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Sample records for stable cytidine analogue

  1. Dipolar Quinoidal Acene Analogues as Stable Isoelectronic Structures of Pentacene and Nonacene

    KAUST Repository

    Shi, Xueliang

    2015-10-08

    Quinoidal thia-acene analogues, as the respective isoelectronic structures of pentacene and nonacene, were synthesized and an unusual 1,2-sulfur migration was observed during the Friedel-Crafts alkylation reaction. The analogues display a closed-shell quinoidal structure in the ground state with a distinctive dipolar character. In contrast to their acene isoelectronic structures, both compounds are stable because of the existence of more aromatic sextet rings, a dipolar character, and kinetic blocking. They exhibit unique packing in single crystals resulting from balanced dipole-dipole and [C-H⋯π]/[C-H⋯S] interactions.

  2. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  3. A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man.

    OpenAIRE

    O'Grady, J; Hedges, A; Whittle, B J; Al-Sinawi, L A; Mekki, Q A; Burke, C; Moody, S G; Moti, M J; Hassan, S

    1984-01-01

    The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 be...

  4. Biological activity of insect juvenile hormone analogues against the stable fly and toxicity studies in domestic animals.

    Science.gov (United States)

    Wright, J E; Smalley, H E

    1977-01-01

    The insect JHAs are effective inhibitors of adult stable fly development. Laboratory and field evaluation studies demonstrated that area application of the analogues to larval breeding sites was efficacious for stable fly control in cattle feed lots and in marine grasses. Analytical methods by quantification with gas chromatography with flame ionization detection was developed to measure residual properties as well as aging and leaching in fly breeding media. The analogues did not interfere with the oviposition and development of the endoparasites, M. raptor and S. endius. Toxicity studies against swine, hamsters, and sheep showed that when compounds of high purity were used that no toxic effects were observed in any of the species.

  5. Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX

    DEFF Research Database (Denmark)

    Sheykhzade, Majid; Abdolalizadeh, Bahareh; Koole, Cassandra

    2018-01-01

    The purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and SAX, a metabolically stable CGRP analog, in isolated rat and human artery segments (vasoactivity), in recombinant human CGRP receptors (cAMP accumulation), and in native rat receptors (receptor...

  6. The stable prostacyclin-analogue, iloprost, unlike prostanoids and leukotrienes, potently stimulates cyclic adenosine monophosphate synthesis of primary astroglial cell cultures.

    Science.gov (United States)

    Seregi, A; Schobert, A; Hertting, G

    1988-06-01

    The effect of different eicosanoids on adenosine-3', 5'-cyclic-monophosphate (cAMP) accumulation in primary astroglial cell cultures prepared from newborn rat brain was studied. The stable prostacyclin-analogue, iloprost, effectively stimulated cAMP synthesis in a concentration-dependent, saturable manner, the EC50 being about 3 x 10(-8) M. Prostaglandin (PG) E2 was less potent, without reaching plateau even at 10(-5) M. Prostaglandins D2 and F2 alpha, and the stable thromboxane A2-analogue, U 46619, as well as leukotrienes (LT) B4, C4, D4 and E4 were not effective and did not attenuate basal or isoprenaline (10(-8) M)-stimulated astroglial cAMP formation. This is the first indication for the existence of a prostacyclin receptor coupled positively to the adenylate cyclase in astrocytes. Other eicosanoids are unlikely to be involved in receptor-mediated regulation of astroglial cAMP levels.

  7. Beraprost sodium, a stable prostacyclin analogue, elicits dilation of isolated porcine retinal arterioles: roles of eNOS and potassium channels.

    Science.gov (United States)

    Ono, Shinji; Nagaoka, Taiji; Omae, Tsuneaki; Tanano, Ichiro; Kamiya, Takayuki; Otani, Shinichi; Ishibazawa, Akihiro; Yoshida, Akitoshi

    2014-07-31

    Prostacyclin (PGI2) is usually described as an endoEDRFsthelium-derived relaxing factor, but the vasoreactivity to PGI2 in the retinal arterioles and the underlying mechanisms are not fully understood. We examined the effects of PGI2 on the retinal microcirculation using beraprost sodium (BPS), a stable PGI2 analogue, and the signaling mechanisms involved in this vasomotor activity. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to BPS. Beraprost sodium elicited dose-dependent (0.1 pM-0.1 μM) vasodilation of the retinal arterioles that was abolished by the PGI2 receptor (IP) antagonist CAY10441. Beraprost sodium-induced vasodilation decreased by 50% after the endothelium was removed and was inhibited by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) comparable with denudation. Inhibition of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and blockage of protein kinase A (PKA) by Rp-8-Br-cAMPS were comparable to L-NAME. Beraprost sodium-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium, and the adenosine triphosphate-sensitive potassium (KATP) channel blocker, glibenclamide. Residual vasodilation in the presence of glibenclamide decreased further with subsequent application of ODQ. Beraprost sodium, a stable PGI2 analogue, causes vasodilation of the retinal arterioles mediated via the IP receptor. The current findings suggest that BPS elicits endothelium-dependent and -independent dilation of the retinal arterioles mediated by NO induced by activation of PKA in the endothelium and the KATP channel activation in the vascular smooth muscle, respectively. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  8. Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase

    International Nuclear Information System (INIS)

    Jayakumar, Sundarraj; Patwardhan, R.S.; Pal, Debojyoti; Sharma, Deepak; Sandur, Santosh K.

    2016-01-01

    Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratio and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. - Highlights: • DIMC enhances radiosensitivity of cancer cells by inducing cell death. • DIMC with radiation disrupted the cellular redox and targeted cancer stem cells. • DNA repair is hampered when cells are treated with DIMC. • DIMC inhibited thioredoxin reductase in cancer cells.

  9. Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase

    Energy Technology Data Exchange (ETDEWEB)

    Jayakumar, Sundarraj; Patwardhan, R.S.; Pal, Debojyoti [Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Sharma, Deepak [Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094 (India); Sandur, Santosh K., E-mail: sskumar@barc.gov.in [Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094 (India)

    2016-09-09

    Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratio and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. - Highlights: • DIMC enhances radiosensitivity of cancer cells by inducing cell death. • DIMC with radiation disrupted the cellular redox and targeted cancer stem cells. • DNA repair is hampered when cells are treated with DIMC. • DIMC inhibited thioredoxin reductase in cancer cells.

  10. Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase.

    Science.gov (United States)

    Nowarski, Roni; Britan-Rosich, Elena; Shiloach, Tamar; Kotler, Moshe

    2008-10-01

    Deamination of cytidine residues in single-stranded DNA (ssDNA) is an important mechanism by which apolipoprotein B mRNA-editing, catalytic polypeptide-like (APOBEC) enzymes restrict endogenous and exogenous viruses. The dynamic process underlying APOBEC-induced hypermutation is not fully understood. Here we show that enzymatically active APOBEC3G can be detected in wild-type Vif(+) HIV-1 virions, albeit at low levels. In vitro studies showed that single enzyme-DNA encounters result in distributive deamination of adjacent cytidines. Nonlinear translocation of APOBEC3G, however, directed scattered deamination of numerous targets along the DNA. Increased ssDNA concentrations abolished enzyme processivity in the case of short, but not long, DNA substrates, emphasizing the key role of rapid intersegmental transfer in targeting the deaminase. Our data support a model by which APOBEC3G intersegmental transfer via monomeric binding to two ssDNA segments results in dispersed hypermutation of viral genomes.

  11. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  12. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Barceló Carlos

    2005-12-01

    Full Text Available Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  13. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Carlos Barceló

    2011-05-01

    Full Text Available Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  14. Myeloprotection by Cytidine Deaminase Gene Transfer in Antileukemic Therapy

    Directory of Open Access Journals (Sweden)

    Nico Lachmann

    2013-03-01

    Full Text Available Gene transfer of drug resistance (CTX-R genes can be used to protect the hematopoietic system from the toxicity of anticancer chemotherapy and this concept recently has been proven by overexpression of a mutant O6-methylguaninemethyltransferase in the hematopoietic system of glioblastoma patients treated with temozolomide. Given its protection capacity against such relevant drugs as cytosine arabinoside (ara-C, gemcitabine, decitabine, or azacytidine and the highly hematopoiesis-specific toxicity profile of several of these agents, cytidine deaminase (CDD represents another interesting candidate CTX-R gene and our group recently has established the myeloprotective capacity of CDD gene transfer in a number of murine transplant studies. Clinically, CDD overexpression appears particularly suited to optimize treatment strategies for acute leukemias and myelodysplasias given the efficacy of ara-C (and to a lesser degree decitabine and azacytidine in these disease entities. This article will review the current state of the art with regard to CDD gene transfer and point out potential scenarios for a clinical application of this strategy. In addition, risks and potential side effects associated with this approach as well as strategies to overcome these problems will be highlighted.

  15. Stereoselective synthesis of phosphoramidate alpha(2-6)sialyltransferase transition-state analogue inhibitors.

    Science.gov (United States)

    Skropeta, Danielle; Schwörer, Ralf; Schmidt, Richard R

    2003-10-06

    The asymmetric synthesis of novel, potent phosphoramidate alpha(2-6)sialyltransferase transition-state analogue inhibitors such as (R)-9 (K(i)=68 microM) is described, via condensation of cytidine phosphitamide 6 with key chiral, non-racemic alpha-aminophosphonates, prepared in >98% ee by Mitsunobu azidation followed by Staudinger reduction of the corresponding chiral, non-racemic alpha-hydroxyphosphonates.

  16. APOBEC3 cytidine deaminases in double-strand DNA break repair and cancer promotion.

    Science.gov (United States)

    Nowarski, Roni; Kotler, Moshe

    2013-06-15

    High frequency of cytidine to thymidine conversions was identified in the genome of several types of cancer cells. In breast cancer cells, these mutations are clustered in long DNA regions associated with single-strand DNA (ssDNA), double-strand DNA breaks (DSB), and genomic rearrangements. The observed mutational pattern resembles the deamination signature of cytidine to uridine carried out by members of the APOBEC3 family of cellular deaminases. Consistently, APOBEC3B (A3B) was recently identified as the mutational source in breast cancer cells. A3G is another member of the cytidine deaminases family predominantly expressed in lymphoma cells, where it is involved in mutational DSB repair following ionizing radiation treatments. This activity provides us with a new paradigm for cancer cell survival and tumor promotion and a mechanistic link between ssDNA, DSBs, and clustered mutations. Cancer Res; 73(12); 3494-8. ©2013 AACR. ©2013 AACR.

  17. BALANOL ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid...

  18. Stable Analogues of OSB-AMP: Potent Inhibitors of MenE the o-succinylbenzoate-CoA Synthetase from Bacterial Menaquinone Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Lu X.; Swaminathan S.; Zhou R.; Sharma I.; Li X.; Kumar G.; Tonge P. J.; Tan D. S.

    2012-01-02

    MenE, the o-succinylbenzoate (OSB)-CoA synthetase from bacterial menaquinone biosynthesis, is a promising new antibacterial target. Sulfonyladenosine analogues of the cognate reaction intermediate, OSB-AMP, have been developed as inhibitors of the MenE enzymes from Mycobacterium tuberculosis (mtMenE), Staphylococcus aureus (saMenE) and Escherichia coli (ecMenE). Both a free carboxylate and a ketone moiety on the OSB side chain are required for potent inhibitory activity. OSB-AMS (4) is a competitive inhibitor of mtMenE with respect to ATP (K{sub i} = 5.4 {+-} 0.1 nM) and a noncompetitive inhibitor with respect to OSB (K{sub i} = 11.2 {+-} 0.9 nM). These data are consistent with a Bi Uni Uni Bi Ping-Pong kinetic mechanism for these enzymes. In addition, OSB-AMS inhibits saMenE with K{sub i}{sup app} = 22 {+-} 8 nM and ecMenE with K{sub i}{sup OSB} = 128 {+-} 5 nM. Putative active-site residues, Arg222, which may interact with the OSB aromatic carboxylate, and Ser302, which may bind the OSB ketone oxygen, have been identified through computational docking of OSB-AMP with the unliganded crystal structure of saMenE. A pH-dependent interconversion of the free keto acid and lactol forms of the inhibitors is also described, along with implications for inhibitor design.

  19. Cytidine triphosphate synthase activity and mRNA expression in normal human blood cells

    NARCIS (Netherlands)

    Verschuur, A. C.; van Gennip, A. H.; Muller, E. J.; Voûte, P. A.; Vreken, P.; van Kuilenburg, A. B.

    1999-01-01

    Cytidine triphosphate (CTP) synthase is one of the key enzymes in pyrimidine nucleotide anabolic pathways. The activity of this enzyme is elevated in various malignancies including acute lymphocytic leukemia (ALL). In this study we investigated the activity of CTP synthase in various human blood

  20. A terbium(III)-organic framework for highly selective sensing of cytidine triphosphate.

    Science.gov (United States)

    Zhao, Xi Juan; He, Rong Xing; Li, Yuan Fang

    2012-11-21

    Highly selective sensing of cytidine triphosphate (CTP) against other triphosphate nucleosides including ATP, GTP and UTP is successfully achieved with a luminescent terbium(III)-organic framework (TbOF) of [Tb(2)(2,3-pzdc)(2)(ox)(H(2)O)(2)](n) (2,3-pzdc(2-) = 2,3-pyrazinedicarboxylate, ox(2-) = oxalate).

  1. Preparation of alpha-5-aza-2'-deoxy-[6-3H]cytidine

    Czech Academy of Sciences Publication Activity Database

    Elbert, Tomáš; Černý, B.

    2008-01-01

    Roč. 73, č. 5 (2008), s. 701-704 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z40550506 Keywords : alfa-5aza-2'-deoxy-cytidine Subject RIV: CC - Organic Chemistry Impact factor: 0.784, year: 2008

  2. Computer simulation of the free energy of peptides with the local states method: analogues of gonadotropin releasing hormone in the random coil and stable states.

    Science.gov (United States)

    Meirovitch, H; Koerber, S C; Rivier, J E; Hagler, A T

    1994-07-01

    The Helmholtz free energy F (rather than the energy) is the correct criterion for stability; therefore, calculation of F is important for peptides and proteins that can populate a large number of metastable states. The local states (LS) method proposed by H. Meirovitch [(1977) Chemical Physics Letters, Vol. 45, p. 389] enables one to obtain upper and lower bounds of the conformational free energy, FB (b,l) and FA (b,l), respectively, from molecular dynamics (MD) or Monte Carlo samples. The correlation parameter b is the number of consecutive dihedral or valence angles along the chain that are taken into account explicitly. The continuum angles are approximated by a discretization parameter l; the larger are b and l, the better the approximations; while FA can be estimated efficiently, it is more difficult to estimate FB. The method is further developed here by applying it to MD trajectories of a relatively large molecule (188 atoms), the potent "Asp4-Dpr10" antagonist [cyclo(4/10)-(Ac-delta 3Pro1-D-pFPhe2-D-Trp3-Asp4-Tyr5-D-Nal6-Leu7-Arg8 -Pro9- Dpr10-NH2)] of gonadotropin releasing hormone (GnRH). The molecule was simulated in vacuo at T = 300 K in two conformational states, previously investigated [J. Rizo et al. Journal of the American Chemical Society, (1992) Vol. 114, p. 2860], which differ by the orientation of the N-terminal tail, above (tail up, TU) and below (tail down, TD) the cyclic heptapeptide ring. As in previous applications of the LS method, we have found the following: (1) While FA is a crude approximation for the correct F, results for the difference, delta FA = FA (TD)-FA (TU) converge rapidly to 5.6 (1) kcal/mole as the approximation is improved (i.e., as b and l are increased), which suggests that this is the correct value for delta F; therefore TD is more stable than TU. (The corresponding difference in entropy, T delta SA = 1.3(2) kcal/mole, is equal to the value obtained by the harmonic approximation.) (2) The lowest approximation, which has

  3. A stable analogue of thromboxane A2, 9,11-epithio-11,12-methanothromboxane A2, stimulates bone resorption in vitro and osteoclast-like cell formation in mouse marrow culture.

    Science.gov (United States)

    Saito, S; Yamasaki, K; Yamada, S; Matsumoto, A; Akatsu, T; Takahashi, N; Shibasaki, Y; Suda, T; Fukuhara, T

    1991-01-01

    Thromboxane A2 (TXA2) is a powerful promoter of platelet aggregation and smooth muscle contraction. However, this compound is highly unstable and is rapidly hydrated to a more stable metabolite, thromboxane B2 (TXB2). TXA2 has been considered to be involved in bone resorption, in particular bone loss caused by inflammatory diseases and by orthodontic treatment. However precise mechanisms of bone resorption caused by TXA2 have not yet been proved because of its highly unstable nature. Recently, a chemically stable analogue of TXA2, 9,11-epithio-11,12-methanothromboxane A2 (STA2), was successfully synthesized. Using this synthetic compound, we examined its in vitro bone resorbing activity and induction of osteoclast-like cells in a mouse marrow culture system in comparison with related compounds with bone resorbing activity. Like prostaglandin E2 (PGE2), a well-known bone resorbing agent, STA2 time- and dose-dependently stimulated the release of 45Ca from prelabelled mouse calvariae. Both STA2 and PGE2 induced the accumulation of cAMP in mouse calvariae. The TXA2 antagonist, ONO-3708, inhibited STA2-induced release of 45Ca. TXB2 induced neither bone resorption nor cAMP accumulation. When mouse marrow cells were cultured with STA2 for 8 days, osteoclast-like multinucleated cells appeared in parallel with the increase of the amount of STA2 added. Again TXB2 showed no effect on osteoclast-like cell formation. These results indicate a role for TXA2 in some form of bone resorption.

  4. Epigenetic function of Activation-Induced Cytidine Deaminase (AID and its link to lymphomagenesis

    Directory of Open Access Journals (Sweden)

    Pilar M Dominguez

    2014-12-01

    Full Text Available Activation-induced cytidine deaminase (AID is essential for somatic hypermutation (SHM and class switch recombination (CSR of immunoglobulin (Ig genes during B cell maturation and immune response. Expression of AID is tightly regulated due to its mutagenic and recombinogenic potential, which is known to target not only Ig genes, but also non-Ig genes, contributing to lymphomagenesis. In recent years a new epigenetic function of AID and its link to DNA demethylation came to light in several developmental systems. In this review, we summarize existing evidence linking deamination of unmodified and modified cytidine by AID to base-excision repair (BER and mismatch repair (MMR machinery resulting in passive or active removal of DNA methylation mark, with the focus on B cell biology. We also discuss potential contribution of AID-dependent DNA hypomethylation to lymphomagenesis.

  5. Reduction of nucleotides by ionizing radiation: uridine 5' phosphate, and cytidine 3' phosphate

    International Nuclear Information System (INIS)

    Box, H.C.; Potter, W.R.; Budzinski, E.E.

    1974-01-01

    Anions formed by the addition of an electron to the uracil base were observed in single crystals of the barium salt of uridine 5' phosphate x irradiated at 4.2 0 K. The hyperfine coupling tensor for the C 6 -H proton was deduced from ENDOR measurements; the principal values are -59.12, -32.92 and -16.24 MHz. Similar measurements were made on single crystals of cytidine 3' phosphate. The principal values for the C 6 -H proton hyperfine coupling in the anion formed on the cytosine base are -59.26, -33.98 and -14.68 MHz. (U.S.)

  6. The reduction of nucleotides by ionizing radiation: uridine 5' phosphate and cytidine 3' phosphate

    International Nuclear Information System (INIS)

    Box, H.C.; Potter, W.R.; Budzinski, E.E.

    1975-01-01

    Anions formed by the addition of an electron to the uracil base were observed in single crystals of the barium salt of uridine 5' phosphate x-irradiated at 4.2 degreeK. The hyperfine coupling tensor for the C 6 --H proton was deduced from ENDOR measurements; the principal values are -59.12, -32.92, and -16.24 MHz. Similar measurements were made on single crystals of cytidine 3' phosphate. The principal values for the C 6 --H proton hyperfine coupling in the anion formed on the cytosine base are -59.26, -33.98, and -14.68 MHz

  7. The association constant of 5',8-cyclo-2'-deoxyguanosine with cytidine

    Directory of Open Access Journals (Sweden)

    Amedeo eCapobianco

    2015-03-01

    Full Text Available The association of 5',8-cyclo-2'-deoxyguanosine (cdG, a DNA tandem lesion, with its complementary base cytosine has been studied by voltammetry and NMR in chloroform, using properly silylated derivatives of the two nucleobases for increasing their solubilities. Both voltammetric data and NMR titrations indicated that the Watson-Crick complex of cytidine with cdG is weaker than that with guanosine, the difference being approximately of one order of magnitude between the two association constants.

  8. Two nucleoside uptake systems in Lactococcus lactis: Competition between purine nucleosides and cytidine allows for modulation of intracellular nucleotide pools

    DEFF Research Database (Denmark)

    Martinussen, Jan; Wadskov-Hansen, Steen Lyders Lerche; Hammer, Karin

    2003-01-01

    and with an H3BO3-LiOH buffer for separation in the second dimension. We report here the sizes of the ribo- and deoxyribonucleotide pools in laboratory strain MG1363 during growth in a defined medium. We found that purine and pyrimidine-requiring strains may be used to establish physiological conditions...... in batch fermentations with altered nucleotide pools and growth rates by addition of nucleosides in different combinations. Addition of cytidine together with inosine to a purine-requiring strain leads to a reduction in the internal purine nucleotide pools and a decreased growth rate. This effect...... was found between uridine and either cytidine or inosine. These findings suggest that there are two different high-affinity nucleoside transporters, one system responsible for uridine uptake and another system responsible for the uptake of all purine nucleosides and cytidine....

  9. Analogue computing methods

    CERN Document Server

    Welbourne, D

    1965-01-01

    Analogue Computing Methods presents the field of analogue computation and simulation in a compact and convenient form, providing an outline of models and analogues that have been produced to solve physical problems for the engineer and how to use and program the electronic analogue computer. This book consists of six chapters. The first chapter provides an introduction to analogue computation and discusses certain mathematical techniques. The electronic equipment of an analogue computer is covered in Chapter 2, while its use to solve simple problems, including the method of scaling is elaborat

  10. ESR study of irradiated single crystals of the cocrystalline complex of cytidine: Salicylic acid

    International Nuclear Information System (INIS)

    Close, D.M.; Sagstuen, E.

