Y) were developed by solid-state reaction route. • The phosphor

  19. Re-patterning of H3K27me3, H3K4me3 and DNA methylation during fibroblast conversion into induced cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Ziqing Liu

    2016-03-01

    Full Text Available Direct conversion of fibroblasts into induced cardiomyocytes (iCMs offers an alternative strategy for cardiac disease modeling and regeneration. During iCM reprogramming, the starting fibroblasts must overcome existing epigenetic barriers to acquire the CM-like chromatin pattern. However, epigenetic dynamics along this reprogramming process have not been studied. Here, we took advantage of our recently generated polycistronic system and determined the dynamics of two critical histone marks, H3K27me3 and H3K4me3, in parallel with gene expression at a set of carefully selected cardiac and fibroblast loci during iCM reprogramming. We observed reduced H3K27me3 and increased H3K4me3 at cardiac promoters as early as day 3, paralleled by a rapid significant increase in their mRNA expression. In contrast, H3K27me3 at loci encoding fibroblast marker genes did not increase until day 10 and H3K4me3 progressively decreased along the reprogramming process; these changes were accompanied by a gradual decrease in the mRNA expression of fibroblast marker genes. Further analyses of fibroblast-enriched transcription factors revealed a similarly late deposition of H3K27me3 and decreased mRNA expression of Sox9, Twist1 and Twist2, three important players in epithelial−mesenchymal transition. Our data suggest early rapid activation of the cardiac program and later progressive suppression of fibroblast fate at both epigenetic and transcriptional levels. Additionally, we determined the DNA methylation states of representative cardiac promoters and found that not every single CpG was equally demethylated during early stages of iCM reprogramming. Rather, there are specific CpGs, whose demethylation states correlated tightly with transcription activation, that we propose are the major contributing CpGs. Our work thus reveals a differential re-patterning of H3K27me3, H3K4me3 at cardiac and fibroblast loci during iCM reprogramming and could provide future genome

  20. Loss of Mitogen-Activated Protein Kinase Kinase Kinase 4 (MAP3K4) Reveals a Requirement for MAPK Signalling in Mouse Sex Determination

    Science.gov (United States)

    Bogani, Debora; Siggers, Pam; Brixey, Rachel; Warr, Nick; Beddow, Sarah; Edwards, Jessica; Williams, Debbie; Wilhelm, Dagmar; Koopman, Peter; Flavell, Richard A.; Chi, Hongbo; Ostrer, Harry; Wells, Sara; Cheeseman, Michael; Greenfield, Andy

    2009-01-01

    Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY) gonad, sex-determining region of the Y (SRY) protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK) signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg) mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4), a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas). These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and create a novel

  1. Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4 reveals a requirement for MAPK signalling in mouse sex determination.

    Directory of Open Access Journals (Sweden)

    Debora Bogani

    2009-09-01

    Full Text Available Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY gonad, sex-determining region of the Y (SRY protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4, a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas. These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and

  2. The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons.

    Science.gov (United States)

    Larhammar, Martin; Huntwork-Rodriguez, Sarah; Rudhard, York; Sengupta-Ghosh, Arundhati; Lewcock, Joseph W

    2017-11-15

    The c-Jun- N -terminal kinase (JNK) signaling pathway regulates nervous system development, axon regeneration, and neuronal degeneration after acute injury or in chronic neurodegenerative disease. Dual leucine zipper kinase (DLK) is required for stress-induced JNK signaling in neurons, yet the factors that initiate DLK/JNK pathway activity remain poorly defined. In the present study, we identify the Ste20 kinases MAP4K4, misshapen-like kinase 1 (MINK1 or MAP4K6) and TNIK Traf2- and Nck-interacting kinase (TNIK or MAP4K7), as upstream regulators of DLK/JNK signaling in neurons. Using a trophic factor withdrawal-based model of neurodegeneration in both male and female embryonic mouse dorsal root ganglion neurons, we show that MAP4K4, MINK1, and TNIK act redundantly to regulate DLK activation and downstream JNK-dependent phosphorylation of c-Jun in response to stress. Targeting MAP4K4, MINK1, and TNIK, but not any of these kinases individually, is sufficient to protect neurons potently from degeneration. Pharmacological inhibition of MAP4Ks blocks stabilization and phosphorylation of DLK within axons and subsequent retrograde translocation of the JNK signaling complex to the nucleus. These results position MAP4Ks as important regulators of the DLK/JNK signaling pathway. SIGNIFICANCE STATEMENT Neuronal degeneration occurs in disparate circumstances: during development to refine neuronal connections, after injury to clear damaged neurons, or pathologically during disease. The dual leucine zipper kinase (DLK)/c-Jun- N -terminal kinase (JNK) pathway represents a conserved regulator of neuronal injury signaling that drives both neurodegeneration and axon regeneration, yet little is known about the factors that initiate DLK activity. Here, we uncover a novel role for a subfamily of MAP4 kinases consisting of MAP4K4, Traf2- and Nck-interacting kinase (TNIK or MAP4K7), and misshapen-like kinase 1 (MINK1 or MAP4K6) in regulating DLK/JNK signaling in neurons. Inhibition of

  3. The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance linked ATP binding cassette drug transporter ABCG2.

    Science.gov (United States)

    Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V

    2007-12-01

    Vitamin K3 (menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2, which are essential for blood clotting. The naturally occurring structural analogue of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We here report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette drug transporter, ABCG2. Vitamin K3 and plumbagin specifically inhibited the ABCG2-mediated efflux of mitoxantrone but did not have any effect on the ABCB1-mediated efflux of rhodamine 123. This inhibition of ABCG2 function was due to their interaction at the substrate-binding site(s). Vitamin K3 and plumbagin inhibited the binding of [(125)I]iodoarylazidoprazosin, a substrate of ABCG2, to this transporter in a concentration-dependent manner with IC(50) values of 7.3 and 22.6 micromol/L, respectively, but had no effect on the binding of the photoaffinity analogue to ABCB1. Both compounds stimulated ABCG2-mediated ATP hydrolysis and also inhibited the mitoxantrone-stimulated ATPase activity of the ABCG2 transporter, but did not have any significant effect on the ATPase activity of ABCB1. In a cytotoxicity assay, ABCG2-expressing HEK cells were 2.8- and 2.3-fold resistant to plumbagin and vitamin K3, respectively, compared with the control cells, suggesting that they are substrates of this transporter. Collectively, these data show for the first time that vitamin K3 is a substrate of the ABCG2 transporter. Thus, ABCG2 may have a role in the regulation of vitamin K3 levels in the body. In addition, vitamin K3 and its structural derivative, plumbagin, could potentially be used to modulate ABCG2 function.

  4. DECONVOLUTION OF IMAGES FROM BLAST 2005: INSIGHT INTO THE K3-50 AND IC 5146 STAR-FORMING REGIONS

    International Nuclear Information System (INIS)

    Roy, Arabindo; Netterfield, Calvin B.; Ade, Peter A. R.; Griffin, Matthew; Hargrave, Peter C.; Mauskopf, Philip; Bock, James J.; Brunt, Christopher M.; Chapin, Edward L.; Gibb, Andrew G.; Halpern, Mark; Marsden, Gaelen; Devlin, Mark J.; Dicker, Simon R.; Klein, Jeff; France, Kevin; Gundersen, Joshua O.; Hughes, David H.; Martin, Peter G.; Olmi, Luca

    2011-01-01

    We present an implementation of the iterative flux-conserving Lucy-Richardson (L-R) deconvolution method of image restoration for maps produced by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). Compared to the direct Fourier transform method of deconvolution, the L-R operation restores images with better-controlled background noise and increases source detectability. Intermediate iterated images are useful for studying extended diffuse structures, while the later iterations truly enhance point sources to near the designed diffraction limit of the telescope. The L-R method of deconvolution is efficient in resolving compact sources in crowded regions while simultaneously conserving their respective flux densities. We have analyzed its performance and convergence extensively through simulations and cross-correlations of the deconvolved images with available high-resolution maps. We present new science results from two BLAST surveys, in the Galactic regions K3-50 and IC 5146, further demonstrating the benefits of performing this deconvolution. We have resolved three clumps within a radius of 4.'5 inside the star-forming molecular cloud containing K3-50. Combining the well-resolved dust emission map with available multi-wavelength data, we have constrained the spectral energy distributions (SEDs) of five clumps to obtain masses (M), bolometric luminosities (L), and dust temperatures (T). The L-M diagram has been used as a diagnostic tool to estimate the evolutionary stages of the clumps. There are close relationships between dust continuum emission and both 21 cm radio continuum and 12 CO molecular line emission. The restored extended large-scale structures in the Northern Streamer of IC 5146 have a strong spatial correlation with both SCUBA and high-resolution extinction images. A dust temperature of 12 K has been obtained for the central filament. We report physical properties of ten compact sources, including six associated protostars, by fitting

  5. Increased growth and root Cu accumulation of Sorghum sudanense by endophytic Enterobacter sp. K3-2: Implications for Sorghum sudanense biomass production and phytostabilization.

    Science.gov (United States)

    Li, Ya; Wang, Qi; Wang, Lu; He, Lin-Yan; Sheng, Xia-Fang

    2016-02-01

    Endophytic bacterial strain K3-2 was isolated from the roots of Sorghum sudanense (an bioenergy plant) grown in a Cu mine wasteland soils and characterized. Strain K3-2 was identified as Enterobacter sp. based on 16S rRNA gene sequence analysis. Strain K3-2 exhibited Cu resistance and produced 1-aminocyclopropane-1-carboxylate (ACC) deaminase, indole-3-acetic acid (IAA), siderophores, and arginine decarboxylase. Pot experiments showed that strain K3-2 significantly increased the dry weight and root Cu accumulation of Sorghum sudanense grown in the Cu mine wasteland soils. Furthermore, increase in total Cu uptake (ranging from 49% to 95%) of the bacterial inoculated-Sorghum sudanense was observed compared to the control. Notably, most of Cu (83-86%) was accumulated in the roots of Sorghum sudanense. Furthermore, inoculation with strain K3-2 was found to significantly increase Cu bioconcentration factors and the proportions of IAA- and siderophore-producing bacteria in the root interiors and rhizosphere soils of Sorghum sudanense compared with the control. Significant decrease in the available Cu content was also observed in the rhizosphere soils of the bacterial-inoculated Sorghum sudanense. The results suggest that the endophytic bacterial strain K3-2 may be exploited for promoting Sorghum sudanense biomass production and Cu phytostabilization in the Cu mining wasteland soils. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Vitamin K 3 family members - Part II: Single crystal X-ray structures, temperature-induced packing polymorphism, magneto-structural correlations and probable anti-oncogenic candidature

    Science.gov (United States)

    Rane, Sandhya; Ahmed, Khursheed; Salunke-Gawali, Sunita; Zaware, Santosh B.; Srinivas, D.; Gonnade, Rajesh; Bhadbhade, Mohan

    2008-12-01

    Temperature-induced packing polymorphism is observed for vitamin K 3 (menadione, 3-methyl-1,4-naphthoquinone, 1). Form 1a crystallizes at 300 K and 1b at 277 K both in the same space group P2 1/ c. Form 1b contains one molecule per asymmetric unit, performing anisotropy in g-factor viz. g z = 2.0082, g y = 2.0055 and g x = 2.0025, whereas form 1a contains two molecules in its asymmetric unit. Vitamin K 3 family members 2, [2-hydroxy vitamin K 3] and 3, [2-hydroxy-1-oximino vitamin K 3] also perform intrinsic neutral active naphthosemiquinone valence tautomers even in dark having spin concentrations due to hydrogen bonding and aromatic stacking interactions which are compared to vitamin K 3. The significant lateral C-H⋯O and O-H⋯π bifurcated or π-π ∗ interactions are discussed for molecular associations and radical formations. X-ray structure of 3 revealed π-π ∗ stack dimers as radicals signatured in EPR as triplet with five hyperfine splits [ Ā( 14N) = 11.9 G]. The centrosymmetric biradicals in 3 show diamagnetism at high temperature but below 10 K it shows paramagnetism with μeff as 0.19 B.M. Vitamin K 3 and its family members inhibit biological activities of acid phosphatase ( APase), which are proportional to their spin concentrations. This may relate to their probable anti-oncogenic candidature in future.

  7. Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter.

    Science.gov (United States)

    Soo, Benjamin P C; Tay, Julian; Ng, Shirelle; Ho, Steven C L; Yang, Yuansheng; Chao, Sheng-Hao

    2017-08-01

    Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines.

  8. The flexible loop L1 of the H3K4 demethylase JARID1B ARID domain has a crucial role in DNA-binding activity

    International Nuclear Information System (INIS)

    Yao, Wenming; Peng, Yu; Lin, Donghai

    2010-01-01

    JARID1B, a member of the JmjC demethylase family, has a crucial role in H3K4me3 demethylation. The ARID domain is a potential DNA-binding domain of JARID1B. Previous studies indicate that a GC-rich DNA motif is the specific target of the ARID domain. However, the details of the interaction between the ARID domain and duplex DNA require further study. Here, we utilized NMR spectroscopy to assign the backbone amino acids and mapped the DNA-binding sites of the human JARID1B ARID domain. Perturbations to 1 H- 15 N correlation spectra revealed that the flexible loop L1 of ARID was the main DNA-binding interface. EMSA and intrinsic fluorescence experiments demonstrated that mutations on loop L1 strongly reduced the DNA-binding activity of JARID1B ARID. Furthermore, transfection of mutant forms resulted in a distinct loss of intrinsic H3K4 demethylase activity, implying that the flexible loop L1 made a major contribution to sustaining the DNA-binding ability of JARID1B ARID domain.

  9. Structural investigation on K3Gd5(PO4)6 in between 20 K to 1073 K

    International Nuclear Information System (INIS)

    Bevara, Samatha; Achary, S.N.; Tyagi, A.K.; Mishra, K.K.; Ravindran, T.R.; Sinha, A.K.; Sastry, P.U.

    2016-01-01

    Evolution of crystal structure of K 3 Gd 5 (PO 4 ) 6 in the temperature range from 20 K to 1073 K, as observed from combined variable temperature X-ray diffraction (using both synchrotron source and Cu K α lab source) and Raman spectroscopic studies is communicated in the manuscript. The title compound has an open tunnel containing three dimensional structure built by periodic arrangements of (Gd 5 (PO 4 ) 6 ) 3- ions which in turn are formed by PO 4 tetrahedra and GdO n (n = 8 and 9) polyhedra and these tunnels are occupied by K + ions. The XRD patterns in the entire temperature range of study indicated no change in the crystal structural, which is also supported by differential thermal analyses and Raman spectroscopy. Average axial thermal expansion coefficients between 20K and 1073 K are : α a =10.6 x 10 -6 K -1 , α b = 5.5 x 10 -6 K -1 and α c = 16.4 X 10.6 -6 K -1 . (author)

  10. An attempt to evaluate the effect of vitamin K3 using as an enhancer of anticancer agents.

    Science.gov (United States)

    Matzno, Sumio; Yamaguchi, Yuka; Akiyoshi, Takeshi; Nakabayashi, Toshikatsu; Matsuyama, Kenji

    2008-06-01

    The possibility of vitamin K3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 microM and Hill coefficient of 3.1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G2/M phase in a dose-dependent manner. G2/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G2 phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G2/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G2 phase-dependent drugs in hepatic cancer chemotherapy.

  11. Amperometric pyruvate sensor based on a pyruvate dehydrogenase-immobilized carbon paste electrode containing vitamin K3 as a mediator

    Energy Technology Data Exchange (ETDEWEB)

    Miki, K. [Nara National College of Technology, Nara (Japan); Kinoshita, H. [Kawassui Women`s College, Nagasaki (Japan); Yamamoto, Y. [Kyoto Municipal Junior College of Nursing, Kyoto (Japan); Taniguchi, N. [Kyoto Research Center for Hygiene, Kyoto (Japan); Ikeda, T. [Kyoto University, Kyoto (Japan). Faculty of Agriculture

    1995-12-05

    Pyruvate dehydrogenase (PDH) was immobilized on the surface of a carbon paste electrode containing vitamin K3 (2-Methyl-1,4-naphthoquinone, VK), and the electrode surface was covered with a dialysis membrane. The enzyme electrode produced an anodic current starting from -0.2 V to reach a limiting current at +0.1 V vs. Ag/AgCl due to the enzyme-catalyzed oxidation of pyruvate in a phosphate buffer solution of pH 7.0. The current response to pyruvate depended on the amounts of both the immobilized-PDH and VK mixed in the carbon paste electrode at low amount of the enzyme and VK, and became independent at above 0.15 mg PDH and 0.65% (w/w) VK. The electrode with 0.15mg PDH and 0.65% (w/w) VK could be used as a pyruvate sensor to measure in the range of 2 ,{mu}M to 3mM. The response time was about 60 sec, and the current was independent of pH in the range of 5.7 - 7.2. The presence of L-ascorbic acid didn`t interfere with this measurement. Phosphate ion could also be determined with this electrode in a citrate buffer solution. 14 refs., 6 figs., 1 tab.

  12. alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.

    Science.gov (United States)

    Tomasetti, M; Strafella, E; Staffolani, S; Santarelli, L; Neuzil, J; Guerrieri, R

    2010-04-13

    A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

  13. Frequency-doubled green picosecond laser based on K3B6O10Br nonlinear optical crystal

    Science.gov (United States)

    Meng, Luping; Zhang, Ling; Hou, Zhanyu; Wang, Lirong; Xu, Hui; Shi, Meng; Wang, Lingwu; Yang, Yingying; Qi, Yaoyao; He, Chaojian; Yu, Haijuan; Lin, Xuechun; Su, Fufang; Xia, Mingjun; Li, Rukang

    2018-05-01

    We report a frequency-doubled green picosecond (ps) laser based on K3B6O10Br (KBB) nonlinear optical crystal with cutting angle of θ = 34.7° and φ = 30°. Through intracavity frequency doubling using a type I phase-matched KBB crystal with dimensions of 4 mm × 4 mm × 13.2 mm, the average output power of 185.00 mW green ps laser was obtained with a repetition rate of 80 MHz and pulse width of 25.0 ps. In addition, we present external frequency doubling using KBB crystal. The average output power of 3.00 W green ps laser was generated with a repetition rate of 10 kHz and pulse width of 38.1 ps, which corresponds to a pulse energy of 0.30 mJ and a peak power 7.89 MW, respectively. The experimental results show that KBB crystal is a promising nonlinear optical material.

  14. Radiation catalytical effects in the pre-irradiated and thermally treated catalyst BASF K-3-10

    International Nuclear Information System (INIS)

    Motl, A.

    1987-01-01

    The effects of different heat treatment methods on radiation catalysis, induced by pre-irradiation of the BASF K-3-10 catalyst by γ- or β-radiation or by fast neutrons were investigated. It was found that calcination of the irradiated non-reduced catalyst resulted in a strong decrease in or even a total disappearance of the final radiation catalytical effects; however, at the same time the catalytical activity of the unirradiated catalyst was found to increase. The calcination of the catalyst in a nitrogen atmosphere after reduction also led to a substantial decrease in the resulting positive radiation catalytical effects and the exceedance of a certain calcination temperature also resulted in a decrease in the unirradiated catalyst activity. It could be concluded that calcination in nitrogen of the reduced irradiated samples decreased the radiation catalytical effects to a lesser degree than the calcination in the air of the non-reduced irradiated samples. In both cases, a different thermal stability of effects induced by different types of ionizing radiation was observed and it was found that it increased in the sequence beta radiation - gamma radiation - fast neutrons. The investigation of the γ radiation dose dependence of the radiation catalytical effect on the catalyst calcined before irradiation in the presence of air showed that the final radiation catalytical effects were lower than those observed in case of similarly irradiated but non-calcined samples. The dose dependence of the effect had the same character in both cases. (author). 3 tabs., 8 refs

  15. K4M9 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  16. Growth performance parameters, bone calcification and immune response of in ovo injection of 25-hydroxycholecalciferol and vitamin K3 in male ross 308 broilers.

    Science.gov (United States)

    Abbasi, Tahereh; Shakeri, Malak; Zaghari, Mojtaba; Kohram, Hamid

    2017-03-01

    This experiment aimed to evaluate the effects of in ovo injection of 25-hydroxycholecalciferol (25-OH-D 3 ) and Vitamin K 3 on growth performance, bone calcification and immune system responses in male Ross 308 broilers. Twelve treatment groups with a total number of 768 experimental hatching eggs, four replications and 16 eggs in each replication were selected to form a completely randomized design of factorial arrangement. Treatments included: (1) distilled water, (2) 0.4 μg D 3 , (3) 0.4 μg D 3  + 2 μg K 3 , (4) 0.4 μg D 3  + 6 μg K 3 , (5) 0.6 μg D 3 , (6) 0.6 μg D 3  + 2 μg K 3 , (7) 0.6 μg D 3  + 6 μg K 3 , (8) 0.8 μg D 3 , (9) 0.8 μg D 3  + 2 μg K 3 , (10) 0.8 μg D 3  + 6 μg K 3 , (11) 2 μg K 3 and (12) 6 μg K 3 . Eggs were transferred to corresponding hatching baskets on the 18th day of incubation and received 0.5 ml of experimental solutions specific to each treatment. The results of our experiments showed that Treatment No. 4 ranked the best out of those administered; holding the highest level of weight gain, feed intake during the breeding period (grower and finisher), bone calcium and phosphorus concentration, and tibia fractural force, (p Vitamins D 3 and K 3 in ovo injection has beneficial effects on growth performance, immune system and bone development. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The naphthoquinones, vitamin K3 and its structural analog plumbagin, are substrates of the multidrug resistance-linked ABC drug transporter ABCG2

    Science.gov (United States)

    Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V.

    2008-01-01

    Vitamin K3 (Menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2 which are essential for blood clotting. The naturally occurring structural analog of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We, here, report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette (ABC) drug transporter, ABCG2. Vitamin K3 and plumbagin specifically inhibited the ABCG2-mediated efflux of mitoxantrone, but did not have any effect on the ABCB1-mediated efflux of rhodamine 123. This inhibition of ABCG2 function was due to their interaction at the substrate-binding site(s). They inhibited the binding of [125I]-Iodoarylazidoprazosin (IAAP), a substrate of ABCG2, to this transporter in a concentration-dependent manner with IC50 values of 7.3 and 22.6 μM, respectively, but had no effect on the binding of this photoaffinity analog to ABCB1. Both compounds stimulated ABCG2-mediated ATP hydrolysis and also inhibited the mitoxantrone-stimulated ATPase activity of this transporter, but did not have any significant effect on the ATPase activity of ABCB1. In a cytotoxicity assay, ABCG2-expressing HEK cells were 2.8- and 2.3-fold resistant to plumbagin and vitamin K3, respectively, compared to the control cells, suggesting that they are substrates of this transporter. Collectively, these data demonstrate for the first time that vitamin K3 is a substrate of the ABCG2 transporter. Thus, ABCG2 may have a role in the regulation of vitamin K3 levels in the body. In addition, vitamin K3 and its structural derivative, plumbagin, could potentially be used to modulate ABCG2 function. PMID:18065489

  18. Immune responses to novel allergens and modulation of inflammation by vitamin K3 analogue: a ROS dependent mechanism.

    Science.gov (United States)

    Kohli, Vineet; Sharma, Deepak; Sandur, Santosh Kumar; Suryavanshi, Shweta; Sainis, Krishna B

    2011-02-01

    The possibility of newer allergens being responsible for atopy needs to be explored at regional level due to environmental variables. Current studies were undertaken to identify common environmental allergens causing atopy in a defined population of India and to correlate the presence of various risk factors with the clinical presentation of allergy. Newer allergens like human dander and rice grain dust were identified and reported as the most common cause of atopy in this region. Atopy, elevated serum total IgE and familial tendency, was observed in 88%, 69% and 58% of allergic patients respectively. Further, allergen-specific immune responses like lymphocyte proliferation and cytokine secretion were studied in vitro using peripheral blood mononuclear cells (PBMC) isolated from both allergic and non-allergic individuals. Although, some allergens induced significant lymphocyte proliferation in vitro, allergen-induced cytokine secretion except that of TNF-α was not seen. Significantly higher ratio of secreted IL-4/IFN-γ cytokines was observed in PBMC isolated from allergic subjects in response to PHA. Plumbagin (vitamin K3 analogue) completely inhibited PHA-induced cytokine production in PBMC, in both allergic and non-allergic individuals. Plumbagin modulated the levels of intracellular reactive oxygen species and glutathione and suppressed PHA induced activation of NF-κB in human PBMC. The results thus show in human PMBC, for the first time, the anti-allergic and anti-inflammatory effects of plumbagin and underscore its therapeutic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Effects of Intermediates between Vitamins K2 and K3 on Mammalian DNA Polymerase Inhibition and Anti-Inflammatory Activity

    Directory of Open Access Journals (Sweden)

    Takeshi Azuma

    2011-02-01

    Full Text Available Previously, we reported that vitamin K3 (VK3, but not VK1 or VK2 (=MK-4, inhibits the activity of human DNA polymerase γ (pol γ. In this study, we chemically synthesized three intermediate compounds between VK2 and VK3, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK3 was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC50 value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF-α induced by lipopolysaccharide (LPS. Moreover, MK-2 was found to inhibit the action of nuclear factor (NF-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK2 and VK3 intermediates, such as MK-2, that are promising anti-inflammatory candidates.

  20. In silico and in vitro characterization of anti-amyloidogenic activity of vitamin K3 analogues for Alzheimer's disease.

    Science.gov (United States)

    Huy, Pham Dinh Quoc; Yu, Yao-Chung; Ngo, Son Tung; Thao, Tran Van; Chen, Chin-Piao; Li, Mai Suan; Chen, Yi-Cheng

    2013-04-01

    Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 15 synthesized vitamin K3 (VK3) analogues were studied for their anti-amyloidogenic activity. Biological and spectroscopic assays were used to characterize the effect of VK3 analogues on amyloidogenic properties of Aβ, such as aggregation, free radical formation, and cell viability. Molecular dynamics simulation was used to calculate the binding affinity and mode of VK3 analogue binding to Aβ. Both numerical and experimental results showed that several VK3 analogues, including VK3-6, VK3-8, VK3-9, VK3-10, and VK3-224 could effectively inhibit Aβ aggregation and conformational conversion. The calculated inhibition constants were in the μM range for VK3-10, VK3-6, and VK3-9 which was similar to the IC50 of curcumin. Cell viability assays indicated that VK3-9 could effectively reduce free radicals and had a protective effect on cytotoxicity induced by Aβ. The results clearly demonstrated that VK3 analogues could effectively inhibit Aβ aggregation and protect cells against Aβ induced toxicity. Modified VK3 analogues can possibly be developed as effective anti-amyloidogenic drugs for the treatment of AD. VK3 analogues effectively inhibit Aβ aggregation and are highly potent as anti-amyloidogenic drugs for therapeutic treatment of AD. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Vitamin K1 versus vitamin K3 for prevention of subclinical vitamin deficiency: a randomized controlled trial.

    Science.gov (United States)

    Chawla, D; Deorari, A K; Saxena, R; Paul, V K; Agarwal, R; Biswas, A; Meena, A

    2007-11-01

    To compare efficacy of intramuscular phytomenadione (fat soluble vitamin K or vitamin K1) with menadione (water soluble vitamin K or vitamin K3) in prevention of subclinical vitamin K deficiency. A doubleblind randomized controlled trial. Tertiary care hospital. Healthy term neonates were randomized to receive 1 mg of either phytomenadione (Group I, n = 85) or menadione (Group II, n = 85) intramuscularly within 2 hours of birth. PIVKA-II, a sensitive and specific marker of vitamin K deficiency was measured by ELISA method (Diagnostica Stago, France). Plasma level > 2 ng/mL was labeled as detectable PIVKA-II. Birth weight (2914 +/- 318 vs 2958 +/- 312 g), gestation (38.4 +/- 1.2 vs 38.4 +/- 1.0 wk) and other baseline variables were comparable between the two groups. 48.2% (41/85) neonates in Group I and 44.7%(38/85) neonates in Group II had detectable PIVKAII levels ([Relative Risk (95% confidence interval): 1.1 (0.8-1.5); P = 0.76]). Median PIVKA-II levels in Group I and Group II were 1.99 ng/mL and 1.97 ng/mL respectively (P = 0.26). At 72 +/- 12 h of age, mean packed cell volume and mean serum bilirubin levels were comparable in the two groups. Comparable PIVKAII detection rate and PIVKAII levels in neonates receiving phytomenadione or menadione indicate their similar efficacy in prevention of vitamin K deficiency. However, high PIVKAII detection rate observed with both preparations indicates recent vitamin K deficiency and may be due to either inadequate dose of vitamin K or persistence of PIVKAII of fetal origin.

  2. Binding selectivity of vitamin K3 based chemosensors towards nickel(II) and copper(II) metal ions

    Science.gov (United States)

    Patil, Amit; Lande, Dipali N.; Nalkar, Archana; Gejji, Shridhar P.; Chakrovorty, Debamitra; Gonnade, Rajesh; Moniz, Tânia; Rangel, Maria; Pereira, Eulália; Salunke-Gawali, Sunita

    2017-09-01

    The vitamin K3 derivatives 2-methyl-3-[(pyridin-2-ylmethyl)-amino]-1,4-naphthoquinone (M-1), 2-methyl-3-[(pyridin-2-ylethyl)-amino]-1,4-naphthoquinone (M-2), 2-methyl-3-((2-(thiophen-2-yl)methyl)amino)naphthalene-1,4-dione (M-3) and 2-methyl-3-((2-(thiophen-2-yl)ethyl)amino)naphthalene-1,4-dione (M-4) have been synthesized, characterized and studied for their chemosensor abilities towards transition metal ions. Crystal structures of M-1 to M-4 revealed a variety of Nsbnd H⋯O, Csbnd H⋯O, Csbnd H⋯π and π⋯π interactions. Minor variations in such interactions by chemical stimuli such as metal ions, results in change in color that can be visualized by naked eyes. It has been shown that electronic structure and 1H NMR, vibrational as well as electronic spectra from the density functional theory agree well with the experiments. The metal ion binding in ethanol, ethanol-water and in mild base triethylamine brings forth recognizing ability of M-1 toward Ni2+ whereas M-2 exhibits large sensing ability for Cu2+ ion. Interestingly M-1 display varying metal ion binding specificity in different solvents with the association constant in ethanol being 11,786 M-1 for Ni2+ compared to 9462 M-1 for the Cu2+. A reversal in preferential binding of M-2 with the respective association constants being 4190 M-1 and 6370 M-1 is discernible.

  3. An analysis of the relationship between K--5 elementary school teachers' perceptions of principal instructional leadership and their science teaching efficacy

    Science.gov (United States)

    Clark, Ian

    The purpose of this study is to analyze the relationship between K-5 elementary school teachers' perceptions of principal instructional leadership and their science teaching efficacy. The influence of background variables on both leadership and efficacy is also analyzed. A sequential mixed methods approach was used in this study. The survey sample was comprised of teachers in the elementary divisions of schools from the nine international school regional associations. Teacher participation was obtained through an email containing an online survey link. Following the analysis of survey responses (N=356), in-depth interviews (N=17) were conducted. Reliability for the instructional leadership scale was found to be .94 (coefficient alpha) and .69 for the personal science teaching efficacy (PSTE) scale. The results show a significant correlation between elementary school teachers' perceptions of principal instructional leadership and their PSTE levels, with the most significant correlation that between the study of a science-related major or minor at college and higher PSTE scores. Strong correlations were also found between PSTE levels and having principals who discussed goals at faculty meetings, participated in science curricular review, supported recognition of student progress, encouraged new skills and concepts, discussed student progress with faculty, and used assessments to see science progress towards easily understood goals. PSTE levels were also higher in schools where principals had grade or school level science coordinators in place and where they supported the use of science kits.

  4. Subcutaneous injection of thallium-201 chloride and gallium-67 citrate at acupuncture point K-3; An animal experiment and human-being study

    Energy Technology Data Exchange (ETDEWEB)

    Johg, Shiang-Bin; Wu, Chung-Chieng; Chen, Ming-Feng; Wu, Sheng-Nan (Kaohsiung Medical Coll., Taiwan (China))

    1992-09-01

    Subcutaneous (SC) injection of [sup 99m]Tc pertechnetate ([sup 99m]Tc) at acupuncture points K-3 is a new method of lower-limb radionuclide venography. To investigate the mechanism of absorption of [sup 99m]Tc from SC injected sites into vascular system, various radioisotopes such as [sup 201]Tl chloride ([sup 201]Tl) and [sup 67]Ga citrate ([sup 67]Ga) were SC injected at K-3 points in animal and human-beings experiments. It was found that [sup 99m]Tc and [sup 201]Tl were absorbed rapidly from K-3 points through venous system and into whole body soft tissue. However, [sup 67]Ga with a larger effective ionic radius than [sup 201]Tl was not absorbed throughout the observation of 5 minutes. Furthermore, intravenous administration of digitalis, a Na[sup +]-K[sup +] pump blocker, did not inhibit the absorption of [sup 99m]Tc and [sup 201]Tl after SC injection at K-3 points. These results suggest that absorption of radionuclides on SC injection at K-3 points is mainly through the passive pathway of diffusion rather than the active transport, and the effective ionic radius may be a major factor influencing the absorption rate of the radionuclides. (author).

  5. Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro.

    Science.gov (United States)

    Oztopçu, Pinar; Kabadere, Selda; Mercangoz, Ayşe; Uyar, Ruhi

    2004-09-01

    Glioblastoma multiforme is characterized as highly invasive and rapidly growing astrocytomas, and scientists have sought for efficient treatment against malignant gliomas for a long time. Therefore, we compared the respond of rat glioma (C6) and glioblastoma multiforme cells derived from two patients to vitamins K1, K2 and K3. The cells were exposed to 100, 250, 500, 750 and 1000 microM of vitamins K1 and K2, and 1, 10, 25, 50, 75 and 100 microM of vitamin K3 for 24 hours in an incubator atmosphere of 5% CO2, 37 degrees C and 100% humidity. Cell viability was estimated by MTT assay. Vitamin K1 showed no growth effect on all the glioma cells examined. Vitamin K2 did not cause any change in number of C6, however induced growth inhibition in a dose-dependent manner on glioblastoma multiforme. The IC50 values of vitamin K2 were 960 microM and 970 microM for glioblastoma multiforme, respectively. Vitamin K3 had also growth inhibitory effect in a dose-dependent manner on both C6 and glioblastoma multiforme. The IC50 values were 41 microM, 24 microM and 23 microM for vitamin K3, respectively. We concluded that vitamin K3 is more effective than vitamin K2 for inhibition of cancer cell growth, and might have an alternative value as an anticancer drug against glioblastoma multiforme.

  6. High resolution beam line of the U400M cyclotron and RIB accumulation and cooling in the K4 storage ring

    International Nuclear Information System (INIS)

    Rodin, A.M.; Sidorchuk, S.I.; Stepantsov, S.V.

    1996-01-01

    The high resolution beam line ACCULINNA put into operation on a primary beam line of the JINR U400M cyclotron is discussed in the framework of the TREBLE project. The capability of the beam line for producing radioactive ion beams is demonstrated by means of nuclear fragmentation of the primary 14 N beam, with the energy of 51 MeV · A, on the 170 mg/cm 2 carbon target. Characteristics of the obtained 6 He, 8 He and 8 B radioactive beams are presented. A scheme of accumulation and cooling on the orbit of the storage ring K4 is proposed for a low intensity radioactive beam obtained from this beam line. 8 refs., 6 figs., 1 tab

  7. Glucose-independent persistence of PAI-1 gene expression and H3K4 tri-methylation in type 1 diabetic mouse endothelium: implication in metabolic memory.

    Science.gov (United States)

    Takizawa, Fumihiko; Mizutani, Shuki; Ogawa, Yoshihiro; Sawada, Naoki

    2013-03-29

    Clinical trials with type 1 and type 2 diabetes have identified a phenomenon known as "metabolic memory" in which previous periods of hyperglycemia result in the long-lasting deleterious impact on cardiovascular events. Emerging evidence shows that transient hyperglycemic exposure of human endothelial cells induces histone 3 lysine 4 mono-methylation (H3K4me1) on the promoter and persistent mRNA expression of RelA and IL-8 genes, suggesting that epigenetic histone modification and chromatin structure remodeling is a key event underlying metabolic memory. This burgeoning hypothesis, however, critically remains to be tested for relevance in the disease process of diabetes in vivo, and for broader applicability to an array of genes involved in endothelial dysfunction. To address this, we used type 1 diabetes mouse model induced by streptozocin to be hyperglycemic for 8 weeks, and isolated endothelial cells that were used either freshly after isolation or after 2 to 3-week cell culture in normoglycemic conditions. mRNA expression profiling in diabetic mouse endothelial cells revealed significant and persistent up-regulation of Serpine1 encoding PAI-1, the hypo-fibrinolytic mediator leading to thrombotic diseases in diabetes, along with Rock2, Fn1 and Ccl2, whereas only Serpine 1 was persistently elevated in high glucose-treated mouse endothelial cells. Chromosome immunoprecipitation assay in type 1 diabetic mouse endothelial cells showed predominant enrichment of H3K4 tri-methylation on Serpine1 promoter, suggesting a unique epigenetic regulation in diabetic mice as opposed to high glucose-treated human ECs. Our study demonstrates the importance of combining in vivo models of diabetes with high glucose-treated cell culture to better assess the epigenetic mechanisms relevant to disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. K-3 vitamininin sıçan glioma (C6) ve insan glioblastomamultiforme hücre çoğalmasına invitro etkileri

    OpenAIRE

    Öztopçu, Pınar; Kabadere, Selda; Uyar, Ruhi

    2005-01-01

    Amaç: Glioblastoma multiforme beyin dokusu içerisine hızla yayılan ve onu yıkıma ugratan, sinir sisteminde görülme sıklıgı yüksek oldukça tehlikeli bir tümör çesididir. K-3 vitamininin çesitli kanser hücre dizileri üzerinde hücre çogalmasını baskılayıcı etkisi oldugu bildirilmektedir. Çalısmamızda K-3 vitamininin, sıçan glioma (C6) ve insan glioblastoma multiforme hücrelerinin çogalması üzerindeki baskılayıcı etkilerini karsılastırarak belirlemeyi amaçladık. Yöntem: K-3 vitamin...

  9. Determination of hyperin in seed of Cuscuta chinensis Lam. by enhanced chemiluminescence of CdTe quantum dots on calcein/K3Fe(CN)6 system.

    Science.gov (United States)

    Kang, Jing; Li, Xuwen; Geng, Jiayang; Han, Lu; Tang, Jieli; Jin, Yongri; Zhang, Yihua

    2012-10-15

    In this paper, 3-mercaptocarboxylic acid (MPA) modified CdTe quantum dots (QDs) were used as sensitizers, to enhance the chemiluminescence (CL) of the calcein/K(3)Fe(CN)(6) system. A new CL system of CdTe/calcein/K(3)Fe(CN)(6) was developed. The effects of reactant concentrations and the particle sizes of CdTe QDs on the CL emission were investigated in detail. The possible enhancement mechanism of the CL was also further investigated based on the photoluminescence (PL) and CL spectra. Polyphenols such as chlorogenic acid, quercetin, hyperin, catechin and kaempferol, were observed to inhibit the CL signal of the CdTe/calcein/K(3)Fe(CN)(6) system and determined by the proposed method. The proposed method was applied to the determination of hyperin in seed of Cuscuta chinensis Lam. and the results obtained were satisfactory. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity.

    Science.gov (United States)

    Acharya, Bipul R; Choudhury, Diptiman; Das, Amlan; Chakrabarti, Gopal

    2009-07-28

    Vitamin K3 (2-methyl-1,4-naphthoquinone), also known as menadione, is the synthetic precursor of all the naturally occurring vitamin K in the body. Vitamin K is necessary for the production of prothrombin and five other blood-clotting factors in humans. We have examined the effects of menadione on cellular microtubules ex vivo as well as its binding with purified tubulin and microtubules in vitro. Cell viability experiments using human cervical epithelial cancer cells (HeLa) and human oral epithelial cancer cells (KB) indicated that the IC(50) values for menadione are 25.6 +/- 0.6 and 64.3 +/- 0.36 microM, respectively, in those cells. Mendione arrests HeLa cells in mitosis. Immunofluorescence studies using an anti-alpha-tubulin antibody showed a significant irreversible depolymeriztion of the interphase microtubule network and spindle microtubule in a dose-dependent manner. In vitro polymerization of purified tubulin into microtubules is inhibited by menadione with an IC(50) value of 47 +/- 0.65 microM. The binding of menadione with tubulin was studied using menadione fluorescence and intrinsic tryptophan fluorescence of tubulin. Binding of menadione to tubulin is slow, taking 35 min for equilibration at 25 degrees C. The association reaction kinetics is biphasic in nature, and the association rate constants for fast and slow phases are 189.12 +/- 17 and 32.44 +/- 21 M(-1) s(-1) at 25 degrees C, respectively. The stoichiometry of menadione binding to tubulin is 1:1 (molar ratio) with a dissociation constant from 2.44 +/- 0.34 to 3.65 +/- 0.25 microM at 25 degrees C. Menadione competes for the colchicine binding site with a K(i) of 2.5 muM as determined from a modified Dixon plot. The obtained data suggested that menadione binds at the colchicine binding site to tubulin. Thus, we can conclude one novel mechanism of inhibition of cancer cell proliferation by menadione is through tubulin binding.

  11. High performance liquid chromatographic-mass spectrometric assay for the quantitation of BMS-204352 in dog K(3)EDTA plasma.

    Science.gov (United States)

    Yao, Ming; Mantha, Subbarao; Shah, Vinod R; Vachharajani, Nimish N; Arnold, Mark E; Pursley, Janice M; Srinivas, Nuggehally R

    2002-05-01

    A high performance liquid chromatographic-mass spectrometric (LC/MS) assay was developed and validated for the determination of BMS-204352 in dog K(3)EDTA plasma. A 0.5 mL aliquot of control plasma was spiked with BMS-204352 and internal standard (IS) and buffered with 1 mL of 5 mM ammonium acetate. The mixture was then extracted with 3 mL of toluene. After separation and evaporation of the organic phase to dryness using nitrogen at 40 degrees C, the residue was reconstituted in the mobile phase and 25 microL of the sample were injected onto a Hypersil C(18) column (2 x 50 mm; 3 microm) at a flow rate of 0.5 mL/min. The mobile phase was consisted of two solvent mixtures (A and B). Solvent A was composed of 5 mM ammonium acetate and 0.1% triethylamine in 75:25 v/v water:methanol, pH adjusted to 5.5 with glacial acetic acid, and solvent B was 5 mM ammonium acetate in methanol. A linear gradient system was used to elute the analytes. The mass spectrometer was programmed to admit the de-protonated molecules at m/z 352.7 (IS) and m/z 357.9 (BMS-204352). Standard curves of BMS-204352 were linear (r(2) > or = 0.998) over the concentration range of 0.5-1000 ng/mL. The mean predicted quality control (QC) concentrations deviated less than 5.1% from the corresponding nominal values (ie 4, 80, 400 and 2000 ng/mL); the within- and between-assay precision of the assay were within 5.5% relative standard deviation. Stability of BMS-204352 was confirmed after at least three freeze/thaw cycles and BMS-204532 was stable in dog plasma when stored frozen at or below -20 degrees C for at least 16 weeks in spiked QC samples and for at least 4 1/2 weeks for in vivo study samples. BMS-204352 and IS were stable in the injection solvent at room temperature for at least 24 h. The assay was applied to delineate the pharmacokinetic disposition of BMS-204352 in dogs following a single intravenous dose administration. In conclusion, the assay is accurate, precise, specific, sensitive and

  12. CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chun-Ru [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Liao, Wei-Siang [Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Wu, Ya-Hui [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Murugan, Kaliyappan [Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan (China); Chen, Chinpiao, E-mail: chinpiao@mail.ndhu.edu.tw [Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan (China); Chao, Jui-I, E-mail: jichao@faculty.nctu.edu.tw [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 30068, Taiwan (China)

    2013-12-15

    Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer. - Highlights: • CR108 is more effective on the cell death than other vitamin K3 derivatives. • CR108 induces apoptosis and tumor inhibition by ROS and mitochondrial dysfunction. • CR108 induces apoptosis by p38 kinase activation and survivin inhibition. • CR108 is a potent vitamin K3 analog that can develop for breast cancer therapy.

  13. CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction

    International Nuclear Information System (INIS)

    Yang, Chun-Ru; Liao, Wei-Siang; Wu, Ya-Hui; Murugan, Kaliyappan; Chen, Chinpiao; Chao, Jui-I

    2013-01-01

    Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer. - Highlights: • CR108 is more effective on the cell death than other vitamin K3 derivatives. • CR108 induces apoptosis and tumor inhibition by ROS and mitochondrial dysfunction. • CR108 induces apoptosis by p38 kinase activation and survivin inhibition. • CR108 is a potent vitamin K3 analog that can develop for breast cancer therapy

  14. Efecto de la suplementación de vitamina K3 sobre el comportamiento productivo y calidad ósea de pollos de engorde

    OpenAIRE

    Duarte, CRA; Bratti, FC; Murakami, AE; Fernandes, JIM; Ospina-Rojas, IC; Furlan, AC

    2014-01-01

    La vitamina K participa en los procesos de coagulación sanguínea y también tiene un importante papel en la formación de los huesos. Así, el objetivo de este estudio fue evaluar la suplementación de diferentes niveles de vitamina K3 sobre el comportamiento productivo y indicadores óseos de pollos de engorde. Se utilizaron 1.500 pollos de engorde, distribuidos en un diseño experimental completamente al azar. Los tratamientos consistieron en una dieta control conteniendo 1,6 mg de vitamina K3/kg...

  15. The Combination of Vitamin K3 and Vitamin C Has Synergic Activity against Forms of Trypanosoma cruzi through a Redox Imbalance Process.

    Science.gov (United States)

    Cristina Desoti, Vânia; Lazarin-Bidóia, Danielle; Martins Ribeiro, Fabianne; Cardoso Martins, Solange; da Silva Rodrigues, Jean Henrique; Ueda-Nakamura, Tania; Vataru Nakamura, Celso; Farias Ximenes, Valdecir; de Oliveira Silva, Sueli

    2015-01-01

    Chagas' disease is an infection that is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. Because of severe side effects and variable efficacy, the current treatments for Chagas' disease are unsatisfactory, making the search for new chemotherapeutic agents essential. Previous studies have reported various biological activities of naphthoquinones, such as the trypanocidal and antitumor activity of vitamin K3. The combination of this vitamin with vitamin C exerted better effects against various cancer cells than when used alone. These effects have been attributed to an increase in reactive oxygen species generation. In the present study, we evaluated the activity of vitamin K3 and vitamin C, alone and in combination, against T. cruzi. The vitamin K3 + vitamin C combination exerted synergistic effects against three forms of T. cruzi, leading to morphological, ultrastructural, and functional changes by producing reactive species, decreasing reduced thiol groups, altering the cell cycle, causing lipid peroxidation, and forming autophagic vacuoles. Our hypothesis is that the vitamin K3 + vitamin C combination induces oxidative imbalance in T. cruzi, probably started by a redox cycling process that leads to parasite cell death.

  16. Vitamin K3 induces antiproliferative effect in cervical epithelial cells transformed by HPV 16 (SiHa cells) through the increase in reactive oxygen species production.

    Science.gov (United States)

    de Carvalho Scharf Santana, Natália; Lima, Natália Alves; Desoti, Vânia Cristina; Bidóia, Danielle Lazarin; de Souza Bonfim Mendonça, Patrícia; Ratti, Bianca Altrão; Nakamura, Tânia Ueda; Nakamura, Celso Vataru; Consolaro, Marcia Edilaine Lopes; Ximenes, Valdecir Farias; de Oliveira Silva, Sueli

    2016-10-01

    Cervical cancer is characterized as an important public health problem. According to latest estimates, cancer of the cervix is the fourth most common cancer among women. Due to its high prevalence, the search for new and efficient drugs to treat this infection is continuous. The progression of HPV-associated cervical cancer involves the expression of two viral proteins, E6 and E7, which are rapidly degraded by the ubiquitin-proteasome system through the increase in reactive oxygen species generation. Vitamins are essential to human substances, participate in the regulation of metabolism, and facilitate the process of energy transfer. Some early studies have indicated that vitamin K3 exerts antitumor activity by inducing cell death by apoptosis through an increase in the generation of reactive oxygen species. Thus, we evaluated the antiproliferative effect and a likely mechanism of action of vitamin K3 against cervical epithelial cells transformed by HPV 16 (SiHa cells) assessing the production of total ROS, the mitochondrial membrane potential, the cell morphology, the cell volume, and the cell membrane integrity. Our results show that vitamin K3 induces an increase in ROS production in SiHa cells, triggering biochemical and morphological events, such as depolarization of mitochondrial membrane potential and decreasing cell volume. Our data showed that vitamin K3 generates an oxidative imbalance in SiHa cells, leading to mechanisms that induce cell death by apoptosis.

  17. The Combination of Vitamin K3 and Vitamin C Has Synergic Activity against Forms of Trypanosoma cruzi through a Redox Imbalance Process.

    Directory of Open Access Journals (Sweden)

    Vânia Cristina Desoti

    Full Text Available Chagas' disease is an infection that is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. Because of severe side effects and variable efficacy, the current treatments for Chagas' disease are unsatisfactory, making the search for new chemotherapeutic agents essential. Previous studies have reported various biological activities of naphthoquinones, such as the trypanocidal and antitumor activity of vitamin K3. The combination of this vitamin with vitamin C exerted better effects against various cancer cells than when used alone. These effects have been attributed to an increase in reactive oxygen species generation. In the present study, we evaluated the activity of vitamin K3 and vitamin C, alone and in combination, against T. cruzi. The vitamin K3 + vitamin C combination exerted synergistic effects against three forms of T. cruzi, leading to morphological, ultrastructural, and functional changes by producing reactive species, decreasing reduced thiol groups, altering the cell cycle, causing lipid peroxidation, and forming autophagic vacuoles. Our hypothesis is that the vitamin K3 + vitamin C combination induces oxidative imbalance in T. cruzi, probably started by a redox cycling process that leads to parasite cell death.

  18. [Effects of vitamin K3 on the contractile activity of the colonic smooth muscles of guinea pig through the calcium activated potassium channel].

    Science.gov (United States)

    Li, Jun; Luo, He-sheng; He, Xiao-gu

    2006-07-25

    To study the mechanism of relaxation of gastrointestinal smooth muscles by vitamin K(3). Stripes of proximal colon were collected from guinea pigs. Suspension of single cells was created from these stripes. TD-112S transducer was used to measure the contraction of the stripes stimulated by vitamin K(3) of the concentrations of 40, 100, 400, and 800 micromol/L respectively. The Ca(2+)-activated K(+) current [IK(Ca)] of the cytomembrane of the colon smooth muscle was recorded with an EPC 10 amplifier under conventional whole cell patterns. The contraction frequencies of the muscle stripes stimulated by vitamin K(3) of the concentrations of 40, 100, 400, and 800 micromol/L were 79% +/- 4%, 58% +/- 5%, 33% +/- 4%, and 12% +/- 3% respectively of that of the control group (all P Vitamin K(3) inhibits the contractile activity of the colonic muscle stripes and increases the IK(Ca) of single myocytes concentration-dependently. The mechanism is activation of the Ca(2+)-activated K(+) channel, thus promoting the potassium efflux.

  19. Comparative evaluation of debris extruded apically by using, Protaper retreatment file, K3 file and H-file with solvent in endodontic retreatment

    Directory of Open Access Journals (Sweden)

    Chetna Arora

    2012-01-01

    Full Text Available Aim: The aim of this study was to evaluate the apical extrusion of debris comparing 2 engine driven systems and hand instrumentation technique during root canal retreatment. Materials and Methods: Forty five human permanent mandibular premolars were prepared using the step-back technique, obturated with gutta-percha/zinc oxide eugenol sealer and cold lateral condensation technique. The teeth were divided into three groups: Group A: Protaper retreatment file, Group B: K3, file Group C: H-file with tetrachloroethylene. All the canals were irrigated with 20ml distilled water during instrumentation. Debris extruded along with the irrigating solution during retreatment procedure was carefully collected in preweighed Eppendorf tubes. The tubes were stored in an incubator for 5 days, placed in a desiccator and then re-weighed. Weight of dry debris was calculated by subtracting the weight of the tube before instrumentation and from the weight of the tube after instrumentation. Data was analyzed using Two Way ANOVA and Post Hoc test. Results : There was statistically significant difference in the apical extrusion of debris between hand instrumentation and protaper retreatment file and K3 file. The amount of extruded debris caused by protaper retreatment file and K3 file instrumentation technique was not statistically significant. All the three instrumentation techniques produced apically extruded debris and irrigant. Conclusion: The best way to minimize the extrusion of debris is by adapting crown down technique therefore the use of rotary technique (Protaper retreatment file, K3 file is recommended.

  20. The CO2 Abundance in Comets C2012 K1 (PanSTARRS), C2012 K5 (LINEAR), and 290P Jager as Measured with Spitzer

    Science.gov (United States)

    McKay, Adam J.; Kelley, Michael S.P.; Cochran, Anita L.; Bodewits, Dennis; DiSanti, Michael A.; Dello Russo, Neil; Lisse, Carey M.

    2015-01-01

    Carbon dioxide is one of the most abundant ices present in comets and is therefore important for understanding cometary composition and activity. We present analysis of observations of CO2 and [O I] emission in three comets to measure the CO2 abundance and evaluate the possibility of employing observations of [O I] emission in comets as a proxy for CO2. We obtained NIR imaging sensitive to CO2 of comets C/2012 K1 (PanSTARRS), C/2012 K5 (LINEAR), and 290P/Jager with the IRAC instrument on Spitzer. We acquired observations of [O I] emission in these comets with the ARCES echelle spectrometer mounted on the 3.5-m telescope at Apache Point Observatory and observations of OH with the Swift observatory (PanSTARRS) and with Keck HIRES (Jager). The CO2/H2O ratios derived from the Spitzer images are 12.6 +/- 1.3% (PanSTARRS), 28.9 +/- 3.6% (LINEAR), and 31.3 +/- 4.2% (Jager). These abundances are derived under the assumption that contamination from CO emission is negligible. The CO2 abundance for PanSTARRS is close to the average abundance measured in comets at similar heliocentric distance to date, while the abundances measured for LINEAR and Jager are significantly larger than the average abundance. From the coma morphology observed in PanSTARRS and the assumed gas expansion velocity, we derive a rotation period for the nucleus of about 9.2 h. Comparison of H2O production rates derived from ARCES and Swift data, as well as other observations, suggest the possibility of sublimation from icy grains in the inner coma. We evaluate the possibility that the [O I] emission can be employed as a proxy for CO2 by comparing CO2/H2O ratios inferred from the [O I] lines to those measured directly by Spitzer. We find that for PanSTARRS we can reproduce the observed CO2 abundance to an accuracy of approximately 20%. For LINEAR and Jager, we were only able to obtain upper limits on the CO2 abundance inferred from the [O I] lines. These upper limits are consistent with the CO2 abundances

  1. Thermoluminescence and glow curves analysis of γ-exposed Eu3+ doped K3Y(PO4)2 nanophosphors

    International Nuclear Information System (INIS)

    Gupta, Palvi; Bedyal, A.K.; Kumar, Vinay; Singh, Vivek K.; Khajuria, Y.; Ntwaeaborwa, O.M.; Swart, H.C.

    2016-01-01

    Highlights: • First time, a detailed comparative study of the glow curves and kinetic parameters was made on K 3 Y(PO 4 ) 2 nanophosphor. • Combustion method was employed to synthesize the Eu 3+ doped K 3 Y(PO 4 ) 2 nanophosphor. • The nanophosphor exhibited sublinear response suggesting that it is suitable for TL dosimetry. - Abstract: Eu 3+ doped K 3 Y(PO 4 ) 2 nanophosphor was synthesized by combustion synthesis using urea as a fuel. The crystal structure and particle morphology of the nanophosphor were investigated by using X-ray diffraction and transmission electron microscopy, respectively. A Thermoluminescence (TL) study was carried out after exposing the samples to gamma radiation. The TL glow curves exhibited a prominent peak at 407 K and a small hump at 478 K. The intensity of the peaks increased with the increase in the dose of the gamma rays (0.01–5 kGy). The K 3 Y(PO 4 ) 2 : Eu 3+ (2.5 mol%) nanophosphor exhibited sublinear TL response to γ-radiation over a wide range of gamma doses (0.01–5 kGy). The TLanal program was used to analyze the glow curves of the K 3 Y(PO 4 ) 2 nanophosphor at different doses (0.2–5 kGy) and different heating rates (3–10 K/s). A comparative study was done for kinetic trapping parameters that were determined by the peak shape methods of Chen, Grossweiner and Lushchik. The frequency factors (s) for each glow peak were also calculated. The values of the activation energy (E) obtained by the TLanal program were in good agreement with those obtained by the peak shape methods. The effect of different amount of doses and different heating rates are discussed.

  2. Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function

    Directory of Open Access Journals (Sweden)

    Brendan E. Russ

    2017-12-01

    Full Text Available Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs, we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+ chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation.

  3. The MLL1-H3K4me3 Axis-Mediated PD-L1 Expression and Pancreatic Cancer Immune Evasion.

    Science.gov (United States)

    Lu, Chunwan; Paschall, Amy V; Shi, Huidong; Savage, Natasha; Waller, Jennifer L; Sabbatini, Maria E; Oberlies, Nicholas H; Pearce, Cedric; Liu, Kebin

    2017-01-01

    Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mechanism of PD-L1 expression regulation in the context of pancreatic cancer immune evasion. Pancreatic cancer mouse models and human specimens were used to determine PD-L1 and PD-1 expression and cancer immune evasion. Histone methyltransferase inhibitors, RNAi, and overexpression were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation. All statistical tests were two-sided. PD-L1 is expressed in 60% to 90% of tumor cells in human pancreatic carcinomas and in nine of 10 human pancreatic cancer cell lines. PD-1 is expressed in 51.2% to 52.1% of pancreatic tumor-infiltrating cytotoxic T lymphocytes (CTLs). Tumors grow statistically significantly faster in FasL-deficient mice than in wild-type mice (P = .03-.001) and when CTLs are neutralized (P = .03-evasion. Targeting the MLL1-H3K4me3 axis is an effective approach to enhance the efficacy of checkpoint immunotherapy against pancreatic cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Report to the CCT on COOMET comparison COOMET.T-K3.1 (previously COOMET.T-S1): Key regional comparison of the national standards of temperature in the range from the triple point of water to the freezing point of zinc

    Science.gov (United States)

    Pokhodun, A. I.

    2010-01-01

    In the framework of the CIPM MRA, a first COOMET comparison "Comparison of the ITS-90 realizations in the range from 0.01 °C to 429.7485 °C (from the triple point of water to the freezing point of zinc)", registered in the KCDB under the identifier "COOMET.T-K3", was carried out in 2005-2007. Four national metrology institutes took part in this comparison: VNIIM (Russian Federation), SMU (Slovakia), BelGIM (Republic of Belarus) and NSC IM (Ukraine), and two of them (VNIIM and SMU) ensured the linkage with key comparisons CCT-K3 and CCT-K4, in order to disseminate the metrological equivalence to the measurement standards of NSC IM and BelGIM. NSC IM, however, had to withdraw its results, and at the meeting of Technical Committee T-10 of COOMET it was decided to carry out a supplementary bilateral comparison between VNIIM and the NSC IM for realization of the ITS-90 in the same range of temperature. This was registered in the KCDB under the identifier COOMET.T-S1 and measurements were performed in 2008-2009. From the results presented in this report, it is possible to draw the conclusion that the COOMET supplementary comparison COOMET.T-S1 demonstrates the CMC uncertainties claimed by the NSC IM for the melting point of gallium 0.236 mK (k = 2), and the freezing points of indium 1.040 mK (k = 2), tin 0.858 mK (k = 2) and zinc 0.944 mK (k = 2). In September 2012 the Working Group on key Comparisons (WG 7) of the CCT upgraded this comparison to a COOMET key comparison of the 'CCT-K3' type. It is now identified as COOMET.T-K3.1. In April 2013 this report was superseded by item 03006 in the Technical Supplement of 2013. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  5. MLL5, a trithorax homolog, indirectly regulates H3K4 methylation, represses cyclin A2 expression, and promotes myogenic differentiation

    Science.gov (United States)

    Sebastian, Soji; Sreenivas, Prethish; Sambasivan, Ramkumar; Cheedipudi, Sirisha; Kandalla, Prashanth; Pavlath, Grace K.; Dhawan, Jyotsna

    2009-01-01

    Most cells in adult tissues are nondividing. In skeletal muscle, differentiated myofibers have exited the cell cycle permanently, whereas satellite stem cells withdraw transiently, returning to active proliferation to repair damaged myofibers. We have examined the epigenetic mechanisms operating in conditional quiescence by analyzing the function of a predicted chromatin regulator mixed lineage leukemia 5 (MLL5) in a culture model of reversible arrest. MLL5 is induced in quiescent myoblasts and regulates both the cell cycle and differentiation via a hierarchy of chromatin and transcriptional regulators. Knocking down MLL5 delays entry of quiescent myoblasts into S phase, but hastens S-phase completion. Cyclin A2 (CycA) mRNA is no longer restricted to S phase, but is induced throughout G0/G1, with activation of the cell cycle regulated element (CCRE) in the CycA promoter. Overexpressed MLL5 physically associates with the CCRE and impairs its activity. MLL5 also regulates CycA indirectly: Cux, an activator of CycA promoter and S phase is induced in RNAi cells, and Brm/Brg1, CCRE-binding repressors that promote differentiation are repressed. In knockdown cells, H3K4 methylation at the CCRE is reduced, reflecting quantitative global changes in methylation. MLL5 appears to lack intrinsic histone methyl transferase activity, but regulates expression of histone-modifying enzymes LSD1 and SET7/9, suggesting an indirect mechanism. Finally, expression of muscle regulators Pax7, Myf5, and myogenin is impaired in MLL5 knockdown cells, which are profoundly differentiation defective. Collectively, our results suggest that MLL5 plays an integral role in novel chromatin regulatory mechanisms that suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells. PMID:19264965

  6. KDM1A triggers androgen-induced miRNA transcription via H3K4me2 demethylation and DNA oxidation.

    Science.gov (United States)

    Yang, Shu; Zhang, Jiyuan; Zhang, Yalong; Wan, Xuechao; Zhang, Congzhe; Huang, Xiaohui; Huang, Wenhua; Pu, Honglei; Pei, Chaohan; Wu, Hai; Huang, Yan; Huang, Shengdong; Li, Yao

    2015-06-15

    Androgen receptor (AR) is a ligand dependent transcription factor that regulates the transcription of target genes. AR activity is closely involved in the maintenance and progression of prostate cancer. After the binding with androgen, AR moves into nucleus and binds to DNA sequence containing androgen response elements (ARE). Flavin-dependent monoamine oxidase KDM1A is necessary for AR driven transcription while the mechanism remains unclear. The association between androgen-dependent transcription and oxidation was tested through pharmaceutical inhibitions and siRNA knockdown of DNA oxidation repair components in prostate cancer cells. The recruitment of involved proteins and the histone methylation dynamics on ARE region was explored by chromatin immunoprecipitation (ChIP). Oxidation inhibition reduced AR dependent expression of KLK3, TMPRSS2, hsa-miR-125b2, and hsa-miR-133b. And such reduction could be restored by H2 O2 treatment. KDM1A recruitment and H3K4me2 demethylation on ARE regions, which produce H2 O2 , are associated with AR targets transcription. AR targets transcription and coupled oxidation recruit 8-oxoguanine-DNA glycosylase (OGG1) and the nuclease APEX1 to ARE regions. Such recruitment depends on KDM1A, and is necessary for AR targets transcription. Our work underlined the importance of histone demethylation and DNA oxidation/repairing machinery in androgen-dependent transcription. The present finds have implications for research into new druggable targets for prostate cancer relying on the cascade of AR activity regulation. © 2015 Wiley Periodicals, Inc.

  7. Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(DJ Recombination

    Directory of Open Access Journals (Sweden)

    Louise S. Matheson

    2017-11-01

    Full Text Available V(DJ recombination is essential for the generation of diverse antigen receptor (AgR repertoires. In B cells, immunoglobulin kappa (Igκ light chain recombination follows immunoglobulin heavy chain (Igh recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS of VH genes are highly predictive of recombination in mouse pro-B cells. It is unknown whether local chromatin states contribute to Vκ gene choice during Igκ recombination. Here we adapt VDJ-seq to profile the Igκ VκJκ repertoire and present a comprehensive readout in mouse pre-B cells, revealing highly variable Vκ gene usage. Integration with genome-wide datasets for histone modifications, DNase hypersensitivity, transcription factor binding and germline transcription identified PU.1 binding at the RSS, which was unimportant for Igh, as highly predictive of whether a Vκ gene will recombine or not, suggesting that it plays a binary, all-or-nothing role, priming genes for recombination. Thereafter, the frequency with which these genes recombine was shaped both by the presence and level of enrichment of several other chromatin features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to the Igh locus, the chromatin landscape of the promoter, as well as of the RSS, contributes to Vκ gene recombination. Thus, multiple facets of local chromatin features explain much of the variation in Vκ gene usage. Together, these findings reveal shared and divergent roles for epigenetic features and transcription factors in AgR V(DJ recombination and provide avenues for further investigation of chromatin signatures that may underpin V(DJ-mediated chromosomal translocations.