    1983-01-01

    Irradiation at 77 K of single crystals of the 1:1 complex of cytidine and salicylic acid produces a phenoxyl radical formed by oxidation of the salicylic acid. Anisotropic hyperfine coupling tensors have been determined for this radical which are associated with the para and ortho hydrogens. No cytidine oxidation products (alkoxy or hydroxyalkyl radicals) were observed at 77 K. Following the decay of the phenoxyl radical at room temperature, four radicals were detected. These include the cytosine 5--yl and 6--yl radicals, formed by H addition to the cytosine ring, and an anisotropic doublet. By UV irradiation at room temperature, it is possible to convert a significant fraction of 6-yl radicals into 5-yl radicals. Hyperfine coupling and g tensors determined for the anisotropic doublet indicate that this radical is formed in the C/sub 1'/-C/sub 2'/ region of the sugar moiety. These results indicate a shift in radiation damage away from the salicylic acid upon warming, and show that the radiation chemistry of the cocrystalline complex is different from that of the isolated bases

  11. APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

    Science.gov (United States)

    Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

    2012-07-12

    APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

  12. Analogue MIMO Detection

    Directory of Open Access Journals (Sweden)

    McNamara Darren

    2006-01-01

    Full Text Available In this contribution we propose an analogue receiver that can perform turbo detection in MIMO systems. We present the case for a receiver that is built from nonlinear analogue devices, which perform detection in a "free-flow" network (no notion of iterations. This contribution can be viewed as an extension of analogue turbo decoder concepts to include MIMO detection. These first analogue implementations report reductions of few orders of magnitude in the number of required transistors and in consumed energy, and the same order of improvement in processing speed. It is anticipated that such analogue MIMO decoder could bring about the same advantages, when compared to traditional digital implementations.

  13. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID during Inflammation-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tsutomu Chiba

    2011-06-01

    Full Text Available Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID, a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  14. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Atsushi; Marusawa, Hiroyuki, E-mail: maru@kuhp.kyoto-u.ac.jp; Chiba, Tsutomu [Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

    2011-06-22

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  15. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    International Nuclear Information System (INIS)

    Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu

    2011-01-01

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

  16. Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Stav Sapoznik

    2016-02-01

    Full Text Available In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection.

  17. APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Manikandan Periyasamy

    2015-10-01

    Full Text Available Estrogen receptor α (ERα is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER and to repair by non-homologous end-joining (NHEJ pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action.

  18. An arsenical analogue of adenosine diphosphate.

    Science.gov (United States)

    Webster, D; Sparkes, M J; Dixon, H B

    1978-01-01

    An analogue of ADP was made in which the terminal phosphono-oxy group, -O-PO(OH)2, has been replaced by the arsonomethyl group, -CH2-AsO(OH)2. This compound cannot form a stable analogue of ATP because anhydrides of arsonic acids are rapidly hydrolysed, so that any enzyme that phosphorylates ADP and accepts this analogue as a substrate should release orthophosphate in its presence. The analogue proves to be a poor substrate for 3-phosphoglycerate kinase (V/Km is diminished by a factor of 10(2)-10(3)) and a very poor substrate for pyruvate kinase (V/Km is diminished by a factor of 10(5)-10(6)). No substrate action was detected with adenyl kinase and creatine kinase. PMID:204292

  19. Activation-induced cytidine deaminase in B cells of hepatits C virus-related cryoglobulinaemic vasculitis.

    Science.gov (United States)

    Russi, S; Dammacco, F; Sansonno, S; Pavone, F; Sansonno, D

    2015-12-01

    Immunoglobulin variable region heavy chain (IgVH ) somatic gene diversification is instrumental in the transformation process that characterizes hepatitis C virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to which activation-induced cytidine deaminase (AID), an enzyme essential for IgV gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV) remains unclear. AID mRNA expression in the peripheral blood of 102 chronically hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26 healthy subjects was investigated using real-time reverse transcription-polymerase chain reaction (RT-PCR). The features of activation-induced cytidine deaminase (AID) protein and mRNA transcripts were explored in liver tissue biopsies and portal tracts isolated using laser capture microdissection. In chronically HCV-infected patients, AID mRNA expression was almost threefold higher in those with than in those without CV and sevenfold higher than in healthy subjects (median-fold: 6.68 versus 2.54, P = 0.03 and versus 0.95, P = 0.0003). AID transcript levels were significantly higher in polyclonal than in clonally restricted B cell preparations in either CV or non-CV patients (median-fold, 15.0 versus 2.70, P = 0.009 and 3.46 versus 1.58, P = 0.02, respectively). AID gene expression was found to be related negatively to age and virological parameters. AID protein was found in portal tracts containing inflammatory cells that, in several instances, expressed AID mRNA transcripts. Our data indicate that the aberrant expression of AID may reflect continuous B cell activation and sustained survival signals in HCV-related CV patients. © 2015 British Society for Immunology.

  20. Activation-induced cytidine deaminase (AID) is necessary for the epithelial–mesenchymal transition in mammary epithelial cells

    OpenAIRE

    Muñoz, Denise P.; Lee, Elbert L.; Takayama, Sachiko; Coppé, Jean-Philippe; Heo, Seok-Jin; Boffelli, Dario; Di Noia, Javier M.; Martin, David I. K.

    2013-01-01

    The epithelial to mesenchymal transition (EMT) is a driving force behind normal morphogenesis and tumor metastasis. We have found evidence that the EMT in both malignant and nonmalignant mammary epithelial cells requires the enzyme activation-induced cytidine deaminase (AID). AID is induced in mammary epithelial cell lines by inflammatory stimuli that also induce the EMT. Deficiency of AID in these cells blocks morphological and transcriptional changes typical of the EMT and increases promote...

  1. Boron hydride analogues of the fullerenes

    International Nuclear Information System (INIS)

    Quong, A.A.; Pederson, M.R.; Broughton, J.Q.

    1994-01-01

    The BH moiety is isoelectronic with C. We have studied the stability of the (BH) 60 analogue of the C 60 fullerene as well as the dual-structure (BH) 32 icosahedron, both of them being putative structures, by performing local-density-functional electronic calculations. To aid in our analysis, we have also studied other homologues of these systems. We find that the latter, i.e., the dual structure, is the more stable although the former is as stable as one of the latter's lower homologues. Boron hydrides, it seems, naturally form the dual structures used in algorithmic optimization of complex fullerene systems. Fully relaxed geometries are reported as well as electron affinities and effective Hubbard U parameters. These systems form very stable anions and we conclude that a search for BH analogues of the C 60 alkali-metal supeconductors might prove very fruitful

  2. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yi, E-mail: yihooyi@gmail.com; Ericsson, Ida, E-mail: ida.ericsson@ntnu.no; Doseth, Berit, E-mail: berit.doseth@ntnu.no; Liabakk, Nina B., E-mail: nina.beate.liabakk@ntnu.no; Krokan, Hans E., E-mail: hans.krokan@ntnu.no; Kavli, Bodil, E-mail: bodil.kavli@ntnu.no

    2014-03-10

    Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation.

  3. Activation-Induced Cytidine Deaminase and Aberrant Germinal Center Selection in the Development of Humoral Autoimmunities

    Science.gov (United States)

    Zaheen, Ahmad; Martin, Alberto

    2011-01-01

    Humoral immunity, which is the branch of the immune system governed by B cells, protects the body from extracellular pathogens through the secretion of immunoglobulins. Given the unpredictability of exogenous antigens, B cells must be accommodating to numerous genetic alterations to mold immunoglobulin specificity to recognize offending pathogens. Abnormalities in this process leave the host susceptible to permanent pathological modifications and in particular humoral autoimmunities in which secreted immunoglobulins mistake host proteins as pathogenic targets. Underlying the development of self-reactive immunoglobulins is activation-induced cytidine deaminase (AID), a mutagenic enzyme responsible for modifying the specificity of B cells by producing point mutations at the immunoglobulin gene locus. Ideally, these mutations result in an increased affinity for exogenous antigens. However, in pathological scenarios, these mutations produce or enhance a B cell's ability to target the host. AID-induced mutations occur in the germinal center microenvironment of peripheral lymphoid tissue, where pathogenic B-cell clones must evade overwhelming selection pressures to be released systemically. Recent research has revealed numerous genes and pathways responsible for eliminating self-reactive clones within the germinal center. On the basis of these studies, this review aims to clarify the link between AID and the generation of pathogenic immunoglobulins. Furthermore, it describes the selective pressures that pathogenic B cells must bypass within the germinal center to secrete immunoglobulins that ultimately result in disease. PMID:21281778

  4. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors

    International Nuclear Information System (INIS)

    Hu, Yi; Ericsson, Ida; Doseth, Berit; Liabakk, Nina B.; Krokan, Hans E.; Kavli, Bodil

    2014-01-01

    Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation

  5. The cytidine repressor participates in the regulatory pathway of indole in Pantoea agglomerans.

    Science.gov (United States)

    Jia, Mengqi; Yu, Xuemei; Jiang, Jing; Li, Zihua; Feng, Yongjun

    2017-09-01

    Indole, an important signal molecule in both intraspecies and interspecies, regulates a variety of bacterial behaviors, but its regulatory mechanism is still unknown. Pantoea agglomerans YS19, a preponderant endophytic bacterium isolated from rice, does not produce indole, yet it senses exogenous indole. In this study, a mutant of YS19-Rp r whose target gene expression was downregulated by indole was selected through mTn5 transposon mutagenesis. Using the TAIL-PCR technique, the mutation gene was identified as a cytR homologue, which encodes a cytidine repressor (CytR) protein, a bacterial transcription factor involved in a complex regulation scheme. The negative regulation of indole in cytR, which is equivalent to the mutation in cytR, promotes the expression of a downstream gene deoC, which encodes the key enzyme deoxyribose-phosphate aldolase in participating in pentose metabolism. We found that DeoC is one of the regulatory proteins of P. agglomerans that is involved in counteracting starvation. Furthermore, the expression of deoC was induced by starvation conditions, accompanied by a decrease in cytR expression. This finding suggests that the indole signal and the mutation of cytR relieve inhibition of CytR in the transcription of deoC, facilitating better adaptation of the bacterium to the adverse conditions of the environment. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  6. Significance of determination of serum cytidine deaminase (CD) levels for diagnosis of active rheumatoid arthritis (RA)

    International Nuclear Information System (INIS)

    Xiao Chuangqing; Jang Xiaogong; He Yunnan

    2005-01-01

    Objective: To determine the clinical value of measurement of serum cytidine deaminase (CD) levels in patients with active rheumatoid arthritis (RA). Methods: Serum levels of CD were detected with spectrophotometry, in 33 patients with active RA and 60 controls. The erythrocyte sedimentation rate (ESR) and CRP content were also determined in both groups. Results: The ser- um CD contents in patients with active RA(14.80 ± 2.11U/ml) were significantly higher than those in controls(4.86±1.86 U/ml,P<0.01). The CRP contents (51.46 ± 20.43mg/L) and ESR readings(85.03 ± 27.6mm/h) in the patients were also significantly higher than those in the controls(3.40 ± 2.21mg/L and 13.04 ± 4.89mm/h respectively, all P<0.01). In the patients, the serum CD contents were linearly positively correlated with the ESR contents and CRP readings (r=0.6324 and 0.8013 respectively, P <0.01). Conclusion: Serum CD is an early biochemical marker for diagnosis of active rheumatoid arthritis and is also of prognostic value. (authors)

  7. Site-directed mutagenesis studies on the uridine monophosphate binding sites of feedback inhibition in carbamoyl phosphate synthetase and effects on cytidine production by Bacillus amyloliquefaciens.

    Science.gov (United States)

    Fang, Haitian; Liu, Huiyan; Chen, Ning; Zhang, Chenglin; Xie, Xixian; Xu, Qingyang

    2013-06-01

    A major problem when pyrimidine de novo biosynthesis is used for cytidine production is the existence of many negative regulatory factors. Cytidine biosynthesis in Bacillus amyloliquefaciens proceeds via a pathway that is controlled by uridine monophosphate (UMP) through feedback inhibition of carbamoyl phosphate synthetase (CPS), the enzyme that converts CO2, NH3, and glutamine to carbamoyl phosphate. In this study, the gene carB encoding the large subunit of CPS from B. amyloliquefaciens CYT1 was site directed, and the UMP binding sites of feedback inhibition in Bam-CPS are described. The residues Thr-941, Thr-970, and Lys-986 in CPS from B. amyloliquefaciens were subjected to site-directed mutagenesis to alter UMP's feedback inhibition of CPS. To find feedback-resistant B. amyloliquefaciens, the influence of the T941F, T970A, K986I, T941F/K986I, and T941F/T970A/K986I mutations on CPS enzymatic properties was studied. The recombinant B. amyloliquefaciens with mutated T941F/K986I and T941F/T970A/K986I CPS showed a 3.7- and 5.7-fold increase, respectively, in cytidine production in comparison with the control expressing wild-type CPS, which was more suitable for further application of the cytidine synthesis. To a certain extent, the 5 mutations were found to release the enzyme from UMP inhibition and to improve B. amyloliquefaciens cytidine-producing strains.

  8. Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases.

    Science.gov (United States)

    Zielonka, Jörg; Bravo, Ignacio G; Marino, Daniela; Conrad, Elea; Perković, Mario; Battenberg, Marion; Cichutek, Klaus; Münk, Carsten

    2009-08-01

    The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equine and of several of the human and nonprimate A3 proteins against the Equine infectious anemia virus (EIAV), the Simian immunodeficiency virus (SIV), and the Adeno-associated virus type 2 (AAV-2). Hematopoietic cells of horses express at least five different A3s: A3Z1b, A3Z2a-Z2b, A3Z2c-Z2d, A3Z2e, and A3Z3, whereas circulating macrophages, the natural target of EIAV, express only part of the A3 repertoire. The five A3Z2 tandem copies arose after three consecutive, recent duplication events in the horse lineage, after the split between Equidae and Carnivora. The duplicated genes show different antiviral activities against different viruses: equine A3Z3 and A3Z2c-Z2d are potent inhibitors of EIAV while equine A3Z1b, A3Z2a-Z2b, A3Z2e showed only weak anti-EIAV activity. Equine A3Z1b and A3Z3 restricted AAV and all equine A3s, except A3Z1b, inhibited SIV. We hypothesize that the horse A3 genes are undergoing a process of subfunctionalization in their respective viral specificities, which might provide the evolutionary advantage for keeping five copies of the original gene.

  9. /sup 31/P nuclear magnetic resonance chemical shielding tensors of L-0-serine phosphate and 3'-cytidine monophosphate

    Energy Technology Data Exchange (ETDEWEB)

    Kohler, S.J.; Klein, M.P.

    1977-12-07

    /sup 31/P nuclear magnetic resonance chemical shielding tensors have been measured from single crystals of L-O-serine phosphate and 3'-cytidine monophosphate. The principal elements of the shielding tensors are -48, -2, and 51 ppM for serine phosphate and -68, -13, and 64 ppM for 3'-cytidine monophosphate, relative to 85% H/sub 3/PO/sub 4/. In both cases four orientations of the shielding tensor on the molecule are possible; in both instances one orientation correlates well with the P--O bond directions. This orientation of the shielding tensor places the most downfield component of the tensor in the plane containing the two longest P--O bonds and the most upfield component of the shielding tensor in the plane containing the two shortest P--O bonds. A similar orientation was reported for the /sup 31/P shielding tensor of phosphorylethanolamine and a comparison is made between the three molecules.

  10. Natural Analogue Synthesis Report

    Energy Technology Data Exchange (ETDEWEB)

    A. M. Simmons

    2002-05-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport

  11. NATURAL ANALOGUE SYNTHESIS REPORT

    International Nuclear Information System (INIS)

    Simmons, A.M.

    2004-01-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature along with results of quantitative studies conducted specifically for the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement-drift degradation, waste-form degradation, waste-package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated-zone (SZ) transport, impact of radionuclide release on the biosphere

  12. CEC natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1986-01-01

    The second meeting of the CEC Natural Analogue Working Group took place on June 17-19, 1986, hosted by the Swiss NAGRA in Interlaken (CH). A review of recent progress in natural analogue programmes was carried out, and complemented by detailed discussions about geomicrobiology, archaeological analogues, natural colloids, and use of analogues to increase confidence in safety assessments for radioactive waste disposal. A statement drafted by the Group, and the presentations made, are put together in this report

  13. CEC Natural Analogue Working Group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1989-01-01

    The central theme for the third meeting of the CEC analogue working group was ''How can analogue data be used for performance assessments, both in support of the results and for presentation to the public''. This report puts together the most recent achievements in this field, together with a review of on-going natural analogue programmes

  14. Natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.

    1986-01-01

    A Natural Analogue Working Group was established by the Commission of the European Communities in 1985. The purpose of this group is to bring together modellers with earth scientists and others, so that maximum benefit can be obtained from natural analogue studies with a view to safe geological disposal of radioactive waste. The first meeting of this group was held in Brussels from November 5 to 7, 1985. The discussions mainly concerned the identification of the modellers' needs and of the earth scientists' capacity to provide for them. Following the debates, a written statement was produced by the Group; this document forms the core of the present Report. Notes and outlines of many of the presentations made are grouped in four appendixes. The valuable contribution of all those involved in the meeting is gratefully acknowledged

  15. Quantum analogue computing.

    Science.gov (United States)

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  16. The Palmottu analogue project

    International Nuclear Information System (INIS)

    Ahonen, L.; Blomqvist, R.; Suksi, J.

    1993-01-01

    The report gives a summary of the results of investigations carried out in 1992 at the Palmottu natural analogue study site, which is a small U-Th mineralization in Nummi-Pusula, southwestern Finland. Additionally, the report includes several separate articles dealing with various aspects of the Palmottu Analogue Project: (1) deep groundwater flow, (2) interpretation of hydraulic connections, (3) characterization of groundwater colloids, (4) uranium mineral-groundwater equilibrium, (5) water-rock interaction and (6) modelling of in situ matrix diffusion. The Palmottu Analogue Project aims at a more profound understanding of radionuclide transport processes in fractured crystalline bedrock. The essential factors controlling transport are groundwater flow and interaction between water and rock. Accordingly, the study includes (1) structural interpretations partly based on geophysical measurements, (2) hydrological studies including hydraulic drill-hole measurements, (3) flow modelling, (4) hydrogeochemical characterization of groundwater, uranium chemistry and colloid chemistry, (5) mineralogical studies, (6) geochemical interpretation and modelling, (7) studies of radionuclide mobilization and retardation including matrix diffusion, and (8) modelling of uranium series data. Palaeohydrogeological aspects, due to the anticipated future glaciation of the Fennoscandian Shield, are of special interest. Quaternary sediments are studied to gain information on post-glacial migration in the overburden. (orig.)

  17. Of the Nine Cytidine Deaminase-Like Genes in Arabidopsis, Eight Are Pseudogenes and Only One Is Required to Maintain Pyrimidine Homeostasis in Vivo.

    Science.gov (United States)

    Chen, Mingjia; Herde, Marco; Witte, Claus-Peter

    2016-06-01

    CYTIDINE DEAMINASE (CDA) catalyzes the deamination of cytidine to uridine and ammonia in the catabolic route of C nucleotides. The Arabidopsis (Arabidopsis thaliana) CDA gene family comprises nine members, one of which (AtCDA) was shown previously in vitro to encode an active CDA. A possible role in C-to-U RNA editing or in antiviral defense has been discussed for other members. A comprehensive bioinformatic analysis of plant CDA sequences, combined with biochemical functionality tests, strongly suggests that all Arabidopsis CDA family members except AtCDA are pseudogenes and that most plants only require a single CDA gene. Soybean (Glycine max) possesses three CDA genes, but only two encode functional enzymes and just one has very high catalytic efficiency. AtCDA and soybean CDAs are located in the cytosol. The functionality of AtCDA in vivo was demonstrated with loss-of-function mutants accumulating high amounts of cytidine but also CMP, cytosine, and some uridine in seeds. Cytidine hydrolysis in cda mutants is likely caused by NUCLEOSIDE HYDROLASE1 (NSH1) because cytosine accumulation is strongly reduced in a cda nsh1 double mutant. Altered responses of the cda mutants to fluorocytidine and fluorouridine indicate that a dual specific nucleoside kinase is involved in cytidine as well as uridine salvage. CDA mutants display a reduction in rosette size and have fewer leaves compared with the wild type, which is probably not caused by defective pyrimidine catabolism but by the accumulation of pyrimidine catabolism intermediates reaching toxic concentrations. © 2016 American Society of Plant Biologists. All Rights Reserved.

  18. Current prodrug strategies for improving oral absorption of nucleoside analogues

    Directory of Open Access Journals (Sweden)

    Youxi Zhang

    2014-04-01

    Full Text Available Nucleoside analogues are first line chemotherapy in various severe diseases: AIDS (acquired immunodeficiency disease syndrome, cytomegalovirus infections, cancer, etc. However, many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability. In order to get around this drawback, prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug. Alternatively, prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues. Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1. The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport, but is readily degraded to the parent drug once at the target. This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.

  19. Random mutagenesis MAPPIT analysis identifies binding sites for Vif and Gag in both cytidine deaminase domains of Apobec3G.

    Directory of Open Access Journals (Sweden)

    Isabel Uyttendaele

    Full Text Available The mammalian two-hybrid system MAPPIT allows the detection of protein-protein interactions in intact human cells. We developed a random mutagenesis screening strategy based on MAPPIT to detect mutations that disrupt the interaction of one protein with multiple protein interactors simultaneously. The strategy was used to detect residues of the human cytidine deaminase Apobec3G that are important for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins. The strategy is able to identify the previously described head-to-head homodimerization interface in the N-terminal domain of Apobec3G. Our analysis further detects two new potential interaction surfaces in the N-and C-terminal domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization.