  8. X-ray photoelectron spectroscopy as detection tool for coordinated or uncoordinated fluorine atoms demonstrated on fluoride systems NaF, K2TaF7, K3TaF8, K2ZrF6, Na7Zr6F31 and K3ZrF7

    Science.gov (United States)

    Boča, Miroslav; Barborík, Peter; Mičušík, Matej; Omastová, Mária

    2012-07-01

    While systems K3TaF8 and K3ZrF7 were prepared by modified molten salt method modified wet pathway was used for reproducible preparation of Na7Zr6F31. Its congruently melting character was demonstrated on simultaneous TG/DSC measurements and XRD patterns. X-ray photoelectron spectroscopy was applied for identification of differently bonded fluorine atoms in series of compounds NaF, K2TaF7, K3TaF8, K2ZrF6, Na7Zr6F31 and K3ZrF7. Three different types of fluorine atoms were described qualitatively and quantitatively. Uncoordinated fluorine atoms (F-) provide signals at lowest binding energies, followed by signals from terminally coordinated fluorine atoms (M-F) and then bridging fluorine atoms (M-F-M) at highest energy. Based on XPS F 1s signals assigned to fluorine atoms in compounds with correctly determined structure it was suggested that fluorine atoms in K3ZrF7 have partially bridging character.

  9. CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction.

    Science.gov (United States)

    Yang, Chun-Ru; Liao, Wei-Siang; Wu, Ya-Hui; Murugan, Kaliyappan; Chen, Chinpiao; Chao, Jui-I

    2013-12-15

    Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer. © 2013.

  10. The Combination of Vitamin K3 and Vitamin C Has Synergic Activity against Forms of Trypanosoma cruzi through a Redox Imbalance Process

    OpenAIRE

    Cristina Desoti, V?nia; Lazarin-Bid?ia, Danielle; Martins Ribeiro, Fabianne; Cardoso Martins, Solange; da Silva Rodrigues, Jean Henrique; Ueda-Nakamura, Tania; Vataru Nakamura, Celso; Farias Ximenes, Valdecir; de Oliveira Silva, Sueli

    2015-01-01

    Chagas' disease is an infection that is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. Because of severe side effects and variable efficacy, the current treatments for Chagas' disease are unsatisfactory, making the search for new chemotherapeutic agents essential. Previous studies have reported various biological activities of naphthoquinones, such as the trypanocidal and antitumor activity of vitamin K3. The combination of this vitamin with vitamin C exert...

  11. Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3.

    Science.gov (United States)

    Taper, Henryk S

    2008-01-01

    The alterations of deoxyribonuclease DNase activity in cancer cells were the basis of the utilization of mixed vitamins C and K3 in a nontoxic, adjuvant cancer therapy. In order to localize exactly the altered activities of DNase in cancer cells, histochemical methods were utilized. The deficiency of alkaline and acid DNase activity appeared to be characteristic for non-necrotic cells of malignant human and animal tumors. This enzymatic deficiency appeared in experimental carcinogenesis before the phenotypic signs of malignancy. Tumor promoters directly reduced the activity of both DNases. The incidence of spontaneous malignant human and animal tumors appeared to be inversely proportional to the intensity of the activity of both DNases in normal cells and tissues from which these tumors were derived. The fact that alkaline and acid DNase activity was reactivated during the spontaneous and therapeutically induced necrosis of cancer cells suggests that this enzymatic deficiency of DNase activity in cancer cells was due to the action of specific inhibitors of DNases. Characteristic variations of serum alkaline DNase activity in positive responders to therapy, examined in more than 800 cancer-bearing patients, may be the basis for the development of a useful test for therapeutic prognosis and for monitoring of cancer bearing patients. Acid DNase was selectively reactivated in malignant tumor cells by vitamin C (sodium ascorbate), whereas alkaline DNase was reactivated by vitamin K3. Joint vitamin C and K3 administration produced in vitro and in vivo tumor growth inhibition, potentiation and sensitization of chemo- and/or radiotherapy and a decrease in the number of metastases in animals with experimental tumors. Joint vitamin C and K3 administration may be considered as a possible new, non-toxic, adjuvant cancer therapy, which can be easily introduced into the classic protocols of clinical cancer therapy without any supplementary risk for patients.

  12. Vitamin K3-2,3-epoxide induction of apoptosis with activation of ROS-dependent ERK and JNK protein phosphorylation in human glioma cells.

    Science.gov (United States)

    Wu, Jender; Chien, Chih-Chiang; Yang, Liang-Yo; Huang, Guan-Cheng; Cheng, Min-Chi; Lin, Che-Tong; Shen, Shing-Chuan; Chen, Yen-Chou

    2011-08-15

    2-Methyl-1,4-naphthoquinone (menadione or vitamin K3; EPO) and K3-2,3-epoxide (EPO1), but not vitamin K3-3-OH (EPO2), exhibited cytotoxicity that caused DNA fragmentation and chromatin condensation in U87 and C6 cells. EPO1 showed more-potent cytotoxicity than EPO, and the IC(50) values of EPO and EPO1 in U87 cells were 37.5 and 15.7μM, respectively. Activation of caspase 3 enzyme activity with cleavage of caspase 3 protein was detected in EPO1-treated U87 and C6 cells, and the addition of the caspase 3 peptidyl inhibitor, DEVD-FMK, reduced the cytotoxic effect of EPO1. An increase in the intracellular ROS level by EPO1 was observed in the DCHF-DA analysis, and EPO1-induced apoptosis and caspase 3 protein cleavage were prevented by adding the antioxidant, N-acetyl-cysteine (NAC), with decreased ROS production elicited by EPO1. Activation of ERK and JNK, but not p38, via phosphorylation induction was identified in EPO1- but not EPO- or EPO2-treated U87 and C6 cells, and this was blocked by adding NAC. However, the ERK inhibitor, PD98059, and the JNK inhibitor, SP600125, showed no effect on EPO1-induced cytotoxicity in either cell type. Our findings demonstrate that 2,3-epoxide substitution significantly potentiates the apoptotic effect of vitamin K3 via stimulating ROS production, which may be useful in the chemotherapy of glioblastoma cells. Copyright © 2011. Published by Elsevier Ireland Ltd.

  13. Inhibitory effect of vitamin C in combination with vitamin K3 on tumor growth and metastasis of Lewis lung carcinoma xenografted in C57BL/6 mice.

    Science.gov (United States)

    Chen, Ming-Feng; Yang, Chih-Min; Su, Cheng-Ming; Liao, Jiunn-Wang; Hu, Miao-Lin

    2011-01-01

    Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

  14. Quantitative evaluation of apical extrusion of intracanal bacteria using rotary ProTaper, K3XF, twisted and hand K-file system: An ex vivo study.

    Science.gov (United States)

    Ghogre, Priyanka; Chourasia, Hemant Ramesh; Agarwal, Manish; Singh, M P; Gurav, Sandeep; Ghogre, Rahul

    2015-01-01

    The aim of this study was to evaluate the number of intracanal bacteria extruded apically during root canal preparation using rotary ProTaper, K3XF, twisted, and hand K-file system. Seventy extracted single-rooted human mandibular premolar teeth were used. Access cavities were prepared and the teeth were mounted in glass vials. Root canals were then contaminated with a pure culture of Enterococcus faecalis (ATCC 29212) and incubated at 37°C for 24 h. The contaminated roots were divided into four experimental groups of 15 teeth each and one control group of 10 teeth. Group 1: ProTaper; Group 2: K3XF; Group 3: Twisted file; Group 4: Hand K-file; Group 5: Control group. Bacteria extruded from the apical foramen during instrumentation were collected into vials. The microbiological samples were incubated in culture media for 24 h. Colonies of bacteria were counted and the results were given as number of colony-forming units (CFU)/ml. The obtained data were analyzed using the Kruskal-Wallis one-way analysis of variance and Mann-Whitney U-tests. There was a significant difference between the rotary and hand instrumentation system related to the apically extruded intracanal bacteria. Both the rotary and hand instrumentation systems extruded intracanal bacteria through the apical foramen. K3XF file system showed least bacterial extrusion amongst all instrumentation groups.

  15. Energy transfer mechanism from Gd3+ to Sm3+ in K3Gd(PO4)2:Sm3+ phosphor

    International Nuclear Information System (INIS)

    Gupta, Palvi; Bedyal, A K; Kumar, Vinay; Khajuria, Y; Sharma, Vishal; Ntwaeaborwa, O M; Swart, H C

    2015-01-01

    Undoped K 3 Gd(PO 4 ) 2 and trivalent samarium (0.5–2.5 mol%) doped K 3 Gd(PO 4 ) 2 phosphors were synthesized by the solid-state method. The phase formation, optical and luminescence properties were investigated by x-ray diffraction (XRD), diffuse reflectance (DR) spectroscopy, and photoluminescence (PL) spectroscopy. The fluorescence decay spectra of the obtained phosphors were also recorded to study the energy transfer from sensitizer (Gd 3+ ) to activator (Sm 3+ ). Energy transfer effects from sensitizer to activator caused by rare-earth ions were mainly observed in the obtained PL and lifetime spectra. The decay curves of K 3 Gd(PO 4 ) 2 phosphor with different Sm 3+ ions concentrations were found to be non-exponential and the data is well fitted with the Inokuti–Hirayama (I–H) model. The energy transfer parameters such as critical distance for the transfer processes were determined. The Commission Internationale de l’Eclairage (CIE) chromatic coordinates and color-correlated temperature were also determined for the prepared phosphor. (paper)

  16. Epigenetics and sex differences in the brain: A genome-wide comparison of histone-3 lysine-4 trimethylation (H3K4me3) in male and female mice.

    Science.gov (United States)

    Shen, Erica Y; Ahern, Todd H; Cheung, Iris; Straubhaar, Juerg; Dincer, Aslihan; Houston, Isaac; de Vries, Geert J; Akbarian, Schahram; Forger, Nancy G

    2015-06-01

    Many neurological and psychiatric disorders exhibit gender disparities, and sex differences in the brain likely explain some of these effects. Recent work in rodents points to a role for epigenetics in the development or maintenance of neural sex differences, although genome-wide studies have so far been lacking. Here we review the existing literature on epigenetics and brain sexual differentiation and present preliminary analyses on the genome-wide distribution of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male and female mice. H3K4me3 is a histone mark primarily organized as 'peaks' surrounding the transcription start site of active genes. We microdissected the bed nucleus of the stria terminalis and preoptic area (BNST/POA) in adult male and female mice and used ChIP-Seq to compare the distribution of H3K4me3 throughout the genome. We found 248 genes and loci with a significant sex difference in H3K4me3. Of these, the majority (71%) had larger H3K4me3 peaks in females. Comparisons with existing databases indicate that genes and loci with increased H3K4me3 in females are associated with synaptic function and with expression atlases from related brain areas. Based on RT-PCR, only a minority of genes with a sex difference in H3K4me3 has detectable sex differences in expression at baseline conditions. Together with previous findings, our data suggest that there may be sex biases in the use of epigenetic marks. Such biases could underlie sex differences in vulnerabilities to drugs or diseases that disrupt specific epigenetic processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. K4Nb6O17·4.5H2O: A novel dual functional material with quick photoreduction of Cr(VI) and high adsorptive capacity of Cr(III)

    International Nuclear Information System (INIS)

    Ma, Yuli; Liu, Xiaoqing; Li, Yang; Su, Yiguo; Chai, Zhanli; Wang, Xiaojing

    2014-01-01

    Graphical abstract: A well crystalline K 4 Nb 6 O 17 ·4.5H 2 O with a wide layer spacing possesses an excellent disposal performance for chromium species of Cr(VI) and Cr(III) as well as the superior recyclability due to its high stability and convenient regeneration process. - Highlights: • A nano-sheet K 4 Nb 6 O 17 ·4.5H 2 O with a large layer spacing was synthesized. • K 4 Nb 6 O 17 ·4.5H 2 O showed a superior photoreduction of Cr(VI) in an acidic solution. • The sample showed a high adsorption capacity of Cr(III) in a near neutral solution. • K 4 Nb 6 O 17 ·4.5H 2 O regenerated conveniently by immersing in a KOH solution. • A complete removal of chromium species was retained after recycling five times. - Abstract: A series of orthorhombic phase K 4 Nb 6 O 17 ·4.5H 2 O was synthesized via a hydrothermal approach. When presented in an acidic pH range, K 4 Nb 6 O 17 ·4.5H 2 O showed a strong ability in quick reduction from Cr(VI) to Cr(III). The resulted Cr(III) ions were removed by an effective adsorption through simply adjusting the solution pH from strong acidity to near neutrality, owing to the sample's unique nano-sheet structure with a wide layer spacing. The Cr(III) ions adsorbed onto samples were released again for reusing by eluting with 1 mol L −1 HCl solution, and K 4 Nb 6 O 17 ·4.5H 2 O regenerated by immersing in a KOH solution. The reduction efficiency of Cr(VI) was still up to 98% after irradiation for 60 min, and the removal efficiency of Cr(III) ions was as high as 83% even after five cycles. Therefore, K 4 Nb 6 O 17 ·4.5H 2 O is clearly demonstrated to be an excellent dual functional material with quick photoreduction of Cr(VI) and high adsorptive capacity of Cr(III). The relevant materials reported herein might be found various environment-related applications

  18. The influence of simulated clinical use on the flexibility of rotary ProTaper Universal, K3 and EndoSequence nickel-titanium instruments.

    Science.gov (United States)

    Viana, A C D; Pereira, E S J; Bahia, M G A; Buono, V T L

    2013-09-01

    To investigate the influence of cyclic flexural and torsional loading on the flexibility of ProTaper Universal, K3 and EndoSequence nickel-titanium instruments, in view of the hypothesis that these types of loading would decrease the flexibility of the selected NiTi rotary files. The instruments evaluated were S2 and F1 ProTaper Universal, sizes 20 and 25, .06 taper K3, and sizes 20 and 25, .06 taper EndoSequence. Flexibility was determined by 45° bending tests according to ISO 3630-1 specification. Values of the bending moment (MB ) obtained with new instruments were considered as the control group (CG). Bending tests were then conducted in instruments previously fatigued to one-fourth and three-fourths of their average fatigue life (fatigue groups, FG¼ and FG¾), as well as after cyclic torsional loading (torsional group, TG). Fatigue tests were carried out in a bench device that allowed the files to rotate freely inside an artificial canal with an angle of curvature of 45° and a radius of 5 mm. Cyclic torsional loading tests were performed that entailed rotating the instrument from zero angular deflection to 180° and then returning to zero applied torque in 20 cycles. Data were analysed using one-way analysis of variance at a significance level of 5%. Simulated clinical use by means of flexural fatigue tests did not affect the flexibility of the instruments, except for a significant increase in flexibility observed in a few instruments (P instruments and after cyclic torsional loading showed no significant differences between them (P > 0.05). The flexibility of rotary ProTaper Universal, K3 and EndoSequence NiTi instruments, measured in bending tests, was not adversely affected by simulated clinical use in curved root canals. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  19. Pillarization of layer double hydroxides (Mg/Al with keggin type K4[α-SiW12O40]•nH2O and its application as adsorbent of procion red dye

    Directory of Open Access Journals (Sweden)

    Intan Permata Sari

    2017-07-01

    Full Text Available Pillarization of layered double hydroxides with polyoxometalate K4[α-SiW12O40]•nH2O at various times i.e. 3, 6, 9, 12, 24, 36 and 48 hours has been done. The pillared product was characterized by FT-IR spectrophotometer and XRD. The optimum pillared layered double hydroxides of polyoxometalate K4[α-SiW12O40]•nH2O was used as an adsorbent of procion red dye. The results of characterization using FT-IR spectrophotometer is not yet show the optimum pillarization process. The characterisation using XRD the successfully of pillared layered double hydroxides of polyoxometalate K4[α-SiW12O40]•nH2O showing the existence of diffraction angle 8.5o with intensity 355. Furthermore, the pillared layered double hydroxides of polyoxometalate K4[α-SiW12O40]•nH2O with time variation of 12 hours was applied as an adsorbent of procion red dye. The results show the adsorption rate was 0.523 min-1, the highest of absorption capacity at 70oC was 10.8 mol/g, the highest energy of absorption 70 oC was 125 kJ/mol. The enthalpy (∆H and entropy (∆S, decrease as the increasing concentration of procion red dye. Keywords: layered double hydroxides, polyoxometalate, pillaration, procion red, adsorption

  20. Differential equations for correlators on the torus: Two-point correlation function of isospin-1 primary fields in the k=3 SU(2) WZW theory

    International Nuclear Information System (INIS)

    Durganandini, P.

    1990-01-01

    We systematize the procedure developed by Mathur, Mukhi and Sen to derive differential equations for correlators in rational conformal field theories on the torus in those cases when it is necessary to study not only leading-order behaviour but also the nonleading behaviour of the solutions in the asymptotic limit Imτ→∞, Imz→∞. As an illustration, we derive the differential equation for the two-point correlator of the isospin-1 primary fields in the k=3 SU(2) WZW model on the torus. (orig.)

  1. Optical and crystal chemistry studies of Na3Ln(PO4)2-K3Ln(PO4)2 (Ln=Eu, Gd)

    International Nuclear Information System (INIS)

    Mesnaoui, M.; Maazaz, M.

    1987-01-01

    In these systems, large single phase domains are separated by two phase regions. The structural evolution as a function of composition is analysed both by X-ray diffraction and by using Eu 3+ and Gd 3+ as luminescent local structural probes. Due to layer type structure of the K 3 Ln(PO 4 ) 2 phases an exchange reaction resulting in total substitution of sodium for potassium can be carried out with formation of metastable Na 3 Ln(PO 4 ) 2 phases, the structure of which is close to those of the potassium compounds. 10 refs.; 18 figs [fr

  2. Study and identification of paramagnetic centers by EPR technique in K3Cu(CN)4 crystals irradiated with X-rays

    International Nuclear Information System (INIS)

    Tancredo, A.

    1984-01-01

    Paramagnetic centers created in K 3 Cu(CN) 4 crystals by X-ray irradiation, using EPR technique are studied. The crystals are irradiated in following conditions: a) liquid nitrogen temperatures, b) room temperatures. Crystals field models of the paramagnetic centers which determine the following local symmetric in order to satisfy experimental results: a) Cu ++ in C sub(3v) symmetric and b) K 0 in distorted octahedral symmetry are proposed. The decay of these centers and the observation that Cu ++ ions are very much instable and disappear at T = 148K are studied. The K 0 atom remain up to T approximatelly 300K. (E.G.) [pt

  3. Genome sequence of Prevotella intermedia SUNY aB G8-9K-3, a biofilm forming strain with drug-resistance.

    Science.gov (United States)

    Moon, Ji-Hoi; Kim, Minjung; Lee, Jae-Hyung

    Prevotella intermedia has long been known to be as the principal etiologic agent of periodontal diseases and associated with various systemic diseases. Previous studies showed that the intra-species difference exists in capacity of biofilm formation, antibiotic resistance, and serological reaction among P. intermedia strains. Here we report the genome sequence of P. intermedia SUNY aB G8-9K-3 (designated ATCC49046) that displays a relatively high antimicrobial resistant and biofilm-forming capacity. Genome sequencing information provides important clues in understanding the genetic bases of phenotypic differences among P. intermedia strains. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  4. Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

    Science.gov (United States)

    Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

    2017-05-01

    We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

  5. Comparison of apical transportation and change of working length in K3, NRT AND PROFILE rotary instruments using transparent resin block

    Directory of Open Access Journals (Sweden)

    Min-Jung Yoon

    2011-01-01

    Full Text Available Objectives The purpose of this study is to compare the apical transportation and working length change in curved root canals created in resin blocks, using 3 geometrically different types of Ni-Ti files, K3, NRT, and Profile. Materials and Methods The curvature of 30 resin blocks was measured by Schneider technique and each groups of Ni-Ti files were allocated with 10 resin blocks at random. The canals were shaped with Ni-Ti files by Crown-down technique. It was analyzed by Double radiograph superimposition method (Backman CA 1992, and for the accuracy and consistency, specially designed jig, digital X-ray, and CAD/CAM software for measurement of apical transportation were used. The amount of apical transportation was measured at 0, 1, 3, 5 mm from 'apical foramen - 0.5 mm' area, and the alteration of the working length before and after canal shaping was also measured. For statistics, Kruskal-Wallis One Way Analysis was used. Results There was no significant difference between the groups in the amount of working length change and apical transportation at 0, 1, and 3 mm area (p = 0.027, however, the amount of apical transportation at 5 mm area showed significant difference between K3 and Profile system (p = 0.924. Conclusions As a result of this study, the 3 geometrically different Ni-Ti files showed no significant difference in apical transportation and working length change and maintained the original root canal shape.

  6. Mechanical reduction of the intracanal Enterococcus faecalis population by Hyflex CM, K3XF, ProTaper Next, and two manual instrument systems: an in vitro comparative study.

    Science.gov (United States)

    Tewari, Rajendra K; Ali, Sajid; Mishra, Surendra K; Kumar, Ashok; Andrabi, Syed Mukhtar-Un-Nisar; Zoya, Asma; Alam, Sharique

    2016-05-01

    In the present study, the effectiveness of three rotary and two manual nickel titanium instrument systems on mechanical reduction of the intracanal Enterococcus faecalis population was evaluated. Mandibular premolars with straight roots were selected. Teeth were decoronated and instrumented until 20 K file and irrigated with physiological saline. After sterilization by ethylene oxide gas, root canals were inoculated with Enterococcus faecalis. The specimens were randomly divided into five groups for canal instrumentation: Manual Nitiflex and Hero Shaper nickel titanium files, and rotary Hyflex CM, ProTaper Next, and K3XF nickel titanium files. Intracanal bacterial sampling was done before and after instrumentation. After serial dilution, samples were plated onto the Mitis Salivarius agar. The c.f.u. grown were counted, and log10 transformation was calculated. All instrumentation systems significantly reduced the intracanal bacterial population after root canal preparation. ProTaper Next was found to be significantly more effective than Hyflex CM and manual Nitiflex and Hero Shaper. However, ProTaper Next showed no significant difference with K3XF. Canal instrumentation by all the file systems significantly reduced the intracanal Enterococcus faecalis counts. ProTaper Next was found to be most effective in reducing the number of bacteria than other rotary or hand instruments. © 2014 Wiley Publishing Asia Pty Ltd.

  7. K3R7 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  8. Modeling local structure using crystal field and spin Hamiltonian parameters: the tetragonal FeK3+-OI2- defect center in KTaO3 crystal

    International Nuclear Information System (INIS)

    Gnutek, P; Rudowicz, C; Yang, Z Y

    2009-01-01

    The local structure and the spin Hamiltonian (SH) parameters, including the zero-field-splitting (ZFS) parameters D and (a+2F/3), and the Zeeman g factors g || and g perpendicular , are theoretically investigated for the Fe K 3+ -O I 2- center in KTaO 3 crystal. The microscopic SH (MSH) parameters are modeled within the framework of the crystal field (CF) theory employing the CF analysis (CFA) package, which also incorporates the MSH modules. Our approach takes into account the spin-orbit interaction as well as the spin-spin and spin-other-orbit interactions omitted in previous studies. The superposition model (SPM) calculations are carried out to provide input CF parameters for the CFA/MSH package. The combined SPM-CFA/MSH approach is used to consider various structural models for the Fe K 3+ -O I 2- defect center in KTaO 3 . This modeling reveals that the off-center displacement of the Fe 3+ ions, Δ 1 (Fe 3+ ), combined with an inward relaxation of the nearest oxygen ligands, Δ 2 (O 2- ), and the existence of the interstitial oxygen O I 2- give rise to a strong tetragonal crystal field. This finding may explain the large ZFS experimentally observed for the Fe K 3+ -O I 2- center in KTaO 3 . Matching the theoretical MSH predictions with the available structural data as well as electron magnetic resonance (EMR) and optical spectroscopy data enables predicting reasonable ranges of values of Δ 1 (Fe 3+ ) and Δ 2 (O 2- ) as well as the possible location of O I 2- ligands around Fe 3+ ions in KTaO 3 . The defect structure model obtained using the SPM-CFA/MSH approach reproduces very well the ranges of the experimental SH parameters D, g || and g perpendicular and importantly yields not only the correct magnitude of D but also the sign, unlike previous studies. More reliable predictions may be achieved when experimental data on (a+2F/3) and/or crystal field energy levels become available. Comparison of our results with those arising from alternative models existing

  9. Intermolecular C-H···O, Cl···Cl and π-π interactions in the 2-dichloromethyl derivative of vitamin K3.

    Science.gov (United States)

    Soave, Raffaella; Colombo, Pietro

    2013-12-15

    The title 1,4-naphthoquinone, 2-dichloromethyl-3-methyl-1,4-dihydronaphthalene-1,4-dione, C12H8Cl2O2, is a chlorinated derivative of vitamin K3, which is a synthetic compound also known as menadione. Molecules of (I) are planar and lie on a crystallographic mirror plane (Z' = 0.5) in the space group Pnma. They are connected to each other by C-H···O hydrogen bonds, forming two-dimensional layers parallel to the ac plane. In addition, Cl···Cl and π-π interactions link adjacent molecules in different layers, thus forming zigzag ribbons along the b axis, such that a three-dimensional architecture is generated.

  10. Study on the inclusion interaction of p-sulfonated calix[n]arenes with Vitamin K3 using methylene blue as a spectral probe.

    Science.gov (United States)

    Lu, Qin; Gu, Jiashan; Yu, Huapeng; Liu, Chun; Wang, Lun; Zhou, Yunyou

    2007-09-01

    The characteristics of host-guest complexation between p-sulfonated calix[n]arene (SCnA, n = 4, 6) and Vitamin K(3) (VK(3)) were investigated by fluorescence spectrometry and absorption spectrometry using methylene blue (MB) as a probe. Interaction with MB and SCnA led to an obvious decrease in fluorescence intensity of MB, accompanying with shifts of emission peaks. Absorption peaks also showed interesting changes; however, when VK(3) was added, fluorescence intensity and absorbance recovered and a slight and slow red shift was observed. The obtained results showed that the inclusion ability of p-sulphonated calix[n]arenes towards VK(3) was the order: p-sulphonated calix[6]arene (SC6A) >p-sulphonated calix[4]arene (SC4A). Relative mechanism was proposed to explain the inclusion process.

  11. The correlation of cathodic peak potentials of vitamin K(3) derivatives and their calculated electron affinities. The role of hydrogen bonding and conformational changes.

    Science.gov (United States)

    Nasiri, Hamid Reza; Panisch, Robin; Madej, M Gregor; Bats, Jan W; Lancaster, C Roy D; Schwalbe, Harald

    2009-06-01

    2-methyl-1,4-naphtoquinone 1 (vitamin K(3), menadione) derivatives with different substituents at the 3-position were synthesized to tune their electrochemical properties. The thermodynamic midpoint potential (E(1/2)) of the naphthoquinone derivatives yielding a semi radical naphthoquinone anion were measured by cyclic voltammetry in the aprotic solvent dimethoxyethane (DME). Using quantum chemical methods, a clear correlation was found between the thermodynamic midpoint potentials and the calculated electron affinities (E(A)). Comparison of calculated and experimental values allowed delineation of additional factors such as the conformational dependence of quinone substituents and hydrogen bonding which can influence the electron affinities (E(A)) of the quinone. This information can be used as a model to gain insight into enzyme-cofactor interactions, particularly for enzyme quinone binding modes and the electrochemical adjustment of the quinone motif.

  12. On the geometry of a smooth model of a fibre product of families of K3 surfaces

    International Nuclear Information System (INIS)

    Nikol'skaya, O V

    2014-01-01

    The Hodge conjecture on algebraic cycles is proved for a smooth projective model X of a fibre product X 1 × C X 2 of nonisotrivial 1-parameter families of K3 surfaces (possibly with degeneracies) X k →C (k=1,2) over a smooth projective curve C under the assumption that, for generic geometric fibres X 1s and X 2s , the ring End Hg(X 1s ) NS Q (X 1s ) ⊥ is an imaginary quadratic field, rankNS(X 1s )≠18, and End Hg(X 2s ) NS Q (X 2s ) ⊥ is a totally real field or else rankNS(X 1s )

  13. Variables process effect in the pure ferritic metal contribution deposited with an tubular metal-cored E111T5-K3 wire

    International Nuclear Information System (INIS)

    Svoboda, Hernan G; Ramini de Rissone, N.M; Surian, E; De Vedia, L

    2004-01-01

    The welding deposit performed with an ANSI-AWS E111T5-K3 type from the system C-Mn-Ni-Mo metal coring tubular welding, with a low slag generation was studied. Different operatives configurations with two thermal contribution levels (1 kJ and 1.5 kJ) and two types of protector gases (CO 2 and Ar-20%CO 2 ) at two welding position (under hand and ascendant vertical) were analyzed. The resulting pure contributor metal from the different process configurations was chemical, mechanically and structural characterized and the effect of the different process conditions was evaluated. The microstructure is fundamentally composed by FS(NA) and AF. For similar values of hardness and strength, good values of tenacity were observed and they show little variation with the process variables studied (AG)

  14. Electronic interaction in an outer-sphere mixed-valence double salt: a polarized neutron diffraction study of K(3)(MnO(4))(2).

    Science.gov (United States)

    Cannon, Roderick D; Jayasooriya, Upali A; Tilford, Claire; Anson, Christopher E; Sowrey, Frank E; Rosseinsky, David R; Stride, John A; Tasset, Francis; Ressouche, Eric; White, Ross P; Ballou, Rafik

    2004-11-01

    The mixed-valence double salt K(3)(MnO(4))(2) crystallizes in space group P2(1)/m with Z = 2. The manganese centers Mn1 and Mn2 constitute discrete "permanganate", [Mn(VII)O(4)](-), and "manganate", [Mn(VI)O(4)](2-), ions, respectively. There is a spin-ordering transition to an antiferromagnetic state at ca. T = 5 K. The spin-density distribution in the paramagnetic phase at T = 10 K has been determined by polarized neutron diffraction, confirming that unpaired spin is largely confined to the nominal manganate ion Mn2. Through use of both Fourier refinement and maximum entropy methods, the spin on Mn1 is estimated as 1.75 +/- 1% of one unpaired electron with an upper limit of 2.5%.

  15. Synthesis and characterization of n-alkylamino derivatives of vitamin K3: Molecular structure of 2-propylamino-3-methyl-1,4-naphthoquinone and antibacterial activities

    Science.gov (United States)

    Chadar, Dattatray; Camilles, Maria; Patil, Rishikesh; Khan, Ayesha; Weyhermüller, Thomas; Salunke-Gawali, Sunita

    2015-04-01

    We would like to introduce eight analogues of n-alkylamino derivatives of vitamin K3 (2-methyl-1,4-naphthoquinone) viz, 2-(n-alkylamino)-3-methyl-1,4-naphthoquinone (where n-alkyl is methyl; LM-1, ethyl; LM-2, propyl; LM-3, butyl; LM-4, pentyl; LM-5, hexyl; LM-6, heptyl; LM-7, octyl; LM-8). All the above analogues have been successfully synthesized from vitamin K3 and characterized using different analytical techniques. Furthermore, in order to understand the mechanistic aspects of formation of LM-1 to LM-8 compounds, we could propose the mechanism. The FT-IR analysis of LM-1 to LM-8 indicate the presence of characteristic band of Nsbnd H group ∼3287-3364 cm-1, the variation was attributed to extensive intramolecular hydrogen bonding interaction. The molecular structure of LM-3 compound has been confirmed by single crystal X-ray diffraction analysis. LM-3 compound crystallises in triclinic space group P1. There were four independent molecules in asymmetric unit cell and their molecular interactions observed via Nsbnd H⋯O, Csbnd H⋯O and π-π stacking of quinonoid rings. Pharmacological potential of all compounds has been evaluated in terms of their antibacterial activities against Pseudomonas aeruginosa and Staphylococcus aureus. All the compounds were active against both the strains while LM-2 was found to be more effective with a minimum inhibition concentration of 0.3125 μg/mL and 0.156 μg/mL respectively.

  16. Activation of the 2-5OAS/RNase L pathway in CVB1 or HAV/18f infected FRhK-4 cells does not require induction of OAS1 or OAS2 expression

    International Nuclear Information System (INIS)

    Kulka, Michael; Calvo, Mona S.; Ngo, Diana T.; Wales, Samantha Q.; Goswami, Biswendu B.