  20. Ag(I)-mediated homo and hetero pairs of guanosine and cytidine: monitoring by circular dichroism spectroscopy.

    Science.gov (United States)

    Goncharova, Iryna

    2014-01-24

    Ag(I)-containing compounds are attractive as antibacterial and antifungal agents. The renewed interest in the application of silver(I) compounds has led to the need for detailed knowledge of the mechanism of their action. One of the possible ways is the coordination of Ag(I) to G-C pairs of DNA, where Ag(+) ions form Ag(I)-mediated base pairs and inhibit the transcription. Herein, a systematic chiroptical study on silver(I)-mediated homo and mixed pairs of the C-G complementary-base derivatives cytidine(C) and 5'-guanosine monophosphate(G) in water is presented. Ag(I)-mediated homo and hetero pairs of G and C and their self-assembled species were studied under two pH levels (7.0 and 10.0) by vibrational (VCD) and electronic circular dichroism(ECD). VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. Based on results of the VCD experiments, the different geometries of the homo pairs were proposed under pH 7.0 and 10.0. ECD was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the metal or proton mediated pairs of nucleobases and the systems studied here. On the basis of the obtained data, the formation of the self-assembled species of cytidine with a structure similar to the i-motif structure in DNA was proposed at pH 10.0. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    acids, $g(b)-amino acids and/or longer chain $g(v)-amino acids, and a difunctional group which preferably is a cyclic entity, in particular, an aromatic or heteroaromatic entity acting as an intercalator group. Specific compounds and a library of such compounds may be prepared using conventional solid......The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g(a)-amino...

  2. Transaxial analogue tomography

    International Nuclear Information System (INIS)

    Duinker, S.; Geluk, R.J.; Mulder, H.

    1978-01-01

    After an introduction on computerized tomography (CT) scanners summarizing the various generations, the general outline of the concept of a transaxial tomography system is given, which is entirely based on analogue instead of digital techniques (AT system). In particular, the use of X-ray image-intensifier systems as a means of detecting the transmission profiles of the object in a so-called half-field detection method are discussed as well as various possibilities of detector scanning. It is further discussed how in a purely electronic way with the aid of a scan-converter, density profiles representative of parallel beams can be derived from the family of profiles as obtained from the fan-shaped beams in the actual experiment. A practical opto-electronic solution of the analogue spatial filtering problem is described as to how to process, on a real-time basis, parallel density profiles so that after back-projection tomographic images which are free from point-spreading effects will be obtained. Finally, after a brief indication of certain technical details for which corrective measures have to be worked out in the course of practical realization, the main relative advantages of AT scanners in comparison to CT scanners are enumerated. (Auth.)

  3. Analogue forecasting of New Zealand climate anomalies

    Science.gov (United States)

    Mullan, A. Brett; Thompson, Craig S.

    2006-03-01

    An analogue forecast scheme is described for multifield prediction of monthly and seasonal New Zealand climate anomalies on the basis of the methodology of Livezey and Barnston ([1988]) for US seasonal temperatures. The method is applied to predicting terciles of temperature and precipitation for six regions of New Zealand. Empirical orthogonal function analysis is used to reduce sea surface temperature and sea-level pressure predictors down to a set of five independent indices, which incorporate variations due to El Niño-Southern Oscillation, Indian Ocean sea temperatures and a wave 3 pattern in the Southern Hemisphere westerlies. A full bootstrap cross-validation procedure is carried out, along with Monte Carlo tests, to assess the skill of the method on independent data and to determine the significance of the results. Significant skill is found for seasonal temperature forecasts for the summer and winter seasons; there is less success in predicting monthly temperatures or rainfall at either timescale. Considerable care is required to constrain the climate state vector, from which analogues are defined, and to constrain the search procedure itself, in order to produce results that are stable with respect to small parameter changes in the model. For the New Zealand region, 5 to 7 is found to be the optimum number of closest analogues, and the inclusion of anti-analogues improves the predictions, at least in the seasonal case. Skill in predicting regional temperature and rainfall is shown to be related to a combination of skill in predicting sea-level pressure patterns and to how strongly these patterns project onto temperature and rainfall anomalies.

  4. Stable isotopes

    International Nuclear Information System (INIS)

    Evans, D.K.

    1986-01-01

    Seventy-five percent of the world's stable isotope supply comes from one producer, Oak Ridge Nuclear Laboratory (ORNL) in the US. Canadian concern is that foreign needs will be met only after domestic needs, thus creating a shortage of stable isotopes in Canada. This article describes the present situation in Canada (availability and cost) of stable isotopes, the isotope enrichment techniques, and related research programs at Chalk River Nuclear Laboratories (CRNL)

  5. Alligator Rivers analogue project

    International Nuclear Information System (INIS)

    Duerden, P.

    1990-01-01

    Australian Nuclear Science and Technology Organization has extensively evaluated uranium ore bodies in the Alligator Rivers Uranium Province in Australia as analogues of radioactive waste repositories. The work was extended for a three-year program as an international project based on the Koongarra uranium deposit and sponsored by the OECD Nuclear Energy Agency. The technical program comprises six major sub-projects involving modelling and experimental work: modelling of radionuclide migration; hydrogeology of the Koongarra uranium deposit; uranium/thorium series disequilibria studies; groundwater and colloid studies; fission product studies; transuranic nuclide studies; an outline of the technical programs and a summary of progress in the technical sub-projects is given. This is followed by a series of technical reports which briefly describe current research tasks, and which have been separately indexed

  6. A Short Term Analogue Memory

    DEFF Research Database (Denmark)

    Shah, Peter Jivan

    1992-01-01

    A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...

  7. Optimization of catalyst-solvent system for preparation of alpha-5,6-dihydro-5-aza-2'-deoxy-[6-3H]-cytidine

    Czech Academy of Sciences Publication Activity Database

    Elbert, Tomáš

    2011-01-01

    Roč. 54, č. 5 (2011), s. 285-285 ISSN 0362-4803. [Workshop of the International Isotope Society - Central European Division. The Synthesis and Applications of Isotopes and Isotopically Labelled Compounds /17./. 23.09.2010-24.09.2010, Bad Soden] Institutional research plan: CEZ:AV0Z40550506 Keywords : tritium * labelled compounds * alfa-5,6-dihydro-5-aza-2'-deoxy-cytidine Subject RIV: CC - Organic Chemistry

  8. Synthesis, hybridization characteristics, and fluorescence properties of oligonucleotides modified with nucleobase-functionalized locked nucleic acid adenosine and cytidine monomers.

    Science.gov (United States)

    Kaura, Mamta; Kumar, Pawan; Hrdlicka, Patrick J

    2014-07-03

    Conformationally restricted nucleotides such as locked nucleic acid (LNA) are very popular as affinity-, specificity-, and stability-enhancing modifications in oligonucleotide chemistry to produce probes for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. Considerable efforts have been devoted in recent years to optimize the biophysical properties of LNA through additional modification of the sugar skeleton. We recently introduced C5-functionalization of LNA uridines as an alternative and synthetically more straightforward approach to improve the biophysical properties of LNA. In the present work, we set out to test the generality of this concept by studying the characteristics of oligonucleotides modified with four different C5-functionalized LNA cytidine and C8-functionalized LNA adenosine monomers. The results strongly suggest that C5-functionalization of LNA pyrimidines is indeed a viable approach for improving the binding affinity, target specificity, and/or enzymatic stability of LNA-modified ONs, whereas C8-functionalization of LNA adenosines is detrimental to binding affinity and specificity. These insights will impact the future design of conformationally restricted nucleotides for nucleic acid targeting applications.

  9. Activation-induced cytidine deaminase (AID) is necessary for the epithelial–mesenchymal transition in mammary epithelial cells

    Science.gov (United States)

    Muñoz, Denise P.; Lee, Elbert L.; Takayama, Sachiko; Coppé, Jean-Philippe; Heo, Seok-Jin; Boffelli, Dario; Di Noia, Javier M.; Martin, David I. K.

    2013-01-01

    Activation-induced cytidine deaminase (AID), which functions in antibody diversification, is also expressed in a variety of germ and somatic cells. Evidence that AID promotes DNA demethylation in epigenetic reprogramming phenomena, and that it is induced by inflammatory signals, led us to investigate its role in the epithelial–mesenchymal transition (EMT), a critical process in normal morphogenesis and tumor metastasis. We find that expression of AID is induced by inflammatory signals that induce the EMT in nontransformed mammary epithelial cells and in ZR75.1 breast cancer cells. shRNA–mediated knockdown of AID blocks induction of the EMT and prevents cells from acquiring invasive properties. Knockdown of AID suppresses expression of several key EMT transcriptional regulators and is associated with increased methylation of CpG islands proximal to the promoters of these genes; furthermore, the DNA demethylating agent 5 aza-2'deoxycytidine (5-Aza-dC) antagonizes the effects of AID knockdown on the expression of EMT factors. We conclude that AID is necessary for the EMT in this breast cancer cell model and in nontransformed mammary epithelial cells. Our results suggest that AID may act near the apex of a hierarchy of regulatory steps that drive the EMT, and are consistent with this effect being mediated by cytosine demethylation. This evidence links our findings to other reports of a role for AID in epigenetic reprogramming and control of gene expression. PMID:23882083

  10. SU-C-303-01: Activation-Induced Cytidine Deaminase Confers Cancer Resistance to Radiation Therapy

    International Nuclear Information System (INIS)

    Yi, S; La Count, S; Liu, J; Bai, X; Lu, L

    2015-01-01

    Purpose: To study the role of activation-induced cytidine deaminase (AID) in malignant cell resistance to radiation therapy. Methods: We first developed several small devices that could be used to adopt radiation beams from clinical high dose rate brachy therapy (HDR) or linac-based megavoltage machines to perform pre-clinical cell and mouse experiments. Then we used these devices to deliver radiation to AID-positive and AID-silenced cancer cells or tumors formed by these cells in mice. Cells and mice bearing tumors received the same dose under the same experimental conditions. For cells, we observed the apoptosis and the cell survival rate over time. For mice bearing tumors, we measured and recorded the tumor sizes every other day for 4 weeks. Results: For cell experiments, we found that the AID-positive cells underwent much less apoptosis compared with AID-silenced cells upon radiation. And for mouse experiments, we found that AID-positive tumors grew significantly faster than the AID-silenced tumors despite of receiving the same doses of radiation. Conclusion: Our study suggests that AID may confer cancer resistance to radiation therapy, and AID may be a significant biomarker predicting cancer resistance to radiation therapy for certain cancer types

  11. A combined nuclear and nucleolar localization motif in activation-induced cytidine deaminase (AID) controls immunoglobulin class switching.

    Science.gov (United States)

    Hu, Yi; Ericsson, Ida; Torseth, Kathrin; Methot, Stephen P; Sundheim, Ottar; Liabakk, Nina B; Slupphaug, Geir; Di Noia, Javier M; Krokan, Hans E; Kavli, Bodil

    2013-01-23

    Activation-induced cytidine deaminase (AID) is a DNA mutator enzyme essential for adaptive immunity. AID initiates somatic hypermutation and class switch recombination (CSR) by deaminating cytosine to uracil in specific immunoglobulin (Ig) gene regions. However, other loci, including cancer-related genes, are also targeted. Thus, tight regulation of AID is crucial to balance immunity versus disease such as cancer. AID is regulated by several mechanisms including nucleocytoplasmic shuttling. Here we have studied nuclear import kinetics and subnuclear trafficking of AID in live cells and characterized in detail its nuclear localization signal. Importantly, we find that the nuclear localization signal motif also directs AID to nucleoli where it colocalizes with its interaction partner, catenin-β-like 1 (CTNNBL1), and physically associates with nucleolin and nucleophosmin. Moreover, we demonstrate that release of AID from nucleoli is dependent on its C-terminal motif. Finally, we find that CSR efficiency correlates strongly with the arithmetic product of AID nuclear import rate and DNA deamination activity. Our findings suggest that directional nucleolar transit is important for the physiological function of AID and demonstrate that nuclear/nucleolar import and DNA cytosine deamination together define the biological activity of AID. This is the first study on subnuclear trafficking of AID and demonstrates a new level in its complex regulation. In addition, our results resolve the problem related to dissociation of deamination activity and CSR activity of AID mutants. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. HILIC LC-MS for the determination of 2'-C-methyl-cytidine-triphosphate in rat liver.

    Science.gov (United States)

    Pucci, Vincenzo; Giuliano, Claudio; Zhang, Rena; Koeplinger, Kenneth Alan; Leone, Joseph F; Monteagudo, Edith; Bonelli, Fabio

    2009-05-01

    A very accurate and selective LC-MS/MS method was developed and validated for the quantification of 2'-C-modified nucleoside triphosphate in liver tissue samples. An efficient pretreatment procedure of liver tissue samples was developed, using a fully automated SPE procedure with 96-well SPE plate (weak anion exchange sorbent, 30 mg). Nucleotide hydrophilic interaction chromatography has been performed on an aminopropyl column (100 mm x 2.0 mm, 3 microm) using a gradient mixture of ACN and ACN/water (5:95 v/v) with 20 mM ammonium acetate at pH 9.45 as mobile phase at 300 microL/min flow rate. The 2'-C-modified nucleoside triphosphate was detected in the negative ESI mode in multiple reaction monitoring (MRM) mode. Calibration curve was linear over the 0.05-50 microM concentration range. Satisfying results, confirming the high reliability of the established LC-MS/MS method, were obtained for intraday precision (CV = 2.5-9.1%) and accuracy (92.6-94.8%) and interday precision (CV = 9.6-11.5%) and accuracy (94.4-102.4%) as well as for recovery (82.0-112.6%) and selectivity. The method has been successfully applied for pharmacokinetic studies of 2'-C-methyl-cytidine-triphosphate in liver tissue samples.

  13. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...... of CorA. METHODS: HC-CorA were quantified in paired samples of cord serum from newborns and serum from mothers (n = 69). RESULTS: The CorA-concentration was higher in cord serum (median = 380, range: 41-780 pmol/L) than in serum from the mothers (median = 160, range: 64-330 pmol/L), (p...-analysis showed CorA-peaks with retention times of 13.5, 14,5 and 16.5 min in samples from both the mother and cord serum. The peak with retention time 16.5 min constituted 24% (mother) and 45% (cord serum) of the total amount CorA, and eluted as does dicyanocobinamide. CONCLUSION: Our results support that Cor...

  14. Chemoenzymatic preparation of germacrene analogues.

    Science.gov (United States)

    Cascón, Oscar; Touchet, Sabrina; Miller, David J; Gonzalez, Veronica; Faraldos, Juan A; Allemann, Rudolf K

    2012-10-09

    A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies.

  15. Chemoenzymatic preparation of germacrene analogues

    OpenAIRE

    Cascón, Oscar; Touchet, Sabrina; Miller, David James; Gonzalez, Veronica; Faraldos, Juan A.; Allemann, Rudolf Konrad

    2012-01-01

    A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies.

  16. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)

    2010-07-15

    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

  17. Theoretical study on absorption and emission spectra of adenine analogues.

    Science.gov (United States)

    Liu, Hongxia; Song, Qixia; Yang, Yan; Li, Yan; Wang, Haijun

    2014-04-01

    Fluorescent nucleoside analogues have attracted much attention in studying the structure and dynamics of nucleic acids in recent years. In the present work, we use theoretical calculations to investigate the structural and optical properties of four adenine analogues (termed as A1, A2, A3, and A4), and also consider the effects of aqueous solution and base pairing. The results show that the fluorescent adenine analogues can pair with thymine to form stable H-bonded WC base pairs. The excited geometries of both adenine analogues and WC base pairs are similar to the ground geometries. The absorption and emission maxima of adenine analogues are greatly red shifted compared with nature adenine, the oscillator strengths of A1 and A2 are stronger than A3 and A4 in both absorption and emission spectra. The calculated low-energy peaks in the absorption spectra are in good agreement with the experimental data. In general, the aqueous solution and base pairing can slightly red-shift both the absorption and emission maxima, and can increase the oscillator strengths of absorption spectra, but significantly decrease the oscillator strengths of A3 in emission spectra.

  18. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Directory of Open Access Journals (Sweden)

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  19. FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients

    Science.gov (United States)

    Serdjebi, Cindy; Gagnière, Johan; Desramé, Jérôme; Fein, Francine; Guimbaud, Rosine; François, Eric; André, Thierry; Seitz, Jean-François; Montérymard, Carole; Arsene, Dominique; Volet, Julien; Abakar-Mahamat, Abakar; Lecomte, Thierry; Guerin-Meyer, Véronique; Legoux, Jean-Louis; Deplanque, Gaël; Guillet, Pierre; Ciccolini, Joseph; Lepage, Côme; Dahan, Laetitia

    2015-01-01

    Purpose Because cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships. Experimental design One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute’s Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine. Results Five patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity evidencing an impact in terms of toxicities or in CDA activity. Regarding pharmacokinetics, a wide inter-individual variability has been observed in patients. Conclusion This study, which included only 4.6% of CDA-deficient patients, failed in identifying CDA status as a predictive marker of toxicities with gemcitabine. A lack of statistical power because of smoothing effect of CDA variability as compared with real life

  20. Identification of conjugate adducts formed in the reactions of malonaldehyde-acetaldehyde and malonaldehyde-formaldehyde with cytidine.

    Science.gov (United States)

    Pluskota-Karwatka, Donata; Le Curieux, Frank; Munter, Tony; Sjöholm, Rainer; Kronberg, Leif

    2002-02-01

    Malonaldehyde was reacted with cytidine in buffered aqueous solutions in the presence of acetaldehyde or formaldehyde. The reaction mixtures were analyzed by HPLC, and the products were isolated by preparative C18 chromatography and structurally characterized by UV absorbance, fluorescence emission, (1)H and (13)C NMR spectroscopy, and mass spectrometry. The major adducts formed in the reaction of malonaldehyde and acetaldehyde were identified as 7-(beta-D-ribofuranosyl)-4-methyl-6-oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3-carbaldehyde (M(1)AA-Cyd) and 1-(beta-D-ribofuranosyl)-4-(3,5-diformyl-4-methyl-1,4-dihydro-1-pyridyl)pyrimidine (M(2)AA-Cyd). In the reaction of malonaldehyde and formaldehyde, the major product was identified as 7-(beta-D-ribofuranosyl)-6-oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3-carbaldehyde (M(1)FA-Cyd). The highest yields of M(1)AA-Cyd and M(2)AA-Cyd, 3.2 and 0.5 mol %, respectively, were obtained in the reaction performed at pH 4.6 and 37 degrees C for 8 days, while M(1)FA-Cyd was produced at a yield of 0.3 mol % after 3 days of reaction at pH 4.0 and 37 degrees C. The products consist of units derived from malonaldehyde and acetaldehyde (M(1)AA-Cyd and M(2)AA-Cyd) or from malonaldehyde and formaldehyde (M(1)FA-Cyd), and are thus further examples of nucleoside modifications containing structural elements derived from aldehyde condensation reactions. Trace amounts of the adducts may be formed at physiological conditions and may be involved in the mutagenicity of the studied aldehydes.

  1. Asymmetric Modification of Hepatitis B Virus (HBV) Genomes by an Endogenous Cytidine Deaminase inside HBV Cores Informs a Model of Reverse Transcription.

    Science.gov (United States)

    Nair, Smita; Zlotnick, Adam

    2018-05-15

    Cytidine deaminases inhibit replication of a broad range of DNA viruses by deaminating cytidines on single-stranded DNA (ssDNA) to generate uracil. While several lines of evidence have revealed hepatitis B virus (HBV) genome editing by deamination, it is still unclear which nucleic acid intermediate of HBV is modified. Hepatitis B virus has a relaxed circular double-stranded DNA (rcDNA) genome that is reverse transcribed within virus cores from a RNA template. The HBV genome also persists as covalently closed circular DNA (cccDNA) in the nucleus of an infected cell. In the present study, we found that in HBV-producing HepAD38 and HepG2.2.15 cell lines, endogenous cytidine deaminases edited 10 to 25% of HBV rcDNA genomes, asymmetrically with almost all mutations on the 5' half of the minus strand. This region corresponds to the last half of the minus strand to be protected by plus-strand synthesis. Within this half of the genome, the number of mutations peaks in the middle. Overexpressed APOBEC3A and APOBEC3G could be packaged in HBV capsids but did not change the amount or distribution of mutations. We found no deamination on pregenomic RNA (pgRNA), indicating that an intact genome is encapsidated and deaminated during or after reverse transcription. The deamination pattern suggests a model of rcDNA synthesis in which pgRNA and then newly synthesized minus-sense single-stranded DNA are protected from deaminase by interaction with the virus capsid; during plus-strand synthesis, when enough dsDNA has been synthesized to displace the remaining minus strand from the capsid surface, the single-stranded DNA becomes deaminase sensitive. IMPORTANCE Host-induced mutation of the HBV genome by APOBEC proteins may be a path to clearing the virus. We examined cytidine-to-thymidine mutations in the genomes of HBV particles grown in the presence or absence of overexpressed APOBEC proteins. We found that genomes were subjected to deamination activity during reverse transcription

  2. Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report.

    Science.gov (United States)

    Patiroglu, Turkan; Akar, H Haluk; van der Burg, Mirjam; Unal, Ekrem

    2015-09-01

    The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively.

  3. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1994-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets, with a few more additions - with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers - exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the foree of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc. (orig.)

  4. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1993-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc

  5. Synthesis of pyrimidine containing nucleoside β-(R/S)-hydroxyphosphonate analogues

    OpenAIRE

    Meurillon, Maïa; Chaloin, Laurent; Peyrottes, Suzanne; Périgaud, Christian

    2011-01-01

    A concise route to nucleoside β-hydroxyphosphonate analogues is described. The use of a nucleoside β-ketophosphonate as the key intermediate allowed both the (R) and (S) isomers of β-hydroxyphosphonate analogues in the pyrimidine series to be accessed. Such derivatives may be considered as stable mimics of 5′-monophosphate nucleosides and, therefore, could be the starting point for the development of potential therapeutic agents.

  6. Introduction to electronic analogue computers

    CERN Document Server

    Wass, C A A

    1965-01-01

    Introduction to Electronic Analogue Computers, Second Revised Edition is based on the ideas and experience of a group of workers at the Royal Aircraft Establishment, Farnborough, Hants. This edition is almost entirely the work of Mr. K. C. Garner, of the College of Aeronautics, Cranfield. As various advances have been made in the technology involving electronic analogue computers, this book presents discussions on the said progress, including some acquaintance with the capabilities of electronic circuits and equipment. This text also provides a mathematical background including simple differen

  7. Functionalized tricyclic cytosine analogues provide nucleoside fluorophores with improved photophysical properties and a range of solvent sensitivities.