    2009-01-01

    The latent, constitutively expressed protein RNase L is activated in coxsackievirus and HAV strain 18f infected FRhK-4 cells. Endogenous oligoadenylate synthetase (OAS) from uninfected and virus infected cell extracts synthesizes active forms of the triphosphorylated 2-5A oligomer (the only known activator of RNase L) in vitro and endogenous 2-5A is detected in infected cell extracts. However, only the largest OAS isoform, OAS3, is readily detected throughout the time course of infection. While IFNβ treatment results in an increase in the level of all three OAS isoforms in FRhK-4 cells, IFNβ pretreatment does not affect the temporal onset or enhancement of RNase L activity nor inhibit virus replication. Our results indicate that CVB1 and HAV/18f activate the 2-5OAS/RNase L pathway in FRhK-4 cells during permissive infection through endogenous levels of OAS, but contrary to that reported for some picornaviruses, CVB1 and HAV/18f replication is insensitive to this activated antiviral pathway.

  17. Acetylated Histone H3K9 is associated with meiotic recombination hotspots, and plays a role in recombination redundantly with other factors including the H3K4 methylase Set1 in fission yeast

    Science.gov (United States)

    Yamada, Shintaro; Ohta, Kunihiro; Yamada, Takatomi

    2013-01-01

    Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double-strand break (DSB) formation at hotspots, but the role and precise landscape of involved modifications remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is elevated, and H3K4me3 is not significantly enriched. Mutating H3K9 to non-acetylatable alanine mildly reduced levels of the DSB-inducing protein Rec12 (the fission yeast homologue of Spo11) and DSB at hotspots, indicating that H3K9ac may be involved in DSB formation by enhancing the interaction between Rec12 and hotspots. In addition, we found that the lack of the H3K4 methyltransferase Set1 generally increased Rec12 binding to chromatin but partially reduced DSB formation at some loci, suggesting that Set1 is also involved in DSB formation. These results suggest that meiotic DSB formation is redundantly regulated by multiple chromatin-related factors including H3K9ac and Set1 in fission yeast. PMID:23382177

  18. Discovery Handbook for Grades K-5.

    Science.gov (United States)

    Johnson, Terry

    This resource packet addresses the need for interpretive materials of the prehistory and early history of the state of Arkansas. These curriculum-focused activities, based on flyers and books created by the Arkansas Archaeology Survey, encourage integration of archaeological and historical study into classroom instruction. The teacher's guide is…

  19. A new set of K3Fe3(PO4)4·yH2O (0 ≤ y ≤ 1) layered phases obtained by topotactic reactions

    Science.gov (United States)

    Trad, Khiem; Wattiaux, Alain; Ben Amara, Mongi; Delmas, Claude; Carlier, Dany

    2018-06-01

    K3Fe3(PO4)4·H2O powder was synthesized by Na+/K+ exchange reaction from Na3Fe3(PO4)4 in aqueous medium. The replacement of the sodium cations by the potassium larger ones and water molecules causes a structural distortion leading to P2/n monoclinic K3Fe3(PO4)4·H2O. This new layered phase was characterized by XRD, Mössbauer spectroscopy and magnetic measurements. The study of its thermal stability reveals that other new layered K3Fe3(PO4)4·yH2O with (0 ≤ y ≤ 1) phases can be stabilized up to 600 °C and finally at higher temperature a new K3Fe3(PO4)4 polymorph with a different structural type is irreversibility formed.

  20. Crystal structure of salt-tolerant glutaminase from Micrococcus luteus K-3 in the presence and absence of its product L-glutamate and its activator Tris.

    Science.gov (United States)

    Yoshimune, Kazuaki; Shirakihara, Yasuo; Wakayama, Mamoru; Yumoto, Isao

    2010-02-01

    Glutaminase from Micrococcus luteus K-3 [Micrococcus glutaminase (Mglu); 456 amino acid residues (aa); 48 kDa] is a salt-tolerant enzyme. Our previous study determined the structure of its major 42-kDa fragment. Here, using new crystallization conditions, we determined the structures of the intact enzyme in the presence and absence of its product L-glutamate and its activator Tris, which activates the enzyme by sixfold. With the exception of a 'lid' part (26-29 aa) and a few other short stretches, the structures were all very similar over the entire polypeptide chain. However, the presence of the ligands significantly reduced the length of the disordered regions: 41 aa in the unliganded structure (N), 21 aa for L-glutamate (G), 8 aa for Tris (T) and 6 aa for both L-glutamate and Tris (TG). L-glutamate was identified in both the G and TG structures, whereas Tris was only identified in the TG structure. Comparison of the glutamate-binding site between Mglu and salt-labile glutaminase (YbgJ) from Bacillus subtilis showed significantly smaller structural changes of the protein part in Mglu. A comparison of the substrate-binding pocket of Mglu, which is highly specific for L-glutamine, with that of Erwinia carotovora asparaginase, which has substrates other than L-glutamine, shows that Mglu has a larger substrate-binding pocket that prevents the binding of L-asparagine with proper interactions.

  1. Spectrofluorimetric study on the inclusion interaction between vitamin K3 with p-(p-sulfonated benzeneazo)calix[6]arene and determination of VK3.

    Science.gov (United States)

    Zhou, Yunyou; Xu, Hongwei; Wu, Lian; Liu, Chun; Lu, Qin; Wang, Lun

    2008-11-15

    The characteristics of host-guest complexation between p-(p-sulfonated benzeneazo) calix[6]arene (SBC6A) and vitamin K3 (VK3) were investigated by fluorescence spectrometry. A 1:1 stoichiometry for the complexation was established and was verified by Job's plot. An association constant of 4.95 x 10(3)L mol(-1) at 20 degrees C was calculated by applying a deduced equation. The interaction mechanism of the inclusion complex was discussed. It was found that the fluorescence of SBC6A could be remarkably quenched by an appropriate amount of VK3 especially when non-ionic surfactant Triton X-100 existed. According to the obtained results, a novel sensitive spectrofluorimetric method for the determination of VK3 based on supramolecular complex was developed with a linear range of 5.0 x 10(-7) -3.0 x 10(-5)mol L(-1) and a detection limit of 2.0 x 10(-7)mol L(-1). The proposed method was used to determine VK3 in commercial preparations with satisfactory results.

  2. Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism.

    Science.gov (United States)

    Bonilla-Porras, Angelica R; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

    2011-06-10

    Secondary therapy-related acute lymphoblastic leukemia might emerge following chemotherapy and/or radiotherapy for primary malignancies. Therefore, other alternatives should be pursued to treat leukemia. It is shown that vitamin K3- or vitamin C- induced apoptosis in leukemia cells by oxidative stress mechanism involving superoxide anion radical and hydrogen peroxide generation, activation of NF-κB, p53, c-Jun, protease caspase-3 activation and mitochondria depolarization leading to nuclei fragmentation. Cell death was more prominent when Jurkat and K562 cells are exposed to VC and VK3 in a ratio 1000:1 (10 mM: 10 μM) or 100:1 (300 μM: 3 μM), respectively. We provide for the first time in vitro evidence supporting a causative role for oxidative stress in VK3- and VC-induced apoptosis in Jurkat and K562 cells in a domino-like mechanism. Altogether these data suggest that VK3 and VC should be useful in the treatment of leukemia.

  3. Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism

    Directory of Open Access Journals (Sweden)

    Velez-Pardo Carlos

    2011-06-01

    Full Text Available Abstract Background Secondary therapy-related acute lymphoblastic leukemia might emerge following chemotherapy and/or radiotherapy for primary malignancies. Therefore, other alternatives should be pursued to treat leukemia. Results It is shown that vitamin K3- or vitamin C- induced apoptosis in leukemia cells by oxidative stress mechanism involving superoxide anion radical and hydrogen peroxide generation, activation of NF-κB, p53, c-Jun, protease caspase-3 activation and mitochondria depolarization leading to nuclei fragmentation. Cell death was more prominent when Jurkat and K562 cells are exposed to VC and VK3 in a ratio 1000:1 (10 mM: 10 μM or 100:1 (300 μM: 3 μM, respectively. Conclusion We provide for the first time in vitro evidence supporting a causative role for oxidative stress in VK3- and VC-induced apoptosis in Jurkat and K562 cells in a domino-like mechanism. Altogether these data suggest that VK3 and VC should be useful in the treatment of leukemia.

  4. APMP/TCRI key comparison report of measurement of air kerma for medium-energy x-rays (APMP.RI(I)-K3)

    International Nuclear Information System (INIS)

    Lee, J.H.; Hwang, W.S.; Kotler, L.H.; Webb, D.V.; Buermann, L.; Burns, D.T.; Takeyeddin, M.; Shaha, V.V.; Srimanoroth, S.; Meghzifene, A.; Hah, S.H.; Chun, K.J.; Kadni, T.B.; Takata, N.; Msimang, Z.

    2008-01-01

    The APMP/TCRI Dosimetry Working Group performed the APMP.RI(I)-K3 key comparison of measurement of air kerma for medium-energy x-rays (100 kV to 250 kV) between 2000 and 2003. In total, 11 institutes took part in the comparison, among which 8 were APMP member laboratories. Two commercial cavity ionization chambers were used as transfer instruments and circulated among the participants. All the participants established the 100 kV, 135 kV, 180 kV and 250 kV x-ray beam qualities equivalent to those of the BIPM. The results showed that the maximum difference between the participants and the BIPM in the medium-energy x-ray range, evaluated using the comparison data of the linking laboratories ARPANSA and PTB, is less than 1.4%. The degrees of equivalence between the participants are presented and this comparison confirms the calibration capabilities of the participating laboratories. (authors)

  5. Spectrofluorimetric study on the inclusion interaction between vitamin K 3 with p-( p-sulfonated benzeneazo)calix[6]arene and determination of VK 3

    Science.gov (United States)

    Zhou, Yunyou; Xu, Hongwei; Wu, Lian; Liu, Chun; Lu, Qin; Wang, Lun

    2008-11-01

    The characteristics of host-guest complexation between p-( p-sulfonated benzeneazo) calix[6]arene (SBC6A) and vitamin K 3 (VK 3) were investigated by fluorescence spectrometry. A 1:1 stoichiometry for the complexation was established and was verified by Job's plot. An association constant of 4.95 × 10 3 L mol -1 at 20 °C was calculated by applying a deduced equation. The interaction mechanism of the inclusion complex was discussed. It was found that the fluorescence of SBC6A could be remarkably quenched by an appropriate amount of VK 3 especially when non-ionic surfactant Triton X-100 existed. According to the obtained results, a novel sensitive spectrofluorimetric method for the determination of VK 3 based on supramolecular complex was developed with a linear range of 5.0 × 10 -7-3.0 × 10 -5 mol L -1 and a detection limit of 2.0 × 10 -7 mol L -1. The proposed method was used to determine VK 3 in commercial preparations with satisfactory results.

  6. APMP/TCRI key comparison report of measurement of air kerma for medium-energy x-rays (APMP.RI(I)-K3)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J.H.; Hwang, W.S. [Institute of Nuclear Energy Research, Longtan, Taiwan (China); Kotler, L.H.; Webb, D.V. [Australian Radiation Protection and Nuclear Safety Agency, Yallambie (Australia); Buermann, L. [Physikalisch Technische Bundesanstalt, Braunschweig (Germany); Burns, D.T. [Bureau International de Poids et Mesures, 92 - Sevres (France); Takeyeddin, M. [Atomic Energy Commission, Damascus (Syrian Arab Republic); Shaha, V.V. [Bhabha Atomic Research Centre, Mumbai (India); Srimanoroth, S. [Department of Medical Sciences, Nonthaburi (Thailand); Meghzifene, A. [International Atomic Energy Agency, Vienna (Austria); Hah, S.H.; Chun, K.J. [Korea Research Institute of Standards and Science, Yusong (Korea, Republic of); Kadni, T.B. [Malaysian Nuclear Agency, Kajang (Malaysia); Takata, N. [National Metrology Institute of Japan, Tsukuba (Japan); Msimang, Z. [National Metrology Institute of South Africa, Pretoria (South Africa)

    2008-10-15

    The APMP/TCRI Dosimetry Working Group performed the APMP.RI(I)-K3 key comparison of measurement of air kerma for medium-energy x-rays (100 kV to 250 kV) between 2000 and 2003. In total, 11 institutes took part in the comparison, among which 8 were APMP member laboratories. Two commercial cavity ionization chambers were used as transfer instruments and circulated among the participants. All the participants established the 100 kV, 135 kV, 180 kV and 250 kV x-ray beam qualities equivalent to those of the BIPM. The results showed that the maximum difference between the participants and the BIPM in the medium-energy x-ray range, evaluated using the comparison data of the linking laboratories ARPANSA and PTB, is less than 1.4%. The degrees of equivalence between the participants are presented and this comparison confirms the calibration capabilities of the participating laboratories. (authors)

  7. Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia.

    Science.gov (United States)

    Adriaens, Michiel E; Prickaerts, Peggy; Chan-Seng-Yue, Michelle; van den Beucken, Twan; Dahlmans, Vivian E H; Eijssen, Lars M; Beck, Timothy; Wouters, Bradly G; Voncken, Jan Willem; Evelo, Chris T A

    2016-01-01

    A comprehensive assessment of the epigenetic dynamics in cancer cells is the key to understanding the molecular mechanisms underlying cancer and to improving cancer diagnostics, prognostics and treatment. By combining genome-wide ChIP-seq epigenomics and microarray transcriptomics, we studied the effects of oxygen deprivation and subsequent reoxygenation on histone 3 trimethylation of lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in a breast cancer cell line, serving as a model for abnormal oxygenation in solid tumors. A priori, epigenetic markings and gene expression levels not only are expected to vary greatly between hypoxic and normoxic conditions, but also display a large degree of heterogeneity across the cell population. Where traditionally ChIP-seq data are often treated as dichotomous data, the model and experiment here necessitate a quantitative, data-driven analysis of both datasets. We first identified genomic regions with sustained epigenetic markings, which provided a sample-specific reference enabling quantitative ChIP-seq data analysis. Sustained H3K27me3 marking was located around centromeres and intergenic regions, while sustained H3K4me3 marking is associated with genes involved in RNA binding, translation and protein transport and localization. Dynamic marking with both H3K4me3 and H3K27me3 (hypoxia-induced bivalency) was found in CpG-rich regions at loci encoding factors that control developmental processes, congruent with observations in embryonic stem cells. In silico -identified epigenetically sustained and dynamic genomic regions were confirmed through ChIP-PCR in vitro, and obtained results are corroborated by published data and current insights regarding epigenetic regulation.

  8. Vitamin K3 increased BMD at 1 and 2 months post-surgery and the maximum stress of the middle femur in the rat.

    Science.gov (United States)

    Hong, You-jia; Liu, Sheng; Jiang, Ning-yi; Jiang, Sen; Liang, Jiu-gen

    2015-02-01

    The therapeutic effects of vitamin K3 (VK3) on osteoporosis are still unknown. In this study, we hypothesized that VK3 possesses therapeutic effects on osteoporosis; to verify this hypothesis, the ovariectomized rat was used as an osteoporosis model. Fifty-six Sprague-Dawley female rats aged 8 to 9 months were randomly assigned to 4 groups: sham surgery, ovariectomy with saline, ovariectomy with low-dose VK3, and ovariectomy with high-dose VK3. Intramuscular injection of VK3 was performed every other day beginning 1 month postoperatively. The therapeutic effects of VK3 on osteoporosis were evaluated by measurement of bone mineral density (BMD), bone biochemical markers, biomechanical properties, and bone morphometric parameters. The overall average BMD in VK3-treated groups increased to a level between those of the ovariectomy group and the sham surgery group. The procollagen I N-terminal peptide level peaked at 2 months after surgery in all groups except in the group that had undergone ovariectomy with low-dose VK3. The tartrate-resistant acid phosphatase 5b level increased more slowly at 4 months after surgery than at 2 months after surgery in the VK3-treated groups. The ovariectomy with high-dose VK3 group had the highest maximum stress of the middle femur of all groups. With VK3 treatment, the trabecular bone area percentage increased. All morphometric indicators for the middle tibia in the VK3-treated groups reached the levels found in the sham surgery group. In summary, VK3 therapy increased BMD at 1 and 2 months postsurgery and the maximum stress of the middle femur. In addition, VK3 therapy slowed the increase in bone turnover in ovariectomized rats. Furthermore, VK3 can improve morphometric indicators for the middle tibia. Our preliminary study indicates that VK3 has a potential therapeutic effect on osteoporosis and is worthy of further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Biophysical and computational comparison on the binding affinity of three important nutrients to β-lactoglobulin: folic acid, ascorbic acid and vitamin K3.

    Science.gov (United States)

    Shahraki, Somaye; Heydari, Ali; Saeidifar, Maryam; Gomroki, Masoumeh

    2017-11-06

    Small globular protein, β-lactoglobulin (βLG), which has significant affinity toward many drugs, is the most abundant whey protein in milk. In this study, the interaction of βLG with three important nutrients, ascorbic acid (ASC), folic acid (FOL), and vitamin K3 (VK3) was investigated by spectroscopic methods (UV-visible and fluorescence) along with molecular docking technique. The results of fluorescence measurements showed that studied nutrients strongly quenched βLG fluorescence in static (FOL and ACS) or static-dynamic combined quenching (VK3) mode. The values of binding constants (K βLG-ASC  ~ 4.34 × 10 4  M -1 , K βLG-FOL ~ 1.67 × 10 4  M -1 and K βLG-VK3 ~ 13.49 × 10 4  M -1 at 310 K) suggested that VK3 and FOL had stronger binding affinity toward βLG than ASC. Thermodynamic analysis indicated that hydrophobic interactions are the major forces in the stability of FOL-βLG complex with enthalpy- and entropy-driving mode while, hydrogen bonds and van der Waals interactions play a major role for βLG-ASC and βLG-VK3 associations. The results of 3D fluorescence FT-IR and UV-Visible measurements indicated that the binding of above nutrients to βLG may induce conformational and micro-environmental changes of protein. Also, there is a reciprocal complement between spectroscopic techniques and molecular docking modeling. The docking results indicate that the ASC, FOL, and VK3 bind to residues located in the subdomain B of βLG. Finally, this report suggests that βLG could be used as an effective carrier of above nutrients in functional foods.

  10. Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death.

    Science.gov (United States)

    Tomasetti, Marco; Nocchi, Linda; Neuzil, Jiri; Goodwin, Jacob; Nguyen, Maria; Dong, Lanfeng; Manzella, Nicola; Staffolani, Sara; Milanese, Claudio; Garrone, Beatrice; Alleva, Renata; Borghi, Battista; Santarelli, Lory; Guerrieri, Roberto

    2012-01-01

    The redox-silent vitamin E analog α-tocopheryl succinate (α-TOS) was found to synergistically cooperate with vitamin K3 (VK3) plus ascorbic acid (AA) in the induction of cancer cell-selective apoptosis via a caspase-independent pathway. Here we investigated the molecular mechanism(s) underlying cell death induced in prostate cancer cells by α-TOS, VK3 and AA, and the potential use of targeted drug combination in the treatment of prostate cancer. The generation of ROS, cellular response to oxidative stress, and autophagy were investigated in PC3 prostate cancer cells by using drugs at sub-toxic doses. We evaluated whether PARP1-mediated apoptosis-inducing factor (AIF) release plays a role in apoptosis induced by the combination of the agents. Next, the effect of the combination of α-TOS, VK3 and AA on tumor growth was examined in nude mice. VK3 plus AA induced early ROS formation associated with induction of autophagy in response to oxidative stress, which was reduced by α-TOS, preventing the formation of autophagosomes. α-TOS induced mitochondrial destabilization leading to the release of AIF. Translocation of AIF from mitochondria to the nucleus, a result of the combinatorial treatment, was mediated by PARP1 activation. The inhibition of AIF as well as of PARP1 efficiently attenuated apoptosis triggered by the drug combination. Using a mouse model of prostate cancer, the combination of α-TOS, VK3 and AA was more efficient in tumor suppression than when the drugs were given separately, without deleterious side effects. α-TOS, a mitochondria-targeting apoptotic agent, switches at sub-apoptotic doses from autophagy-dependent survival of cancer cells to their demise by promoting the induction of apoptosis. Given the grim prognosis for cancer patients, this finding is of potential clinical relevance.

  11. Administration of Menadione, Vitamin K3, Ameliorates Off-Target Effects on Corneal Epithelial Wound Healing Due to Receptor Tyrosine Kinase Inhibition.

    Science.gov (United States)

    Rush, Jamie S; Bingaman, David P; Chaney, Paul G; Wax, Martin B; Ceresa, Brian P

    2016-11-01

    The antiangiogenic receptor tyrosine kinase inhibitor (RTKi), 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-[[[[4-(1-pyrrolidinyl) butyl] amino] carbonyl]amino]-4-isothiazolecarboxamide hydrochloride, targets VEGFR2 (half maximal inhibitory concentration [IC50] = 11 nM); however, off-target inhibition of epidermal growth factor receptor (EGFR) occurs at higher concentrations. (IC50 = 5.8 μM). This study was designed to determine the effect of topical RTKi treatment on EGF-mediated corneal epithelial wound healing and to develop new strategies to minimize off-target EGFR inhibition. In vitro corneal epithelial wound healing was measured in response to EGF using a transformed human cell line (hTCEpi cells). In vivo corneal wound healing was assessed using a murine model. In these complementary assays, wound healing was measured in the presence of varying RTKi concentrations. Immunoblot analysis was used to examine EGFR and VEGFR2 phosphorylation and the kinetics of EGFR degradation. An Alamar Blue assay measured VEGFR2-mediated cell biology. Receptor tyrosine kinase inhibitor exposure caused dose-dependent inhibition of EGFR-mediated corneal epithelial wound healing in vitro and in vivo. Nanomolar concentrations of menadione, a vitamin K3 analog, when coadministered with the RTKi, slowed EGFR degradation and ameliorated the inhibitory effects on epithelial wound healing both in vitro and in vivo. Menadione did not alter the RTKi's IC50 against VEGFR2 phosphorylation or its inhibition of VEGF-induced retinal endothelial cell proliferation. An antiangiogenic RTKi exhibited off-target effects on the corneal epithelium that can be minimized by menadione without deleteriously affecting its on-target VEGFR2 blockade. These data indicate that menadione has potential as a topical supplement for individuals suffering from perturbations in corneal epithelial homeostasis, especially as an untoward side effect of kinase inhibitors.

  12. Alternative therapeutic approach to renal-cell carcinoma: induction of apoptosis with combination of vitamin K3 and D-fraction.

    Science.gov (United States)

    Degen, Michael; Alexander, Bobby; Choudhury, Muhammad; Eshghi, Majid; Konno, Sensuke

    2013-12-01

    Because of a dismal prognosis for advanced renal-cell carcinoma (RCC), an alternative therapeutic approach, using vitamin K3 (VK3) and D-fraction (DF) was investigated. VK3 is a synthetic VK derivative and DF is a bioactive mushroom extract, and they have been shown to have antitumor activity. We examined if the combination of VK3 and DF would exhibit the improved anticancer effect on RCC in vitro. Human RCC, ACHN cell line, were treated with varying concentrations of VK3, DF, or a combination of the two. Cell viability was assessed at 72 hours by MTT assay. To explore the possible anticancer mechanism, studies on cell cycle, chromatin modifications, and apoptosis were conducted. VK3 alone led to a ~20% reduction in cell viability at 4 μM, while DF alone induced a 20% to 45% viability reduction at ≥ 500 μg/mL. A combination of VK3 (4 μM) and DF (300 μg/mL) led to a drastic >90% viability reduction, however. Cell cycle analysis indicated that VK3/DF treatment induced a G1 cell cycle arrest, accompanied by the up-regulation of p21(WAF1) and p27(Kip1). Histone deacetylase (HDAC) was also significantly (~60%) inactivated, indicating chromatin modifications. In addition, Western blot analysis revealed that the up-regulation of Bax and activation of poly-(ADP-ribose)-polymerase (PARP) were seen in VK3/DF-treated cells, indicating induction of apoptosis. The combination of VK3 and DF can lead to a profound reduction in ACHN cell viability, through a p21(WAF1)-mediated G1 cell cycle arrest, and ultimately induces apoptosis. Therefore, the combination of VK3/DF may have clinical implications as an alternative, improved therapeutic modality for advanced RCC.

  13. H32, a non-quinone sulfone analog of vitamin K3, inhibits human hepatoma cell growth by inhibiting Cdc25 and activating ERK.

    Science.gov (United States)

    Kar, Siddhartha; Wang, Meifang; Ham, Seung Wook; Carr, Brian I

    2006-10-01

    We previously synthesized a K-vitamin derivative, Cpd 5, which was a potent growth inhibitor of human tumor cells, including Hep3B hepatoma cells. However, being a quinone compound, Cpd 5 has the potential for generating toxic reactive oxygen species (ROS). We therefore synthesized a nonquinone sulfone derivative, H32, which has a sufone group substituting the quinone. The IC50 of H32 for Hep3B cells was found to be 2.5 microM, which was 2.5 and 3.2 times more potent than Cpd 5 and vitamin K3 respectively. It induced apoptosis in Hep3B cells but did not generate ROS when compared to Cpd 5. Interestingly, under similar culture conditions, normal rat hepatocytes were 14-fold more and 7-fold more resistant to the growth inhibitory effects of H32 than Hep3B and PLC/PRF5 cells respectively. H32 preferentially inhibited the activities of the cell cycle controlling Cdc25A phosphatase likely by binding to its catalytic cysteine. As a consequence, it induced inhibitory tyrosine phosphorylation of the Cdc25 substrate kinases Cdk2 and Cdk4 in Hep3B cells and the cells undergo an arrest in the G1 phase of the cell cycle. H32 also induced persistent phosphorylation of the MAPK protein ERK1/2, but marginal JNK1/2 and p38 phosphorylation. The ERK inhibitor U0126, added at least 30 min prior to H32, antagonized the growth inhibition induced by H32. However, the JNK and p38 inhibitors, JNKI-II and SB203580, were not able to antagonize H32 induced growth inhibition. Thus, H32 differentially inhibited growth of normal and liver tumor cells by preferentially inhibiting the actions of Cdc25 phosphatases and inducing persistent ERK phosphorylation.

  14. Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death.

    Directory of Open Access Journals (Sweden)

    Marco Tomasetti

    Full Text Available BACKGROUND: The redox-silent vitamin E analog α-tocopheryl succinate (α-TOS was found to synergistically cooperate with vitamin K3 (VK3 plus ascorbic acid (AA in the induction of cancer cell-selective apoptosis via a caspase-independent pathway. Here we investigated the molecular mechanism(s underlying cell death induced in prostate cancer cells by α-TOS, VK3 and AA, and the potential use of targeted drug combination in the treatment of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: The generation of ROS, cellular response to oxidative stress, and autophagy were investigated in PC3 prostate cancer cells by using drugs at sub-toxic doses. We evaluated whether PARP1-mediated apoptosis-inducing factor (AIF release plays a role in apoptosis induced by the combination of the agents. Next, the effect of the combination of α-TOS, VK3 and AA on tumor growth was examined in nude mice. VK3 plus AA induced early ROS formation associated with induction of autophagy in response to oxidative stress, which was reduced by α-TOS, preventing the formation of autophagosomes. α-TOS induced mitochondrial destabilization leading to the release of AIF. Translocation of AIF from mitochondria to the nucleus, a result of the combinatorial treatment, was mediated by PARP1 activation. The inhibition of AIF as well as of PARP1 efficiently attenuated apoptosis triggered by the drug combination. Using a mouse model of prostate cancer, the combination of α-TOS, VK3 and AA was more efficient in tumor suppression than when the drugs were given separately, without deleterious side effects. CONCLUSIONS/SIGNIFICANCE: α-TOS, a mitochondria-targeting apoptotic agent, switches at sub-apoptotic doses from autophagy-dependent survival of cancer cells to their demise by promoting the induction of apoptosis. Given the grim prognosis for cancer patients, this finding is of potential clinical relevance.

  15. Enhanced photoelectrocatalytic decomposition of copper cyanide complexes and simultaneous recovery of copper with a Bi2MoO6 electrode under visible light by EDTA/K4P2O7.

    Science.gov (United States)

    Zhao, Xu; Zhang, Juanjuan; Qiao, Meng; Liu, Huijuan; Qu, Jiuhui

    2015-04-07

    Simultaneous photoelectrocatalytic (PEC) oxidation of cyanides and recovery of copper in a PEC reactor with a Bi(2)MoO(6) photoanode was investigated at alkaline conditions under visible light irradiation. The surface variation of the Bi(2)MoO(6) photoanode and titanium cathode was characterized. The Cu mass distribution onto the anode, in the solution, and onto the cathode was fully investigated. In the individual PEC oxidation of copper cyanides, the formation of a black copper oxide on the anode occurred. By keeping the initial cyanide concentration at 0.01 mM, the effect of EDTA/K(4)P(2)O(7) was examined at different molar ratios of EDTA/K(4)P(2)O(7) to cyanide. It was indicated that the oxidation of cyanides increased and simultaneous copper electrodeposition with zero value onto the cathode was feasible at pH 11. Under the optimal conditions, the total cyanide concentration was lowered from 250 to 5.0 mg/L, and the Cu recovery efficiency deposited onto the cathode was higher than 90%. Cyanate was the only product. The role of the photogenerated hole in the oxidation of cyanide ions was confirmed.

  16. Cryogenic laboratory (80 K - 4 K)

    International Nuclear Information System (INIS)

    Brad, Sebastian; Steflea, Dumitru

    2002-01-01

    The technology of low temperature at the beginning of this century, developed for the production of oxygen, nitrogen and rare gases, was the basis for setting up the cryogenic technology in all the companies with these activity fields. The cryogenics section of today comprises engineering and construction of cryogenic plants for science, research and development, space technology, nuclear power techniques. Linde has designed and built a reliable small scale Helium liquefier. This fully automatic cryoliquefier operates for purification, liquefaction as well as re-liquefaction of Helium-gas, evaporated in cryostat systems. The basic equipment of the Linde L5 are the liquefier apparatus, transfer line, medium pressure buffer vessel, automatic purifier, compressor with mechanical oil separation unit, oil adsorber, electrical control unit. The accessories of the Linde L5 are the liquid helium storage tank, high-pressure gas supply, helium recovery unit, and cryocomponents. The cycle compressor C 101 designed as a single stage screw compressor supplies the liquefaction process with approx. 10 g/s of helium at a pressure of 10 to 12 bar and a temperature of approx. 300 K. In the first plate heat exchanger E 201 the gas is cooled down to approx. 70 K. Then the He high-pressure flow is divided: about 7 g/s reach the turbine X 201 via valve 203 (turbine entry) and are expanded there to approx. 4.6 bar, the gas cooling down to 64 K. After further cooling in the heat exchanger E 203 to about 16 K, another power-consuming expansion to 1.2 bar takes place. The implied cooling of the gas results in a temperature of 12 K at the outlet of the turbine X 202. This gas is then transferred to the low-pressure side of the heat exchanger E 204. The smaller part of the He high-pressure gas flow (approx. 3 g/s) is cooled down in the heat exchanger E 202 - E 205 to about 7 K. One part of the cold helium gas (approx. 0.17 g/s) is used in the purifier to cool down the feed gas to air condensing temperature (65 K). In the Joule-Thompson valve, the helium is expanded to 1.2 bar (corresponding to approx. 4.4 K). The resulting helium-liquid-mixture is transferred to the LHe container via a coaxial, vacuum-insulated transfer pipe. The He-cold-gas in the LHe container is transferred back to the low-pressure side of the heat exchanger E 205 to the cold-box via the transfer pipe. In the counter-flow to the cooling high-pressure flow the gas is now heated up to approx. 293 K in the heat exchangers. The gas leaving the cold-box at a pressure of approx. 1.07 bar is transferred to the suction side of the screw compressor together with the feed gas out of the helium reserve container via PC 111. To put into service the helium liquefier Type L5 tests were made to determine the performances and the cryogenic cycle efficiency: modified and complete components and spare parts, in order to adapted to our laboratory conditions; rebuild the liquid helium feeding system for the helium liquid tank and changed all the missed spare parts; redesigned the configuration for helium gas plant supplying system; vacuum test in order to determine that the leakage rates remain within tolerance levels; functioning tests for transfer line, oil-injected screw-compressor, helium recovery unit and electrical control unit. (authors)

  17. Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region

    International Nuclear Information System (INIS)

    Sakamoto, K; Imamura, T; Yano, M; Yoshida, H; Fujiki, A; Hirashima, Y; Hosoi, H

    2014-01-01

    All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML–RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPε and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML

  18. KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans.

    Directory of Open Access Journals (Sweden)

    Agnieszka Gacek-Matthews

    2016-08-01

    Full Text Available Histone posttranslational modifications (HPTMs are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich but are activated when nutrients are limiting. The exact molecular mechanisms by which HPTMs influence silencing and activation, however, are still to be better understood. Here we show by a combined approach of quantitative mass spectrometry (LC-MS/MS, genome-wide chromatin immunoprecipitation (ChIP-seq and transcriptional network analysis (RNA-seq that the core regions of silent A. nidulans SM clusters generally carry low levels of all tested chromatin modifications and that heterochromatic marks flank most of these SM clusters. During secondary metabolism, histone marks typically associated with transcriptional activity such as H3 trimethylated at lysine-4 (H3K4me3 are established in some, but not all gene clusters even upon full activation. KdmB, a Jarid1-family histone H3 lysine demethylase predicted to comprise a BRIGHT domain, a zinc-finger and two PHD domains in addition to the catalytic Jumonji domain, targets and demethylates H3K4me3 in vivo and mediates transcriptional downregulation. Deletion of kdmB leads to increased transcription of about ~1750 genes across nutrient-rich (primary metabolism and nutrient-limiting (secondary metabolism conditions. Unexpectedly, an equally high number of genes exhibited reduced expression in the kdmB deletion strain and notably, this group was significantly enriched for genes with known or predicted functions in secondary metabolite biosynthesis. Taken together, this study extends our general knowledge about multi-domain KDM5 histone demethylases and provides new details on the chromatin-level regulation of fungal secondary metabolite production.