    Science.gov (United States)

    Rodgers, Brittney J; Elsharif, Nada A; Vashisht, Nisha; Mingus, Macy M; Mulvahill, Mark A; Stengel, Gudrun; Kuchta, Robert D; Purse, Byron W

    2014-02-10

    Tricyclic cytosines (tC and tC(O) frameworks) have emerged as a unique class of fluorescent nucleobase analogues that minimally perturb the structure of B-form DNA and that are not quenched in duplex nucleic acids. Systematic derivatization of these frameworks is a likely approach to improve on and diversify photophysical properties, but has not so far been examined. Synthetic methods were refined to improve on tolerance for electron-donating and electron-withdrawing groups, resulting in a series of eight new, fluorescent cytidine analogues. Photophysical studies show that substitution of the framework results in a pattern of effects largely consistent across tC and tC(O) and provides nucleoside fluorophores that are brighter than either parent. Moreover, a range of solvent sensitivities is observed, offering promise that this family of probes can be extended to new applications that require reporting on the local environment. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Cytidine 5’-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats

    Directory of Open Access Journals (Sweden)

    Emril DR

    2016-05-01

    Full Text Available Dessy R Emril,1 Samekto Wibowo,2 Lucas Meliala,2 Rina Susilowati3 1Department of Neurology, Faculty of Medicine, Syiah Kuala University, Banda Aceh, 2Department of Neurology, 3Department of Histology and Cell Biology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, IndonesiaBackground: Cytidine 5’-diphosphocholine (citicoline has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury.Methods: Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT tests were used to assess motoric function.Results: The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17 compared with the crush/saline group (53.33%, n=15, P<0.005. The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001. However, the sciatic functional index analysis did not show significant differences between groups (P=0.35. The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18 and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume.Conclusion: In situ administration of 0.4 mL of 100 μmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery

  9. Superconductive analogue of spin glasses

    International Nuclear Information System (INIS)

    Feigel'man, M.; Ioffe, L.; Vinokur, V.; Larkin, A.

    1987-07-01

    The properties of granular superconductors in magnetic fields, namely the existence of a new superconductive state analogue of the low-temperature superconductive state in spin glasses are discussed in the frame of the infinite-range model and the finite-range models. Experiments for elucidation of spin-glass superconductive state in real systems are suggested. 30 refs

  10. PTH analogues and osteoporotic fractures

    NARCIS (Netherlands)

    Verhaar, H.J.; Lems, W.F.

    2010-01-01

    Importance of the field: At present there are two parathyroid hormone (PTH) analogues (PTH 1 34 and PTH 1 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 34 and PTH 1 84) and in men (PTH 1 34 only) who are at increased risk of having a fracture. Areas

  11. Chemopreventive properties of curcumin analogues ...

    African Journals Online (AJOL)

    Chemopreventive properties of curcumin analogues, hexagamavunone-0 and gamavutone-0, in rat colorectal cancer model. ... Histopathological analysis was performed using H & E staining and immunohistochemistry with antibodies against adenomatous polyposis coli (APC) and cyclooxygenase 2 (COX-2). Results: All ...

  12. A novel pathway for the synthesis of inositol phospholipids uses cytidine diphosphate (CDP)-inositol as donor of the polar head group.

    Science.gov (United States)

    Jorge, Carla D; Borges, Nuno; Santos, Helena

    2015-07-01

    We describe a novel biosynthetic pathway for glycerophosphoinositides in Rhodothermus marinus in which inositol is activated by cytidine triphosphate (CTP); this is unlike all known pathways that involve activation of the lipid group instead. This work was motivated by the detection in the R. marinus genome of a gene with high similarity to CTP:L-myo-inositol-1-phosphate cytidylyltransferase, the enzyme that synthesizes cytidine diphosphate (CDP)-inositol, a metabolite only known in the synthesis of di-myo-inositol phosphate. However, this solute is absent in R. marinus. The fate of radiolabelled CDP-inositol was investigated in cell extracts to reveal that radioactive inositol was incorporated into the chloroform-soluble fraction. Mass spectrometry showed that the major lipid product has a molecular mass of 810 Da and contains inositol phosphate and alkyl chains attached to glycerol by ether bonds. The occurrence of ether-linked lipids is rare in bacteria and has not been described previously in R. marinus. The relevant synthase was identified by functional expression of the candidate gene in Escherichia coli. The enzyme catalyses the transfer of L-myo-inositol-1-phosphate from CDP-inositol to dialkylether glycerol yielding dialkylether glycerophosphoinositol. Database searching showed homologous proteins in two bacterial classes, Sphingobacteria and Alphaproteobacteria. This is the first report of the involvement of CDP-inositol in phospholipid synthesis. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Stable beams

    CERN Multimedia

    2015-01-01

    Stable beams: two simple words that carry so much meaning at CERN. When LHC page one switched from "squeeze" to "stable beams" at 10.40 a.m. on Wednesday, 3 June, it triggered scenes of jubilation in control rooms around the CERN sites, as the LHC experiments started to record physics data for the first time in 27 months. This is what CERN is here for, and it’s great to be back in business after such a long period of preparation for the next stage in the LHC adventure.   I’ve said it before, but I’ll say it again. This was a great achievement, and testimony to the hard and dedicated work of so many people in the global CERN community. I could start to list the teams that have contributed, but that would be a mistake. Instead, I’d simply like to say that an achievement as impressive as running the LHC – a machine of superlatives in every respect – takes the combined effort and enthusiasm of everyone ...

  14. Novel acetylcholine and carbamoylcholine analogues

    DEFF Research Database (Denmark)

    Hansen, Camilla Petrycer; Jensen, Anders Asbjørn; Christensen, Jeppe K.

    2008-01-01

    A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity...... for this subtype over alpha 3beta 4, alpha 4beta 4, and alpha 7 nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced alpha 4beta 2 selectivities exhibited...... by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial alpha 4beta 2 nAChR agonist with negligible activities at the alpha 3beta 4 and alpha 7 subtypes, thus being one of the few truly functionally selective alpha 4beta 2 nACh...

  15. Haplopappus gracilis cell strains resistant to pyrimidine analogues.

    Science.gov (United States)

    Jones, G E; Hann, J

    1979-03-01

    Strains of Haplopappus gracilis (Nutt.) Gray cells resistant to 6-azauracil have been isolated from cultures of diploid cells. These strains are also resistant to 8-azaguanine, as is their parent. The variants are 100- to 125-fold more resistant to 6-azauracil than their parent, and they exhibit different spectra of cross resistance to other pyrimidine analogues. The phenotype of each variant is stable in the absence of selection. The majority of cells in cultures of the variants are diploid; all others examined were tetraploid. Initial rates of uptake of uracil are not reduced in the variants. Fluorouracil, to which two variants are resistant, is taken up by one of them as well as by the parent. Responses of the other two to fluorouracil are not correlated with decreased ability to accumulate this analogue.

  16. Substrate analogues for isoprenoid enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  17. A Novel Regulator of Activation-Induced Cytidine Deaminase/APOBECs in Immunity and Cancer: Schrödinger’s CATalytic Pocket

    Directory of Open Access Journals (Sweden)

    Mani Larijani

    2017-04-01

    Full Text Available Activation-induced cytidine deaminase (AID and its relative APOBEC3 cytidine deaminases boost immune response by mutating immune or viral genes. Because of their genome-mutating activities, AID/APOBECs are also drivers of tumorigenesis. Due to highly charged surfaces, extensive non-specific protein–protein/nucleic acid interactions, formation of polydisperse oligomers, and general insolubility, structure elucidation of these proteins by X-ray crystallography and NMR has been challenging. Hence, almost all available AID/APOBEC structures are of mutated and/or truncated versions. In 2015, we reported a functional structure for AID using a combined computational–biochemical approach. In so doing, we described a new regulatory mechanism that is a first for human DNA/RNA-editing enzymes. This mechanism involves dynamic closure of the catalytic pocket. Subsequent X-ray and NMR studies confirmed our discovery by showing that other APOBEC3s also close their catalytic pockets. Here, we highlight catalytic pocket closure as an emerging and important regulatory mechanism of AID/APOBEC3s. We focus on three sub-topics: first, we propose that variable pocket closure rates across AID/APOBEC3s underlie differential activity in immunity and cancer and review supporting evidence. Second, we discuss dynamic pocket closure as an ever-present internal regulator, in contrast to other proposed regulatory mechanisms that involve extrinsic binding partners. Third, we compare the merits of classical approaches of X-ray and NMR, with that of emerging computational–biochemical approaches, for structural elucidation specifically for AID/APOBEC3s.

  18. Structural and functional characterization of the Helicobacter pylori cytidine 5'-monophosphate-pseudaminic acid synthase PseF: molecular insight into substrate recognition and catalysis mechanism

    Directory of Open Access Journals (Sweden)

    Wahid SUH

    2017-10-01

    Full Text Available Syeda Umme Habiba Wahid Department of Microbiology, University of Chittagong, Chittagong, Bangladesh Abstract: The bacterium Helicobacter pylori is a human gastric pathogen that can cause a wide range of diseases, including chronic gastritis, peptic ulcer and gastric carcinoma. It is classified as a definitive (class I human carcinogen by the International Agency for Research on Cancer. Flagella-mediated motility is essential for H. pylori to initiate colonization and for the development of infection in human beings. Glycosylation of the H. pylori flagellum with pseudaminic acid (Pse; 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-nonulosonic acid is essential for flagella assembly and function. The sixth step in the Pse biosynthesis pathway, activation of Pse by addition of a cytidine 5′-monophosphate (CMP to generate CMP-Pse, is catalyzed by a metal-dependent enzyme pseudaminic acid biosynthesis protein F (PseF using cytidine 5′-triphosphate (CTP as a cofactor. No crystal–structural information for PseF is available. This study describes the first three-dimensional model of H. pylori PseF obtained using biocomputational tools. PseF harbors an α/β-type hydrolase fold with a β-hairpin (HP dimerization domain. Comparison of PseF with other structural homologs allowed identification of crucial residues for substrate recognition and the catalytic mechanism. This structural information would pave the way to design novel therapeutics to combat bacterial infection. Keywords: H. pylori, motility, glycosylation, homology modeling, pseudaminic acid

  19. Identification and quantitation of cobalamin and cobalamin analogues in human feces

    Science.gov (United States)

    Allen, Robert H.; Stabler, Sally P.

    2010-01-01

    Background Cobalamin (vitamin-B12) and cobalamin analogues are present in human feces, but a complete identification has not been established, and the amounts present have not been determined. Objective We aimed to develop a liquid chromatography-mass spectrometry method for cobalamin and cobalamin analogues and to identify and quantitiate the amounts present in human feces. Design Fecal samples were obtained from 20 human subjects in good general health. The samples were analyzed for the presence and amounts of cobalamin and 12 cobalamin analogues that were synthesized with and without the incorporation of stable isotopes. Results Cobalamin and 7 cobalamin analogues were identified and quantitated in human feces. The mean for the total amount present in 18 subjects whose daily intake was ≤ 25 ug cobalamin from vitamin supplements was 1309 ng cobalamin equivalents/g wet wt of feces. Cobalamin (1.4%) and cobinamide (1.8%) (an incomplete corrinoid) represented a small portion of the total amount. Six cobalamin analogues that contain a base other than the 5,6-dimethylbenzimidizidole in cobalamin were present. The bases and their mean amounts (in %) are 2-methyladenine (60.6%), p-cresol (16.3%), adenine (12.5%), 2-(methylthio)adenine (15.5%), 5-hydroxybenzimidazole (1.8%), and phenol (0.1%). One subject ingested 1 mg cobalamin/d and another ingested 2 mg cobalamin/d, and they appeared to convert most of the cobalamin to cobinamide and the 4 analogues that contain the bases – 2-methyladenine, p-cresol, adenine and 2-(methylthio)adenine. Conclusion Cobalamin analogues are present in human feces and account for > 98% of the total of cobalamin plus cobalamin analogues. A major portion of large amounts of ingested cobalamin appears to be converted to cobalamin analogues. PMID:18469256

  20. The Valles natural analogue project

    International Nuclear Information System (INIS)

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and 39 Ar/ 4O isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks

  1. Enzymatic ligation for synthesis of single-chain analogue of monellin by transglutaminase.

    Science.gov (United States)

    Ota, M; Sawa, A; Nio, N; Ariyoshi, Y

    1999-08-01

    Monellin, a sweet protein, consists of two noncovalently associated polypeptide chains: an A chain of 44 amino acid residues and a B chain of 50 residues. Microbial transglutaminase (MTGase) was used for ligation of the monellin subunits without any protecting groups, and without activation of the C alpha-carboxyl group at the C-terminus. Since a peptide fragment LLQG is a good substrate for MTGase to form an amide bond between the gamma-amide group of the Gln residue and the epsilon-amino group of Lys, a monellin B chain analogue in which LLQG was elongated at the C-terminus (B-LLQG) was synthesized by solid-phase synthesis. The monellin A chain analogue in which KGK was elongated at the N-terminus (KGK-A) was synthesized by the same method as that of the B chain analogue. The KGK-A chain and the B-LLQG chain were coupled by MTGase to give single-chain analogue of monellin. The single-chain analogue of monellin was characterized by analytical reverse phase high performance liquid chromatography, electrospray ionization, and amino acid analyses. All analyses gave satisfactory results. The single-chain analogue of monellin was more heat stable than natural monellin.

  2. Stable Isotope Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Tissue samples (skin, bone, blood, muscle) are analyzed for stable carbon, stable nitrogen, and stable sulfur analysis. Many samples are used in their entirety for...

  3. Condensed matter analogues of cosmology

    Science.gov (United States)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the

  4. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    Malik Chalal

    2014-06-01

    Full Text Available Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew. Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold. The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups and antimicrobial activity.

  5. Activation-induced cytidine deaminase expression in CD4+ T cells is associated with a unique IL-10-producing subset that increases with age.

    Directory of Open Access Journals (Sweden)

    Hongyan Qin

    Full Text Available Activation-induced cytidine deaminase (AID, produced by the Aicda gene, is essential for the immunoglobulin gene (Ig alterations that form immune memory. Using a Cre-mediated genetic system, we unexpectedly found CD4(+ T cells that had expressed Aicda (exAID cells as well as B cells. ExAID cells increased with age, reaching up to 25% of the CD4(+ and B220(+ cell populations. ExAID B cells remained IgM(+, suggesting that class-switched memory B cells do not accumulate in the spleen. In T cells, AID was expressed in a subset that produced IFN-γ and IL-10 but little IL-4 or IL-17, and showed no evidence of genetic mutation. Interestingly, the endogenous Aicda expression in T cells was enhanced in the absence of B cells, indicating that the process is independent from the germinal center reaction. These results suggest that in addition to its roles in B cells, AID may have previously unappreciated roles in T-cell function or tumorigenesis.

  6. Role of Genetic Polymorphisms of Deoxycytidine Kinase and Cytidine Deaminase to Predict Risk of Death in Children with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Aurora Medina-Sanson

    2015-01-01

    Full Text Available Cytarabine is one of the most effective antineoplastic agents among those used for the treatment of acute myeloid leukemia. However, some patients develop resistance and/or severe side effects to the drug, which may interfere with the efficacy of the treatment. The polymorphisms of some Ara-C metabolizing enzymes seem to affect outcome and toxicity in AML patients receiving cytarabine. We conducted this study in a cohort of Mexican pediatric patients with AML to investigate whether the polymorphisms of the deoxycytidine kinase and cytidine deaminase enzymes are implicated in clinical response and toxicity. Bone marrow and/or peripheral blood samples obtained at diagnosis from 27 previously untreated pediatric patients with de novo AML were processed for genotyping and in vitro chemosensitivity assay, and we analyzed the impact of genotypes and in vitro sensitivity on disease outcome and toxicity. In the multivariate Cox regression analysis, we found that age at diagnosis, wild-type genotype of the CDA A79C polymorphism, and wild-type genotype of the dCK C360G polymorphism were the most significant prognostic factors for predicting the risk of death.

  7. International video project on natural analogues

    International Nuclear Information System (INIS)

    Guentensperger, Marcel

    1993-01-01

    A natural analogue can be defined as a natural process which has occurred in the past and is studied in order to test predictions about the future evolution of similar processes. In recent years, natural analogues have been used increasingly to test the mathematical models required for repository performance assessment. Analogues are, however, also of considerable use in public relations as they allow many of the principles involved in demonstrating repository safety to be illustrated in a clear manner using natural systems with which man is familiar. The international Natural Analogue Working Group (NAWG), organised under the auspices of the CEC, has recognised that such PR applications are of considerable importance and should be supported from a technical level. At the NAWG meeting in Pitlochry, Scotland (June 1990), it was recommended that the possibilities for making a video film on this topic be investigated and Nagra was requested to take the lead role in setting up such a project

  8. Natural analogues and radionuclide transport model validation

    International Nuclear Information System (INIS)

    Lever, D.A.

    1987-08-01

    In this paper, some possible roles for natural analogues are discussed from the point of view of those involved with the development of mathematical models for radionuclide transport and with the use of these models in repository safety assessments. The characteristic features of a safety assessment are outlined in order to address the questions of where natural analogues can be used to improve our understanding of the processes involved and where they can assist in validating the models that are used. Natural analogues have the potential to provide useful information about some critical processes, especially long-term chemical processes and migration rates. There is likely to be considerable uncertainty and ambiguity associated with the interpretation of natural analogues, and thus it is their general features which should be emphasized, and models with appropriate levels of sophistication should be used. Experience gained in modelling the Koongarra uranium deposit in northern Australia is drawn upon. (author)

  9. Stable convergence and stable limit theorems

    CERN Document Server

    Häusler, Erich

    2015-01-01

    The authors present a concise but complete exposition of the mathematical theory of stable convergence and give various applications in different areas of probability theory and mathematical statistics to illustrate the usefulness of this concept. Stable convergence holds in many limit theorems of probability theory and statistics – such as the classical central limit theorem – which are usually formulated in terms of convergence in distribution. Originated by Alfred Rényi, the notion of stable convergence is stronger than the classical weak convergence of probability measures. A variety of methods is described which can be used to establish this stronger stable convergence in many limit theorems which were originally formulated only in terms of weak convergence. Naturally, these stronger limit theorems have new and stronger consequences which should not be missed by neglecting the notion of stable convergence. The presentation will be accessible to researchers and advanced students at the master's level...

  10. Between Analogue and Digital Diagrams

    Directory of Open Access Journals (Sweden)

    Zoltan Bun

    2012-10-01

    Full Text Available This essay is about the interstitial. About how the diagram, as a method of design, has lead fromthe analogue deconstruction of the eighties to the digital processes of the turn of the millennium.Specifically, the main topic of the text is the interpretation and the critique of folding (as a diagramin the beginning of the nineties. It is necessary then to unfold its relationship with immediatelypreceding and following architectural trends, that is to say we have to look both backwards andforwards by about a decade. The question is the context of folding, the exchange of the analogueworld for the digital. To understand the process it is easier to investigate from the fields of artand culture, rather than from the intentionally perplicated1 thoughts of Gilles Deleuze. Both fieldsare relevant here because they can similarly be used as the yardstick against which the era itselfit measured. The cultural scene of the eighties and nineties, including performing arts, movies,literature and philosophy, is a wide milieu of architecture. Architecture responds parallel to itsera; it reacts to it, and changes with it and within it. Architecture is a medium, it has always beena medium, yet the relations are transformed. That’s not to say that technical progress, for exampleusing CAD-software and CNC-s, has led to the digital thinking of certain movements ofarchitecture, (it is at most an indirect tool. But the ‘up-to-dateness’ of the discipline, however,a kind of non-servile reading of an ‘applied culture’ or ‘used philosophy’2 could be the key.(We might recall here, parenthetically, the fortunes of the artistic in contemporary mass society.The proliferation of museums, the magnification of the figure of the artist, the existence of amassive consumption of printed and televised artistic images, the widespread appetite for informationabout the arts, all reflect, of course, an increasingly leisured society, but also relateprecisely to the fact

  11. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  12. CD40 Ligand (CD154) Incorporated into HIV Virions Induces Activation-Induced Cytidine Deaminase (AID) Expression in Human B Lymphocytes

    Science.gov (United States)

    Epeldegui, Marta; Thapa, Dharma R.; De La Cruz, Justin; Kitchen, Scott; Zack, Jerome A.; Martínez-Maza, Otoniel

    2010-01-01

    Most AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) arises from errors in immunoglobulin heavy-chain gene (IgH) class switch recombination (CSR) or somatic hypermutation (SHM), events that occur in germinal center (GC) B cells and require the activity of activation induced cytidine deaminase (AID). Several oncogenic viruses (EBV, HCV, HPV) can induce AID gene (AID) expression, and elevated AID expression is seen in circulating lymphocytes prior to AIDS-NHL diagnosis. Here, we report that HIV produced in peripheral blood mononuclear cells (PBMC) induced AID expression in normal human B cells. Since HIV produced in PBMC contains host cell CD40 ligand (CD40L) incorporated into the viral membrane, and CD40L is known to induce AID expression in human B cells, the role of virion-associated CD40L in HIV-induced AID expression was examined. Only viruses expressing functional CD40L were seen to induce AID expression; CD40L-negative HIV did not induce AID expression. The induction of AID expression by CD40L+ HIV was abrogated by addition of blocking anti-CD40L antibody. AID protein was detected in B cells exposed to CD40L+ HIV using intracellular multicolor flow cytometry, with most AID producing B cells expressing the CD71 activation marker on their surface. Therefore, HIV virions that express CD40L induce AID expression in B cells, and this induction appears to be due to a direct interaction between CD40L on these viruses and CD40 on B cells. These findings are consistent with a role for HIV in the direct stimulation of B cells, potentially leading to the accumulation of molecular lesions that have the potential to contribute to the development of NHL. PMID:20625427

  13. CD40 ligand (CD154 incorporated into HIV virions induces activation-induced cytidine deaminase (AID expression in human B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Marta Epeldegui

    2010-07-01

    Full Text Available Most AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL arises from errors in immunoglobulin heavy-chain gene (IgH class switch recombination (CSR or somatic hypermutation (SHM, events that occur in germinal center (GC B cells and require the activity of activation induced cytidine deaminase (AID. Several oncogenic viruses (EBV, HCV, HPV can induce AID gene (AID expression, and elevated AID expression is seen in circulating lymphocytes prior to AIDS-NHL diagnosis. Here, we report that HIV produced in peripheral blood mononuclear cells (PBMC induced AID expression in normal human B cells. Since HIV produced in PBMC contains host cell CD40 ligand (CD40L incorporated into the viral membrane, and CD40L is known to induce AID expression in human B cells, the role of virion-associated CD40L in HIV-induced AID expression was examined. Only viruses expressing functional CD40L were seen to induce AID expression; CD40L-negative HIV did not induce AID expression. The induction of AID expression by CD40L+ HIV was abrogated by addition of blocking anti-CD40L antibody. AID protein was detected in B cells exposed to CD40L+ HIV using intracellular multicolor flow cytometry, with most AID producing B cells expressing the CD71 activation marker on their surface. Therefore, HIV virions that express CD40L induce AID expression in B cells, and this induction appears to be due to a direct interaction between CD40L on these viruses and CD40 on B cells. These findings are consistent with a role for HIV in the direct stimulation of B cells, potentially leading to the accumulation of molecular lesions that have the potential to contribute to the development of NHL.