  19. A comparative evaluation of cleaning efficacy (debris and smear layer removal) of hand and two NiTi rotary instrumentation systems (K3 and ProTaper): a SEM study.

    Science.gov (United States)

    Reddy, K Balakoti; Dash, Shreemoy; Kallepalli, Sowmya; Vallikanthan, Sangeetha; Chakrapani, N; Kalepu, Vamsi

    2013-11-01

    The present study was conducted to compare the cleaning efficacy (debris and smear layer removal) of hand and two NiTi rotary instrumentation systems (K3 and ProTaper). Sixty single rooted human maxillary anterior teeth decoronated at the cementoenamel junction were used. All the specimens were divided into four groups of 15 teeth each, group I--ProTaper rotary instrumentation done, group II--K3 rotary instrumentation done, group III--Stainless steel K-file instrumentation done, group IV--root canal irrigation without instrumentation. Root canal preparation was done in a crown down manner and 3% sodium hypochlorite was used as irrigant after each file followed by final rinse with 5 ml of 17% EDTA solution, then specimens were scanning electron microscopic (SEM) examination. Statistical analysis was done using one-way ANOVA followed by post hoc Tukey's HSD test. Group I showed highly statistical significant difference compared to other groups. There was no statistically significant difference considering smear layer at any levels among the groups with no smear layer formation in group IV. ProTaper rotary instrumentation showed the maximum cleaning efficacy followed by K3 rotary instrumentation in the coronal, middle and apical thirds of the root canal. ProTaper rotary instruments are more efficient than hand and K3 rotary instruments during root canal treatment.

  20. A study of luminescence from Eu"3"+, Ce"3"+, Tb"3"+ and Ce"3"+/Tb"3"+ in new potassium gadolinium phosphate K_3Gd_5(PO_4)_6

    International Nuclear Information System (INIS)

    Meng, Fangui; Zhang, Hongzhi; Chen, Cuili; Kim, Sun Il; Seo, Hyo Jin; Zhang, Xinmin

    2016-01-01

    New potassium gadolinium phosphate [K_3Gd_5(PO_4)_6] doped with Eu"3"+, Ce"3"+, Tb"3"+ and co-doped with Ce"3"+ and Tb"3"+ phosphors were prepared by high temperature solid state synthesis. Phase purity of the powders was checked by X-ray powder diffraction. Luminescence and excitation spectra of samples were reported. In particular, the interaction mechanism between Eu"3"+ ions was investigated in terms of the Inokuti–Hirayama model; it was found that the interactions between Eu"3"+ can be assigned to dipole–dipole interaction. K_3Gd_5(PO_4)_6:Eu"3"+ could act as a candidate for solid state lighting due to its strong absorption band in the near-UV region (350–400 nm). The energy transfer from Ce"3"+ to Tb"3"+ was confirmed and the mechanism was studied using Dexter's theory; it is concluded that electric dipole–dipole interaction predominates in the energy transfer process from Ce"3"+ to Tb"3"+ in the K_3Gd_5(PO_4)_6 host. The energy transfer efficiency and critical distance were also investigated. - Highlights: • Optical properties of K_3Gd_5(PO_4)_6:RE"3"+ are investigated for the first time. • The interaction mechanism between Eu"3"+ ions is attributed to dipole–dipole type. • K_3Eu_5(PO_4)_6 is a candidate phosphor for application to solid state lighting. • There exists an efficient energy transfer from Ce"3"+ to Tb"3"+ (η is up to 95%). • The mechanism of energy transfer process is electric dipole–dipole interaction.

  1. Determination of vitamins D2, D3, K1 and K3 and some hydroxy metabolites of vitamin D3 in plasma using a continuous clean-up-preconcentration procedure coupled on-line with liquid chromatography-UV detection.

    Science.gov (United States)

    Ortiz Boyer, F; Fernández Romero, J M; Luque de Castro, M D; Quesada, J M

    1999-03-01

    A semi-automatic procedure for the continuous clean-up and concentration of several fat-soluble vitamins prior to their separation by HPLC and UV detection is reported. The procedure is based on the use of a minicolumn packed with aminopropylsilica as sorbent located prior to the chromatographic detection system. The overall process was developed and applied to the main liposoluble vitamins (A, D2, D3, E, K1, K3) and several hydroxy metabolites of vitamin D3 [25-(OH)-D3,24,25-(OH)2-D3 and 1,25-(OH)2-D3]. All the analytes were monitored at a compromise wavelength of 270 nm. Calibration graphs were constructed between 0.01 and 100 ng ml-1 for vitamin D2 and D3 and their hydroxy metabolites, between 0.1 and 100 ng ml-1 for vitamin A, K1 and K3 and between 1 and 100 ng ml-1 for vitamin E, with excellent regression coefficients (> or = 0.9901) in all cases. The precision was established at two concentration levels with acceptable RSDs in all instances (between 3.6 and 8.7%). The method was appropriate for the determination of vitamin D2, D3, K1 and K3 and the 24,25-dihydroxy and 25-hydroxy metabolites of vitamin D3 in human plasma. The method was applied to plasma samples spiked with the target analytes and the recoveries ranged between 78 and 109%.

  2. SO4--SO3- radical pair formation in Ce doped and Ce, U co-doped K3Na(SO4)2: EPR evidence and its role in TSL

    International Nuclear Information System (INIS)

    Natarajan, V.; Seshagiri, T.K.; Kadam, R.M.; Sastry, M.D.

    2002-01-01

    Thermally stimulated luminescence (TSL) and electron paramagnetic resonance (EPR) studies were carried out on cerium doped and cerium-uranium co-doped K 3 Na(SO 4 ) 2 samples after γ-irradiation. Three glow peaks around 352, 415 and 475 K were observed and their spectral characteristics have shown that Ce 3+ and UO 2 2+ act as the emission centres in K 3 Na(SO 4 ) 2 :Ce and K 3 Na(SO 4 ) 2 :Ce, U, respectively. In Ce-U co-doped sample, energy transfer from cerium to uranium takes place. The commonly occurring radiation-induced centres in sulphates, viz SO 3 - and SO 4 - were observed by EPR and SO 4 - radical ion was found to take part in the TSL emission at 415 K. The hitherto unknown information, however, is the formation of SO 4 - -SO 3 - radical pair creating deep traps in these lattices, apparently assisted by the dopants. This is the first observation of such radical pair formation leading to the identification of deep traps in this lattice. The radical pair, (SO 3 - -SO 4 - ) which is stable up to 970 K, decreases the intensity of the peak at 415 K due to the depletion of SO 4 - centres

  3. Feleucin-BO1: a novel antimicrobial non-apeptide amide from the skin secretion of the toad, Bombina orientalis, and design of a potent broad-spectrum synthetic analogue, feleucin-K3.

    Science.gov (United States)

    Hou, Xiaojuan; Du, Qiang; Li, Renjie; Zhou, Mei; Wang, Hui; Wang, Lei; Guo, Can; Chen, Tianbao; Shaw, Chris

    2015-03-01

    Feleucins-BV1 and -BV2 are recently described prototypes of a novel antimicrobial non-apeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin-BO1 (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 μm) but was inactive (> 250 μm) against the Gram-negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3 (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly enhanced potency and spectrum of activity. The MICs of F-K3 against the reference micro-organisms were 7 μm (S. aureus), 14 μm (E. coli) and 7 μm (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility. © 2014 John Wiley & Sons A/S.

  4. AMİNOPROPİL SİLİKAJEL İMMOBİLİZE KALİKS[4]AREN POLİMERİ (K[4]APS KULLANILARAK p-NİTROFENOLÜN SULU ÇÖZELTİLERDEN GİDERİMİ

    Directory of Open Access Journals (Sweden)

    Vahti Aladağlı

    2015-11-01

    Full Text Available Bu çalışma yeni polimerik kaliksaren türevinin hazırlanması ve p-nitrofenolün (PNF adsorpsiyonunda sorbent malzemesi olarak uygulanmasını içermektedir. Kaliksaren türevleri 1-5'in hazırlanmasından sonra, 5 no'lu moleküle aminopropil silika jel destek maddesi tutturularak polimerik kaliksaren 6 türevi elde edildi. Bütün bileşikler, FTIR, 1H NMR, elemental analizi, TGA ve SEM gibi metotlar kullanılarak karakterize edildi. Aminopropil silika jel immobilize kaliks[4]aren (K[4]APS 6, PNF adsorpsiyonu çalışmalarında sorbent olarak kullanılmış ve pH, etkileşim süresi, konsantrasyon, proses sıcaklığı ve sorbent dozajı gibi parametreler çalışıldı. Sonuçlara göre, 6 no'lu molekülün PNF adsorpsiyonu için optimum koşullar pH 6, etkileşim süresi 1 saat, PNF konsantrasyonu 5.0x10-5 M, sorbent dozajı 0.025g ve proses sıcaklığı 25oC olarak bulundu. PNF adsorpsiyon mekanizması, Langmuir ve Freundlich izotermleri ile değerlendirildi

  5. THE VOLATILE COMPOSITION OF COMET C/2003 K4 (LINEAR) AT NEAR-IR WAVELENGTHS—COMPARISONS WITH RESULTS FROM THE NANÇAY RADIO TELESCOPE AND FROM THE ODIN, SPITZER, AND SOHO SPACE OBSERVATORIES

    Energy Technology Data Exchange (ETDEWEB)

    Paganini, L.; Mumma, M. J.; Villanueva, G. L.; DiSanti, M. A.; Bonev, B. P., E-mail: lucas.paganini@nasa.gov [Goddard Center for Astrobiology, NASA GSFC, MS 690, Greenbelt, MD 20771 (United States)

    2015-07-20

    We observed comet C/2003 K4 (LINEAR) using NIRSPEC at the Keck Observatory on UT 2004 November 28, when the comet was at 1.28 AU from the Sun (post-perihelion) and 1.38 AU from Earth. We detected six gaseous species (H{sub 2}O, OH*, C{sub 2}H{sub 6}, CH{sub 3}OH, CH{sub 4}, and HCN) and obtained upper limits for three others (H{sub 2}CO, C{sub 2}H{sub 2}, and NH{sub 3}). Our results indicate a water production rate of (1.72 ± 0.18) × 10{sup 29} molecules s{sup −1}, in reasonable agreement with production rates from SOHO (on the same day), Odin (one day earlier), and Nançay (about two weeks earlier). We also report abundances (relative to water) for seven trace species: CH{sub 3}OH (∼1.8%), CH{sub 4} (∼0.9%), and C{sub 2}H{sub 6} (∼0.4%) that were consistent with mean values among Oort cloud (OC) comets, while NH{sub 3} (<0.55%), HCN (∼0.07%), H{sub 2}CO (<0.07%), and C{sub 2}H{sub 2} (<0.04%) were “lower” than the mean values in other OC comets. We extracted inner-coma rotational temperatures for four species (H{sub 2}O, C{sub 2}H{sub 6}, CH{sub 3}OH, and CH{sub 4}), all of which are consistent with 70 K (within 1σ). The extracted ortho-para ratio for water was 3.0 ± 0.15, corresponding to spin temperatures larger than 39 K (at the 1σ level) and agreeing with those obtained with the Spitzer Space Telescope at the 2σ level.

  6. Report on EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 (EUROMET project no. 813): Comparison of air kerma and absorbed dose to water measurements of 60Co radiation beams for radiotherapy

    International Nuclear Information System (INIS)

    Csete, I.; Leiton, A.G.; Sochor, V.; Lapenas, A.; Grindborg, J.E.; Jokelainen, I.; Bjerke, H.; Dobrovodsky, J.; Megzifene, A.; Hourdakis, C.J.; Ivanov, R.; Vekic, B.; Kokocinski, J.; Cardoso, J.; Buermann, L.; Tiefenboeck, W.; Stucki, G.; Van Dijk, E.; Toni, M.P.; Minniti, R.; McCaffrey, J.P.; Silva, C.N.M.; Kharitonov, I.; Webb, D.; Saravi, M.; Delaunay, F.

    2010-01-01

    The results of an unprecedented international effort involving 26 countries are reported. The EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 key comparisons were conducted with the goal of supporting the relevant calibration and measurement capabilities (CMC) planned for publication by the participant laboratories. The measured quantities were the air kerma (K air ) and the absorbed dose to water (Dw) in 60 Co radiotherapy beams. The comparison was conducted by the pilot laboratory MKEH (Hungary), in a star-shaped arrangement from January 2005 to December 2008. The calibration coefficients of four transfer ionization chambers were measured using two electrometers. The largest deviation between any two calibration coefficients for the four chambers in terms of air kerma and absorbed dose to water was 2.7% and 3.3% respectively. An analysis of the participant uncertainty budgets enabled the calculation of degrees of equivalence (DoE), in terms of the deviations of the results and their associated uncertainties. As a result of this EUROMET project 813 comparison, the BIPM key comparison database (KCDB) will include eleven new Kair and fourteen new D w DoE values of European secondary standard dosimetry laboratories (SSDLs), and the KCDB will be updated with the new DoE values of the other participant laboratories. The pair-wise degrees of equivalence of participants were also calculated. In addition to assessing calibration techniques and uncertainty calculations of the participants, these comparisons enabled the experimental determinations of N Dw /N Kair ratios in the 60 Co gamma radiation beam for the four radiotherapy transfer chambers. (authors)

  7. Report on EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 (EUROMET project no. 813): Comparison of air kerma and absorbed dose to water measurements of {sup 60}Co radiation beams for radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Csete, I. [National Office of Measures (OMH) - pilot laboratory and corresponding author (Hungary); Leiton, A.G. [Research Centre for Energy, Environment and Technology (CMRI-CIEMAT) (Spain); Sochor, V. [Czech Metrology Institute (CMI) (Czech Republic); Lapenas, A. [Latvian National Metrology Center (LNMC-RMTC) (Latvia); Grindborg, J.E. [Swedish Radiation Protection Authority (SSI) (Sweden); Jokelainen, I. [Radiation and Nuclear Safety Authority (STUK) (Finland); Bjerke, H. [Norwegian Radiation Protection Authority (NRPA) (Norway); Dobrovodsky, J. [Slovak Institute of Metrology (SMU) (Slovakia); Megzifene, A. [International Atomic Energy Agency, IAEA, Vienna (Austria); Hourdakis, C.J. [Hellenic Atomic Energy Committee (HAEC-HIRCL) (Greece); Ivanov, R. [National Centre of Metrology (NCM) (Bulgaria); Vekic, B. [Rudjer Boskovic Institute (IRB) (Croatia); Kokocinski, J. [Central Office of Measures (GUM) (Poland); Cardoso, J. [Institute for Nuclear Technology (ITN-LMRIR) (Portugal); Buermann, L. [Physikalisch Technische Bundesanstalt (PTB) (Germany); Tiefenboeck, W. [Bundesamt fur Eich und Vermesungswesen (BEV) (Austria); Stucki, G. [17 Bundesamt fur Metrologie (METAS) (Switzerland); Van Dijk, E. [NMi Van Swinden Laboratorium (NMi) (Netherlands); Toni, M.P. [ENEA-CR Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti (ENEA) (Italy); Minniti, R. [20 National Institute of Standards and Technology (NIST) (United States); McCaffrey, J.P. [National Research Council Canada (NRC) (Canada); Silva, C.N.M. [National Metrology Laboratory of Ionizing Radiation (LNMRI-IRD) (Brazil); Kharitonov, I. [D I Mendeleyev Institute for Metrology (VNIIM) (RU); Webb, D. [Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) (Australia); Saravi, M. [National Atomic Energy Commission (CNEA-CAE) (Argentina); Delaunay, F. [Laboratoire National Henri Becquerel (LNE-LNHB) (France)

    2010-06-15

    The results of an unprecedented international effort involving 26 countries are reported. The EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 key comparisons were conducted with the goal of supporting the relevant calibration and measurement capabilities (CMC) planned for publication by the participant laboratories. The measured quantities were the air kerma (K{sub air}) and the absorbed dose to water (Dw) in {sup 60}Co radiotherapy beams. The comparison was conducted by the pilot laboratory MKEH (Hungary), in a star-shaped arrangement from January 2005 to December 2008. The calibration coefficients of four transfer ionization chambers were measured using two electrometers. The largest deviation between any two calibration coefficients for the four chambers in terms of air kerma and absorbed dose to water was 2.7% and 3.3% respectively. An analysis of the participant uncertainty budgets enabled the calculation of degrees of equivalence (DoE), in terms of the deviations of the results and their associated uncertainties. As a result of this EUROMET project 813 comparison, the BIPM key comparison database (KCDB) will include eleven new Kair and fourteen new D{sub w} DoE values of European secondary standard dosimetry laboratories (SSDLs), and the KCDB will be updated with the new DoE values of the other participant laboratories. The pair-wise degrees of equivalence of participants were also calculated. In addition to assessing calibration techniques and uncertainty calculations of the participants, these comparisons enabled the experimental determinations of N{sub Dw}/N{sub Kair} ratios in the {sup 60}Co gamma radiation beam for the four radiotherapy transfer chambers. (authors)

  8. Micro–Positron Emission Tomography/Contrast-Enhanced Computed Tomography Imaging of Orthotopic Pancreatic Tumor–Bearing Mice Using the αvβ3 Integrin Tracer 64Cu-Labeled Cyclam-RAFT-c(-RGDfK-4

    Directory of Open Access Journals (Sweden)

    Winn Aung

    2013-09-01

    Full Text Available The purpose of this study was to develop a clinically relevant orthotopic xenotransplantation model of pancreatic cancer and to perform a preclinical evaluation of a new positron emission tomography (PET imaging probe, 64Cu-labeled cyclam-RAFT-c(-RGDfK-4 peptide (64Cu-RAFT-RGD, using this model. Varying degrees of αvβ3 integrin expression in several human pancreatic cancer cell lines were examined by flow cytometry and Western blotting. The cell line BxPC-3, which is stably transfected with a red fluorescence protein (RFP, was used for surgical orthotopic implantation. Orthotopic xenograft was established in the pancreas of recipient nude mice. An in vivo probe biodistribution and receptor blocking study, preclinical PET imaging coregistered with contrast-enhanced computed tomography (CECT comparing 64Cu-RAFT-RGD and 18F-fluoro-2-deoxy-D-glucose (18F-FDG accumulation in tumor, postimaging autoradiography, and histologic and immunohistochemical examinations were done. Biodistribution evaluation with a blocking study confirmed that efficient binding of probe to tumor is highly αvβ3 integrin specific. 64Cu-RAFT-RGD PET combined with CECT provided for precise and easy detection of cancer lesions. Autoradiography, histologic, and immunohistochemical examinations confirmed the accumulation of 64Cu-RAFT-RGD in tumor versus nontumor tissues. In comparative PET studies, 64Cu-RAFT-RGD accumulation provided better tumor contrast to background than 18F-FDG. Our results suggest that 64Cu-RAFT-RGD PET imaging is potentially applicable for the diagnosis of αvβ3 integrin–expressing pancreatic tumors.

  9. Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J Recombination.

    Science.gov (United States)

    Matheson, Louise S; Bolland, Daniel J; Chovanec, Peter; Krueger, Felix; Andrews, Simon; Koohy, Hashem; Corcoran, Anne E

    2017-01-01

    V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa ( Igκ ) light chain recombination follows immunoglobulin heavy chain ( Igh ) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells. It is unknown whether local chromatin states contribute to Vκ gene choice during Igκ recombination. Here we adapt VDJ-seq to profile the Igκ VκJκ repertoire and present a comprehensive readout in mouse pre-B cells, revealing highly variable Vκ gene usage. Integration with genome-wide datasets for histone modifications, DNase hypersensitivity, transcription factor binding and germline transcription identified PU.1 binding at the RSS, which was unimportant for Igh , as highly predictive of whether a Vκ gene will recombine or not, suggesting that it plays a binary, all-or-nothing role, priming genes for recombination. Thereafter, the frequency with which these genes recombine was shaped both by the presence and level of enrichment of several other chromatin features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to the Igh locus, the chromatin landscape of the promoter, as well as of the RSS, contributes to Vκ gene recombination. Thus, multiple facets of local chromatin features explain much of the variation in Vκ gene usage. Together, these findings reveal shared and divergent roles for epigenetic features and transcription factors in AgR V(D)J recombination and provide avenues for further investigation of chromatin signatures that may underpin V(D)J-mediated chromosomal translocations.

  10. Investigating small molecules to inhibit germinal center kinase-like kinase (GLK/MAP4K3) upstream of PKCθ phosphorylation: Potential therapy to modulate T cell dependent immunity.

    Science.gov (United States)

    May-Dracka, Tricia L; Arduini, Robert; Bertolotti-Ciarlet, Andrea; Bhisetti, Govinda; Brickelmaier, Margot; Cahir-McFarland, Ellen; Enyedy, Istvan; Fontenot, Jason D; Hesson, Thomas; Little, Kevin; Lyssikatos, Joe; Marcotte, Douglas; McKee, Timothy; Murugan, Paramasivam; Patterson, Thomas; Peng, Hairuo; Rushe, Mia; Silvian, Laura; Spilker, Kerri; Wu, Ping; Xin, Zhili; Burkly, Linda C

    2018-06-01

    Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the treatment of autoimmune diseases. This approach circumvents previous unsuccessful approaches to target PKCθ directly. The use of structure based drug design, aided by the first crystal structure of GLK, led to the discovery of several inhibitors that demonstrate potent inhibition of GLK biochemically and in relevant cell lines. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. World Food Day Curriculum, Grades K-3.

    Science.gov (United States)

    Zander, Janet

    Hunger and malnutrition lead to the deaths of 13-18 million people a year; 75 percent of these victims are children. World Food Day was created to focus attention on the world's food and farm problems and to encourage the world's people to become directly involved in the solution of these problems. It is sponsored jointly by the United Nations…

  12. Optimasi Lahan Dengan Sistem Tumpangsari Jagung Manis (Zea Mays Saccharata, Strurt) Dan Kangkung Sutera (Ipomea Reptans) Di Pekanbaru

    OpenAIRE

    Surtinah, Surtinah; Susi, Neng; Lestari, Sri Utami

    2016-01-01

    Penelitian dilaksanakan secara eksperimen dengan menggunakan rancangan lingkungan acak lengkap dengan 3 kali ulangan, dan rancangan perlakuan yaitu waktu tanam kangkung sebagai tanaman tumpangsari pada budidaya jagung manis ( K ) yang terdiri dari : k1 = waktu tanam bersamaan; k2 = waktu tanam kangkung 1 minggu setelah tanam jagung manis; k3 = waktu tanam kangkung 2 minggu setelah tanam jagung manis; k4 = waktu tanam kangkung 3 minggu setelah tanam jagung manis; k5= penanaman jagung manis tu...

  13. An open-framework bimetallic chalcogenide structure K3Rb3Zn4Sn3Se13 built on a unique [Zn4Sn3Se16]12- cluster: synthesis, crystal structure, ion exchange and optical properties

    International Nuclear Information System (INIS)

    Wu Min; Su Weiping; Jasutkar, Niren; Huang, Xiaoying; Li Jing

    2005-01-01

    Single crystals of K 3 Rb 3 Zn 4 Sn 3 Se 13 were synthesized by solvothermal method. The building block in this structure is a [Zn 4 Sn 3 Se 16 ] 12- cluster which consists of four ZnSe 4 and three SnSe 4 tetrahedra connected through corner-sharing of Se atoms. The 3D network contains intersecting channels running parallel to the crystallographic [2 1 1], [1-1-1] and [12-1] directions. The disordered K + and Rb + cations reside in these channels. Ion exchange of Cs + with disordered Rb + /K + ions in the structure showed a partial replacement of 15.8%. Optical diffuse reflectance experiments were carried out and gave a sharp absorption edge at 2.6 eV

  14. Over 15 MA/cm2 of critical current density in 4.8 µm thick, Zr-doped (Gd,Y)Ba2Cu3Ox superconductor at 30 K, 3T.

    Science.gov (United States)

    Majkic, Goran; Pratap, Rudra; Xu, Aixia; Galstyan, Eduard; Selvamanickam, Venkat

    2018-05-03

    An Advanced MOCVD (A-MOCVD) reactor was used to deposit 4.8 µm thick (Gd,Y)BaCuO tapes with 15 mol% Zr addition in a single pass. A record-high critical current density (J c ) of 15.11 MA/cm 2 has been measured over a bridge at 30 K, 3T, corresponding to an equivalent (I c ) value of 8705 A/12 mm width. This corresponds to a lift factor in critical current of ~11 which is the highest ever reported to the best of author's knowledge. The measured critical current densities at 3T (B||c) and 30, 40 and 50 K, respectively, are 15.11, 9.70 and 6.26 MA/cm 2 , corresponding to equivalent Ic values of 8705, 5586 and 3606 A/12 mm and engineering current densities (J e ) of 7068, 4535 and 2928 A/mm 2 . The engineering current density (J e ) at 40 K, 3T is 7 times higher than that of the commercial HTS tapes available with 7.5 mol% Zr addition. Such record-high performance in thick films (>1 µm) is a clear demonstration that growing thick REBCO films with high critical current density (J c ) is possible, contrary to the usual findings of strong J c degradation with film thickness. This achievement was possible due to a combination of strong temperature control and uniform laminar flow achieved in the A-MOCVD system, coupled with optimization of BaZrO 3 nanorod growth parameters.

  15. Calculation of the total electron excitation cross section in the Born approximation using Slater wave functions for the Li (2s yields 2p), Li (2s yields 3p), Na (3s yields 4p), Mg (3p yields 4s), Ca (4s yields 4p) and K (4s yields 4p) excitations. M.S. Thesis

    Science.gov (United States)

    Simsic, P. L.

    1974-01-01

    Excitation of neutral atoms by inelastic scattering of incident electrons in gaseous nebulae were investigated using Slater Wave functions to describe the initial and final states of the atom. Total cross sections using the Born Approximation are calculated for: Li(2s yields 2p), Na(3s yields 4p), k(4s yields 4p). The intensity of emitted radiation from gaseous nebulae is also calculated, and Maxwell distribution is employed to average the kinetic energy of electrons.

  16. Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor

    DEFF Research Database (Denmark)

    Kristensen, Line Hyltoft; Nielsen, Anders Laerke; Helgstrand, Charlotte

    2012-01-01

    Dynamic methylations and demethylations of histone lysine residues are important for gene regulation and are facilitated by histone methyltransferases and histone demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2 specific lysine demethylase belonging to the family of JmjC domain containing...... lysine specific HDMs (JHDMs). Several studies have linked KDM5B to breast, prostate and skin cancer, highlighting its potential as a drug target. However, most inhibitor studies have focused on other JHDMs, and inhibitors for KDM5B remain to be explored. Here, we report the expression, purification...... and characterization of the catalytic core of recombinant KDM5B (residues 1-769, ccKDM5B). We show that ccKDM5B, recombinantly expressed in insect cells, demethylates H3K4me3 and H3K4me2 in vitro. The kinetic characterization showed that ccKDM5B has a K(m) (app) value of 0.5 µM for its tri-methylated substrate H3...

  17. Solvothermal indium fluoride chemistry: Syntheses and crystal structures of K5In3F14, β-(NH4)3InF6 and [NH4]3[C6H21N4]2[In4F21

    International Nuclear Information System (INIS)

    Jayasundera, Anil C.A.; Goff, Richard J.; Li Yang; Finch, Adrian A.; Lightfoot, Philip

    2010-01-01

    The solvothermal syntheses and crystal structures of three indium fluorides are presented. K 5 In 3 F 14 (1) and β-(NH 4 ) 3 InF 6 (2) are variants on known inorganic structure types chiolite and cryolite, respectively, with the latter exhibiting a complex and apparently novel structural distortion. [NH 4 ] 3 [C 6 H 21 N 4 ] 2 [In 4 F 21 ] (3) represents a new hybrid composition displaying a unique trimeric metal fluoride building unit. - Graphical abstract: Solvothermal synthesis has been used to prepare three indium fluorides, including a novel hybrid material containing a unique [In 3 F 15 ] trimer templated by tren.

  18. Effects of K3[Fe(CN)6] slurry's pH value and applied potential on tungsten removal rate for chemical-mechanical planarization application

    Energy Technology Data Exchange (ETDEWEB)

    Akonko, S.B.; Li, D.Y.; Ziomek-Moroz, M.; Hawk, J.A.; Miller, A.; Cadien, K.

    2005-07-01

    Chemical-mechanical planarization (CMP) is an important process for building multilevel interconnections for electronic devices. Directly planarizing tungsten, which is used as via or contact in microelectronic circuits, by wear is a difficult process because of its high hardness. Therefore, an effective approach has been developed to facilitate planarizing tungsten surface by removing a continuously growing passive film on tungsten when exposed to a low-pH potassium ferricyanide slurry. Since the passive film is softer than tungsten, this chemical mechanical planarization process is effective. In this work, in order to determine effects of corrosion and wear on tungsten removal rate, attempts were made to investigate corrosion, wear, and corrosive wear behavior of tungsten in K3[Fe(CN)6] slurries. Electrochemical and tribological experiments were carried out for different slurry pH values and potentials using a rotating pin-on-disc tribometer. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were employed to characterize surface films formed at the different pH levels and potentials. It was demonstrated that the tungsten removal rate increased with increasing slurry pH and potential. Mechanisms involved are discussed.

  19. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats.

    Science.gov (United States)

    Hirota, Yoshihisa; Tsugawa, Naoko; Nakagawa, Kimie; Suhara, Yoshitomo; Tanaka, Kiyoshi; Uchino, Yuri; Takeuchi, Atsuko; Sawada, Natsumi; Kamao, Maya; Wada, Akimori; Okitsu, Takashi; Okano, Toshio

    2013-11-15

    Mice have the ability to convert dietary phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) and store the latter in tissues. A prenyltransferase enzyme, UbiA prenyltransferase domain-containing 1 (UBIAD1), is involved in this conversion. There is evidence that UBIAD1 has a weak side chain cleavage activity for phylloquinone but a strong prenylation activity for menadione (vitamin K3), which has long been postulated as an intermediate in this conversion. Further evidence indicates that when intravenously administered in mice phylloquinone can enter into tissues but is not converted further to menaquinone-4. These findings raise the question whether phylloquinone is absorbed and delivered to tissues in its original form and converted to menaquinone-4 or whether it is converted to menadione in the intestine followed by delivery of menadione to tissues and subsequent conversion to menaquinone-4. To answer this question, we conducted cannulation experiments using stable isotope tracer technology in rats. We confirmed that the second pathway is correct on the basis of structural assignments and measurements of phylloquinone-derived menadione using high resolution MS analysis and a bioassay using recombinant UBIAD1 protein. Furthermore, high resolution MS and (1)H NMR analyses of the product generated from the incubation of menadione with recombinant UBIAD1 revealed that the hydroquinone, but not the quinone form of menadione, was an intermediate of the conversion. Taken together, these results provide unequivocal evidence that menadione is a catabolic product of oral phylloquinone and a major source of tissue menaquinone-4.

  20. Menadione (Vitamin K3) induces apoptosis of human oral cancer cells and reduces their metastatic potential by modulating the expression of epithelial to mesenchymal transition markers and inhibiting migration.

    Science.gov (United States)

    Suresh, Shruthy; Raghu, Dinesh; Karunagaran, Devarajan

    2013-01-01

    Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient's survival rate due to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in various cancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition (EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reduced the expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independent growth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate in oral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blocking EMT in oral cancer cells.