  14. Quantitative comparisons of analogue models of brittle wedge dynamics

    Science.gov (United States)

    Schreurs, Guido

    2010-05-01

    Analogue model experiments are widely used to gain insights into the evolution of geological structures. In this study, we present a direct comparison of experimental results of 14 analogue modelling laboratories using prescribed set-ups. A quantitative analysis of the results will document the variability among models and will allow an appraisal of reproducibility and limits of interpretation. This has direct implications for comparisons between structures in analogue models and natural field examples. All laboratories used the same frictional analogue materials (quartz and corundum sand) and prescribed model-building techniques (sieving and levelling). Although each laboratory used its own experimental apparatus, the same type of self-adhesive foil was used to cover the base and all the walls of the experimental apparatus in order to guarantee identical boundary conditions (i.e. identical shear stresses at the base and walls). Three experimental set-ups using only brittle frictional materials were examined. In each of the three set-ups the model was shortened by a vertical wall, which moved with respect to the fixed base and the three remaining sidewalls. The minimum width of the model (dimension parallel to mobile wall) was also prescribed. In the first experimental set-up, a quartz sand wedge with a surface slope of ˜20° was pushed by a mobile wall. All models conformed to the critical taper theory, maintained a stable surface slope and did not show internal deformation. In the next two experimental set-ups, a horizontal sand pack consisting of alternating quartz sand and corundum sand layers was shortened from one side by the mobile wall. In one of the set-ups a thin rigid sheet covered part of the model base and was attached to the mobile wall (i.e. a basal velocity discontinuity distant from the mobile wall). In the other set-up a basal rigid sheet was absent and the basal velocity discontinuity was located at the mobile wall. In both types of experiments

  15. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  16. Analogue alternative the electronic analogue computer in Britain and the USA, 1930-1975

    CERN Document Server

    Small, James S

    2013-01-01

    We are in the midst of a digital revolution - until recently, the majority of appliances used in everyday life have been developed with analogue technology. Now, either at home or out and about, we are surrounded by digital technology such as digital 'film', audio systems, computers and telephones. From the late 1940s until the 1970s, analogue technology was a genuine alternative to digital, and the two competing technologies ran parallel with each other. During this period, a community of engineers, scientists, academics and businessmen continued to develop and promote the analogue computer.

  17. Total synthesis of sannanine and analogues thereof

    Indian Academy of Sciences (India)

    BADHER NAVEEN

    2018-03-02

    Mar 2, 2018 ... concise manner. The key strategies involve Friedländer quinoline synthesis, demethylation, in situ oxidation and amination process. ..... (b) Hargreaves R, David C L, Whitesell L and Skibo E. B 2003 Design of Quinolinedione-Based Geldanamycin. Analogues Bioorg. Med. Chem. Lett. 13 3075; (c) Arg-.

  18. Ultrasound exfoliation of inorganic analogues of graphene

    Czech Academy of Sciences Publication Activity Database

    Štengl, Václav; Henych, Jiří; Slušná, Michaela; Ecorchard, Petra

    2014-01-01

    Roč. 9, APR (2014), s. 1-14 ISSN 1556-276X R&D Projects: GA ČR(CZ) GA14-05146S Institutional support: RVO:61388980 Keywords : Ultrasound * Exfoliation * Graphene inorganic analogues Subject RIV: CA - Inorganic Chemistry Impact factor: 2.779, year: 2014

  19. The World Is either Digital or Analogue

    NARCIS (Netherlands)

    Berto, F.; Tagliabue, J.

    2014-01-01

    We address an argument by Floridi (Synthese 168(1):151-178, 2009; 2011a), to the effect that digital and analogue are not features of reality, only of modes of presentation of reality. One can therefore have an informational ontology, like Floridi’s Informational Structural Realism, without

  20. Somatostatin analogue scintigraphy and tuberculosis: case report

    International Nuclear Information System (INIS)

    Biancheri, I.; Rudenko, B.; Vautrin, P.; Raddoul, J.; Lamfichek, N.; Kantelip, B.; Mantion, G.

    2005-01-01

    Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

  1. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While

  2. The Palmottu analogue project: overview for 1993

    International Nuclear Information System (INIS)

    Ruskeeniemi, T.; Blomqvist, R.; Suksi, J.; Niini, H.

    1994-01-01

    This article gives a summary of the activities carried out within the Palmottu analogue project in 1993. It consists of (1) an introductory part, followed by (2) a geological description of the site, and (3)an up-to-date summary of the results of the project. (orig.) (33 refs., 6 figs.)

  3. Native copper as a natural analogue for copper canisters

    International Nuclear Information System (INIS)

    Marcos, N.

    1989-12-01

    This paper discusses the occurrence of native copper as found in geological formations as a stability analogue of copper canisters that are planned to be used for the disposal of spent nuclear fuel in the Finnish bedrock. A summary of several publications on native copper occurrences is presented. The present geochemical and geohydrological conditions in which copper is met with in its metallic state show that metallic copper is stable in a wide range of temperatures. At low temperatures native copper is found to be stable where groundwater has moderate pH (about 7), low Eh (< +100 mV), and low total dissolved solids, especially chloride. Microscopical and microanalytical studies were carried out on a dozen of rock samples containing native copper. The results reveal that the metal shows no significant alteration. Only the surface of copper grains is locally coated. In the oldest samples there exist small corrosion cracks; the age of the oldest samples is over 1,000 million years. A review of several Finnish groundwater studies suggests that there are places in Finland where the geohydrological conditions are favourable for native copper stability. (orig.)

  4. The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide riboside.

    Science.gov (United States)

    Pankiewicz, Krzysztof W; Watanabe, Kyoichi A; Lesiak-Watanabe, Krystyna; Goldstein, Barry M; Jayaram, Hiremagalur N

    2002-04-01

    Oncolytic C-nucleosides, tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) and benzamide riboside (3-beta-D-ribofuranosylbenzamide) are converted in cell into active metabolites thiazole-4-carboxamide- and benzamide adenine dinucleotide, TAD and BAD, respectively. TAD and BAD as NAD analogues were found to bind at the nicotinamide adenine dinucleotide (cofactor NAD) site of inosine monophosphate dehydrogenase (IMPDH), an important target in cancer treatment. The synthesis and evaluation of anticancer activity of a number of C-nucleosides related to tiazofurin and nicotinamide riboside then followed and are reviewed herein. Interestingly, pyridine C-nucleosides (such as C-nicotinamide riboside) are not metabolized into the corresponding NAD analogues in cell. Their conversion by chemical methods is described. As dinucleotides these compounds show inhibition of IMPDH in low micromolar level. Also, the synthesis of BAD in metabolically stable bis(phosphonate) form is discussed indicating the usefulness of such preformed inhibitors in drug development. Among tiazofurin analogues, Franchetti and Grifantini found, that the replacement of the sulfur by oxygen (as in oxazafurin) but not the removal of nitrogen (tiophenfurin) of the thiazole ring resulted in inactive compounds. The anti cancer activity of their synthetic dinucleotide analogues indicate that inactive compounds are not only poorly metabolized in cell but also are weak inhibitors of IMPDH as dinucleotides.

  5. Natural product analogues: towards a blueprint for analogue-focused synthesis.

    Science.gov (United States)

    Bebbington, Magnus W P

    2017-08-14

    For the first time a general overview of approaches to the synthesis of natural product analogues is presented. This reflects a process of evolution of natural product synthesis which has accelerated in the years since the implementation of diversity-oriented synthesis, which has emerged in parallel with collective synthesis, diverted total synthesis and the preparation of truncated natural products optimised for biological activity. A method involving computational assessment for the validation of core-modified natural product analogues is discussed.

  6. Ambivalent Incorporation of the Fluorescent Cytosine Analogues tC and tCo by Human DNA Polymerase α and Klenow Fragment #

    Science.gov (United States)

    Stengel, Gudrun; Purse, Byron W.; Wilhelmsson, L. Marcus; Urban, Milan; Kuchta, Robert D.

    2009-01-01

    We studied the incorporation of the fluorescent cytidine analogues 1, 3-diaza-2-oxo-phenothiazine (tC) and 1, 3-diaza-2-oxo-phenoxazine (tCo) by human DNA polymerase α and Klenow fragment of DNA polymerase I (E. coli). These tricyclic nucleobases possess the regular hydrogen bonding interface of cytosine but are significantly size expanded toward the major groove. Despite the size alteration both DNA polymerases insert dtCTP and dtCoTP with remarkable catalytic efficiency. Polymerization opposite guanine is comparable to the insertion of dCTP, while the insertion opposite adenine is only ∼4-11 times less efficient than the formation of a T-A base pair. Both enzymes readily extend the formed tC(o)-G and tC(o)-A base pairs, and can incorporate at least 4 consecutive nucleotide analogues. Consistent with these results, both DNA polymerases efficiently polymerize dGTP and dATP when tC and tCo are in the template strand. KF inserts dGTP with a 4- to 9-fold higher probability than dATP, while pol α favors dGTP over dATP by a factor of 30-65. Overall, the properties of tC(o) as templating base and as incoming nucleotide are surprisingly symmetrical and may be universal for A and B family DNA polymerases. This finding suggests that the aptitude for ambivalent base pairing is a consequence of the electronic properties of tC(o). PMID:19580325

  7. Ambivalent incorporation of the fluorescent cytosine analogues tC and tCo by human DNA polymerase alpha and Klenow fragment.

    Science.gov (United States)

    Stengel, Gudrun; Purse, Byron W; Wilhelmsson, L Marcus; Urban, Milan; Kuchta, Robert D

    2009-08-11

    We studied the incorporation of the fluorescent cytidine analogues 1,3-diaza-2-oxophenothiazine (tC) and 1,3-diaza-2-oxophenoxazine (tCo) by human DNA polymerase alpha and Klenow fragment of DNA polymerase I (Escherichia coli). These tricyclic nucleobases possess the regular hydrogen bonding interface of cytosine but are significantly expanded in size toward the major groove. Despite the size alteration, both DNA polymerases insert dtCTP and dtCoTP with remarkable catalytic efficiency. Polymerization opposite guanine is comparable to the insertion of dCTP, while the insertion opposite adenine is only approximately 4-11 times less efficient than the formation of a T-A base pair. Both enzymes readily extend the formed tC(o)-G and tC(o)-A base pairs and can incorporate at least four consecutive nucleotide analogues. Consistent with these results, both DNA polymerases efficiently polymerize dGTP and dATP when tC and tCo are in the template strand. Klenow fragment inserts dGTP with a 4-9-fold higher probability than dATP, while polymerase alpha favors dGTP over dATP by a factor of 30-65. Overall, the properties of tC(o) as a templating base and as an incoming nucleotide are surprisingly symmetrical and may be universal for A and B family DNA polymerases. This finding suggests that the aptitude for ambivalent base pairing is a consequence of the electronic properties of tC(o).

  8. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    1982-09-01

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  9. Stable Boundary Layer Issues

    NARCIS (Netherlands)

    Steeneveld, G.J.

    2012-01-01

    Understanding and prediction of the stable atmospheric boundary layer is a challenging task. Many physical processes are relevant in the stable boundary layer, i.e. turbulence, radiation, land surface coupling, orographic turbulent and gravity wave drag, and land surface heterogeneity. The

  10. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    IAS Admin

    After Maynard-Smith and Price [1] mathematically derived why a given behaviour or strategy was adopted by a certain proportion of the population at a given time, it was shown that a strategy which is currently stable in a population need not be stable in evolutionary time (across generations). Additionally it was sug-.

  11. Tryptophan analogues. 1. Synthesis and antihypertensive activity of positional isomers.

    Science.gov (United States)

    Safdy, M E; Kurchacova, E; Schut, R N; Vidrio, H; Hong, E

    1982-06-01

    A series of tryptophan analogues having the carboxyl function at the beta-position was synthesized and tested for antihypertensive activity. The 5-methoxy analogue 46 exhibited antihypertensive activity in the rat via the oral route and was much more potent than the normal tryptophan analogue. The methyl ester was found to be a critical structural feature for activity.

  12. Upgrading of analogue gamma cameras with PC based computer system

    International Nuclear Information System (INIS)

    Fidler, V.; Prepadnik, M.

    2002-01-01

    Full text: Dedicated nuclear medicine computers for acquisition and processing of images from analogue gamma cameras in developing countries are in many cases faulty and technologically obsolete. The aim of the upgrading project of International Atomic Energy Agency (IAEA) was to support the development of the PC based computer system which would cost 5.000 $ in total. Several research institutions from different countries (China, Cuba, India and Slovenia) were financially supported in this development. The basic demands for the system were: one acquisition card an ISA bus, image resolution up to 256x256, SVGA graphics, low count loss at high count rates, standard acquisition and clinical protocols incorporated in PIP (Portable Image Processing), on-line energy and uniformity correction, graphic printing and networking. The most functionally stable acquisition system tested on several international workshops and university clinics was the Slovenian one with a complete set of acquisition and clinical protocols, transfer of scintigraphic data from acquisition card to PC through PORT, count loss less than 1 % at count rate of 120 kc/s, improvement of integral uniformity index by a factor of 3-5 times, reporting, networking and archiving solutions for simple MS network or server oriented network systems (NT server, etc). More than 300 gamma cameras in 52 countries were digitized and put in the routine work. The project of upgrading the analogue gamma cameras yielded a high promotion of nuclear medicine in the developing countries by replacing the old computer systems, improving the technological knowledge of end users on workshops and training courses and lowering the maintenance cost of the departments. (author)

  13. Functional and structural characteristics of anticancer peptide Pep27 analogues

    Directory of Open Access Journals (Sweden)

    Seo Youn-Kyung

    2005-07-01

    Full Text Available Abstract Background A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. Results Pep27anal2 characterized substituting (2R→W, (4E→W, (11S→W and (13Q→W in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC50 values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601. Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. Conclusion The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents.

  14. Somatostatin analogues for acute bleeding oesophageal varices

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C.; Hrobjartsson, A.

    2008-01-01

    BACKGROUND: Somatostatin and its derivatives are sometimes used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver. OBJECTIVES: To study whether somatostatin or its analogues improve survival or reduce the need for blood transfusions in patients...... with bleeding oesophageal varices. SEARCH STRATEGY: PubMed and The Cochrane Library were searched (November 2007). Reference lists of publications, contacts with authors. SELECTION CRITERIA: All randomised trials comparing somatostatin or analogues with placebo or no treatment in patients suspected of acute...... or recent bleeding from oesophageal varices. DATA COLLECTION AND ANALYSIS: The outcome measures extracted were: mortality, blood transfusions, use of balloon tamponade, initial haemostasis and rebleeding. Intention-to-treat analyses including all randomised patients were conducted if possible; a random...

  15. Studies of natural analogues and geological systems

    International Nuclear Information System (INIS)

    Brandberg, F.; Grundfelt, B.; Hoeglund, L.; Skagius K.; Karlsson, F.; Smellie, J.

    1993-04-01

    This review has involved studies of natural analogues and natural geological systems leading to the identification and quantification of processes and features of importance to the performance and safety of repositories for radioactive waste. The features and processes selected for the study comprise general geochemical issues related to the performance of the near- and far-field, the performance and durability of construction materials and the effects of glaciation. For each of these areas a number of potentially important processes for repository performance have been described, and evidence for their existence, as well as quantification of parameters of models describing the processes have been sought from major natural analogue studies and site investigations. The review has aimed at covering a relatively broad range of issues at the expense of in-depth analysis. The quantitative data presented are in most cases compilations of data from the literature; in a few cases results of evaluations made within the current project are included

  16. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...... Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process...

  17. Applications of stable isotopes

    International Nuclear Information System (INIS)

    Letolle, R.; Mariotti, A.; Bariac, T.

    1991-06-01

    This report reviews the historical background and the properties of stable isotopes, the methods used for their measurement (mass spectrometry and others), the present technics for isotope enrichment and separation, and at last the various present and foreseeable application (in nuclear energy, physical and chemical research, materials industry and research; tracing in industrial, medical and agronomical tests; the use of natural isotope variations for environmental studies, agronomy, natural resources appraising: water, minerals, energy). Some new possibilities in the use of stable isotope are offered. A last chapter gives the present state and forecast development of stable isotope uses in France and Europe

  18. The synthesis and pharmacology of ephedrine analogues

    OpenAIRE

    Mullen, Aidan J

    1991-01-01

    In this report we set out to extend recent studies on substituted PAC analogues produced by the fermentation of aromatic aldehydes with Saccharomyces cerevisiae. The medium selected contained glucose as a carbon source for the biotransformation, and sodium pyruvate as an inhibitor for alcohol dehydrogenase, the enzyme responsible for the conversion of the carbinol to a benzyl alcohol derivatives. An investigation of sodium cyanoborohydride for a selective reductive ami...

  19. Electromagnetic wave analogue of electronic diode

    OpenAIRE

    Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.; Fedotov, Vassili A.; Zheludev, Nikolay I.

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by ...

  20. Geometric Analogue of Holographic Reduced Representation

    OpenAIRE

    Aerts, Diederik; Czachor, Marek; De Moor, Bart

    2007-01-01

    Holographic reduced representations (HRR) are based on superpositions of convolution-bound $n$-tuples, but the $n$-tuples cannot be regarded as vectors since the formalism is basis dependent. This is why HRR cannot be associated with geometric structures. Replacing convolutions by geometric products one arrives at reduced representations analogous to HRR but interpretable in terms of geometry. Variable bindings occurring in both HRR and its geometric analogue mathematically correspond to two ...

  1. The Brookhaven electron analogue, 1953--1957

    International Nuclear Information System (INIS)

    Plotkin, M.

    1991-01-01

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary

  2. The Brookhaven electron analogue, 1953--1957

    Energy Technology Data Exchange (ETDEWEB)

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  3. Synthesis of D-nor steroid analogues

    Czech Academy of Sciences Publication Activity Database

    Slavíková, Barbora; Kudová, Eva

    2014-01-01

    Roč. 108, S2 (2014), s142 ISSN 0009-2770. [Conference on Isoprenoids /22./. 07.09.2014-10.09.2014, Praha] R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GAP303/12/1464 Institutional support: RVO:61388963 Keywords : D-nor steroid analogues * patch clamp technique Subject RIV: CC - Organic Chemistry

  4. Pharmacokinetics of lidocaine and bupivacaine and stable isotope labelled analogues : a study in healthy volunteers

    NARCIS (Netherlands)

    Burm, A.G.D.; de Boer, A G; van Kleef, J.W.; Vermeulen, N P; de Leede, L G; Spierdijk, J; Breimer, D D

    1988-01-01

    The pharmacokinetics of lidocaine and bupivacaine and tri-deuteromethyl-labelled lidocaine and bupivacaine were investigated in healthy volunteers. The deuterium-labelled and the unlabelled form of the drug to be investigated were simultaneously infused in 10 min. Plasma concentrations were

  5. New alloferon analogues: synthesis and antiviral properties.

    Science.gov (United States)

    Kuczer, Mariola; Majewska, Anna; Zahorska, Renata

    2013-02-01

    We have extended our study on structure/activity relationship studies of insect peptide alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) by evaluating the antiviral effects of new alloferon analogues. We synthesized 18 alloferon analogues: 12 peptides with sequences shortened from N- or C-terminus and 6 N-terminally modified analogues H-X(1)-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH, where X(1) = Phe (13), Tyr (14), Trp (15), Phg (16), Phe(p-Cl) (17), and Phe(p-OMe) (18). We found that most of the evaluated peptides inhibit the replication of Human Herpesviruses or Coxsackievirus B2 in Vero, HEp-2 and LLC-MK(2) cells. Our results indicate that the compound [3-13]-alloferon (1) exhibits the strongest antiviral activity (IC(50) = 38 μM) among the analyzed compound. Moreover, no cytotoxic activity against the investigated cell lines was observed for all studied peptides at concentration 165 μM or higher. © 2012 John Wiley & Sons A/S.

  6. Analysing Stable Time Series

    National Research Council Canada - National Science Library

    Adler, Robert

    1997-01-01

    We describe how to take a stable, ARMA, time series through the various stages of model identification, parameter estimation, and diagnostic checking, and accompany the discussion with a goodly number...

  7. Analogue to Digital and Digital to Analogue Converters (ADCs and DACs): A Review Update

    CERN Document Server

    Pickering, J.

    2015-06-15

    This is a review paper updated from that presented for CAS 2004. Essentially, since then, commercial components have continued to extend their performance boundaries but the basic building blocks and the techniques for choosing the best device and implementing it in a design have not changed. Analogue to digital and digital to analogue converters are crucial components in the continued drive to replace analogue circuitry with more controllable and less costly digital processing. This paper discusses the technologies available to perform in the likely measurement and control applications that arise within accelerators. It covers much of the terminology and 'specmanship' together with an application-oriented analysis of the realisable performance of the various types. Finally, some hints and warnings on system integration problems are given.

  8. Bioactivity of permselective PVA hydrogels with mixed ECM analogues.

    Science.gov (United States)

    Nafea, Eman H; Poole-Warren, Laura A; Martens, Penny J

    2015-12-01

    The presentation of multiple biological cues, which simulate the natural in vivo cell environment within artificial implants, has recently been identified as crucial for achieving complex cellular functions. The incorporation of two or more biological cues within a largely synthetic network can provide a simplified model of multifunctional ECM presentation to encapsulated cells. Therefore, the aim of this study was to examine the effects of simultaneously and covalently incorporating two dissimilar biological molecules, heparin and gelatin, within a PVA hydrogel. PVA was functionalized with 7 and 20 methacrylate functional groups per chain (FG/c) to tailor the permselectivity of UV photopolymerized hydrogels. Both heparin and gelatin were covalently incorporated into PVA at an equal ratio resulting in a final PVA:heparin:gelatin composition of 19:0.5:0.5. The combination of both heparin and gelatin within a PVA network has proven to be stable over time without compromising the PVA base characteristics including its permselectivity to different proteins. Most importantly, this combination of ECM analogues supplemented PVA with the dual functionalities of promoting cellular adhesion and sequestering growth factors essential for cellular proliferation. Multi-functional PVA hydrogels with synthetically controlled network characteristics and permselectivity show potential in various biomedical applications including artificial cell implants. © 2015 Wiley Periodicals, Inc.