  1. Critical current density above 15 MA cm−2 at 30 K, 3 T in 2.2 μm thick heavily-doped (Gd,Y)Ba2Cu3Ox superconductor tapes

    International Nuclear Information System (INIS)

    Selvamanickam, V; Gharahcheshmeh, M Heydari; Xu, A; Zhang, Y; Galstyan, E

    2015-01-01

    A critical current (I c ) value of 3963 A/12 mm, corresponding to a critical current density (J c ) of 15 MA cm −2 has been achieved at 30 K, 3 T in the orientation of field parallel to the c-axis (B||c) in 2.2 μm thick film (Gd,Y)BaCuO tapes with 20 mol% Zr addition made by metal organic chemical vapor deposition. This J c level is more than a factor of four higher than the J c values of 7.5 mol% Zr-added tapes, which are an industry benchmark. The critical current values in a magnetic field of 3 T parallel to the c-axis in the 2.2 μm thick, 20 mol% Zr-added tape reached 2833 A/12 mm (10.1 MA cm −2 ), 1881 A/12 mm (7.1 MA cm −2 ) and 805 A/12 mm (3.1 MA cm −2 ) at 40 K, 50 K and 65 K respectively. Such high critical current values were possible because of maintaining a strong alignment of BaZrO 3 nanocolumns along the c-axis over the entire film thickness. (fast track communication)

  2. Decision Making Perspectives of Young Children (K-5).

    Science.gov (United States)

    Rogers, Linda J.; McDonald, Linda L.

    1999-01-01

    Applies Blumer's theory of symbolic interactionism to explore how normal children make meaning of their decision making world, both of their own acts and the labyrinthine world adults structure for them. Schema/narratives on friendship, sports, adults, and school reveal knowledge making strategies defined by immediate experiences and a capacity to…

  3. A Poisson process approximation for generalized K-5 confidence regions

    Science.gov (United States)

    Arsham, H.; Miller, D. R.

    1982-01-01

    One-sided confidence regions for continuous cumulative distribution functions are constructed using empirical cumulative distribution functions and the generalized Kolmogorov-Smirnov distance. The band width of such regions becomes narrower in the right or left tail of the distribution. To avoid tedious computation of confidence levels and critical values, an approximation based on the Poisson process is introduced. This aproximation provides a conservative confidence region; moreover, the approximation error decreases monotonically to 0 as sample size increases. Critical values necessary for implementation are given. Applications are made to the areas of risk analysis, investment modeling, reliability assessment, and analysis of fault tolerant systems.

  4. Integration of Collaborative Learning in Grade K-5 EFL Classrooms

    Science.gov (United States)

    Shahamat, Ailar; Mede, Enisa

    2016-01-01

    This study investigated the effectiveness of integrating collaborative learning in Turkish elementary (primary) classrooms where English is acquired as a foreign language. Specifically, it aimed at shedding light on how the participating students and teachers perceive such language classes, what are the effects of integrating this particular…

  5. Integrating the Performing Arts in Grades K-5

    Science.gov (United States)

    Rajan, Rekha S.

    2012-01-01

    Research documents that the arts boost learning, build confidence, and motivate students to participate in class. How do we keep the performing arts alive in this era of increased accountability and decreased funding? Rekha S. Rajan sets the stage for a creative and practical solution with detailed, concrete examples of how to integrate the…

  6. Fluorcanasite, K3Na3Ca5Si12O30(F,OH)4 · H2O, a new mineral species from the Khibiny alkaline pluton, Kola Peninsula, Russia, and new data on canasite

    Science.gov (United States)

    Khomyakov, A. P.; Nechelyustov, G. N.; Krivokoneva, G. K.; Rastsvetaeva, R. K.; Rozenberg, K. A.; Rozhdestvenskaya, I. V.

    2009-12-01

    .21)Σ4 · 0.98H2O. The idealized formula is K3Na3Ca5Si12O30(F,OH)4 · H2O, F > OH or K3Na3Ca5(Si12O30)F4 · H2O. The IR spectrum of the mineral, description of its crystal structure, and comparison with its close analogues, canasite and frankamenite, are given in the paper. New optical parameters and crystal data are presented for the type specimen of canasite from the Materialnaya adit, Mt. Yukspor, Khibiny. Type material is deposited at the Fersman Mineralogical Museum, Russian Academy of Sciences, Moscow.

  7. Menadione (Vitamin K3) Is a Catabolic Product of Oral Phylloquinone (Vitamin K1) in the Intestine and a Circulating Precursor of Tissue Menaquinone-4 (Vitamin K2) in Rats*

    Science.gov (United States)

    Hirota, Yoshihisa; Tsugawa, Naoko; Nakagawa, Kimie; Suhara, Yoshitomo; Tanaka, Kiyoshi; Uchino, Yuri; Takeuchi, Atsuko; Sawada, Natsumi; Kamao, Maya; Wada, Akimori; Okitsu, Takashi; Okano, Toshio

    2013-01-01

    Mice have the ability to convert dietary phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) and store the latter in tissues. A prenyltransferase enzyme, UbiA prenyltransferase domain-containing 1 (UBIAD1), is involved in this conversion. There is evidence that UBIAD1 has a weak side chain cleavage activity for phylloquinone but a strong prenylation activity for menadione (vitamin K3), which has long been postulated as an intermediate in this conversion. Further evidence indicates that when intravenously administered in mice phylloquinone can enter into tissues but is not converted further to menaquinone-4. These findings raise the question whether phylloquinone is absorbed and delivered to tissues in its original form and converted to menaquinone-4 or whether it is converted to menadione in the intestine followed by delivery of menadione to tissues and subsequent conversion to menaquinone-4. To answer this question, we conducted cannulation experiments using stable isotope tracer technology in rats. We confirmed that the second pathway is correct on the basis of structural assignments and measurements of phylloquinone-derived menadione using high resolution MS analysis and a bioassay using recombinant UBIAD1 protein. Furthermore, high resolution MS and 1H NMR analyses of the product generated from the incubation of menadione with recombinant UBIAD1 revealed that the hydroquinone, but not the quinone form of menadione, was an intermediate of the conversion. Taken together, these results provide unequivocal evidence that menadione is a catabolic product of oral phylloquinone and a major source of tissue menaquinone-4. PMID:24085302

  8. Final report on key comparison APMP.M.P-K3: Absolute pressure measurements in gas from 3 × 10-6 Pa to 9 × 10-4 Pa

    Science.gov (United States)

    Yoshida, H.; Arai, K.; Akimichi, H.; Hong, S. S.; Song, H. W.

    2011-01-01

    The results of a key comparison of ultra-high vacuum standards at two national metrology institutes (NMIJ/AIST and KRISS) are reported. This bilateral comparison was carried out from May 2010 to October 2010 within the framework of the Asia-Pacific Metrology Programme (APMP) to determine their degrees of equivalence at pressures in the range from 3 × 10-6 Pa to 9 × 10-4 Pa. The pilot institute was NMIJ/AIST. Two spinning rotor gauges and two hot cathode ionization gauges were used as the transfer standards. NMIJ/AIST used two calibration systems: the dynamic expansion system (NMIJ-DES) and two-stage flow-dividing system (NMIJ-TFS). KRISS used the dynamic expansion system. The transfer standards were sufficiently stable to meet the requirements of the comparison compared with those of previous international comparisons owing to some improvements of the protocol and the transfer standards. The ultra-high vacuum standards of NMIJ/AIST and KRISS were found to be equivalent within their claimed uncertainties in the range from 3 × 10-6 Pa to 9 × 10-5 Pa. The NMIJ-DES results, which have smaller uncertainty than NMIJ-TFS, were transferred to the corresponding CCM key comparison, CCM.P-K3, in the range from 3 × 10-6 Pa to 9 × 10-5 Pa and it is shown that the NMIJ values were equivalent to the CCM key comparison reference value within the claimed uncertainties. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  9. Mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3) overexpression is an early event in esophageal tumorigenesis and is a predictor of poor disease prognosis

    International Nuclear Information System (INIS)

    Hasan, Raghibul; Sharma, Rinu; Saraya, Anoop; Chattopadhyay, Tushar K; DattaGupta, Siddartha; Walfish, Paul G; Chauhan, Shyam S; Ralhan, Ranju

    2014-01-01

    Mitogen-activated protein kinase kinase kinase3 (MAP3K3/MEKK3) was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. Here in we determined the clinical significance of MEKK3 in ESCC. Immunohistochemical analysis of MEKK3 expression was carried out in archived tissue sections from 93 ESCCs, 47 histologically normal and 61 dysplastic esophageal tissues and correlated with clinicopathological parameters and disease prognosis over up to 7.5 years for ESCC patients. MEKK3 expression was significantly increased in esophageal dysplasia and ESCC in comparison with normal mucosa (p trend < 0.001). Kaplan Meier survival analysis showed significantly reduced median disease free survival median DFS = 10 months in patients with MEKK3 positive ESCCs compared to patients with no immunopositivity (median DFS = 19 months, p = 0.04). ESCC patients with MEKK3 positive and lymph node positive tumors had median DFS = 9 months, as compared to median DFS = 21 months in patients who did not show the alterations (p = 0.01). In multivariate Cox regression analysis, combination of MEKK3 overexpression and node positivity [p = 0.015, hazard ratio (HR) = 2.082, 95% CI = 1.154 - 3.756] emerged as important predictor of reduced disease free survival and poor prognosticator for ESCC patients. Alterations in MEKK3 expression occur in early stages of development of ESCC and are sustained during disease progression; MEKK3 in combination with lymph node positivity has the potential to serve as adverse prognosticator in ESCC

  10. Knowledge for Democracy Myanmar (K4DM): Operating costs for ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Political transition is therefore dependent on meeting basic development needs ... informed, and engaged public participation to deepen the democratic process. ... and reach out to strengthen the use of science and evidence by the media.

  11. Design and syntheses of hybrid metal-organic materials based on K3[M(C2O4)3]·3H2O [M(III)=Fe, Al, Cr] metallotectons

    Science.gov (United States)

    Sun, Yayong; Zong, Yingxia; Ma, Haoran; Zhang, Ao; Liu, Kang; Wang, Debao; Wang, Wenqiang; Wang, Lei

    2016-05-01

    By using K3[M(C2O4)3]·3H2O [M(III)=Fe, Al, Cr] (C2O42-=oxalate) metallotectons as the starting material, we have synthesized eight novel complexes with formulas [{Fe(C2O4)2(H2O)2}2]·(H-L1)2·H2O 1, [Fe(C2O4)Cl2]·(H2-L2)0.5·(L2)0.5·H2O 2, [{Fe(C2O4)1.5Cl2}2]·(H-L3)43, [Fe2(C2O4)Cl8]·(H2-L4)2·2H2O 4, K[Al(C2O4)3]·(H2-L5)·2H2O 5, K[Al(C2O4)3]·(H-L6)2·2H2O 6, K[Cr(C2O4)3]·2H2O 7, Na[Fe(C2O4)3]·(H-L6)2·2H2O 8 (with L1=4-dimethylaminopyridine, L2=2,3,5,6-tetramethylpyrazine, L3=2-aminobenzimidazole, L4=1,4-bis-(1H-imidazol-1-yl)benzene, L5=1,4-bis((2-methylimidazol-1-yl)methyl)benzene, L6=2-methylbenzimidazole). Their structures have been determined by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra and thermogravimetric analyses. Compound 3 is a 2D H-bonded supramolecular architecture. Others are 3D supramolecular structures. Compound 1 shows a [Fe(C2O4)2(H2O)2]- unit and 3D antionic H-bonded framework. Compound 2 features a [Fe(C2O4)Cl2]- anion and 1D iron-oxalate-iron chain. Compound 3 features a [Fe2(C2O4)3Cl4]4- unit. Compound 4 features distinct [Fe2(C2O4)Cl8]4- units, which are mutual linked by water molecules to generated a 2D H-bonded network. Compound 5 features infinite ladder-like chains constructed by [Al(C2O4)3]3- units and K+ cations. The 1D chains are further extended into 3D antionic H-bonded framework through O-H···O H-bonds. Compounds 6-8 show 2D [KAl(C2O4)3]2- layer, [KCr(C2O4)3]2- layer and [NaFe(C2O4)3]2- layer, respectively.

  12. Linearized method: A new approach for kinetic analysis of central dopamine D2 receptor specific binding

    International Nuclear Information System (INIS)

    Watabe, Hiroshi; Hatazawa, Jun; Ishiwata, Kiichi; Ido, Tatsuo; Itoh, Masatoshi; Iwata, Ren; Nakamura, Takashi; Takahashi, Toshihiro; Hatano, Kentaro

    1995-01-01

    The authors proposed a new method (Linearized method) to analyze neuroleptic ligand-receptor specific binding in a human brain using positron emission tomography (PET). They derived the linear equation to solve four rate constants, k 3 , k 4 , k 5 , k 6 from PET data. This method does not demand radioactivity curve in plasma as an input function to brain, and can do fast calculations in order to determine rate constants. They also tested Nonlinearized method including nonlinear equations which is conventional analysis using plasma radioactivity corrected for ligand metabolites as an input function. The authors applied these methods to evaluate dopamine D 2 receptor specific binding of [ 11 C] YM-09151-2. The value of B max /K d = k 3 k 4 obtained by Linearized method was 5.72 ± 3.1 which was consistent with the value of 5.78 ± 3.4 obtained by Nonlinearized method

  13. Lärplatta som verktyg för elever i behov av särskilt stöd! : En specialpedagogisk studie om hur elever i åk 4-7 använder lärplatta i klassrummet och hur uppföljning av användningen sker

    OpenAIRE

    Lindgren, Ditte; Nordström, Ulrika

    2017-01-01

    Studiens syfte var att få kunskap om hur lärplatta används som verktyg för elever i behov av särskilt stöd i åk 4-7, samt om lärplattan används utifrån specialpedagogens syfte för den enskilda eleven med den. Använda datainsamlingsmetoder är kvalitativa intervjuer med specialpedagoger, lärare och elever, samt elevobservationer. De frågeställningar som studien sökt svar på är: i vilket syfte valdes lärplatta som verktyg av specialpedagog för elever i behov av särskilt stöd, hur använder elever...

  14. Strong correlation between Jc(T, H||c) and Jc(77 K, 3 T||c) in Zr-added (Gd, Y)BaCuO coated conductors at temperatures from 77 down to 20 K and fields up to 9 T

    International Nuclear Information System (INIS)

    Xu, A; Delgado, L; Heydari Gharahcheshmeh, M; Khatri, N; Liu, Y; Selvamanickam, V

    2015-01-01

    We have conducted a critical current density J c (T, H) study over a wide temperature T from 77 down to 20 K and a magnetic field H up to 9 T on more than 50 ∼ 0.9 μm-thick REBa 2 Cu 3 O 7−δ (RE = rare earth) thin films containing different concentrations of BaZrO 3 (BZO). We found that, independent of the composition, there is a linear correlation between J c (77 K, 3 T||c) and J c (T, H||c) at T down to 20 K and H up to 9 T. Moreover, J c (77 K, 3 T||c) is also linearly correlated to J c (T, H||ab) below 40 K. We ascribed this linear correlation to the dominant pinning source of BZO nanorods, which act as a strong correlated pinning at T above ∼30 K and provide weak uncorrelated point pins at lower temperatures. Our result emphasizes that J c (77 K, 3 T||c) is a key metric for metal-organic chemical vapor deposited REBa 2 Cu 3 O 7−δ coated conductors. (fast track communication)

  15. Oxothiomolybdenum derivatives of the superlacunary crown heteropolyanion {P8W48}: structure of [K4{Mo4O4S4(H2O)3(OH)2}2(WO2)(P8W48O184)]30– and studies in solution.

    Science.gov (United States)

    Korenev, Vladimir S; Floquet, Sébastien; Marrot, Jérôme; Haouas, Mohamed; Mbomekallé, Israël-Martyr; Taulelle, Francis; Sokolov, Maxim N; Fedin, Vladimir P; Cadot, Emmanuel

    2012-02-20

    Reaction of the cyclic lacunary [H(7)P(8)W(48)O(184)](33-) anion (noted P(8)W(48)) with the [Mo(2)S(2)O(2)(H(2)O)(6)](2+) oxothiocation led to two compounds, namely, [K(4){Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(WO(2))(P(8)W(48)O(184))](30-) (denoted 1) and [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) (denoted 2), which were characterized in the solid state and solution. In the solid state, the structure of [K(4){Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(WO(2))(P(8)W(48)O(184))](30-) reveals the presence of two disordered {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) "handles" connected on both sides of the P(8)W(48) ring. Such a disorder is consistent with the presence of two geometrical isomers where the relative disposition of the two {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) handles are arranged in a perpendicular or parallel mode. Such an interpretation is fully supported by (31)P and (183)W NMR solution studies. The relative stability of both geometrical isomers appears to be dependent upon the nature of the internal alkali cations, i.e., Na(+) vs K(+), and increased lability of the two {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) handles, compared to the oxo analogous, was clearly identified by significant broadening of the (31)P and (183)W NMR lines. Solution studies carried out by UV-vis spectroscopy showed that formation of the adduct [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) occurs in the 1.5-4.7 pH range and corresponds to a fast and quantitative condensation process. Furthermore, (31)P NMR titrations in solution reveal formation of the "monohandle" derivative [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(P(8)W(48)O(184))](38-) as an intermediate prior to formation of the "bishandle" derivatives. Furthermore, the electrochemical behavior of [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) was studied in aqueous medium and compared with the parent anion P(8)W(48).

  16. Phase formation in the Li2MoO4–K2MoO4–In2(MoO4)3 system and crystal structures of new compounds K3InMo4O15 and LiK2In(MoO4)3

    International Nuclear Information System (INIS)

    Khal’baeva, Klara M.; Solodovnikov, Sergey F.; Khaikina, Elena G.; Kadyrova, Yuliya M.; Solodovnikova, Zoya A.; Basovich, Olga M.

    2012-01-01

    XRD study of solid-phase interaction in the Li 2 MoO 4 –K 2 MoO 4 –In 2 (MoO 4 ) 3 system was performed. The boundary K 2 MoO 4 –In 2 (MoO 4 ) 3 system is an non-quasibinary join of the K 2 O–In 2 O 3 –MoO 3 system where a new polymolybdate K 3 InMo 4 O 15 isotypic to K 3 FeMo 4 O 15 was found. In the structure (a=33.2905(8), b=5.8610(1), c=15.8967(4) Å, β=90.725(1)°, sp. gr. C2/c, Z=8, R(F)=0.0407), InO 6 octahedra, Mo 2 O 7 diortho groups and MoO 4 tetrahedra form infinite ribbons {[In(MoO 4 ) 2 (Mo 2 O 7 )] 3− } ∞ along the b-axis. Between the chains, 8- to 10-coordinate potassium cations are located. A subsolidus phase diagram of the Li 2 MoO 4 –K 2 MoO 4 –In 2 (MoO 4 ) 3 system was constructed and a novel triple molybdate LiK 2 In(MoO 4 ) 3 was revealed. Its crystal structure (a=7.0087(2), b=9.2269(3), c=10.1289(3) Å, β=107.401(1)°, sp. gr. P2 1 , Z=2, R(F)=0.0280) contains an open framework of vertex-shared MoO 4 tetrahedra, InO 6 octahedra and LiO 5 tetragonal pyramids with nine- and seven-coordinate potassium ions in the framework channels. - Graphical abstract: Exploring the Li 2 MoO 4 –K 2 MoO 4 –In 2 (MoO 4 ) 3 system showed its partial non-quasibinarity and revealed new compounds K 3 InMo 4 O 15 (isotypic to K 3 FeMo 4 O 15 ) and LiK 2 In(MoO 4 ) 3 which were structurally studied. An open framework of the latter is formed by vertex-shared MoO 4 tetrahedra, InO 6 octahedra and LiO 5 tetragonal pyramids. Highlights: ► Subsolidus phase relations in the Li 2 MoO 4 –K 2 MoO 4 –In 2 (MoO 4 ) 3 system were explored. ► The K 2 MoO 4 –In 2 (MoO 4 ) 3 system is a non-quasibinary join of the K 2 O–In 2 O 3 –MoO 3 system. ► New compounds K 3 InMo 4 O 15 and LiK 2 In(MoO 4 ) 3 were obtained and structurally studied. ► K 3 InMo 4 O 15 is isotypic to K 3 FeMo 4 O 15 and carries bands of InO 6 , MoO 4 and Mo 2 O 7 units. ► An open framework of LiK 2 In(MoO 4 ) 3 is formed by polyhedra MoO 4 , InO 6 and LiO 5 .

  17. PENGARUH EKSTRAK JAHE MERAH (Zingiber officinale DAN MADU TERHADAP KADAR KOLESTEROL TOTAL TIKUS MODEL DIABETES MELITUS

    Directory of Open Access Journals (Sweden)

    Alfi Muntafiah

    2017-03-01

    Full Text Available Diabetes mellitus (DM is a disease characterized by elevated blood glucose levels (hyperglycemia caused by deficiency of insulin, and insulin resistance or both. This chronic disease prevalence is increasing nationally and globally. This study aimed to determine the effect of ginger extract and honey various doses on levels of total cholesterol in the Wistar diabetic rat model induced by alloxan. This research is true experimental post-test only with control group design. Subject of the study 30 male Wistar rats weight 150-200 grams, divided into 6 groups: A healthy controls (K1, B DM control (K2, C Treatment with red ginger extract 1000 mg / kg and honey 1 ml / kg (K3, D Treatment with ginger extract red 1000 mg / kg and honey 2 ml / kg (K4, E Treatment with red ginger extract 500 mg / kg and honey 1 ml / kg (K5, F Treatment with red ginger extract 500 mg / kg and honey 2 ml / kg (K6. DM induction by alloxan 160 mg / kg intraperitoneally for 5 days, and the provision of treatment for 14 days. Total cholesterol levels were measured by CHOD-PAP method. Results: The mean total cholesterol levels of healthy control group vs the diabetic control 58.20 ± 8.76 vs. 87.80 ± 5.81 mg / dL. Based on one way ANOVA test, red ginger extract and honey various doses significantly lower total cholesterol level (p <0.05. The mean total cholesterol levels between the group K3 to K4 was not statistically different, as well as K5 with K6. However, mean total cholesterol levels at K3 and K4 differ significantly from the K5 and K6. Conclusion: Combination of red ginger extract and honey can lower total cholesterol levels in diabetic rat model induced by alloxan.

  18. Risk factors, diagnosis and non-surgical treatment for meniscal tears

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Juhl, Carsten Bogh; Ingelsrud, Lina Holm

    2018-01-01

    quantitatively or qualitatively, as appropriate. Strength of evidence was determined according to the Grading of Recommendations Assessment Development and Evaluation framework. Low-quality evidence suggested that overweight (degenerative tears, k=3), male sex (k=4), contact and pivoting sports (k=2...... investigated exercise versus surgery (k=2) or the effect of surgery in addition to exercise (k=5) for degenerative meniscal tears. There was moderate level of evidence for exercise improving self-reported pain (Effect Size (ES)-0.51, 95% CI -1.16 to 0.13) and function (ES -0.06, 95% CI -0.23 to 0...

  19. Thermoregulatory Responses to Intermittent Exercise Are Influenced by Knit Structure of Underwear

    Science.gov (United States)

    1990-01-01

    determined at 120 min, when Swo,(K3) and Swt(K4) were lower compared to both Sw,,(K2) and Swot (K5) 400 (Fig. 3). 300 Skin wettednessEE The knit...dew Pugh LGC (1966) Clothing insulation and accidential hypo- point temperature sensor. J Appl Physiol 52: 1658- 1660 thermia in youth. Nature 209: 1281...insulation. J Appl Physiol 8:539-545 cise and thermal stress. Physiol Rev 54:75-159 Hardy JI), )uBois EF (1938) Basal metabolism, radiation, Saltin B

  20. Chemical and Electrochemical Asymmetric Dihydroxylation of Olefins in I(2)-K(2)CO(3)-K(2)OsO(2)(OH)(4) and I(2)-K(3)PO(4)/K(2)HPO(4)-K(2)OsO(2)(OH)(4) Systems with Sharpless' Ligand.

    Science.gov (United States)

    Torii, Sigeru; Liu, Ping; Bhuvaneswari, Narayanaswamy; Amatore, Christian; Jutand, Anny

    1996-05-03

    Iodine-assisted chemical and electrochemical asymmetric dihydroxylation of various olefins in I(2)-K(2)CO(3)-K(2)OsO(2)(OH)(4) and I(2)-K(3)PO(4)/K(2)HPO(4)-K(2)OsO(2)(OH)(4) systems with Sharpless' ligand provided the optically active glycols in excellent isolated yields and high enantiomeric excesses. Iodine (I(2)) was used stoichiometrically for the chemical dihydroxylation, and good results were obtained with nonconjugated olefins in contrast to the case of potassium ferricyanide as a co-oxidant. The potentiality of I(2) as a co-oxidant under stoichiometric conditions has been proven to be effective as an oxidizing mediator in electrolysis systems. Iodine-assisted asymmetric electro-dihydroxylation of olefins in either a t-BuOH/H(2)O(1/1)-K(2)CO(3)/(DHQD)(2)PHAL-(Pt) or t-BuOH/H(2)O(1/1)-K(3)PO(4)/K(2)HPO(4)/(DHQD)(2)PHAL-(Pt) system in the presence of potassium osmate in an undivided cell was investigated in detail. Irrespective of the substitution pattern, all the olefins afforded the diols in high yields and excellent enantiomeric excesses. A plausible mechanism is discussed on the basis of cyclic voltammograms as well as experimental observations.

  1. Study of the decays D→K3π

    International Nuclear Information System (INIS)

    Anjos, J.C.; Appel, J.A.; Bean, A.; Bracker, S.B.; Browder, T.E.; Cremaldi, L.M.; Duboscq, J.E.; Elliott, J.R.; Escobar, C.O.; Gibney, M.C.; Hartner, G.F.; Huber, J.; Karchin, P.E.; Kumar, B.R.; Losty, M.J.; Luste, G.J.; Mantsch, P.M.; Martin, J.F.; McHugh, S.; Menary, S.R.; Morrison, R.J.; Nash, T.; Pinfold, J.; Punkar, G.; Purohit, M.V.; Ross, W.R.; Santoro, A.F.S.; Schmidt, D.M.; Shoup, A.L.; Sliwa, K.; Sokoloff, M.D.; Souza, M.H.G.; Sperka, D.; Spalding, W.J.; Streetman, M.E.; Stundzia, A.B.; Witherell, M.S.

    1992-01-01

    We report measurements of the decays D 0 →K - π + π + π - , D + → bar K 0 π + π + π - , D + →K - π + π + π 0 , and D 0 → bar K 0 π + π - π 0 from Fermilab photoproduction experiment E691. A complete resonant substructure analysis is used to determine the relative fractions and phases of amplitudes contributing to the decays D 0 →K - π + π + π - , D + → bar K 0 π + π + π - , and D + →K - π + π + π 0

  2. Fanatically Formative: Successful Learning during the Crucial K-3 Years

    Science.gov (United States)

    Sornson, Bob

    2012-01-01

    Helping children experience early learning success and acquire essential skills by third grade is a crucial part of any school reform effort. Yet, many teachers and children are overwhelmed by the ineffective curriculum-driven education system and the "rush to cover" climate in schools. "Fanatically Formative" shows how you can rediscover the joy…

  3. Using Literature To Teach in All Curriculum Areas K-3.

    Science.gov (United States)

    Bainter, Dolores; And Others

    Presented are ideas for learning activities that use books and stories to teach language arts, art, cooking, movement, health, music, and math to kindergarten and primary school students. Activities are organized around such topics as quilts, apples, teeth, hands, feelings, heroes, letters, and such events as birthdays, Mother's and Father's Day,…

  4. Briquettes of rice husk, polyethylene terephthalate (PET), and dried leaves as implementation of wastes recycling

    Science.gov (United States)

    Hariyanto, Sucipto; Usman, Mohammad Nurdianfajar; Citrasari, Nita

    2017-06-01

    This research aim is to determine the best briquettes as implementation of wastes recycle based on scoring method, main component composition, compressive strength, caloric value, water content, vollatile content, and ash content, also the suitability with SNI 01-6235-2000. Main component that used are rice husk, 2mm and 6 mm PET, and dried leaves. Composition variation in this research are marked as K1, K2, K3, K4, and K5 with 2 mm PET plastic and K1, K2, K3, K4, and K5 with 6 mm PET plastic. The total weight of the briquettes is 100 g and divided into 90% main components and 10% tapioca as binder. The compressive strength, caloric value, water content, vollatile content, and ash content were tested according to ASTM D 5865-04, ASTM D 3173-03, ASTM D 3175-02, ASTM D 3174-02. The tested results were used to determine the best briquette by scoring method, and the chosen briquettes is K2 with 6 mm PET plastic. The composition is 70% rice husk, 20% 6 mm PET plastic, and 10% dried leaves with the compressive strength, caloric value, water content, vollatile content, and ash content value is 51,55 kg/cm2; 5123 kal/g; 3,049%; 31,823%, dan 12,869%. The suitable value that meet the criteria according to SNI 01-6235-2000 is compressive strength, caloric value, water content, and ash content.

  5. Constants of acid‒base equilibria in an aqueous amikacin aminoglycoside solution at 298 K

    Science.gov (United States)

    Alekseev, V. G.; Markova, E. V.

    2016-03-01

    The acid dissociation constants of form p K 1 = 7.34 ± 0.01, p K 2 = 7.84 ± 0.01, p K 3 = 8.77 ± 0.01, p K 4 = 9.49 ± 0.01, and p K 5 = 10.70 ± 0.02 of cationic amikacin are determined by pH-metric titration at 25°C against the background of 0.1 mol/L KNO3. K 1, K 2, K 3, and K 4 correspond to the dissociation of protons coordinated to amino groups, while K 5 characterizes the dissociation of the hydroxyl hydrogen atom, testifying to the amphoteric character of amikacin molecules. Applying density functional theory (DFT) with the B3LYP hybrid functional and the 6-311G**++ basis set, the partial charges on the atoms of an amikacin molecule are calculated. It is concluded that the dissociation of H(55)hydrogen atom occurs with a greatest partial charge of +0.53631.

  6. Synthesis of Fe3O4@SiO2@OSi(CH2)3NHRN(CH2PPh2)2PdCl2 type nanocomposite complexes: Highly efficient and magnetically-recoverable catalysts in vitamin K3 synthesis.

    Science.gov (United States)

    Uruş, Serhan

    2016-12-15

    The synthesis of aminomethylphosphine-metal complexes have opened a new perspective to the catalytic applications of organic compounds. Magnetic Fe3O4 nano-core was synthesized using the closed quartz tube with Teflon cover and microwaved 200°C for 1h with power controlled instrument set to max. 600W. Novel nano-composite supported; Fe3O4@SiO2(CH2)3NHArN(CH2PPh2)2 and Fe3O4@SiO2(CH2)3N(CH2PPh2)2 type bis(diphenylphosphinomethyl)amino ligands and their Pd(II) complexes have been synthesized and characterized with FT-IR, SEM, EDX, TEM, UV-Visible, XRD and TG/DTA techniques. All the complexes were used as heterogeneous catalysts in the oxidation of 2-methyl naphthalene (2MN) to 2-methyl-1, 4-naphthoquinone (vitamin K3, menadione, 2MNQ) in the presence of hydrogen peroxide and acetic acid. Selectivity reached about 55-60% with a conversion of 90-96% using the nano-magnetite supported aminomethylphosphine-Pd(II) complexes. The complexes were very active in three times in the catalytic recycling experiments in five catalytic cycles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Missile Defense Agency Ballistic Missile Defense System (BMDS): Programmatic Environmental Impact Statement. Volume 3 Appendices K - N

    Science.gov (United States)

    2007-01-01

    K.2.1 Estrella Julia DC_PHO0049 K.3.2, K.3.3, K.3.5, K.3.12, K.4 Estrella Susan DC_M2012 UCS K.2.1 Etchison Craig DC_M0173 K.3.2, K.3.10, K.3.14... ESTRELLA : Good evening. My name is 12 Julia Estrella and I serve on the National Committee 13 of the United Church of Christ which

  8. A comparative study on the fretting wear properties of advanced zirconium fuel cladding materials

    International Nuclear Information System (INIS)

    Lee, Young Ho; Kim, Hyung Kyu; Park, Jeong Yong; Kim, Jun Hwan

    2005-06-01

    Fretting wear tests were carried out in room and high temperature water in order to evaluate the wear properties of new zirconium nuclear fuel claddings (K2∼K6) and the commercial claddings (M5, zirlo and zircaloy-4). The objective is to compare the wear resistance of K2∼K6 claddings with that of the commercial ones at the same test condition. After the wear tests, the average wear volume and the maximum wear depth were evaluated and compared at each test condition. As a result, it is difficult to select the most wear-resistant cladding between the K2∼K6 claddings and the commercial ones. This is because the average wear volume and maximum depth of each cladding included between the scattering range of measured results. However, wear resistance of the tested claddings based on the average wear volume and maximum wear depth could be summarized as follows: K5 > zircaloy-4 > (K2,K3) > (K4,M5) > K6 > zirlo at room temperature, zircaloy-4 > K5 > (K3,K4,zirlo) > (K2,K6) > M5 at high temperature and pressure. Therefore, it is concluded that K5 cladding among the tested new zirconium alloys has relatively higher wear-resistance in room and high temperature condition. In order to examine the wear mechanism, it is necessary to systematically study with the consideration of the alloying element effect and test environment. In this report, the wear test procedure and the wear evaluation method are described in detail

  9. Responsive Guided Reading in Grades K-5: Simplifying Small-Group Instruction

    Science.gov (United States)

    Berne, Jennifer; Degener, Sophie C.

    2010-01-01

    Guided reading is a staple of elementary literacy instruction, yet planning and conducting reading groups can be time consuming and challenging. This hands-on book presents an innovative approach to guided reading that is manageable even for teachers who are new to small-group, differentiated reading instruction. Numerous classroom examples…

  10. HAT-P-68b: A Transiting Hot Jupiter Around a K5 Dwarf Star

    Science.gov (United States)

    Lindor, Bethlee; Hartman, Joel D.

    2018-01-01

    One of the main goals of the astrophysical society has been to detect sources of life outside of Earth. To aid this search, astronomers have spent the last 2 decades focused on the discovery and characterization of exoplanets. The most effective method for doing so has been transit photometry, wherein we measure the brightness of stars over periods of time. These measurements, or light curves, are later analyzed for dips in brightness caused by objects passing in front of the star. However, variations in these time series can also occur due to non-planetary systems and a meticulous process is needed to distinguish the planets from the various false positives that are detected. HATNet is one of many surveys involved in this endeavor, and in this work I analyze HAT-P-68. First, I model the system as a single star with a transiting planet and derive estimates of the stellar and planetary physical parameters. I also model HAT-P-68 as a number of a false positives such as a pair of stars in an eclipsing binary blended with a background star, and a planet-sized star orbiting a Sun-like star. In order to rule out the possibility that HAT-P-68 is a blend, I carried out a statistical blend analysis of the photometric data and find that all blend models tested can be ruled out. Thus, I conclude that HAT-P-68 is a system with a transiting hot jupiter and consider what future observations would be most promising to further characterize the system.

  11. Progress Report Natsurv 1 K5_2285/3 The Malt Brewing Industry

    CSIR Research Space (South Africa)

    Ramukhwatho, Fhumulani R

    2014-07-01

    Full Text Available of brewing process cycle The generic brewing processes for beer production (Varman and Sutherland, 1994; Unicer, SA, 2005) 5 Breweries Classification Large = 10 Medium = ? Small = 77 Per Barrel produced: Large: > 6 000 000 Medium: ≥ 15 000 ≤ 6... in study 10 Loci of Malt Breweries in SA 11 Key Brewing Processes Brewing Fermentation Storage Bottling Barrelling 12 Preliminary Results from Questionnaire/ literature • Results based on 8 responses (breweries) • Data to date was synthesized...

  12. Remedial Investigation Badger Army Ammunition Plant, Baraboo, Wisconsin. Volume 5. Appendix K.5

    Science.gov (United States)

    1991-01-01

    4 -4 -4 -4 -4.4 -4r44 4 4-4 -4 ~ 4 .010 -4 000000000000000000000000 000000000000000000000000000 *d -4 8 (a *~ SI * 4JI j -OZ2~404 ZtM0G. .P4000I 4bd ...000000000000000 4.3 tD ~-O-.4- 4-%iCiIO f ~~a to -: u t A w 00000000000000000000000000 )1 310000000000000000000000000000 m o >.,V 0i. 01 00 01 r4rle4r e4

  13. http://escholarship.org/uc/item/6sz1k5r3

    Directory of Open Access Journals (Sweden)

    Jonathan G. Wagner

    2015-12-01

    Full Text Available A 52-year-old African American male with a long history of poorly controlled hypertension presented to the emergency department (ED with two days of genital edema and pain. During ED work-up, the patient developed sudden onset of non-pitting, non-pruritic, and non-urticarial upper lip edema. Review of his antihypertensive medication list revealed that he normally took benazepril, highly suggestive of a diagnosis of angiotensin-converting-enzyme inhibitor-related angioedema (ACEIRA. We present the first reported case of penile ACEI-RA that progressed to involve the oropharynx. The ED management of the condition and some of the newer treatment options available for ACEIRA is also briefly discussed.

  14. K-5 mentor teachers' journeys toward reform-oriented science within a professional development school context

    Science.gov (United States)

    Manno, Jacqueline L.

    Reform-oriented science teaching with a specific focus on evidence and explanation provides a student-centered learning environment which encourages children to question, seek answers to those questions, experience phenomena, share ideas, and develop explanations of science concepts based on evidence. One of the ways schools have risen to meet the challenge of ever-increasing demands for success in science and all other curricular areas has been in the development of professional development schools (PDSs). Dedicated to the simultaneous renewal of schools and teacher education programs, the structure of a PDS plays a significant role in the change process. The purpose of this research study was to investigate the nature of change in mentor teachers' beliefs and pedagogical practices toward science teaching in the elementary school as conveyed through their own "stories of practice". The major research questions that guided the study were: (1) How do mentor teachers describe their science teaching practices and how have they changed as a result of participation in PDS? (a) In what ways do PDS mentor teachers' descriptions of practice reflect contemporary reform ideas and practices in science education? (b) To what extent do their stories emphasize technical aspects of teaching versus epistemological changes in their thinking and knowledge? (c) How is student learning in science reflected in teachers' stories of practice? (2) What is the relationship between the levels and types of involvement in PDS to change in thinking about and practices of teaching science? (3) What is the depth of commitment that mentors convey about changes in science teaching practices? Using case study design, the research explored the ways experienced teachers, working within the context of a PDS community, described changes in the ways they think about and teach science. The connection to the issue of change in teaching practices grew out of interest in understanding the relationship between mentor teachers' engagement in PDS activities and their thinking about classroom practice. The main focus of this research study was on change in science teaching within the context of a professional development school. PDS literature and current literature on the learning and teaching of science in grades K-8 provided a theoretical orientation to guide the research. Additionally, literature on the process of change in schools helped to narrow the focus of the study while using a lens of situated learning provided additional insight. Analysis of the interview data generated seven assertions that captured the nature of the change process of mentor teachers. Science-specific professional development as well as strong support and encouragement within an active community of learners played significant roles in the transformation of mentor teachers from traditional or activity-based science teachers into educators who use reform-oriented methods and a lens of evidence and explanation to guide their science teaching. Mentor teachers acknowledged an increase in student interest and excitement toward science as a result of these changes in science teaching practices. In addition, data revealed that mentor teachers remained committed to their changed practice after several years. By examining the change process of mentor teachers in a PDS environment, findings from this study are discussed based on implications regarding the factors that contribute to and affect change as reform-oriented practices are implemented in science, a curricular area that is often neglected by elementary teachers.

  15. Integrating Engineering into Delaware's K-5 Classrooms: A Study of Pedagogical and Curricular Resources

    Science.gov (United States)

    Grusenmeyer, Linda Huey

    This study examines the personal and curricular resources available to Delaware's elementary teachers during a time of innovative curriculum change, i.e., their knowledge, goals and beliefs regarding elementary engineering curriculum and the pedagogical support to teach two Science and Engineering Practices provided by science teaching materials. Delaware was at the forefront of K-12 STEM movement, first to adopt statewide elementary curriculum materials to complement existing science units, and one of the first to adopt the new science standards--Next Generation Science Standards. What supports were available to teachers as they adapted and adopted this new curriculum? To investigate this question, I examined (1) teachers' beliefs about engineering and the engineering curriculum, and (2) the pedagogical supports available to teachers in selected science and engineering curriculum. Teachers' knowledge, goals, and beliefs regarding Delaware's adoption of new elementary engineering curriculum were surveyed using an adapted version of the Design, Engineering, and Technology Survey (Hong, Purser, & Gardella, 2011; Yaser, Baker, Carpius, Krauss, & Roberts, 2006). Also, three open ended questions sought to reveal deeper understanding of teacher knowledge and understanding of engineering; their concerns about personal and systemic resources related to the new curriculum, its logistics, and feasibility; and their beliefs about the potential positive impact presented by the engineering education initiative. Teacher concerns were analyzed using the Concerns-Based Adoption Model (Hall & Hord, 2010). Lay understandings of engineering were analyzed by contrasting naive representations of engineering with three key characteristics of engineering adapted from an earlier study (Capobianco Diefes-Dux, Mena, & Weller, 2011). Survey findings for teachers who had attended training and those who have not yet attended professional development in the new curriculum were compared with few notable differences. Almost all elementary teacher respondents were familiar with engineering and able to define it using one or more key characteristics. They valued the inclusion of engineering in the elementary curriculum; however trained and untrained teachers reported they were not confident about teaching it and were unaware of the new standards related to engineering. Teachers saw potential advantages or benefits of the new curriculum as helping improve science and math understanding, an opportunity to increase vocational awareness, and engaging students and motivating them to learn. Most teachers saw similar barriers to implementation- lack of teacher knowledge, lack of time to learn about engineering and how to teach engineering, and lack of administrative support. Almost all were open to additional in-service training to learn more about this new curriculum. Three fifth grade science units were examined for evidence of teacher pedagogical support in teaching two Science and Engineering Practices (SEP) advocated by the Next Generation Science Standards. An analytic framework was developed based upon two NGSS SEPs: Asking questions, defining problems and Engaging in argument from evidence. Findings revealed that the kits varied greatly in their pedagogical approaches to the two SEPs and differences might be explained by each kit's underlying orientations to the teaching-learning process. Findings from these investigations have implications for the design of professional development and for engineering curricula. They highlight the importance of considering teacher beliefs about curriculum implementation and subject matter, as well as the importance of creating curriculum materials that focus teacher attention toward student thinking and the language rich science and engineering practices. Recommendations also include ongoing professional development to allow teachers time to try out and revise pedagogical routines that support the SEPs studied here.

  16. Inquiry-Based Pre-Engineering Activities for K-4 Students

    Science.gov (United States)

    Perrin, Michele

    2004-01-01

    This paper uses inquiry-based learning to introduce primary students to the concepts and terminology found in four introductory engineering courses: Differential Equations, Circuit Analysis, Thermodynamics, and Dynamics. Simple electronic sensors coupled with everyday objects, such as a troll doll, demonstrate and reinforce the physical principles…

  17. Oncogenic Functions of cdK4 and cdK6

    National Research Council Canada - National Science Library

    Grossel, Martha

    1999-01-01

    .... The retinoblastoma protein (pRb) is one negative regulator of cellular proliferation. Many breast cancers retain functional pRb and therefore must use other mechanisms to alleviate the tumor-suppressive function of pRb...

  18. On the effect of memory in one-dimensional K=4 automata on networks

    Science.gov (United States)

    Alonso-Sanz, Ramón; Cárdenas, Juan Pablo

    2008-12-01

    The effect of implementing memory in cells of one-dimensional CA, and on nodes of various types of automata on networks with increasing degrees of random rewiring is studied in this article, paying particular attention to the case of four inputs. As a rule, memory induces a moderation in the rate of changing nodes and in the damage spreading, albeit in the latter case memory turns out to be ineffective in the control of the damage as the wiring network moves away from the ordered structure that features proper one-dimensional CA. This article complements the previous work done in the two-dimensional context.

  19. Electrochemical Catalysis of Inorganic Complex K4[Fe(CN)6] by Shewanellaoneidensis MR-1

    DEFF Research Database (Denmark)

    Zheng, Zhiyong; Wu, Ranran; Xiao, Yong

    The interaction between metal and bacteria is a universal and important biogeochemical processin environment. As a dissimilatory metal reduction bacterium, the electrochemically activebacteriium Shewanella oneidensis MR-1 can transfer intracellular electrons to minerals. This ability is attribute...... andelectrocatalysis mechanisms of S. oneidensis MR-1 are under investigation. The ability of S. oneidensis MR-1 to catalyze redoxaction of inorganic metal complex compounds will provide an insight on metal cycles in nature....

  20. Children Hungering for Justice: Curriculum on Hunger and Children's Rights, Grades K-4.

    Science.gov (United States)

    Gray, Kaaren St. Armour

    This curriculum is designed to introduce students to the issues of world hunger and children's rights. The curriculum includes more than enough material for two hour-long lessons. Each lesson can stand on its own; however, the interrelated nature of the topics lends itself to presenting both parts of the packet. If time is limited, suggestions are…

  1. SE GESKE~K 4.4.~ f~ 130EREGE~ER4.4.L

    African Journals Online (AJOL)

    de voorwerp klaar gekleur is, word dit in. 'n oond gebak. Saam met edelmetale vorm emalje eksotiese kunswerke. Ofskoon die bratina nie van edelmetaal ver- vaardig is .... trou nie. Die bootvorm van die kovsh is geaksentueer met goue koorddraad. Helder kleurige cloisonne emalje versierings maak die bekertjie besonder ...

  2. Noise temperature of an NbN hot-electron bolometric mixer at frequencies from 0.7 THz to 5.2 THz

    International Nuclear Information System (INIS)

    Schubert, J.; Semenov, A.; Gol'tsman, G.; Huebers, H-W.; Voronov, B.; Gershenzon, E.; Schwaab, G.

    1999-01-01

    We report on noise temperature measurements of an NbN phonon-cooled hot-electron bolometric mixer in the terahertz frequency range. The devices were 3 nm thick films with in-plane dimensions 1.7x0.2μm 2 and 0.9x0.2μm 2 integrated in a complementary logarithmic-spiral antenna. Measurements were performed at seven frequencies ranging from 0.7 THz to 5.2 THz. The measured DSB noise temperatures are 1500 K (0.7 THz), 2200 K (1.4 THz), 2600 K (1.6 THz), 2900 K (2.5 THz), 4000 K (3.1 THz), 5600 K (4.3 THz) and 8800 K (5.2 THz). (author)

  3. Assessing the Effectiveness of New Mexico's K-3 plus Summer Learning Initiative

    Science.gov (United States)

    Cann, Damon; Karakaplan, Mustafa; Lubke, Margaret; Rowland, Cyndi

    2014-01-01

    Students' basic reading and math skills can decline significantly during the summer months. Most attribute this to the prolonged period during which young students are outside of a structured learning environment (Cooper et al 1996). While summer learning loss occurs among all income groups, the effects are more pronounced for those from…

  4. Die toepassing van die K3-model op die televisieteks Colour TV ...

    African Journals Online (AJOL)

    There are very few instruments of use for the editing of multimedia television scripts. Commissioning editors are responsible for both quality assurance and quality control. Where quality control is a retrospective process, quality assurance is intended to anticipate problems that might occur in order to mitigate them during the ...

  5. The vitamin C:vitamin K3 system - enhancers and inhibitors of the anticancer effect.

    Science.gov (United States)

    Lamson, Davis W; Gu, Yu-Huan; Plaza, Steven M; Brignall, Matthew S; Brinton, Cathy A; Sadlon, Angela E

    2010-12-01

    The oxidizing anticancer system of vitamin C and vitamin K₃ (VC:VK₃, producing hydrogen peroxide via superoxide) was combined individually with melatonin, curcumin, quercetin, or cholecalciferol (VD₃) to determine interactions. Substrates were LNCaP and PC-3 prostate cancer cell lines. Three of the tested antioxidants displayed differences in cell line cytotoxicity. Melatonin combined with VC:VK₃ quenched the oxidizing effect, while VC:VK₃ applied 24 hours after melatonin showed no quenching. With increasing curcumin concentrations, an apparent combined effect of VC:VK₃ and curcumin occurred in LNCaP cells, but not PC-3 cells. Quercetin alone was cytotoxic on both cell lines, but demonstrated an additional 50-percent cytotoxicity on PC-3 cells when combined with VC:VK₃. VD₃ was effective against both cell lines, with more effect on PC-3. This effect was negated on LNCaP cells with the addition of VC:VK₃. In conclusion, a natural antioxidant can enhance or decrease the cytotoxicity of an oxidizing anticancer system in vitro, but generalizations about antioxidants cannot be made.

  6. Science Activities Pre-K-3: The Leaves are Falling in Rainbows.

    Science.gov (United States)

    Knight, Michael; Graham, Terry

    Opportunities to learn and discover surround a young child every day. The activities and ideas within this book have been formulated to encourage a child's natural curiosity and sense of wonder and to engage all the child's senses in learning and discovery. The activities focus on the child as a natural explorer and involve children in identifying…

  7. Does Fostering Reasoning Strategies for Relatively Difficult Basic Combinations Promote Transfer by K-3 Students?

    Science.gov (United States)

    Baroody, Arthur J.; Purpura, David J.; Eiland, Michael D.; Reid, Erin E.; Paliwal, Veena

    2016-01-01

    How best to promote fluency with basic sums and differences is still not entirely clear. Some advocate a direct approach--using drill to foster memorization of basic facts by rote. Others recommend an indirect approach that first involves learning reasoning strategies. The purpose of the present study was to evaluate the efficacy of 2…

  8. Poems about Sandwich Cookies, Jelly, and Chocolate: Poetry in K-3 Classrooms

    Science.gov (United States)

    McNair, Jonda C.

    2012-01-01

    The author had presented a session on poetry at a children's literature conference sponsored by The Ohio State University, and afterward two teachers invited her to come to their school and read poetry. The children emailed their responses to her shortly after she spent the entire day conducting poetry reading sessions at an elementary school in…

  9. 13- :K 3 =SJR.:K ~ ;Sj13 ~~K

    African Journals Online (AJOL)

    Brink vir fondse gepleit om die werksaamhede te kan voortsit. Finansiele hulp uit die han- dels- en nywerheidswereld, van oud-stryders- organisasies, die SA Weermag, die landsower- hede, die RGN en die publiek e.a. het gevolg. In Johannesburg het die Adviserende Komitee in verband met die Suid-Afrikaanse oorlogs-.

  10. Rencana Keselamatan dan Kesehatan Kerja (K3) Kontrak pada Pembangunan Gedung Sekolah Dasar Immanuel Pontianak

    OpenAIRE

    Prayetti, Maulidiah Dwi; Rafie, -; Pratiwi, Riyanny

    2017-01-01

    Accident in work can be happened anytime when the construction project has been started, that case happening because of limitation in safety tools, sightseeing to workers, less experience from workers, bad behavior,still bad to planning, or because of the workers usually handling their works and inattentive about the dangerous that always aim them. Accident thats happening can make physical defect or even death.The purpose of this safety and healthy works in construction field to knowing and...

  11. 26 CFR 1.404(k)-3 - Disallowance of deduction for reacquisition payments.

    Science.gov (United States)

    2010-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc... payments as applicable dividends would constitute, in substance, an avoidance or evasion of taxation within...

  12. A Manual for the Anchorage School District Bilingual Education Program Revised Scope and Sequence, K-3.

    Science.gov (United States)

    Heinrich, Maria Nieves Bumanlag Lilagan

    The manual offers a systematic set of procedures and relevant information to facilitate effective use of the Anchorage school district (ASD) bilingual education program (BEP). The historical background of the program's development is presented, available manuals for teaching English to limited English proficiency (LEP) students and related…

  13. HRTEM Study of Oxide Nanoparticles in K3-ODS Ferritic Steel Developed for Radiation Tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Hsiung, L; Fluss, M; Tumey, S; Kuntz, J; El-Dasher, B; Wall, M; Choi, W; Kimura, A; Willaime, F; Serruys, Y

    2009-11-02

    Crystal and interfacial structures of oxide nanoparticles and radiation damage in 16Cr-4.5Al-0.3Ti-2W-0.37 Y{sub 2}O{sub 3} ODS ferritic steel have been examined using high-resolution transmission electron microscopy (HRTEM) techniques. Oxide nanoparticles with a complex-oxide core and an amorphous shell were frequently observed. The crystal structure of complex-oxide core is identified to be mainly monoclinic Y{sub 4}Al{sub 2}O{sub 9} (YAM) oxide compound. Orientation relationships between the oxide and the matrix are found to be dependent on the particle size. Large particles (> 20 nm) tend to be incoherent and have a spherical shape, whereas small particles (< 10 nm) tend to be coherent or semi-coherent and have a faceted interface. The observations of partially amorphous nanoparticles and multiple crystalline domains formed within a nanoparticle lead us to propose a three-stage mechanism to rationalize the formation of oxide nanoparticles containing core/shell structures in as-fabricated ODS steels. Effects of nanoparticle size and density on cavity formation induced by (Fe{sup 8+} + He{sup +}) dual-beam irradiation are briefly addressed.

  14. Electron paramagnetic resonance of K3Rh(CN)6 irradiated with electrons in KCl

    International Nuclear Information System (INIS)

    Vugman, N.V.

    1970-07-01

    Using a simple theory, it was estimated the electronic density of the diamagnetic complex Rh (CN) 3- 6 in a KCl lattice. The g// and g1 values were determined by EPR, and the experimental results fit the theoretical calculations. (M.W.O.) [pt

  15. Irradiation tests of THTR fuel elements in the DRAGON reactor (irradiation experiment DR-K3)

    International Nuclear Information System (INIS)

    Burck, W.; Duwe, R.; Groos, E.; Mueller, H.

    1977-03-01

    Within the scope of the program 'Development of Spherical Fuel Elements for HTR', similar fuel elements (f.e.) have been irradiated in the DRAGON reactor. The f.e. were fabricated by NUKEM and were to be tested under HTR conditions to scrutinize their employability in the THTR. The fuel was in the form of coated particles moulded into A3 matrix. The kernels of the particles were made of mixed oxide of uranium and thorium with an U 235 enrichment of 90%. One aim of the post irradiation examination was the investigation of irradiation induced changes of mechanical properties (dimensional stability and elastic behaviour) and of the corrosion behaviour which were compared with the properties determined with unirradiated f.e. The measurement of the fission gas release in annealing tests and ceramografic examinations exhibited no damage of the coated particles. The measured concentration distribution of fission metals led to conclusions about their release. All results showed, that neither the coated particles nor the integral fuel spheres experienced any significant changes that could impair their utilization in the THTR. (orig./UA) [de

  16. Momentum distribution near k = 3kF in the Tomonaga-Luttinger model

    International Nuclear Information System (INIS)

    Solyom, J.; Penc, K.

    1992-01-01

    In this paper a survey is presented of recent experimental and analytical work carried out under a joint program at the Harwell Laboratory and Imperial College, placing the new work into the context of earlier developments. The basic balance equations for annular flow are introduced and the well-known triangular relationship reiterated. Then, interfacial waves and interfacial friction are reviewed, including some new results in both areas. A key feature in annular flow is the prediction of deposition and entrainment and recent developments are described. The various studies have led to a new framework for predictions of annular flow systems and the application of this framework to adiabatic flows, evaporating flows, steady-state dryout and transient dryout is described. Finally, new models covering the full range of dryout (CHF) ranging from subcooled conditions to high quality conditions are described; here dryout is limited by either film dryout (in annular flow) or by bubble wall crowding (at low quality ) and the new modelling structure allows a natural transition between the two

  17. Die toepassing van die K3-model op die televisieteks Colour TV

    African Journals Online (AJOL)

    “OIL's approach to investigating the coloured market took place in the form of ethnographic research which ... communication strategies” (Botha 2010: 14). ... Op grond van die waarnemings, onderhoude en vraelyste het OIL tot die volgende ..... hold onto your nearest and dearest because this is going to be a kwaai mix bag.

  18. Synthesis and molecular structure of a zinc complex of the vitamin K3 analogue phthiocol

    Science.gov (United States)

    Kathawate, Laxmi; Sproules, Stephen; Pawar, Omkar; Markad, Ganesh; Haram, Santosh; Puranik, Vedavati; Salunke-Gawali, Sunita

    2013-09-01

    The complex [Zn(phthiocol)2(H2O)2]; 1, where phthiocol is 2-hydroxy-3-methyl-1,4-naphthoquinone, has been synthesized and characterized by elemental analysis, FT-IR, 1H NMR, UV-vis spectroscopy, thermogravimetric (TG) analysis, electrochemical and single crystal X-ray diffraction studies. The νCO stretch shifts to lower frequencies upon complexation of phthiocol to Zn2+. 1H NMR spectra show an upfield shift of the benzenoid ring protons in 1. There is a bathochromic shift of the LMCT band in the UV-vis spectra of 1. Single crystal X-ray structure of 1 show distorted octahedral geometry around Zn2+. Two phthiocol ligands are in plane with the metal, while water molecules are trans to this plane. Coordination of deprotonated phthiocol ligands is 'trans, trans' to Zn2+. Intra as well as intermolecular interactions are observed in 1. Molecules of 1 show three dimensional network through CH⋯O and OH⋯O interactions. Additional anodic peaks are observed in cyclic voltammogram of phthiocol ligand due to oxidation of reduced species formed during reduction. One-electron reduction of 1 is shown to be reversible and DFT studies define this redox event as ligand-centered.

  19. MANAJEMEN RISIKO KESELAMATAN DAN KESEHATAN KERJA (K3 PADA PROYEK PEMBANGUNAN CIPUTRA WORLD JAKARTA

    Directory of Open Access Journals (Sweden)

    I Wayan Wiyasa

    2015-02-01

    Full Text Available Abstract :Generally, in Indonesia the subject of Occupational Health and Safety is often forgotten. This is proven with the high number of work accidents in Indonesia. In 2011, there were 99.491 incidents or on average 414 work accidents cases per day. In 2010 there were 98.711 work accidents, 96.314 cases in 2009, 94.736 cases in 2008 and 83.714 cases in 2007. This reserch is intended to asses the possible major risk of Occupational Health and Safety for The Ciputra World Jakarta building Project, and offer solutions to deal with any unexpected risk. This research was conducted with a descriptive and qualitative method. Survey was carried out to get opinions from respondents on Occupational Health & Safety risks during the construction of the Ciputra World Jakarta. There are Seventy eight (78 high risks were identified with the most being Tower Crane operation job, installation of steel column, beam, and wall with 5 risks. The 2 extreme risks were found in column casting and screeding exterior wall with 1 risk. Suggestion given is to organise training relation to Occupational Health and Safety risk to every employee, introduve shift system, allocate alternate day off to employees, provide health/medical check up, and eliminate high risk and dengerous work environment.

  20. Can CH-53K 3D Technical Data Support the Provisioning Process

    Science.gov (United States)

    2017-05-01

    support for all National Stock Number (NSN) items in the Federal Catalog System (FCS) used in supply management operations by the military services...Engineering Data Management Information and Control System ; SSR = supply support request. The data flow between the four activities in the... supportability re- quirements.  JEDMICS. The JEDMICS is a DoD standard engineering data manage - ment and repository system . JEDMICS provides the

  1. Comprehension from the Ground Up: Simplified, Sensible Instruction for the K-3 Reading Workshop

    Science.gov (United States)

    Taberski, Sharon

    2010-01-01

    The author cuts through the pressurized, strategy-overloaded, fluency-crazed atmosphere surrounding reading instruction to lay out the reading and writing workshop practices that are most effective in developing readers in the primary grades. She shares the daily how-tos needed to sustain a literacy block that engages children in authentic reading…

  2. Analisis Sif Kerja, Masa Kerja, dan Budaya K3 dengan Fungsi Paru Pekerja Tambang Batu Bara

    Directory of Open Access Journals (Sweden)

    Qomariyatus Sholihah

    2015-08-01

    study aimed to determine relations of work shift, work period and occupational health and safety (OHS culture with lung function of coal mining worker. This study was control case design with each amount of sample for case and control was 178 respondents. The study was conducted on October – November 2014 at PT X in South Borneo. Results based on chisquare test showed p value = 0.044 for work shift, 0.028 for work period and 0.013 for OHS culture. Based on logistic regression test results, p value for work shift was 0.01 with OR = 3.934. As conclusion, there is a relation between work shift with lung function, then there is no relation found between work period and OHS culture with lung function. Work shift is an independent variable most dominantly influencing the lung function.

  3. Mind Sparklers. Fireworks for Igniting Creativity in Young Minds. Book 1 for Grades K-3.

    Science.gov (United States)

    Myers, Robert E.

    The 40 activities contained in this book were designed to persuade students to think both critically and creatively. The activities call for the use of all 18 of E. Paul Torrance's creative thinking abilities. The theoretical underpinnings for this collection are based upon philosophical and pedagogical beliefs that experiences be positive: if…

  4. Corrosion Testing of Monofrax K-3 Refractory in Defense Waste Processing Facility (DWPF) Alternate Reductant Feeds

    Energy Technology Data Exchange (ETDEWEB)

    Williams, M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Jantzen, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Burket, P. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-04-06

    The Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS) uses a combination of reductants and oxidants while converting high level waste (HLW) to a borosilicate waste form. A reducing flowsheet is maintained to retain radionuclides in their reduced oxidation states which promotes their incorporation into borosilicate glass. For the last 20 years of processing, the DWPF has used formic acid as the main reductant and nitric acid as the main oxidant. During reaction in the Chemical Process Cell (CPC), formate and formic acid release measurably significant H2 gas which requires monitoring of certain vessel’s vapor spaces. A switch to a nitric acid-glycolic acid (NG) flowsheet from the nitric-formic (NF) flowsheet is desired as the NG flowsheet releases considerably less H2 gas upon decomposition. This would greatly simplify DWPF processing from a safety standpoint as close monitoring of the H2 gas concentration could become less critical. In terms of the waste glass melter vapor space flammability, the switch from the NF flowsheet to the NG flowsheet showed a reduction of H2 gas production from the vitrification process as well. Due to the positive impact of the switch to glycolic acid determined on the flammability issues, evaluation of the other impacts of glycolic acid on the facility must be examined.

  5. REGULASI DAN PENERAPAN KESELAMATAN DAN KESEHATAN KERJA (K3 RUMAH SAKIT DI PROPINSI SUMATERA BARAT

    Directory of Open Access Journals (Sweden)

    Bambang Ristiono

    2009-09-01

    Full Text Available The study is related to the implementation of regulation’s policy on hospital safety and occupational health in West Sumatera. Hospital will implement regulation that local government established if there is effective mechanism. Regulation is an authoritative ride regarding to detail procedures that declare on local government policy.  The study aims to describe regulation policy of health department on behalf of Local Government for the implementation of hospital safety and occupational health in order to see effective regulation factors to make hospital obedient and will to implement regulation policy that established. Methods: The method of the study was case study with explorative descriptive. Dependent variable in the study was hospital safety and occupational health in West Sumatera, while the Independent variable was regulation policy of local government in implementing hospital safety and occupational health with factors in it, that cover sanction and reward, watch, regulation focus, human resource, financial, commitment, public control, and transparency. Objective: The study was obtained in Health Department and district hospital in West Sumatera that covers 6 district hospitals, ie. 2 hospitals with 12 accredited statuses, 2 hospitals with 5 accredited statuses, 2 hospitals with unaccredited status, and private hospital. Subject of the study was hospital manager and hospital manager in health Department of West Sumatera Province and district/city. Data were collected by dept. interview and spreading questionnaire that was obtained because of the difficulty of location and the busy of respondents. The result of the study shows that regulation of hospital safety and occupational health is weak, low commitment of hospital management toward hospital safely and occupational health, in order to make effective regulation of hospital safety and occupational health, it need the support of human resource, financial, sanction and reward, transparency, and public control. In order to make hospital safety and occupational health implemented well, health department of West Sumatera Province has to: complete the existing rule and socialized it to all hospitals, presence government and hospitals’ presence, increasing hospital's commitment and support to make effective regulation. The result of study wished to be used local government as a reference in implementing and maintaining regulation policy of hospital safety and occupational health, especially in West Sumatera in the future.

  6. Making Connections. A Curriculum and Activity Guide to Mammoth Cave National Park. [Grades] K-3.

    Science.gov (United States)

    National Park Service (Dept. of Interior), Washington, DC.

    Kentucky's Mammoth Cave National Park is important because of its diversity of life on the surface and underground. Some of the plants in the park include trees such as oaks, hickories, tulip poplars, sycamores, and many types of bushes. The animal population is also very diverse and includes bats, squirrels, deer, raccoons, opossums, chipmunks,…

  7. ANALISIS LAPORAN KEUANGAN BAZAR KEWIRAUSAHAAN PRODUK KREATIF LIMBAH K5PBB MAHASISWA PROGRAM STUDI PENDIDIKAN AKUNTANSI UNIVERSITAS PGRI PALEMBANG

    Directory of Open Access Journals (Sweden)

    Neta Dian Lestari

    2017-11-01

    Full Text Available Facing the business challenges of MEA Era is a challenge that should be faced by us, as an Educator I feel compelled to be able to participate in the success of my students, to face the challenge. The purpose of this study is not only for the Financial Statements of Bazaar, but also seek emphasis on the experience of an entrepreneurial process because through the Bazaar students are required to interact with people, how to offer well and politely to consumers, convince consumers to buy the products they offer and give explanation and the best service for consumers to be satisfied. Based on the result of observations which are conducted by the researcher as many as 15 times, SWOT observation analysis is with an average amount of 65.5% in GOOD Category. The results of financial statements analysis each group to see three important elements are: Elements Report L /R with the percentage of 56.09% High category, Elements of Capital Changes with the percentage of 78.05% Very High category, and Element Balance with the percentage of Current Assets 63.67%, High category, Fixed Assets 14.38% Low category and Liability 78.05% Very High category. This bazaar activity is very useful for students to gain experience and learning to become entrepreneurs. This activity is a very useful activity for students especially students of Accounting Education Studies Program FKIP University PGRI Palembang. By doing this activity, the students are expected to know how to offer and market a product that they make themselves well, and students can know more how to interact well and politely with consumers or customers.