  9. Calcium stable isotope geochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gausonne, Nikolaus [Muenster Univ. (Germany). Inst. fuer Mineralogie; Schmitt, Anne-Desiree [Strasbourg Univ. (France). LHyGeS/EOST; Heuser, Alexander [Bonn Univ. (Germany). Steinmann-Inst. fuer Geologie, Mineralogie und Palaeontologie; Wombacher, Frank [Koeln Univ. (Germany). Inst. fuer Geologie und Mineralogie; Dietzel, Martin [Technische Univ. Graz (Austria). Inst. fuer Angewandte Geowissenschaften; Tipper, Edward [Cambridge Univ. (United Kingdom). Dept. of Earth Sciences; Schiller, Martin [Copenhagen Univ. (Denmark). Natural History Museum of Denmark

    2016-08-01

    This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

  10. The Greenland analogue project. Yearly report 2010

    International Nuclear Information System (INIS)

    Harper, J.; Brinkerhoff, D.; Johnson, J.; Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I.

    2012-04-01

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  11. The Greenland analogue project. Yearly report 2010

    Energy Technology Data Exchange (ETDEWEB)

    Harper, J.; Brinkerhoff, D.; Johnson, J. [University of Montana, Missoula (United States); Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I. [Geological Survey of Finland (Finland)] [and others

    2012-04-15

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  12. Natural Analogues of CO2 Geological Storage

    International Nuclear Information System (INIS)

    Perez del Villar, L.; Pelayo, M.; Recreo, F.

    2007-01-01

    Geological storage of carbon dioxide is nowadays, internationally considered as the most effective method for greenhouse gas emission mitigation, in order to minimize the global climate change universally accepted. Nevertheless, the possible risks derived of this long-term storage have a direct influence on its public acceptance. Among the favourable geological formations to store CO2, depleted oil and gas fields, deep saline reservoirs, and unamiable coal seams are highlighted. One of the most important objectives of the R and D projects related to the CO2 geological storage is the evaluation of the CO2 leakage rate through the above mentioned geological formations. Therefore, it is absolutely necessary to increase our knowledge on the interaction among CO2, storage and sealing formations, as well as on the flow paths and the physical resistance of the sealing formation. The quantification of the CO2 leakage rate is essential to evaluate the effects on the human and animal health, as well as for the ecosystem and water quality. To achieve these objectives, the study of the natural analogues is very useful in order to know the natural leakage rate to the atmosphere, its flow paths, the physical, chemical and mineralogical modifications due to the long term interaction processes among the CO2 and the storage and sealing formations, as well as the effects on the groundwaters and ecosystems. In this report, we have tried to summarise the main characteristics of the natural reservoirs and surficial sources of CO2, which are both natural analogues of the geological storage and CO2 leakage, studied in EEUU, Europe and Australia. The main objective of this summary is to find the possible applications for long-term risk prediction and for the performance assessment by means of conceptual and numerical modelling, which will allow to validate the predictive models of the CO2 storage behaviour, to design and develop suitable monitoring techniques to control the CO2 behaviour

  13. Nuclear waste geochemistry: natural and anthropic analogues

    International Nuclear Information System (INIS)

    Petit, J.C.

    1997-01-01

    The geochemical evolution of nuclear waste storage is difficult to describe, due to the long time scales involved, the radioactivity confinement complexity and the un-natural radionuclides which evolution is not known. In order to carry out a long term prediction, a special approach is used, based on a combination of experiments conducted in laboratories and in situ, modelizations and comparisons with process and material analogues (natural or man-made, such as basaltic and rhyolitic volcanic glasses, plutonium, historical and archaeological artefacts)

  14. Somatostatin analogue scintigraphy in granulomatous diseases

    Energy Technology Data Exchange (ETDEWEB)

    Vanhagen, P.M. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands) Dept. of Immunology, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Krenning, E.P. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands) Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Reubi, J.C. (Inst. of Pathology, Bern Univ. (Switzerland)); Kwekkeboom, D.J. (Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Bakker, W.H. (Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Mulder, A.H. (Dept. of Pathology, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Laissue, I. (Inst. of Pathology, Bern Univ. (Switzerland)); Hoogstede, H.C. (Dept. of Chest Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Lamberts, S.W.J. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands))

    1994-06-01

    In the present study 20 consecutive patients were investigated, 12 with sarcoidosis, one with both sarcoidosis and aspergillosis, four with tuberculosis and three with Wegener's granulomatosis. For in vivo SS-R imaging, total-body scintigraphy was performed 24 and 48 h after the administration of [sup 111]In-octreotide. Granuloma localizations could be visualized in all patients studied; additional sites were found in nine patients with sarcoidosis and in two patients with tuberculosis. In vitro autoradiography of fresh tissue biopsies, using the SS analogue [[sup 125]I-Tyr[sup 3

  15. U.S. Nuclear Regulatory Commission natural analogue research program

    International Nuclear Information System (INIS)

    Kovach, L.A.; Ott, W.R.

    1995-01-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process

  16. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General ... Using some examples of classical games, we show how evolutionary game theory can help understand behavioural decisions of animals.

  17. The Stable Concordance Genus

    OpenAIRE

    Kearney, M. Kate

    2013-01-01

    The concordance genus of a knot is the least genus of any knot in its concordance class. Although difficult to compute, it is a useful invariant that highlights the distinction between the three-genus and four-genus. In this paper we define and discuss the stable concordance genus of a knot, which describes the behavior of the concordance genus under connected sum.

  18. Manifolds admitting stable forms

    Czech Academy of Sciences Publication Activity Database

    Le, Hong-Van; Panák, Martin; Vanžura, Jiří

    2008-01-01

    Roč. 49, č. 1 (2008), s. 101-11 ISSN 0010-2628 R&D Projects: GA ČR(CZ) GP201/05/P088 Institutional research plan: CEZ:AV0Z10190503 Keywords : stable forms * automorphism groups Subject RIV: BA - General Mathematics

  19. Stable isotope studies

    International Nuclear Information System (INIS)

    Ishida, T.

    1992-01-01

    The research has been in four general areas: (1) correlation of isotope effects with molecular forces and molecular structures, (2) correlation of zero-point energy and its isotope effects with molecular structure and molecular forces, (3) vapor pressure isotope effects, and (4) fractionation of stable isotopes. 73 refs, 38 figs, 29 tabs

  20. Interactive Stable Ray Tracing

    DEFF Research Database (Denmark)

    Dal Corso, Alessandro; Salvi, Marco; Kolb, Craig

    2017-01-01

    Interactive ray tracing applications running on commodity hardware can suffer from objectionable temporal artifacts due to a low sample count. We introduce stable ray tracing, a technique that improves temporal stability without the over-blurring and ghosting artifacts typical of temporal post-pr...

  1. The stable subgroup graph

    Directory of Open Access Journals (Sweden)

    Behnaz Tolue

    2018-07-01

    Full Text Available In this paper we introduce stable subgroup graph associated to the group $G$. It is a graph with vertex set all subgroups of $G$ and two distinct subgroups $H_1$ and $H_2$ are adjacent if $St_{G}(H_1\\cap H_2\

  2. Ways to Optimize Analogue Switched Circuits

    Directory of Open Access Journals (Sweden)

    J. Hospodka

    2008-12-01

    Full Text Available This paper describes how analogue switched circuits (switched-capacitor and switched-current circuits can be optimized by means of a personal computer. The optimization of this kind of circuits is not so common and their analysis is more difficult in comparison with continuously working circuits. Firstly, the nonidealities occurring in these circuits whose effect on their characteristics should be optimized are discussed. Then a few ways to analyze analogue switched circuits are shown. From all optimization algorithms applicable for this kind of optimization, two ones that seem to be the most promising are proposed. The differential evolution (one of evolutionary algorithms combined with the simplex method was found to be most appropriate from these two ones. Two types of programs are required for the optimization of these circuits: a program for implementing calculations of the used optimization algorithm and a program for the analysis of the optimized circuit. Several suitable computer programs from both of the groups together with their proper settings according to authors’ experience are proposed. At the end of the paper, an example of a switched-current circuit optimization documenting the previous description is presented.

  3. Andrographolide and analogues in cancer prevention.

    Science.gov (United States)

    Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

    2015-01-01

    Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

  4. Insulin degludec is a new ultra-long-acting insulin analogue

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-06-01

    Full Text Available Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba® is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

  5. Stabilised 111In-labelled DTPA- and DOTA-conjugated neurotensin analogues for imaging and therapy of exocrine pancreatic cancer

    International Nuclear Information System (INIS)

    Visser, M. de; Krenning, E.P.; Jong, M. de; Janssen, P.J.J.M.; Srinivasan, A.; Reubi, J.C.; Waser, B.; Erion, J.L.; Schmidt, M.A.

    2003-01-01

    Neurotensin (NT) receptors are overexpressed in exocrine pancreatic cancer and Ewing's sarcoma. The potential utility of native NT in cancer diagnosis and therapy is, however, limited by its rapid degradation in vivo. Therefore, NT analogues were synthesised with modified lysine and arginine derivatives to enhance stability and coupled either to DTPA, to enable high specific activity labelling with indium-111 for imaging, or to DOTA, to enable high specific activity labelling with β-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 C in human serum) and receptor binding affinity, the five most promising analogues were selected and further evaluated in in vitro internalisation studies in human colorectal adenocarcinoma HT29 cells, which overexpress NT receptors. All five NT analogues bound with high affinity to NT receptors on human exocrine pancreatic tumour sections. The analogues could be labelled with 111 In to a high specific activity. The 111 In-labelled compounds were found to be very stable in serum. Incubation of HT29 cells with the 111 In-labelled analogues at 37 C showed rapid receptor-mediated uptake and internalisation. The most promising analogue, peptide 2530 [DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH] was further tested in vivo in a biodistribution study using HT29 tumour-bearing nude mice. The results of this study showed low percentages of injected dose per gram tissue of this 111 In-labelled 2530 analogue in receptor-negative organs like blood, spleen, pancreas, liver, muscle and femur. Good uptake was found in the receptor-positive HT29 tumour and high uptake was present in the kidneys. Co-injection of excess unlabelled NT significantly reduced tumour uptake, showing that tumour uptake is a receptor-mediated process. With their enhanced stability, maintained high receptor affinity and rapid receptor-mediated internalisation, the 111 In-labelled DTPA- and DOTA-conjugated NT

  6. Embryotoxicity of stable isotopes and use of stable isotopes in studies of teratogenetic mechanisms

    International Nuclear Information System (INIS)

    Spielmann, H.; Nau, H.

    1986-01-01

    Experiments on teratogenic effects of stable isotopes from our own and other laboratories are evaluated. In the first series of investigations, the enrichment of the stable isotope 13 C derived from U- 13 C-glucose was studied in mouse embryos at various stages of development, including limb buds in organ culture. Preimplantation mouse embryos incubated in vitro in 13 C-enriched medium for 48 hours showed normal development during subsequent differentiation in vitro and also in vivo after embryo transfer to faster mothers. These embryos were 15% to 20% enriched in 13 C. Administration of U-13-C-glucose to pregnant mice during organogenesis led to an increase of the absolute 13 C content of the embryo for several days after the end of isotope administration, whereas the enrichment in maternal tissue decreased. No alterations of embryonic development were detected due to stable isotope enrichment. Development of cultured mouse limb buds was unaffected by incubation with 82 mol% U- 13 C-glucose as judged from morphologic and biochemical criteria. The second part of the article describes the value of deuterium-labeled drugs as probes into the mechanism of activation of teratogenic metabolites. A comparison of the pharmacokinetics as well as the teratogenicity between cyclophosphamide and some specific deuterium-labeled analogues showed that the isotope effect observed can be related to a particular metabolic pathway crucial for teratogenic activation by this drug

  7. Uptake and distribution of 137Cs, stable Cs and K in rice plants

    International Nuclear Information System (INIS)

    Tsukada, Hirofumi; Hasegawa, Hidenao

    2003-01-01

    The uptake and distributions of 137 Cs, stable Cs and K were determined for rice plant components, including polished rice, rice bran, hulls, leaves, stems, and roots. The distribution of 137 Cs in polished rice and rice bran was similar to that of stable Cs, while that of K was different. The concentration ratios of Cs/K in leaves increased in older leaf blade positions, which meant that the translocation rate of stable Cs, was slower than that of K. At harvest the dry weight of polished rice accounted for 34% of the entire rice plant, while the distributions of stable Cs in the polished rice and the non-edible parts were 7 and 93%, respectively. These findings suggest that the transfer and distribution of stable Cs in rice plants are different from those of K, and the behavior of stable Cs provides a useful analogue in predicting the fate of 137 Cs in an agricultural environment. (author)

  8. Space Analogue Environments: Are the Populations Comparable?

    Science.gov (United States)

    Sandal, G. M.

    Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that

  9. Stable isotope analysis

    International Nuclear Information System (INIS)

    Tibari, Elghali; Taous, Fouad; Marah, Hamid

    2014-01-01

    This report presents results related to stable isotopes analysis carried out at the CNESTEN DASTE in Rabat (Morocco), on behalf of Senegal. These analyzes cover 127 samples. These results demonstrate that Oxygen-18 and Deuterium in water analysis were performed by infrared Laser spectroscopy using a LGR / DLT-100 with Autosampler. Also, the results are expressed in δ values (‰) relative to V-SMOW to ± 0.3 ‰ for oxygen-18 and ± 1 ‰ for deuterium.

  10. Forensic Stable Isotope Biogeochemistry

    Science.gov (United States)

    Cerling, Thure E.; Barnette, Janet E.; Bowen, Gabriel J.; Chesson, Lesley A.; Ehleringer, James R.; Remien, Christopher H.; Shea, Patrick; Tipple, Brett J.; West, Jason B.

    2016-06-01

    Stable isotopes are being used for forensic science studies, with applications to both natural and manufactured products. In this review we discuss how scientific evidence can be used in the legal context and where the scientific progress of hypothesis revisions can be in tension with the legal expectations of widely used methods for measurements. Although this review is written in the context of US law, many of the considerations of scientific reproducibility and acceptance of relevant scientific data span other legal systems that might apply different legal principles and therefore reach different conclusions. Stable isotopes are used in legal situations for comparing samples for authenticity or evidentiary considerations, in understanding trade patterns of illegal materials, and in understanding the origins of unknown decedents. Isotope evidence is particularly useful when considered in the broad framework of physiochemical processes and in recognizing regional to global patterns found in many materials, including foods and food products, drugs, and humans. Stable isotopes considered in the larger spatial context add an important dimension to forensic science.

  11. Jupiter analogues and planets of active stars

    Directory of Open Access Journals (Sweden)

    Henning T.

    2013-04-01

    Full Text Available Combined results are now available from a 15 year long search for Jupiter analogues around solar-type stars using the ESO CAT + CES, ESO 3.6 m + CES, and ESO 3.6 m + HARPS instruments. They comprise planet (co-discoveries (ι Hor and HR 506 and confirmations (three planets in HR 3259 as well as non-confirmations of planets (HR 4523 and ɛ Eri announced elsewhere. A long-term trend in ɛ Ind found by our survey is probably attributable to a Jovian planet with a period >30 yr, but we cannot fully exclude stellar activity effects as the cause. A 3.8 year periodic variation in HR 8323 can be attributed to stellar activity.

  12. The gravitational analogue of the Witten effect

    International Nuclear Information System (INIS)

    Foda, O.

    1984-06-01

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP-violation, the Witten effect [a shift in the electric charge of a magnetic monopole due to CP-non-conservation] is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a theta R-tilde R term in the Lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed. (author)

  13. Gravitational analogue of the Witten effect

    Energy Technology Data Exchange (ETDEWEB)

    Foda, O. (International Centre for Theoretical Physics, Trieste (Italy))

    1985-07-22

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP violation, the Witten effect (a shift in the electric charge of a magnetic monopole due to CP non-conservation) is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a thetaR tildeR term in the lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed.

  14. The gravitational analogue of the Witten effect

    International Nuclear Information System (INIS)

    Foda, O.

    1985-01-01

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP violation, the Witten effect (a shift in the electric charge of a magnetic monopole due to CP non-conservation) is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a thetaR tildeR term in the lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed. (orig.)

  15. Reflective analogue optical link operating issues

    CERN Document Server

    Batten, Jeremy

    1996-01-01

    The proposed readout of analogue data from CMS tracker will use an optical fibre link. The choice of transmitter/receiver technology, however, has been the subject of intense research and development by the RD23 collaboration. One solution uses passive devices, multi-quantum well modulators, at the detector front end, and continuous wave driving lasers at the readout back end. This system has been tested at Imperial College. We report on the following: problems of noise associated with multimoded behaviour of a degraded laser; measurements of laser wavelength dependence on both drive current and temperature; and modulator reflectance dependence on laser wavelength. We extrapolate the findings to system issues, highlighting the degree of temperature control required of the driving laser.

  16. The glaciogenic reservoir analogue studies project (GRASP)

    DEFF Research Database (Denmark)

    Moscariello, A.; Moreau, Julien; Vegt, P. van der

    increasing the risk associated with developing effectively these reservoirs. Therefore a analogue-based predictive stratigraphical and sedimentological model can help to steer drilling strategy and reduce uncertainties and associated risks. For this purpose the GRASP joint industry programme was established......Tunnel galleys are common features in Palaeozoic glacigenic succession in North Afrcica and Middle East and they are amongst the most challenging target for hydrocarbon exploration and developing drilling in these regions. Similarly, these buried valleys form important groundwater reservoirs...... in Quaternary glaciated areas and their nature and sediment composition is critical to drive a sustainable production strategy and assess their vulnerability. Seismic resolution however, often limits the understanding of channel valleys morphology, 3D geometry and internal reservoir distribution, thus...

  17. Synthesis of an Orthogonal Topological Analogue of Helicene

    DEFF Research Database (Denmark)

    Wixe, Torbjörn; Wallentin, Carl‐Johan; Johnson, Magnus T.

    2013-01-01

    The synthesis of an orthogonal topological pentamer analogue of helicene is presented. This analogue forms a tubular structure with its aromatic systems directed parallel to the axis of propagation, which creates a cavity with the potential to function as a host molecule. The synthetic strategy...

  18. Caged ceramide 1-phosphate analogues: synthesis and properties.

    Science.gov (United States)

    Lankalapalli, Ravi S; Ouro, Alberto; Arana, Lide; Gómez-Muñoz, Antonio; Bittman, Robert

    2009-11-20

    Sphingolipid phosphate analogues bearing 7-(diethylamino)coumarin (DECM) and 4-bromo-5-hydroxy-2-nitrobenzhydryl (BHNB) groups in a photolabile ester bond were synthesized. The ability of the "caged" ceramide 1-phosphate analogues to release the bioactive parent molecule upon irradiation at 400-500 nm was demonstrated by stimulation of macrophage cell proliferation.

  19. Automated Layout Generation of Analogue and Mixed-Signal ASIC's

    DEFF Research Database (Denmark)

    Bloch, Rene

    The research and development carried out in this Ph.D. study focusses on two key areas of the design flow for analogue and mixed-signal integrated circuit design, the mixed-signal floorplanning and the analogue layout generation.A novel approach to floorplanning is presented which provides true i...

  20. Uncertainties and credibility building of safety analyses. Natural analogues

    International Nuclear Information System (INIS)

    Laciok, A.

    2001-07-01

    The substance of natural analogues and their studies is defined as a complementary method to laboratory and in-situ experiments and modelling. The role of natural analogues in the processes of development of repositories is defined, mainly in performance assessment of repository system and communication with public. The criteria for identification of natural analogues which should be evaluated in the phase of initiation of new studies are specified. Review part of this report is divided to study of natural analogues and study of anthropogenic and industrial analogues. The main natural analogue studies performed in various countries, in different geological setting, with various aims are characterized. New results acquired in recently finished studies are included: Palmottu (2nd phase of project financed by European Commission), Oklo (results of research financed also by European Commission), Maqarin (3rd phase) and other information obtained from last meetings and workshops of NAWG. In view of the fact that programmes of development of deep repositories in Czech and Slovak Republics are interconnected, the natural analogues studies carried out in the Czech republic are incorporated in separate chapter - study of uranium accumulation in Tertiary clays at Ruprechtov site and study of degradation of natural glasses. In final part the areas of natural analogue studies as an integral part of development of deep geological repository are proposed along with characterization of broader context and aspects of realization of these studies (international cooperation, preparation and evaluation of procedures, communication with public). (author)

  1. Insulin analogues and severe hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Kristensen, P L; Hansen, L S; Jespersen, M J

    2012-01-01

    The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed...

  2. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg University (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Institute, Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  3. Natural analogues of nuclear waste glass corrosion

    International Nuclear Information System (INIS)

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-01

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses

  4. Natural analogues of nuclear waste glass corrosion.

    Energy Technology Data Exchange (ETDEWEB)

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-06

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

  5. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg Univ. (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Inst., Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  6. Magnetic properties of Proxima Centauri b analogues

    Science.gov (United States)

    Zuluaga, Jorge I.; Bustamante, Sebastian

    2018-03-01

    The discovery of a planet around the closest star to our Sun, Proxima Centauri, represents a quantum leap in the testability of exoplanetary models. Unlike any other discovered exoplanet, models of Proxima b could be contrasted against near future telescopic observations and far future in-situ measurements. In this paper we aim at predicting the planetary radius and the magnetic properties (dynamo lifetime and magnetic dipole moment) of Proxima b analogues (solid planets with masses of ∼ 1 - 3M⊕ , rotation periods of several days and habitable conditions). For this purpose we build a grid of planetary models with a wide range of compositions and masses. For each point in the grid we run the planetary evolution model developed in Zuluaga et al. (2013). Our model assumes small orbital eccentricity, negligible tidal heating and earth-like radiogenic mantle elements abundances. We devise a statistical methodology to estimate the posterior distribution of the desired planetary properties assuming simple lprior distributions for the orbital inclination and bulk composition. Our model predicts that Proxima b would have a mass 1.3 ≤Mp ≤ 2.3M⊕ and a radius Rp =1.4-0.2+0.3R⊕ . In our simulations, most Proxima b analogues develop intrinsic dynamos that last for ≥4 Gyr (the estimated age of the host star). If alive, the dynamo of Proxima b have a dipole moment ℳdip >0.32÷2.9×2.3ℳdip , ⊕ . These results are not restricted to Proxima b but they also apply to earth-like planets having similar observed properties.