  8. Integrating Engineering into Delaware's K-5 Classrooms: A Study of Pedagogical and Curricular Resources

    Science.gov (United States)

    Grusenmeyer, Linda Huey

    2017-01-01

    This study examines the personal and curricular resources available to Delaware's elementary teachers during a time of innovative curriculum change, i.e., their knowledge, goals and beliefs regarding elementary engineering curriculum and the pedagogical support to teach two Science and Engineering Practices provided by science teaching materials.…

  9. Indigenous Education for Critical Democracy: Teacher Approaches and Learning Outcomes in a K-5 Indian Education for All Program

    Science.gov (United States)

    Ngai, Phyllis B.; Koehn, Peter H.

    2011-01-01

    This article focuses on how three dimensions of critical democracy preparation (place-based geographical knowledge, social and political awareness of American Indian history and culture, and orientations conducive to the development of personal connections with American Indians) were impacted by different instructional approaches introduced when…

  10. Assessing K-5 Teacher Leaders' Mathematical Understanding: What Have the Test Makers and the Test Takers Learned?

    Science.gov (United States)

    Ellington, Aimee J.; Whitenack, Joy W.; Inge, Vickie L.; Murray, Megan K.; Schneider, Patti J.

    2012-01-01

    This article describes the design and implementation of an assessment instrument for Numbers and Operations, the first course in a program to train elementary mathematics specialists. We briefly describe the course and its content, and then we elaborate on the process we used to develop the assessment instrument and the corresponding rubric for…

  11. The Effects of New Jersey's K-8 Foreign Language Authorization on K-5 Foreign Language Teaching: Two Teachers' Perspectives

    Science.gov (United States)

    Raymond, Robert B. L.

    2012-01-01

    Recent research in language education policy (LEP) refocuses attention from the role of governments to local stakeholders that shape LEP. However, little attention has been given to teacher agency in LEP implementation for early foreign language (FL) education in the United States. This pilot study considers the role of foreign language elementary…

  12. Vascular flora of Kenya, based on the Flora of Tropical East Africa

    Directory of Open Access Journals (Sweden)

    Yadong Zhou

    2017-11-01

    Full Text Available Kenya, an African country with major higher plant diversity, has a corresponding diversity of plant associations, because of the wide geographic distribution, diverse climatic conditions and soil types. In this article, all vascular plants of Kenya were counted based on the completed "Flora of Tropical East Africa (FTEA", and all families and genera were revised using recent molecular systematics research, forming a "Synoptic List of Families and Genera of Kenyan Vascular Plants (SLFGKVP". In total, there are 225 families, 1538 genera and 6293 indigenous species and and 62 families, 302 genera and 588 exotic species in Kenya. The Fabaceae with 98 genera and 576 Species is the largest family. Two of the seven plant distribution regions of Kenya, K4 and K7 are the most species-richest areas with regard to both total and endemic species, with 3375 and 3191 total species and 174 and 185 endemic species in K4 and K7 respectively. While, K3 and K5 have the highest density of both total and endemic species. K1 has the lowest density of total species, and K2 has the lowest density of endemic species.

  13. Rational Design of Cyclic Antimicrobial Peptides Based on BPC194 and BPC198

    Directory of Open Access Journals (Sweden)

    Anna D. Cirac

    2017-06-01

    Full Text Available A strategy for the design of antimicrobial cyclic peptides derived from the lead compounds c(KKLKKFKKLQ (BPC194 and c(KLKKKFKKLQ (BPC198 is reported. First, the secondary β-structure of BPC194 and BPC198 was analyzed by carrying out molecular dynamics (MD simulations. Then, based on the sequence pattern and the β-structure of BPC194 or BPC198, fifteen analogues were designed and synthesized on solid-phase. The best peptides (BPC490, BPC918, and BPC924 showed minimum inhibitory concentration (MIC values <6.2 μM against Pseudomonas syringae pv. syringae and Xanthomonas axonopodis pv. vesicatoria, and an MIC value of 12.5 to 25 μM against Erwinia amylovora, being as active as BPC194 and BPC198. Interestingly, these three analogues followed the structural pattern defined from the MD simulations of the parent peptides. Thus, BPC490 maintained the parallel alignment of the hydrophilic pairs K1–K8, K2–K7, and K4K5, whereas BPC918 and BPC924 included the two hydrophilic interactions K3–Q10 and K5–K8. In short, MD simulations have proved to be very useful for ascertaining the structural features of cyclic peptides that are crucial for their biological activity. Such approaches could be further employed for the development of new antibacterial cyclic peptides.

  14. Estandarizacion y evaluacion de un enzimoinmunoensayo para diagnostico y seroepidemiologia de triquinosis humana

    Directory of Open Access Journals (Sweden)

    Emílio Coltorti

    1987-12-01

    Full Text Available Se estandarizó un enzimoinmunoensayo (EIE en fase sólida en el que se empleó un antígeno soluble total de T. spiralis y una dilución única de suero, y se evaluó la capacidad del sistema para detectar anticuerpos totales antitriquina con fines diagnósticos y seroepidemiológicos. Las curvas dosis respuesta mostraron que trabajando con una dilución de suero de 1:100 se obtenía una buena diferenciación entre sueros de indivíduos no infectados y pacientes de triquinosis con baja concentración de anticuerpos circulantes y la respuesta fue lineal entre valores de 0.15 y 0.64 unidades de densidad óptica (DO. El estúdio de 720 sueros de población general no infectada revelo una X k = 0.07 y una S = 0.03 unidades de DO. El 98,61% de esta población presentó valores de DO X k + 3S y X k + 4S y < X k + 5S. Se empleó un valor de DO = X k + 5S como nivel diagnóstico para estudiar 4 brotes de triquinosis humana, 80 sueros de pacientes de triquinosis con diferentes títulos en inmunofluorescencia indirecta (IFI y 20 sueros de pacientes de hidatidosis. El EIE propuesto permitió diferenciar en forma confiable y eficiente población infectada de no infectada y tuvo una buena correlación con la IFI. Todos los sueros de pacientes hidatídicos presentaron valores de DO < X k + 4S.

  15. The locally connected compact metric spaces embeddable in the plane

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2004-01-01

    We prove that a 2-connected, locally connected, compact topological space M is homeomorphic to a subset of the 2-sphere if and only if M is metrizable and contains none of the Kuratowski graphs K-5 and K-3,K-3.......We prove that a 2-connected, locally connected, compact topological space M is homeomorphic to a subset of the 2-sphere if and only if M is metrizable and contains none of the Kuratowski graphs K-5 and K-3,K-3....

  16. Optimasi Lahan dengan Sistem Tumpangsari Jagung Manis (Zea mays saccharata, Strurt dan Kangkung Sutera (Ipomea reptans di Pekanbaru

    Directory of Open Access Journals (Sweden)

    Surtinah Surtinah

    2016-03-01

    Full Text Available Penelitian dilaksanakan secara eksperimen dengan menggunakan rancangan lingkungan acak lengkap dengan 3 kali ulangan, dan rancangan perlakuan yaitu waktu tanam kangkung sebagai tanaman tumpangsari pada budidaya jagung manis ( K yang terdiri dari : k1 =  waktu tanam bersamaan; k2 = waktu tanam kangkung 1 minggu setelah tanam jagung manis; k3 = waktu tanam kangkung 2 minggu setelah tanam jagung manis; k4 = waktu tanam kangkung 3 minggu setelah tanam jagung manis; k5= penanaman jagung manis tunggal dengan waktu tanam = k1; k6 = penanaman kangkung tunggal dengan waktu tanam = k1.      Hasil penelitian menunjukan bahwa kangkung sutera dapat ditanam bersamaan dengan waktu tanam jagungmanis, sampai dengan tiga minggu setelah tanam jagung manis.  Hasil jagung manis tidak dipengaruhi oleh waktu tanam kangkung sutera yang berbeda. Nilai Kesetaraan Lahan pada sistem tumpangsari jagung manis dengan kangkung sutera adalah 1,83. Indeks Persaingan antara jagung manis dan kangkung sutera adalah 1,73. Kata kunci : Jagung manis, Kangkung sutera, Tumpangsari, NKL, Indeks Persaingan. Research conducted experiments using a completely randomized design environment with three replications, and design of treatment that is the time of planting silk kale as secondary crops to the cultivation of sweet corn (K consisting of: k1 = planting at the same time; k2 = time of planting silk kale 1 week after planting sweet corn; k3 = time of planting silk kale 2 weeks after planting sweet corn; k4 = time of planting silk kale 3 weeks after planting sweet corn; K5 = single planting sweet corn planting time = k1; k6 = single silk kale planting time = k1. The results showed that silk kale can be planted together with sweet corn planting time, up to three weeks after planting sweet corn. Results of sweet corn is not influenced by the timing of planting different silk kale. Land values in the cropping system Equality sweet corn with silk kale is 1.83. Competition index between

  17. Edge-disjoint Hamiltonian cycles in hypertournaments

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2006-01-01

    We introduce a method for reducing k-tournament problems, for k >= 3, to ordinary tournaments, that is, 2-tournaments. It is applied to show that a k-tournament on n >= k + 1 + 24d vertices (when k >= 4) or on n >= 30d + 2 vertices (when k = 3) has d edge-disjoint Hamiltonian cycles if and only...

  18. VITAL (Vanguard Investigations of Therapeutic Approaches to Lung Cancer)

    Science.gov (United States)

    2009-01-01

    expression are important for driving tumorigenesis. k1 k2 k3 k3 -ab k4-ab k7 k8 k9 k10 k11 k12 k13 k14 k15 Figure 1...normal” area, except cases k3 and k4, which are from LIFE-abnormal while white-light normal area. Nevertheless, there is no obvious disparity among these... vitamin E and β caro- tene on the incidence of lung cancer and other can- cers in male smokers. N Engl J Med 1994;330: 1029–35. 6. Omenn GS, Goodman GE

  19. Investigating the Impact of NGSS-Aligned Professional Development on PreK-3 Teachers' Science Content Knowledge and Pedagogy

    Science.gov (United States)

    Tuttle, Nicole; Kaderavek, Joan N.; Molitor, Scott; Czerniak, Charlene M.; Johnson-Whitt, Eugenia; Bloomquist, Debra; Namatovu, Winnifred; Wilson, Grant

    2016-01-01

    This pilot study investigates the impact of a 2-week professional development Summer Institute on PK-3 teachers' knowledge and practices. This Summer Institute is a component of [program], a large-scale early-childhood science project that aims to transform PK-3 science teaching. The mixed-methods study examined concept maps, lesson plans, and…

  20. 3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice

    DEFF Research Database (Denmark)

    Wang, Yaoming; Zhao, Zhen; Rege, Sanket V

    2016-01-01

    -APC (Lys191-193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell-signaling activity, have shown benefits in preclinical models...... of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic and reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes and lethal body radiation. On the basis of proof-of-concept studies and an excellent safety...

  1. The Growth of Instructional Coaching Partner Conversations in a PreK-3rd Grade Teacher Professional Development Experience

    Science.gov (United States)

    Thomas, Earl E.; Bell, David L.; Spelman, Maureen; Briody, Jennifer

    2015-01-01

    Instructional coaching that supports teachers' with revising teaching practices is not understood. This study sought to understand the impact of the instructional coaching experience by recording coaching conversations/interactions with teachers. The purpose was to determine if the type of coaching conversations changed overtime during three…

  2. Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis.

    Science.gov (United States)

    Shah, Meera; Stebbins, John L; Dewing, Antimone; Qi, Jianfei; Pellecchia, Maurizio; Ronai, Ze'ev A

    2009-12-01

    The E3 ubiquitin ligase Siah2 has been implicated in the regulation of the hypoxia response, as well as in the control of Ras, JNK/p38/NF-kappaB signaling pathways. Both Ras/mitogen-activated protein kinase (MAPK) and hypoxia pathways are important for melanoma development and progression, pointing to the possible use of Siah2 as target for treatment of this tumor type. In the present study, we have established a high-throughput electro-chemiluninescent-based assay in order to screen and identify inhibitors of Siah2 ubiquitin ligase activity. Of 1840 compounds screened, we identified and characterized menadione (MEN) as a specific inhibitor of Siah2 ligase activity. MEN attenuated Siah2 self-ubiquitination, and increased expression of its substrates PHD3 and Sprouty2, with concomitant decrease in levels of HIF-1alpha and pERK, the respective downstream effectors. MEN treatment no longer affected PHD3 or Sprouty2 in Siah-KO cells, pointing to its Siah-dependent effects. Further, MEN inhibition of Siah2 was not attenuated by free radical scavenger, suggesting it is ROS-independent. Significantly, growth of xenograft melanoma tumors was inhibited following the administration of MEN or its derivative. These findings reveal an efficient platform for the identification of Siah inhibitors while identifying and characterizing MEN as Siah inhibitor that attenuates hypoxia and MAPK signaling, and inhibits melanoma tumorigenesis.

  3. DNA polymerase gamma inhibition by vitamin K3 induces mitochondria-mediated cytotoxicity in human cancer cells.

    Science.gov (United States)

    Sasaki, Ryohei; Suzuki, Yoko; Yonezawa, Yuko; Ota, Yosuke; Okamoto, Yoshiaki; Demizu, Yusuke; Huang, Peng; Yoshida, Hiromi; Sugimura, Kazuro; Mizushina, Yoshiyuki

    2008-05-01

    Among the vitamin K (VK) compounds, VK3 exhibits distinct cytotoxic activity in cancer cells and is thought to affect redox cycling; however, the underlying mechanisms remain unclear. Here we demonstrate that VK3 selectively inhibits DNA polymerase (pol) gamma, the key enzyme responsible for mitochondrial DNA replication and repair. VK3 at 30 microM inhibited pol gamma by more than 80%, caused impairment of mitochondrial DNA replication and repair, and induced a significant increase in reactive oxygen species (ROS), leading to apoptosis. At a lower concentration (3 microM), VK3 did not cause a significant increase in ROS, but was able to effectively inhibit cell proliferation, which could be reversed by supplementing glycolytic substrates. The cytotoxic action of VK3 was independent of p53 tumor suppressor gene status. Interestingly, VK3 only inhibited pol gamma but did not affect other pol including human pol alpha, pol beta, pol delta, and pol epsilon. VK1 and VK2 exhibited no inhibitory effect on any of the pol tested. These data together suggest that the inhibition of pol gamma by VK3 is relatively specific, and that this compound seems to exert its anticancer activity by two possible mechanisms in a concentration-dependent manner: (1) induction of ROS-mediated cell death at high concentrations; and (2) inhibition of cell proliferation at lower concentrations likely through the suppression of mitochondrial respiratory function. These findings may explain various cytotoxic actions induced by VK3, and may pave the way for the further use of VK3.

  4. Investigating the Impact of NGSS-Aligned Professional Development on PreK-3 Teachers' Science Content Knowledge and Pedagogy

    Science.gov (United States)

    Tuttle, Nicole; Kaderavek, Joan N.; Molitor, Scott; Czerniak, Charlene M.; Johnson-Whitt, Eugenia; Bloomquist, Debra; Namatovu, Winnifred; Wilson, Grant

    2016-11-01

    This pilot study investigates the impact of a 2-week professional development Summer Institute on PK-3 teachers' knowledge and practices. This Summer Institute is a component of [program], a large-scale early-childhood science project that aims to transform PK-3 science teaching. The mixed-methods study examined concept maps, lesson plans, and classroom observations to measure possible changes in PK-3 teachers' science content knowledge and classroom practice from 11 teachers who attended the 2014 Summer Institute. Analysis of the concept maps demonstrated statistically significant growth in teachers' science content knowledge. Analysis of teachers' lesson plans demonstrated that the teachers could design high quality science inquiry lessons aligned to the Next Generation Science Standards following the professional development. Finally, examination of teachers' pre- and post-Summer Institute videotaped inquiry lessons showed evidence that teachers were incorporating new inquiry practices into their teaching, especially regarding classroom discourse. Our results suggest that an immersive inquiry experience is effective at beginning a shift towards reform-aligned science and engineering instruction but that early elementary educators require additional support for full mastery.

  5. alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Strafella, E.; Staffolani, S.; Santarelli, L.; Neužil, Jiří; Guerrieri, R.

    2010-01-01

    Roč. 102, č. 8 (2010), s. 1224-1234 ISSN 0007-0920 Institutional research plan: CEZ:AV0Z50520701 Keywords : Vitamins * prostate cancer * cell-death Subject RIV: ED - Physiology Impact factor: 4.831, year: 2010

  6. Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis

    Science.gov (United States)

    Shah, Meera; Stebbins, John L.; Dewing, Antimone; Qi, Jianfei; Pellecchia, Maurizio; Ronai, Ze’ev A.

    2010-01-01

    Summary The E3 ubiquitin ligase Siah2 has been implicated in the regulation of the hypoxia response, as well as in the control of Ras, JNK/p38/NF-κB signaling pathways. Both Ras/mitogen-activated protein kinase (MAPK) and hypoxia pathways are important for melanoma development and progression, pointing to the possible use of Siah2 as target for treatment of this tumor type. In the present study, we have established a high-throughput electro-chemiluninescent-based assay in order to screen and identify inhibitors of Siah2 ubiquitin ligase activity. Of 1840 compounds screened, we identified and characterized menadione (MEN) as a specific inhibitor of Siah2 ligase activity. MEN attenuated Siah2 self-ubiquitination, and increased expression of its substrates PHD3 and Sprouty2, with concomitant decrease in levels of HIF-1α and pERK, the respective downstream effectors. MEN treatment no longer affected PHD3 or Sprouty2 in Siah-KO cells, pointing to its Siah-dependent effects. Further, MEN inhibition of Siah2 was not attenuated by free radical scavenger, suggesting it is ROS-independent. Significantly, growth of xenograft melanoma tumors was inhibited following the administration of MEN or its derivative. These findings reveal an efficient platform for the identification of Siah inhibitors while identifying and characterizing MEN as Siah inhibitor that attenuates hypoxia and MAPK signaling, and inhibits melanoma tumorigenesis. PMID:19712206

  7. 26 CFR 31.3121(k)-3 - Request for coverage of individual employed by exempt organization before August 1, 1956.

    Science.gov (United States)

    2010-04-01

    ... director of any part of the employee tax paid with respect to remuneration received by him from the..., 1956, and before August 27, 1958, that such part of the remuneration received by him for services... employer taxes were paid be deemed to constitute remuneration for employment, if: (i) Any of the services...

  8. Happy 50th, Smokey Bear! A Learning Kit about Forests and Fire Safety for Grades K-3.

    Science.gov (United States)

    Hall, Meryl

    In 1994, Smokey Bear turns 50! For a half century, Smokey has been helping children and adults protect forests and wildlands from careless fire. With this kit students can celebrate Smokey's message using a variety of activities that include dramatic play, stories, games, and things to make and do. Through these activities, students learn about…

  9. Potential for Knowledge in Action? An Analysis of Korean Green Energy Related K3-12 Curriculum and Texts

    Science.gov (United States)

    Gress, Douglas R.; Shin, Jungyeop

    2017-01-01

    While understanding green energy development and what drives it are important, there is increasing consensus that sustainability transitions concerning usage need to be viewed in terms of the place specific contexts, including education, that critically mold them. In order to "support" sustainability transitions, information and…

  10. Efficiency of the SASS4 rapid bioassessment protocol in determining river health: A case study on the Mhlathuze River, KwaZulu-Natal, South Africa

    CSIR Research Space (South Africa)

    Vos, P

    2002-01-01

    Full Text Available the labour and time factors confronting freshwater ecologists, since the number of habitats examined and the replicated sample units taken per site are reduced (Chutter, 1994). Dallas (1995, 1997) addressed some of the uncertainties associated with SASS4... 3b 4l 4a 4b 5l 5a 5b 6l 6a 6b I II III VI V Number of taxa ASPT values 2c 2d 2e 3c 3d 3e 4c 4d 4e 5c5d 5e 6c 6d 6e I II III IV V VI VII 2f 2g 2h 3f 3g 3h 4f 4g 4h 5f5g 5h 6g 6h I II III IV V VI 2i 2j 2k 3i 3j 3k 4i4j 4k 5i 5j 5k 6i 6j6k I II III IV V...

  11. PENGGUNAAN KITOSAN CANGKANG BEKICOT (ACHANTINA FULICA UNTUK BAHAN PENGAWET ALAMI BERBAGAI JENIS SAYURAN SEBAGAI SUMBER BELAJAR DALAM PERENCANAAN PEMBELAJARAN BIOTEKNOLOGI

    Directory of Open Access Journals (Sweden)

    Nur Aisyah

    2015-07-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui perbedaan kandungan vitamin C dan pH dalam sayuran bunga kol, kubis dan buncis yang diawetkan dengan kitosan cangkang bekicot selama proses penyimpanan dan untuk mengetahui berapakah konsentrasi kitosan cangkang bekicot yang paling efektif sebagai bahan pengawet sayuran tersebut. Kegiatan penelitian dilakukan melalui True Experimental Research. Tempat dan waktu penelitian dilaksanakan di Laboratorium Kimia Universitas Muhammadiyah Malang yang berlangsung pada tanggal 23 Juni – 6 Juli 2014. Rancangan penelitian yang digunakan adalah Rancangan Acak Kelompok (RAK dengan 6 perlakuan dan 4 kali ulangan pada bunga kol, kubis dan buncis yaitu C0, K0 dan B0 (Kontrol, C1, K1 dan B1 (0,5%, C2, K2 dan B2 (1%, C3, K3 dan B3(1,5%l, C4, K4 dan B4 (2%, C5, K5 dan B5 (2,5%, Analisis data menggunakan analisis varians satu arah dan uji beda jarak nyata Duncan pada taraf signifikansi 0,05. Hasil penelitian menunjukkan ada pengaruh pemberian konsentrasi kitosan cangkang bekicot (Achantina fulica terhadap perbedaan kandungan vitamin C sayuran bunga kol, kubis dan buncis dari hari per hari selama penyimpanan. Perubahan kandungan vitamin C paling kecil terjadi pada perlakuan 1,5% dan paling besar pada perlakuan kontrol. Pemberian konsentrasi kitosan cangkang bekicot (Achantina fulica 1,5% adalah yang paling efektif mempengaruhi kandungan fitamin C sayuran bunga kol, kubis dan buncis. Hasil penelitian diaplikasikan pada perencanaan pembelajaran SMA kelas XII materi bioteknologi

  12. OPTIMASI LAHAN DENGAN SISTEM TUMPANG SARI JAGUNG MANIS (Zea mays saccharata, Sturt DAN KANGKUNG SUTRA (Ipomea reptans DI PEKANBARU

    Directory of Open Access Journals (Sweden)

    Surtinah Surtinah

    2018-04-01

    Full Text Available Research conducted experiments using a completely randomized design environment with three replications, and design of treatment that is the time of planting silk kale as secondary crops to the cultivation of sweet corn (K consisting of: k1 = planting at the same time; k2 = time of planting silk kale 1 week after planting sweet corn; k3 = time of planting silk kale 2 weeks after planting sweet corn; k4 = time of planting silk kale 3 weeks after planting sweet corn; K5 = single planting sweet corn planting time = k1; k6 = single silk kale planting time = k1. The results showed that silk kale can be planted together with sweet corn planting time, up to three weeks after planting sweet corn. Results of sweet corn is not influenced by the timing of planting different silk kale. Land values in the cropping system Equality sweet corn with silk kale is 1.83. Competition index between sweet corn and silk kale is 1.73.

  13. Revamping of entisol soil physical characteristics with compost treatment

    Science.gov (United States)

    Sumono; Loka, S. P.; Nasution, D. L. S.

    2018-02-01

    Physical characteristic of Entisol soil is an important factor for the growth of plant. The aim of this research was to know the effect of compost application on physical characteristics of Entisol soil. The research method used was experimental method with 6 (six) treatments and 3 replications of which K1 = 10 kg Entisol soil without compost, K2 = 9 Kg Entisol soil with 1 kg compost, K3 = 8 kg Entisol soil with 2 kg compost, K4 = 7 kg Entisol soilwith3 kg compost, K5 = 6 kg Entisol soil with 4 kg compost and K6 = 5 kg Entisol soil with 5 kg compost. The observed parameters were soil texture, soil organic matter, soil thickness, porosity, soil pore size, soil permeability and water availability. The results showed that the Entisol soil texture was loamy sand texture, the value of soil organic matter ranged from 0.74% to 4.69%, soil thickness ranged from 13.83 to 20.16 cm, porosity ranged from16% to 37%, soil pore size ranged from 2.859 to 5.493 µm, permeability ranged from 1.24 to 5.64 cm/hour and water availability ranged from 6.67% to 9.12% by each treatment.

  14. Variability of silver fir (Abies alba Mill. cones – variability of cone parameters

    Directory of Open Access Journals (Sweden)

    Aniszewska Monika

    2016-09-01

    Full Text Available This study aimed at determining the shape of closed silver fir cones from the Jawor Forest District (Wroclaw, based purely on measurements of their length and thickness. Using these two parameters, the most accurate estimations were achieved with a fourth-degree polynomial fitting function. We then calculated the cones’ surface area and volume in three different ways: 1 Using the fourth-degree polynomial shape estimation, 2 Introducing indicators of compliance (k1, k2, k3 to calculate the volume and then comparing it to its actual value as measured in a pitcher filled with water, 3 Comparing the surface area of the cones as calculated with the polynomial function to the value obtained from ratios of indicators of compliance (ratios k4 and k5. We found that the calculated surface area and volume were substantially higher than the corresponding measured values. Test values of cone volume and surface area as calculated by our model were 8% and 5% lower, respectively, compared to direct measurements. We also determined the fir cones apparent density to be 0.8 g·cm-3on average. The gathered data on cone surface area, volume and bulk density is a valuable tool for optimizing the thermal peeling process in mill cabinets to acquire high quality seeds.

  15. Ionothermal Synthesis and Magnetic Studies of Novel Two-Dimensional Metal-Formate Frameworks

    International Nuclear Information System (INIS)

    Calderone, P.; Feygenson, M.; Forster, P.M.; Borkowski, L.A.; Teat, S.J.; Aronson, M.C.; Parise, J.B.

    2011-01-01

    Five novel two-dimensional frameworks containing formate-bridged metal-centered octahedra are synthesized ionothermally from two ionic liquids previously unused as solvents in hybrid synthesis, 2-hydroxyethylammonium (HEA) formate, and 1-hydroxy-3-proplyammonium (HPA) formate. Templating effects of the cation from each ionic liquid drive the formation of different structures. [NH 3 C 2 H 4 OH] 2 [M(CHO 2 ) 4 ] (1: M = Co, 2: M = Ni) exhibit the same stoichiometry and connectivity as their manganese analogue (3: M = Mn), but the manganese form exhibits a different topology from 1 and 2. [NH 3 C 3 H6OH][M(CHO 2 ) 3 (H 2 O)] (4: M = Co, 5: M = Mn) were synthesized using the HPA formate ionic liquid with a metal-formate connectivity related to those of 1-3. Canted antiferromagnetic ordering occurs at low temperatures (1: T N = 7.0 K, 2: T N = 4.6 K, 3: T N = 8.0 K, 4: T N = 7.0 K, 5: T N = 9.2 K), similar to the magnetic properties previously reported for other metal-formate hybrid materials.

  16. ABILITY OF BACTERIAL CONSORTIUM: Bacillus coagulans, Bacilus licheniformis, Bacillus pumilus, Bacillus subtilis, Nitrosomonas sp. and Pseudomonas putida IN BIOREMEDIATION OF WASTE WATER IN CISIRUNG WASTE WATER TREATMENT PLANT

    Directory of Open Access Journals (Sweden)

    Ratu SAFITRI

    2015-10-01

    Full Text Available This study was conducted in order to determine the ability of bacterial consortium: Bacillus coagulans, Bacilus licheniformis, Bacillus pumilus, Bacillus subtilis, Nitrosomonas sp., and Pseudomonas putida in bioremediation of wastewater origin Cisirung WWTP. This study uses an experimental method completely randomized design (CRD, which consists of two treatment factors (8x8 factorial design. The first factor is a consortium of bacteria (K, consisting of 8 level factors (k1, k2, k3, k4, k5, k6, k7, and k8. The second factor is the time (T, consisting of a 7 level factors (t0, t1, t2, t3, t4, t5, t6, and t7. Test parameters consist of BOD (Biochemical Oxygen Demand, COD (Chemical Oxygen Demand, TSS (Total Suspended Solid, Ammonia and Population of Microbes during bioremediation. Data were analyzed by ANOVA, followed by Duncan test. The results of this study showed that the consortium of Bacillus pumilus, Bacillus subtilis, Bacillus coagulans, Nitrosomonas sp., and Pseudomonas putida with inoculum concentration of 5% (k6 is a consortium of the most effective in reducing BOD 71.93%, 64.30% COD, TSS 94.85%, and 88.58% of ammonia.

  17. Modulation of the unpaired spin localization in Pentavalent Uranyl Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Vetere, V.; Maldivi, P.; Mazzanti, M. [CEA Grenoble, INAC, SCIB, laboratoire de reconnaissance ionique et chimie de coordination, 38 (France); Vetere, V. [UMR5626, laboratoire de chimie et physique quantique, universite de Toulouse, 31 - Toulouse (France)

    2010-06-15

    The electronic structure of various complexes of pentavalent uranyl species, namely UO{sub 2}{sup +}, is described, using DFT methods, with the aim of understanding how the structure of the ligands may influence the localisation of the unpaired 5f electron of uranium (V) and, finally, the stability of such complexes towards oxidation. Six complexes have been inspected: [UO{sub 2}py{sub 5}]{sup +} (1), [(UO{sub 2}py{sub 5})KI{sub 2}] (2), [UO{sub 2}(salan-{sup t}Bu{sub 2})(py)K] (3), [UO{sub 2}(salophen-{sup t}Bu{sub 2})(thf)K] (4), [UO{sub 2}(salen-{sup t}Bu{sub 2})(py)K] (5), [and UO{sub 2}-cyclo[6]pyrrole]{sup 1-} (6), chosen to explore various ligands. In the five first complexes, the UO{sub 2}{sup +} species is well identified with the unpaired electron localized on the 5f uranium orbital. Additionally, for the salan, salen and salophen ligands, some covalent interactions have been observed, resulting from the presence of both donor and acceptor binding sites. In contrast, the last complex is best described by a UO{sub 2}{sup 2+} uranyl (VI) coordinated by the anionic radical cyclo-pyrrole, the highly delocalized p orbitals set stabilizing the radical behaviour of this ligand. (authors)

  18. The analyze of lung’s GSH number in rats exposed by cigarette smoke and inducted by rambutan peel extract

    Science.gov (United States)

    Lisdiana

    2018-03-01

    The cigarette smoke is one of the pollutants in human and environment. It contains free radical compounds which cause oxidative stress. In the oxidative stress condition, the free radical causing peroxidation of cell membrane lipid as well as damages the cell membrane. One of the biomarkers of oxidative stress happens the number of GSH. The purpose of this study was to analyze the amount of rat's GSH which exposed by cigarette smoke as well as inducted by rambutan pell extract. This study applied to 25 male rats of Wistar which divided into five groups; K1 (control), K2 (negative), K3, K4, and K5 were the treatment groups of rambutan peel extract with various dosage; 3, 6, 12 mg/200 gramBB and cigarette smoke exposure along 30 days. The number of GSH measured by the DTNB of lung tissue. To know the difference of GSH number of each group did the data analysis with one way ANOVA test and LSD advance test. The result of statistic analysis showed that there was a significant difference between the control group and treatment group. The conclusion of this study was the rambutan peel extract with 3 mg/200 gramBB dosage could increase the number of lung's GSH of rats exposed to cigarette smoke.

  19. Assessing Agricultural Literacy Elements of Project Food Land and People in K-5 Using the Food and Fiber Systems Literacy Standards

    Science.gov (United States)

    Powell, David V.; Agnew, David M.

    2011-01-01

    Agricultural literacy has been evolving as a discipline for over 25 years. In agriculture, as other disciplines of education, the body of knowledge can be identified and measured by a set of standards. The Food and Fiber Systems Literacy Standards, developed in the 1990s, have been widely accepted as the standards for agricultural literacy. Also…

  20. Building the Foundation of Acceptance Book by Book: Lesbian, Gay, Bisexual, and/or Transgender-Themed Books for Grades K-5 Multicultural Libraries

    Science.gov (United States)

    Knoblauch, Dee

    2016-01-01

    This article is an analysis of picture books and chapter books involving lesbian, gay, bisexual, and/or transgender characters. Over 30 picture and chapter books were reviewed, each of which would be appropriate for use in elementary classrooms. For grades K-2, several picture books highlight different types of families, including families that…