  7. MAQARIN natural analogue study: phase III

    International Nuclear Information System (INIS)

    Alexander, W.R.; Mazurek, M.; Waber, H.N.; Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K.; Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J.; Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J.; Clark, I.D.; Karlsson, F.; Khoury, H.N.; Salameh, E.; Lagerblad, B.; Longworth, G.; Savage, D.; Smellie, J.A.T.

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH) 2 type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the 'alkali disturbed zone' of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  8. Properties of the single Jovian planet population and the pursuit of Solar system analogues

    Science.gov (United States)

    Agnew, Matthew T.; Maddison, Sarah T.; Horner, Jonathan

    2018-04-01

    While the number of exoplanets discovered continues to increase at a rapid rate, we are still to discover any system that truly resembles the Solar system. Existing and near future surveys will likely continue this trend of rapid discovery. To see if these systems are Solar system analogues, we will need to efficiently allocate resources to carry out intensive follow-up observations. We seek to uncover the properties and trends across systems that indicate how much of the habitable zone is stable in each system to provide focus for planet hunters. We study the dynamics of all known single Jovian planetary systems, to assess the dynamical stability of the habitable zone around their host stars. We perform a suite of simulations of all systems where the Jovian planet will interact gravitationally with the habitable zone, and broadly classify these systems. Besides the system's mass ratio (Mpl/Mstar), and the Jovian planet's semi-major axis (apl) and eccentricity (epl), we find that there are no underlying system properties which are observable that indicate the potential for planets to survive within the system's habitable zone. We use Mpl/Mstar, apl and epl to generate a parameter space over which the unstable systems cluster, thus allowing us to predict which systems to exclude from future observational or numerical searches for habitable exoplanets. We also provide a candidate list of 20 systems that have completely stable habitable zones and Jovian planets orbiting beyond the habitable zone as potential first order Solar system analogues.

  9. Analogue Hawking radiation from astrophysical black-hole accretion

    International Nuclear Information System (INIS)

    Das, Tapas K

    2004-01-01

    We show that spherical accretion onto astrophysical black holes can be considered as a natural example of an analogue system. We provide, for the first time, an exact analytical scheme for calculating the analogue Hawking temperature and surface gravity for general relativistic accretion onto astrophysical black holes. Our calculation may bridge the gap between the theory of transonic astrophysical accretion and the theory of analogue Hawking radiation. We show that the domination of the analogue Hawking temperature over the actual Hawking temperature may be a real astrophysical phenomenon, though observational tests of this fact will at best be difficult and at worst might prove to be impossible. We also discuss the possibilities of the emergence of analogue white holes around astrophysical black holes. Our calculation is general enough to accommodate accreting black holes with any mass

  10. Analogue to Digital and Digital to Analogue (AD/DA) Conversion Techniques: An Overview

    CERN Multimedia

    CERN. Geneva

    2002-01-01

    The basic ideas behind modern Analogue to Digital and Digital to Analogue (AD/DA) conversion methods will be introduced: a general view of the importance of these devices will be given, along with the digital representation of time-varying, real-world analogue signals. Some CERN applications will be outlined. The variety of conversion methods, their limitations, error sources and measurement methods will form the major part of this presentation. A review of the technological progress in this field over the last 30 years will be presented, concluding with the present 'state of the art' and a quick look at what is just around the corner. This Technical Training Seminar is in the framework of the FEED-2002 Lecture Series, and it is a prerequisite to attending to any of the FEED-2002 Terms. FEED-2002 is a two-term course that will review the techniques dealing with closed loop systems, focussing on time-invariant linear systems. (free attendance, no registration required) More information on the FEED-2002 ...

  11. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    Science.gov (United States)

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  12. Stream food web response to a salmon carcass analogue addition in two central Idaho, U.S.A. streams

    Science.gov (United States)

    KOHLER, ANDRE E; RUGENSKI, AMANDA; TAKI, DOUG

    2008-01-01

    Pacific salmon and steelhead once contributed large amounts of marine-derived carbon, nitrogen and phosphorus to freshwater ecosystems in the Pacific Northwest of the United States of America (California, Oregon, Washington and Idaho). Declines in historically abundant anadromous salmonid populations represent a significant loss of returning nutrients across a large spatial scale. Recently, a manufactured salmon carcass analogue was developed and tested as a safe and effective method of delivering nutrients to freshwater and linked riparian ecosystems where marine-derived nutrients have been reduced or eliminated. We compared four streams: two reference and two treatment streams using salmon carcass analogue(s) (SCA) as a treatment. Response variables measured included: surface streamwater chemistry; nutrient limitation status; carbon and nitrogen stable isotopes; periphyton chlorophyll a and ash-free dry mass (AFDM); macroinvertebrate density and biomass; and leaf litter decomposition rates. Within each stream, upstream reference and downstream treatment reaches were sampled 1 year before, during, and 1 year after the addition of SCA. Periphyton chlorophyll a and AFDM and macroinvertebrate biomass were significantly higher in stream reaches treated with SCA. Enriched stable isotope (δ15N) signatures were observed in periphyton and macroinvertebrate samples collected from treatment reaches in both treatment streams, indicating trophic transfer from SCA to consumers. Densities of Ephemerellidae, Elmidae and Brachycentridae were significantly higher in treatment reaches. Macroinvertebrate community composition and structure, as measured by taxonomic richness and diversity, did not appear to respond significantly to SCA treatment. Leaf breakdown rates were variable among treatment streams: significantly higher in one stream treatment reach but not the other. Salmon carcass analogue treatments had no detectable effect on measured water chemistry variables. Our results

  13. Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties.

    Science.gov (United States)

    O'Harte, Finbarr P M; Parthsarathy, Vadivel; Hogg, Christopher; Flatt, Peter R

    2017-12-15

    The adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, (Lys 8 GluPAL)apelin-13 amide, pGlu(Lys 8 GluPAL)apelin-13 amide, Lys 8 GluPAL(Tyr 13 )apelin-13 and Lys 8 GluPAL(Val 13 )apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro. pGlu(Lys 8 GluPAL)apelin-13 amide was the most potent insulinotropic analogue in BRIN-BD11 cells and isolated islets with maximal stimulatory effects of up to 2.7-fold (p glucose uptake in 3T3-L1 adipocytes (2.3-fold, p glucose (39-43%, p glucose tolerance tests in diet-induced obese mice. pGlu(Lys 8 GluPAL)apelin-13 amide and (Lys 8 GluPAL)apelin-13 amide also inhibited feeding (28-40%, p < .001), whereas Lys 8 GluPAL(Val 13 )apelin-13 increased food intake (8%, p < .05) in mice. These data indicate that novel enzymatically stable analogues of apelin-13 may be suitable for future development as therapeutic agents for obesity-diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The Greenland Analogue Project. Yearly Report 2009

    International Nuclear Information System (INIS)

    2010-12-01

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

  15. The Greenland Analogue Project. Yearly Report 2009

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

  16. Marginally Stable Nuclear Burning

    Science.gov (United States)

    Strohmayer, Tod E.; Altamirano, D.

    2012-01-01

    Thermonuclear X-ray bursts result from unstable nuclear burning of the material accreted on neutron stars in some low mass X-ray binaries (LMXBs). Theory predicts that close to the boundary of stability oscillatory burning can occur. This marginally stable regime has so far been identified in only a small number of sources. We present Rossi X-ray Timing Explorer (RXTE) observations of the bursting, high- inclination LMXB 4U 1323-619 that reveal for the first time in this source the signature of marginally stable burning. The source was observed during two successive RXTE orbits for approximately 5 ksec beginning at 10:14:01 UTC on March 28, 2011. Significant mHz quasi- periodic oscillations (QPO) at a frequency of 8.1 mHz are detected for approximately 1600 s from the beginning of the observation until the occurrence of a thermonuclear X-ray burst at 10:42:22 UTC. The mHz oscillations are not detected following the X-ray burst. The average fractional rms amplitude of the mHz QPOs is 6.4% (3 - 20 keV), and the amplitude increases to about 8% below 10 keV.This phenomenology is strikingly similar to that seen in the LMXB 4U 1636-53. Indeed, the frequency of the mHz QPOs in 4U 1323-619 prior to the X-ray burst is very similar to the transition frequency between mHz QPO and bursts found in 4U 1636-53 by Altamirano et al. (2008). These results strongly suggest that the observed QPOs in 4U 1323-619 are, like those in 4U 1636-53, due to marginally stable nuclear burning. We also explore the dependence of the energy spectrum on the oscillation phase, and we place the present observations within the context of the spectral evolution of the accretion-powered flux from the source.

  17. UK Natural Analogue Coordinating Group: fourth annual report

    International Nuclear Information System (INIS)

    Read, D.; Hooker, P.J.

    1992-01-01

    HMIP has a research programme investigating some naturally radioactive sites as geochemical analogues of radionuclide migration. All of the analogue sites under investigation, both in the U.K. and overseas, are located where elevated uranium concentrations occur naturally. Coordination of the programme is achieved through the UK Natural Analogue Co-ordinating Group (NACG) which has met three times in this reporting period. The NACG is steered by the British Geological Survey. Its purpose is to ensure that the different research projects have an integrated function aimed at increasing our understanding of natural geochemical processes. Effort is also being expended in testing research models which may be used in such assessments. (author)

  18. A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

    Directory of Open Access Journals (Sweden)

    Arno Verlee

    2017-02-01

    Full Text Available For the synthesis of m-sulfamoylbenzamide analogues, small molecules which are known for their bioactivity, a chemoselective procedure has been developed starting from m-(chlorosulfonylbenzoyl chloride. Although a chemoselective process in batch was already reported, a continuous-flow process reveals an increased selectivity at higher temperatures and without catalysts. In total, 15 analogues were synthesized, using similar conditions, with yields ranging between 65 and 99%. This is the first automated and chemoselective synthesis of m-sulfamoylbenzamide analogues.

  19. A Low-cost Multi-channel Analogue Signal Generator

    CERN Document Server

    Müller, F; The ATLAS collaboration; Shen, W; Stamen, R

    2009-01-01

    A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The signal generator was successfully used as independent test bed for the ATLAS Level-1 Trigger Pre-Processor, providing up to 16 analogue signals.

  20. Long-term predictions using natural analogues

    International Nuclear Information System (INIS)

    Ewing, R.C.

    1995-01-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10 3 -10 5 years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., open-quotes natural analoguesclose quotes) provide perhaps the only means of partial open-quotes validation,close quotes as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10 3 -10 8 years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the open-quotes validationclose quotes of performance assessments

  1. Adjuvants based on synthetic mycobacterial cord factor analogues: Biophysical properties of neat glycolipids and nano-self-assemblies with DDA

    DEFF Research Database (Denmark)

    Kallerup, Rie Selchau; Franzyk, Henrik; Schiøth, Mikkel Lohmann

    2017-01-01

    Synthetic mycobacterial cord factor analogues, e.g., trehalose 6,6'-dibehenate (TDB), are highly promising adjuvants due to their strong immunopotentiating capabilities, but their biophysical properties have remained poorly characterized. Here, we report the synthesis of an array of synthetic TDB...... and the acyl chains (PEG-TDS). All dispersions were liposomes, but in contrast to the colloidally stable and highly cationic TDX-containing liposomes, the zeta-potential was significantly reduced for DDA/TMX and DDA/PEG-TDS liposomes, suggesting a charge-shielding effect, which compromises the colloidal...... stability. An increased d-spacing was observed for the lamellar phase of neat TDB analogues in excess buffer (TDShighly cooperative...

  2. Adjuvants Based on Synthetic Mycobacterial Cord Factor Analogues: Biophysical Properties of Neat Glycolipids and Nanoself-Assemblies with DDA.

    Science.gov (United States)

    Kallerup, Rie S; Franzyk, Henrik; Schiøth, Mikkel L; Justesen, Sarah; Martin-Bertelsen, Birte; Rose, Fabrice; Madsen, Cecilie M; Christensen, Dennis; Korsholm, Karen S; Yaghmur, Anan; Foged, Camilla

    2017-07-03

    Synthetic mycobacterial cord factor analogues, e.g., trehalose 6,6'-dibehenate (TDB), are highly promising adjuvants due to their strong immunopotentiating capabilities, but their biophysical properties have remained poorly characterized. Here, we report the synthesis of an array of synthetic TDB analogues varying in acyl chain length, degree of acylation, and headgroup display, which was subjected to biophysical characterization of neat nondispersed self-assembled nanostructures in excess buffer and as aqueous dispersions with cationic dimethyldioctadecylammonium (DDA) bromide. The array comprised trehalose mono- (TMX) and diester (TDX) analogues with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), myristate (Myr), and laurate (L)] and an analogue with a short hydrophilic polyethylene glycol (PEG) linker inserted between the trehalose headgroup of TDS and the acyl chains (PEG-TDS). All dispersions were liposomes, but in contrast to the colloidally stable and highly cationic TDX-containing liposomes, the zeta-potential was significantly reduced for DDA/TMX and DDA/PEG-TDS liposomes, suggesting a charge-shielding effect, which compromises the colloidal stability. An increased d-spacing was observed for the lamellar phase of neat TDB analogues in excess buffer (TDS < TMS < PEG-TDS), confirming that the charge shielding is caused by an extended molecular configuration of the more flexible headgroup. Differential scanning calorimetry showed highly cooperative phase transitions for all tested dispersions albeit the monoesters destabilized the lipid bilayers. Langmuir experiments demonstrated that incorporation of TDXs and PEG-TDS stabilized DDA monolayers due to improved hydrogen bonding and reduced intermolecular repulsions. In conclusion, data suggest that the DDA/TDS dispersions exhibit favorable physicochemical properties rendering these DDA/TDS liposomes an attractive vaccine adjuvant, and they emphasize that not only

  3. Solistatinol, a novel phenolic compactin analogue from Penicillium solitum

    DEFF Research Database (Denmark)

    Larsen, Thomas Ostenfeld; Lange, Lene; Schnorr, Kirk

    2007-01-01

    Solistatinol, a novel phenolic compactin analogue, has been isolated from Penicillium solitum using a UV-guided strategy. The structure and relative stereochemistry were determined by NMR spectroscopy and mass spectrometry. The absolute stereochemistry was determined by chemical degradation...

  4. Heterocyclic Analogues of Modafinil as Novel, Atypical Dopamine Transporter Inhibitors.

    Science.gov (United States)

    Kalaba, Predrag; Aher, Nilima Y; Ilić, Marija; Dragačević, Vladimir; Wieder, Marcus; Miklosi, Andras G; Zehl, Martin; Wackerlig, Judith; Roller, Alexander; Beryozkina, Tetyana; Radoman, Bojana; Saroja, Sivaprakasam R; Lindner, Wolfgang; Gonzalez, Eduardo Perez; Bakulev, Vasiliy; Leban, Johann Jakob; Sitte, Harald H; Urban, Ernst; Langer, Thierry; Lubec, Gert

    2017-11-22

    Modafinil is a wake promoting compound with high potential for cognitive enhancement. It is targeting the dopamine transporter (DAT) with moderate selectivity, thereby leading to reuptake inhibition and increased dopamine levels in the synaptic cleft. A series of modafinil analogues have been reported so far, but more target-specific analogues remain to be discovered. It was the aim of this study to synthesize and characterize such analogues and, indeed, a series of compounds were showing higher activities on the DAT and a higher selectivity toward DAT versus serotonin and norepinephrine transporters than modafinil. This was achieved by substituting the amide moiety by five- and six-membered aromatic heterocycles. In vitro studies indicated binding to the cocaine pocket on DAT, although molecular dynamics revealed binding different from that of cocaine. Moreover, no release of dopamine was observed, ruling out amphetamine-like effects. The absence of neurotoxicity of a representative analogue may encourage further preclinical studies of the above-mentioned compounds.

  5. Trustworthiness and Influence: A Reexamination in an Extended Counseling Analogue.

    Science.gov (United States)

    Rothmeier, Rosemarie C.; Dixon, David N.

    1980-01-01

    The study demonstrated that: (1) interviewer trustworthiness can be manipulated in an analogue interview setting; and (2) interviewer trustworthiness is related to interpersonal influence in the interview setting. Findings follow a pattern of outcomes predicted by cognitive dissonance theory. (Author)

  6. Synthesis and antifungal activity of two novel spermidine analogues.

    Science.gov (United States)

    Mackintosh, C A; Slater, L A; McClintock, C A; Walters, D R; Havis, N D; Robins, D J

    1997-03-01

    Two spermidine analogues were synthesised and examined for antifungal activity. Both compounds used as 1 mM post-inoculation sprays reduced infection of barley seedlings by the powdery mildew fungus, Erysiphe graminis f.sp. hordei, infection of broad bean seedlings by the rust fungus, Uromyces viciae-fabae, and infection of apple seedlings by the powdery mildew fungus, Podosphaera leucotricha. Since these fungal pathogens cannot be cultured axenically, the effects of the two spermidine analogues on mycelial growth in vitro, as well as preliminary investigations on polyamine biosynthesis, were undertaken using the oat stripe pathogen, Pyrenophora avenae. Although neither compound affected radial growth of the fungus on plates, both analogues reduced fungal biomass in liquid culture substantially. The two spermidine analogues, used at a concentration of 1 mM, had no significant effect on the conversion of labelled ornithine into polyamines in P. avenae.

  7. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa

    2016-01-01

    women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we...... included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate...... was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference...

  8. Analogue Signal Processing: Collected Papers 1996-97

    DEFF Research Database (Denmark)

    1997-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997....

  9. 3-alkyl fentanyl analogues: Structure-activity-relationship study

    OpenAIRE

    Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

    2012-01-01

    Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

  10. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

  11. The Greenland Analogue Project, Yearly Report 2009

    International Nuclear Information System (INIS)

    2011-08-01

    To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a realistic understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. The project includes three sub-projects (A-C) with specific individual objectives, which collectively aim at contributing knowledge and input to the overall project aim. Three field campaigns were carried out in SPA during 2009. These campaigns focused on: (1) deployment and maintenance of AWS and GPS stations and to test the deep-look radar equipment; (2) investigating the hydrological processes and feedbacks and testing of passive seismic equipment; (3) downloading of weather station data and GPS data and winterizing the equipment. An extensive archive of real-time satellite remote sensing datasets has been obtained to be able to better constraint the surface elevation and dynamics of basal hydrological mechanisms. From this archive it has been possible to obtain Russell Glacier Cachment (RGC)-wide constraints on annual, seasonal and specific temporal snapshots of surface speed, initial lake and moulin distribution, drainage and network connections along with the temporal

  12. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    Science.gov (United States)

    Foing, Bernard

    2014-05-01

    We performed a series of field research campaigns (ILEWG EuroMoonMars) in the extreme Utah desert relevant to Mars environments, and in order to help in the interpretation of Mars missions measurements from orbit (MEX, MRO) or from the surface (MER, MSL), or Moon geochemistry (SMART-1, LRO). We shall give an update on the sample analysis in the context of habitability and astrobiology. Methods & Results: In the frame of ILEWG EuroMoonMars campaigns (2009 to 2013) we deployed at Mars Desert Research station, near Hanksville Utah, a suite of instruments and techniques [A, 1, 2, 9-11] including sample collection, context imaging from remote to local and microscale, drilling, spectrometers and life sensors. We analyzed how geological and geochemical evolution affected local parameters (mineralogy, organics content, environment variations) and the habitability and signature of organics and biota. Among the important findings are the diversity in the composition of soil samples even when collected in close proximity, the low abundances of detectable PAHs and amino acids and the presence of biota of all three domains of life with significant heterogeneity. An extraordinary variety of putative extremophiles was observed [3,4,9]. A dominant factor seems to be soil porosity and lower clay-sized particle content [6-8]. A protocol was developed for sterile sampling, contamination issues, and the diagnostics of biodiversity via PCR and DGGE analysis in soils and rocks samples [10, 11]. We compare the 2009 campaign results [1-9] to new measurements from 2010-2013 campaigns [10-12] relevant to: comparison between remote sensing and in-situ measurements; the study of minerals; the detection of organics and signs of life. Keywords: field analogue research, astrobiology, habitability, life detection, Earth-Moon-Mars, organics References [A] Foing, Stoker & Ehrenfreund (Editors, 2011) "Astrobiology field Research in Moon/Mars Analogue Environments", Special Issue of International

  13. Application of natural analogues in the Yucca Mountain project - overview

    International Nuclear Information System (INIS)

    Simmons, Ardyth M.

    2003-01-01

    The Natural Analogue Synthesis Report (NASR) [1] provides a compilation of information from analogues that test, corroborate, and add confidence to process models and model predictions pertinent to total system performance assessment (TSPA). The report updated previous work [2] with new literature examples and results of quantitative studies conducted by the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate greater understanding of processes expected to occur during postclosure of a proposed Yucca Mountain repository. Natural analogues, as used here, refer to either natural or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have occurred over long time periods (decades to millenia) and large spatial scales (up to tens of kilometers). In the past, the YMP has used analogues for testing and building confidence in conceptual and numerical process models in a number of ways. Yucca Mountain mineral alteration phases provided a self-analogue for postclosure alteration [3]. Thermodynamic parameters for silica minerals of the Wairakai, New Zealand geothermal field were added to databases used in geochemical modeling [4]. Scoping calculations of radionuclide transport using the Yucca Mountain TSPA numerical model were conducted for the Peqa Blanca site [5]. Eruption parameters from the Cerro Negro volcano, Nicaragua, were used to verify codes that model ash plume dispersion [6]. Analogues have also been used in supplemental science and performance analyses to provide multiple lines of evidence in support of both analyses and model reports (AMRs) [7]; in screening arguments for inclusion or exclusion of features, events, and processes (FEP)s in TSPAs; in the quantification of uncertainties [7]; in expert elicitations of volcanic and seismic hazards [8, 9] and in peer reviews [10]. Natural analogues may be applied

  14. Characterisation of insulin analogues therapeutically available to patients

    KAUST Repository

    Adams, Gary G.

    2018-03-29

    The structure and function of clinical dosage insulin and its analogues were assessed. This included \\'native insulins\\' (human recombinant, bovine, porcine), \\'fast-acting analogues\\' (aspart, glulisine, lispro) and \\'slow-acting analogues\\' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

  15. N-fluoroalkylated and N-alkylated analogues of the dopaminergic D-2 receptor antagonist raclopride

    International Nuclear Information System (INIS)

    Lannoye, G.S.; Moerlein, S.M.; Parkinson, D.; Welch, M.J.

    1990-01-01

    A series of raclopride [(S)-2-[(3,5-dichloro-6-methoxy-2- hydroxybenzamido)methyl]-1-ethylpyrrolidine] derivatives bearing pyrrolidino N-fluoroalkyl or -alkyl substituents were synthesized and evaluated as potential dopaminergic receptor-based positron tomography radiopharmaceuticals. Radiosynthetic procedures for producing the corresponding N-[18F]fluoroalkylated analogues of raclopride from 18F- (beta+, t1/2 = 110 min) in high specific activity were also developed. In vitro binding assays using competitive displacement of [3H]spiperone from primate caudate tissue indicated that the N-alkylated analogues of raclopride had Ki values of 5-40 nM, whereas the corresponding values for analogous N-fluoroalkylated derivatives ranged from 90-160 nM. The relatively low D-2 binding affinity of these fluorinated salicylamides was corroborated by in vivo tissue biodistribution results in rodents. On the basis of structure-binding correlations, the impact of intramolecular hydrogen bonding, ligand basicity, and steric bulk on the affinity of the benzamides for D-2 receptor binding are discussed. Strategies are presented for the development of alternative fluorinated salicylamides that are both receptor active and metabolically stable

  16. Dynamical attraction to stable processes

    OpenAIRE

    Fisher, Albert M.; Talet, Marina

    2012-01-01

    We apply dynamical ideas within probability theory, proving an almost-sure invariance principle in log density for stable processes. The familiar scaling property (self-similarity) of the stable process has a stronger expression, that the scaling flow on Skorokhod path space is a Bernoulli flow. We prove that typical paths of a random walk with i.i.d. increments in the domain of attraction of a stable law can be paired with paths of a stable process so that, after applying a non-random regula...

  17. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Science.gov (United States)

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin.

  18. Insulin analogues and cancer: a note of caution

    Directory of Open Access Journals (Sweden)

    Joseph A.M.J.L. eJanssen

    2014-05-01

    Full Text Available Abstract In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogues are safe. In line with these findings, we observed that serum of diabetic patients treated with insulin analogues, compared to that of diabetic patients treated with human insulin, did not induce an increased phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor (IGF-IR. However, the classical model of the IGF-IR signaling may be insufficient to explain (all mitogenic effects of insulin analogues since also non-canonical signaling pathways of the IGF-IR may play a major role in this respect. Although phosphorylation of tyrosine residues of the IGF-IR is generally considered to be the initial activation step within the intracellular IGF-IR signaling pathway, it has been found that cells undergo a signaling switch under hyperglycemic conditions. After this switch, a completely different mechanism is utilized to activate the mitogenic (mitogen-activated protein kinase (MAPK pathways of the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At present it is unknown whether activation of this alternative intracellular pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is stronger in patients treated with (some insulin analogues than in patients treated with human insulin. In addition, it is unknown whether the insulin receptors (IRs also undergo a signaling switch during hyperglycemia. This should be investigated in future studies. Finally, relative overexpression of IR isoform A (IR-A in (pre cancer tissues may play a key role in the development and progression of human cancers during treatment with insulin (analogues. Further

  19. A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Dancey, J; Astrup, L

    2003-01-01

    Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits...... growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year (with possible extension for responders......). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted...

  20. Optical analogues of the Newton-Schrödinger equation and boson star evolution.

    Science.gov (United States)

    Roger, Thomas; Maitland, Calum; Wilson, Kali; Westerberg, Niclas; Vocke, David; Wright, Ewan M; Faccio, Daniele

    2016-11-14

    Many gravitational phenomena that lie at the core of our understanding of the Universe have not yet been directly observed. An example in this sense is the boson star that has been proposed as an alternative to some compact objects currently interpreted as being black holes. In the weak field limit, these stars are governed by the Newton-Schrodinger equation. Here we present an optical system that, under appropriate conditions, identically reproduces such equation in two dimensions. A rotating boson star is experimentally and numerically modelled by an optical beam propagating through a medium with a positive thermal nonlinearity and is shown to oscillate in time while also stable up to relatively high densities. For higher densities, instabilities lead to an apparent breakup of the star, yet coherence across the whole structure is maintained. These results show that optical analogues can be used to shed new light on inaccessible gravitational objects.

  1. The Oklo phenomenon as an analogue of radioactive waste disposal. A review

    International Nuclear Information System (INIS)

    Berzero, A.; D'Alessandro, M.

    1990-01-01

    This work demonstrates the utility of the Oklo uranium ore deposit and natural fission reactors as a long time scale analogue for man-made radioactive waste repositories. Oklo has opened a new horizon representing an unrivalled opportunity to apply isotopic geochemistry to the study of migrations of fission products after an extremely long cooling and storage time and to define the processes involved in the transport of these elements through geological materials. This is the topic of the first section of this report. In the second section the information available on retention or migration at Oklo of the most interesting fission products is presented trying to illustrate how relevant the Oklo experience is in formulating predictions on the destiny of high activity waste disposed of in stable geological formations

  2. Stabilization of neurotensin analogues: effect on peptide catabolism, biodistribution and tumor binding

    Energy Technology Data Exchange (ETDEWEB)

    Bruehlmeier, Matthias E-mail: peter.blaeuenstein@psi.ch; Garayoa, Elisa Garcia; Blanc, Alain; Holzer, Barbara; Gergely, Suzanne; Tourwe, Dirk; Schubiger, Pius August; Blaeuenstein, Peter

    2002-04-01

    Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising targets for imaging and therapeutic purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [{sup 99m}Tc] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (N{alpha}His)Ac--the Tc-binding moiety--combined with a reduced bond 8-9 (CH{sub 2}NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70.

  3. MARKOV GRAPHS OF ONE–DIMENSIONAL DYNAMICAL SYSTEMS AND THEIR DISCRETE ANALOGUES AND THEIR DISCRETE ANALOGUES

    Directory of Open Access Journals (Sweden)

    SERGIY KOZERENKO

    2016-04-01

    Full Text Available One feature of the famous Sharkovsky’s theorem is that it can be proved using digraphs of a special type (the so–called Markov graphs. The most general definition assigns a Markov graph to every continuous map from the topological graph to itself. We show that this definition is too broad, i.e. every finite digraph can be viewed as a Markov graph of some one–dimensional dynamical system on a tree. We therefore consider discrete analogues of Markov graphs for vertex maps on combinatorial trees and characterize all maps on trees whose discrete Markov graphs are of the following types: complete, complete bipartite, the disjoint union of cycles, with every arc being a loop.

  4. Alteration of radiation response in vitro by simultaneous modulation of the de novo and salvage pathways to deoxynucleoside triphosphate pool by (E)-2'-deoxy-(fluoromethylene)cytidine and thymidine analogs

    International Nuclear Information System (INIS)

    Coucke, Philippe A.; Li Yexiong; Cottin, Eliane; Ozsahin, Mahmut; Paschoud, Nicolas; Mirimanoff, Rene-Oliver

    1997-01-01

    Aim: To test different thymidine analogs (zidovudine = AZT, stavudine D4T, and 5-iodo-2-deoxyuridine = IdUrd), active at the level of the salvage pathway, as modifiers of the radiosensitization observed with (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC), an inhibitor of ribonucleotide reductase (RR), a key enzyme in the de novo pathway of deoxynucleoside triphosphate synthesis. The thymidine anologs are interacting with thymidine kinase (TK), the rate-limiting enzyme of the salvage pathway. Materials and methods: A human colon cancer cell line Widr has been exposed for 48 h prior to irradiation to 30 nM of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). Stavudine (D4T) and zidovudine (AZT) were added at a concentration of 25 μM after subcultivation at low density and immediately before irradiation. Iododeoxyuridine (IdUrd) at a concentration of 1 and 2 μM was tested either 48 h before irradiation or applied in the same experimental conditions as D4T or AZT. All the concentrations used were in the physiological range. Prolonged exposure to IdUrd prior to irradiation was tested because of its known radiosensitizing effect. The experimental endpoint was clonogenic survival as measured by a colony forming assay. Results: The different drugs used alone or in combination did not modify significantly the PE of unirradiated WiDr-cells. As previously shown 30 nM FMdC for 48 h, resulted in a small but significant change in the radiation response. The enhancement ratio (SF%-control divided by SF%-drug) at a 2 Gy dose level was 1.20 ± 0.03 for cells exposed to FMdC. AZT and D4T added after subcultivation before irradiation yielded an ER of 1.12 ± 0.05 and 1.13 ± 0.09 respectively. The combination of FMdC and D4T resulted in an ER of 1.39 ± 0.04, whereas AZT combined to FMdC yielded 1.64 ± 0.21. For IdUrd alone, an ER was reached of 1.17 ± 0.05, 1.22 ± 0.08 at 1 and 2 μM respectively if applied immediately after subcultivation, and 1.17 ± 0.06 at 1 μM applied for 48

  5. Preparation and biological evaluation of 111In-, 177Lu- and 90Y-labeled DOTA analogues conjugated to B72.3

    International Nuclear Information System (INIS)

    Mohsin, Huma; Fitzsimmons, Jonathan; Shelton, Tiffani; Hoffman, Timothy J.; Cutler, Cathy S.; Lewis, Michael R.; Athey, Phillip S.; Gulyas, Gyongyi; Kiefer, Garry E.; Frank, R. Keith; Simon, Jaime; Lever, Susan Z.; Jurisson, Silvia S.

    2007-01-01

    Three 1,4,7,10-tetraazacyclododecane-N,N',N '' ,N '' '-tetraacetic acid (DOTA) analogues were evaluated for relative in vivo stability when radiolabeled with 111 In, 90 Y and 177 Lu and conjugated to the monoclonal antibody B72.3. The DOTA analogues evaluated were 'NHS-DOTA' [N-hydroxysuccinimdyl (NHS) group activating one carboxylate], 'Arm-DOTA' (also known as MeO-DOTA; with a p-NCS, o-MeO-benzyl moiety on the methylene group of one acetic acid arm) and 'Back-DOTA' (with a p-NCS-benzyl moiety on a backbone methylene group of the macrocycle). The B72.3 was conjugated to the DOTA analogues to increase the retention time of the radioloabeled conjugates in vivo in mice. The serum stability of the various radiometalated DOTA conjugates showed them to have good stability out to 168 h (all >95% except 111 In-NHS-DOTA-B72.3, which was 91% stable). Hydroxyapatite stability for the 111 In and 177 Lu DOTA-conjugates was >95% at 168 h, while the 90 Y DOTA-conjugates were somewhat less stable (between 90% and 95% at 168 h). The biodistribution studies of the radiometalated DOTA-conjugates showed that no significant differences were observed for the 111 In and 177 Lu analogues; however, the 90 Y analogues showed lower stabilities, as evidenced by their increased bone uptake relative to the other two [2-20% injected dose per gram (% ID/g) for 90 Y and 2-8% ID/g for 111 In and 177 Lu]. The lower stability of the 90 Y analogues could be due to the higher beta energy of 90 Y and/or to the larger ionic radius of Y 3+ . Based on the bone uptake observed, the 177 Lu-NHS-DOTA-B72.3 had slightly lower stability than the 177 Lu-Arm-DOTA-B72.3 and 177 Lu-Back-DOTA-B72.3, but not significantly at all time points. For 90 Y, the analogue showing the lowest stability based on bone uptake was 90 Y-Arm-DOTA-B72.3, perhaps because of the metal's larger ionic radius and potential steric interactions minimizing effective complexation. The 111 In analogues all showed similar biological

  6. A preliminary feasibility study on natural analogue in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chun Soo; Bae, Dae Seok; Kim, Kyung Su; Koh, Yong Kwon; Park, Byung Yun

    2000-03-01

    Preliminary study on the assessment of natural analogue study in Korea for the deep geological disposal of high-level radioactive waste was carried out. The project on natural analogue study in other countries are introduced. The uranium-bearing deposit in Okcheon belt are summarized, which reported to be uranium-bearing minerals in order to assess to feasibility for natural analogue study in Korea. Among the uranium-bearing deposits, the Deokpyeong area, reported to be the highest reservoir and grade, are selected as the study site, and the elementary investigation, including survey of radioactivity and geochemistry are carried out. According to the investigation of surface environment, the radioactivity and uranium content in the surface water and shallow groundwater does not show any anormal values. However, the radioactivity is expected to be increased in depth and the groundwater reacted with uranium-bearing graphite formation shows high unanium content, indicating the potential possibility for natural analogue study in Korea. In future, if more detail study are performed, the assessment of natural analogue study in Korea are expected.

  7. Concise synthesis of new bridged-nicotine analogues

    DEFF Research Database (Denmark)

    Crestey, François; Hooyberghs, Geert; Kristensen, Jesper Langgaard

    2012-01-01

    This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively.......This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively....

  8. Desert spring mounds: a potential analogue to Martian arid environments?

    Science.gov (United States)

    Franchi, F.; Frisia, S.

    2017-09-01

    Spring carbonates have been often considered as putative analogues of Martian arid environments. On Earth these are believed to form by the interaction of highly saline water and microbial communities, which favor the formation of authigenic micrite. Here we present new data from spring mounds in the western Makgadikgadi Pan (Botswana) and the Great Artesian Basin (South Australia). In both areas, upwelling of ground water give rise to mounds and layered deposits which are close morphological analogues of landforms documented on Mars. The authigenic carbonates and evaporites associated with the spring mounds retain evidence of microbial microfabric founded elsewhere, pointing to the potential existence of similar microbial in the extreme Martian conditions.

  9. Medical applications of analogue and digital telephone data links.

    Science.gov (United States)

    Hill, D W; Mable, S E; Payne, J P

    1976-07-20

    The increasing use of digital computer techniques for the analysis of signals such as the EEG, ECG, plethysmograms and cardiac output curves has led to the use of multichannel analogue frequency modulation telephone data links in the forward direction from the patient to the computer and digital links in the return direction. Single-channel analogue links are also being used for the surveillance of cardiac pacemaker patients and the television Viewphone offers the possibility of a visual contact between two centers. Examples will be given of the use of these various forms of telephone link.

  10. Naturally occurring crystalline phases: analogues for radioactive waste forms

    International Nuclear Information System (INIS)

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included

  11. Naturally occurring crystalline phases: analogues for radioactive waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  12. A Low-cost Multi-channel Analogue Signal Generator

    CERN Document Server

    Müller, F; The ATLAS collaboration; Shen, W; Stamen, R

    2009-01-01

    A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The implementation of the signal generator is presented as well as an application where it was successfully utilized.

  13. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    OpenAIRE

    Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

    2016-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

  14. Natural analogues, paradigm for manmade repositories for radioactive wastes

    International Nuclear Information System (INIS)

    Pavelescu, M.; Pavelescu, A.

    2004-01-01

    Natural analogues are given by nature. They show the results of natural processes which have lasted thousands or millions of years. They provide an excellent example of what could happen in an underground site, offering in the same time the opportunity to test by observation and measurement, many of the geochemical processes that are expected to influence in a realistic and appropriate way, the predicted reliability of the radioactive waste repository over long periods of geological time. The natural analogue studies attempt to understand the multiprocessing complexity of the natural system, which contrasts with the limitations of the laboratory experiments and bring arguments to overcome the difficult time scale issue. By this the natural analogues are a useful paradigm for manmade repository for radioactive wastes. The paper discusses the implicit link in the public mind between natural analogues and manmade waste repository with an accent of the positive impact on public acceptance. It is also discussed the decisive qualities of the natural analogues concerning providing valid long term data and increasing the confidence of the public for manmade repositories. The debate is conducting in terms of sustainable development, having at base high-level principles in order to protect humans and their environment, both now and in the future, from potential hazards arising from such wastes. Safe radwaste management involves the application of technology and resources in a regulated manner so that the public, workers and the environment are protected in accordance with the accepted national and international standards. There are at least seven high-level principles which are mentioned in the paper. It is presented the general concept of the deep geological repository, very important for an acceptable solution for the management of nuclear waste, what is a prerequisite for a renewal of nuclear power. Further are introduced natural and archaeological (manufactured) analogue

  15. Shelf-Stable Food Safety

    Science.gov (United States)

    ... is an MRE? Is an MRE shelf stable? What foods are packaged in retort packages? What is aseptic ... type of package is used for aseptic processing? What foods are packaged in aseptic packages? Can I microwave ...

  16. Pharmaceuticals labelled with stable isotopes

    International Nuclear Information System (INIS)

    Krumbiegel, P.

    1986-11-01

    The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13 C, 15 N, and 2 H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2 H, 13 C, and 15 N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

  17. Stable isotope research pool inventory

    International Nuclear Information System (INIS)

    1984-03-01

    This report contains a listing of electromagnetically separated stable isotopes which are available at the Oak Ridge National Laboratory for distribution for nondestructive research use on a loan basis. This inventory includes all samples of stable isotopes in the Research Materials Collection and does not designate whether a sample is out on loan or is in reprocessing. For some of the high abundance naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56

  18. 3CAPS – a structural AP–site analogue as a tool to investigate DNA base excision repair

    Science.gov (United States)

    Schuermann, David; Scheidegger, Simon P.; Weber, Alain R.; Bjørås, Magnar; Leumann, Christian J.; Schär, Primo

    2016-01-01

    Abasic sites (AP-sites) are frequent DNA lesions, arising by spontaneous base hydrolysis or as intermediates of base excision repair (BER). The hemiacetal at the anomeric centre renders them chemically reactive, which presents a challenge to biochemical and structural investigation. Chemically more stable AP-site analogues have been used to avoid spontaneous decay, but these do not fully recapitulate the features of natural AP–sites. With its 3′–phosphate replaced by methylene, the abasic site analogue 3CAPS was suggested to circumvent some of these limitations. Here, we evaluated the properties of 3CAPS in biochemical BER assays with mammalian proteins. 3CAPS-containing DNA substrates were processed by APE1, albeit with comparably poor efficiency. APE1-cleaved 3CAPS can be extended by DNA polymerase β but repaired only by strand displacement as the 5′–deoxyribophosphate (dRP) cannot be removed. DNA glycosylases physically and functionally interact with 3CAPS substrates, underlining its structural integrity and biochemical reactivity. The AP lyase activity of bifunctional DNA glycosylases (NTH1, NEIL1, FPG), however, was fully inhibited. Notably, 3CAPS-containing DNA also effectively inhibited the activity of bifunctional glycosylases on authentic substrates. Hence, the chemically stable 3CAPS with its preserved hemiacetal functionality is a potent tool for BER research and a potential inhibitor of bifunctional DNA glycosylases. PMID:26733580

  19. Synthesis, DNA interaction and antimicrobial activities of three rimantadine analogues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bing-Mi; Zhang, Jun [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Wang, Xin, E-mail: wangxinlnu@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Zhang, Li-Ping; Liu, Yang [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Niu, Hua-Ying [Jinan Dachpharm Development Co., Ltd., Jinan 250100 (China); Liu, Bin, E-mail: liubinzehao@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China)

    2015-03-15

    The interactions of three rimantadine analogues (RAs) with calf thymus deoxyribonucleic acid (ct-DNA) in buffer solution (pH 7.4) were investigated using berberine (BR) as a probe by various methods. Fluorescence studies revealed that the RAs interacted with DNA in vitro and the quenchings were all static. Furthermore, the binding modes of these compounds to DNA were disclosed as groove binding supported by absorption spectroscopy, viscosity measurement and denatured DNA experiment. The antimicrobial activities of the RAs were also evaluated in Staphylococcus aureus and Escherichia coli, and they all exhibited good bacteriostasic effects. The results might provide an important reference for investigation of the molecular mechanism associated with the DNA binding of the RAs. - Highlights: • Three rimantadine analogues were synthesized. • The RAs effectively quenched the intrinsic fluorescence of DNA via a static combination. • These analogues can bind to DNA via groove binding mode. • The antimicrobial activities of three analogues were also evaluated by the disk diffusion method.

  20. Are structural analogues to bisphenol A a safe alternative?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Gitte Alsing

    2013-01-01

    of which are found in foods and have been measured in humans. Due to the structural analogy there is an inherent risk that these compounds may lead to similar effects as BPA. The aim of this study was to characterize the toxicological profile of BPA and the five analogues using in vitro assays assessing...

  1. A new analogue of fatty alcohol from Tamarix hampeana L.

    Science.gov (United States)

    Aykac, Ahmet; Akgül, Yurdanur

    2010-01-01

    New analogues of a long-chain secondary alcohol (1) and laserine (2) were isolated from the flowers of Tamarix hampeana L. The isolated compounds were identified using 1D and 2D NMR, LCMS/APCI, and chemical methods. Laserine was isolated for the first time from T. hampeana L.

  2. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were

  3. Influence of Bakuchiol, a JH analogue from Bemchi ( Psoralea ...

    African Journals Online (AJOL)

    The influence of a juvenile hormone analogue (JHA), bakuchiol on the silk yield of silkworm, Bombyx mori L. was studied involving two popular commercial hybrids, KA x NB4D2 (bivoltine x bivoltine) and PM x NB4D2 (multivoltine x bivoltine). The compound was administered topically to 5th instars at 24, 48, 72 and 96 h as ...

  4. Difference in brain activations during appreciating paintings and photographic analogues

    Directory of Open Access Journals (Sweden)

    Yoshinori eMizokami

    2014-07-01

    Full Text Available Several studies have investigated neural correlates of aesthetic appreciation for paintings but to date the findings have been heterogeneous. This heterogeneity may be attributed to previous studies’ measurement of aesthetic appreciation of not only the beauty of paintings but also the beauty of motifs of the paintings. In order to better elucidate the beauty of paintings, it seems necessary to compare aesthetic appreciation of paintings and photographic analogues which included corresponding real images. We prepared for famous painters’ pictures and their photographic analogues which were set up to resemble each painting in order to investigate the hypothesis that there exist specific neural correlates associated with the aesthetic appreciation for paintings. Forty-four subjects participated in functional magnetic resonance study which required comparisons of aesthetic appreciation of paintings of still life and landscape versus photographic analogues including corresponding real images of still life and landscape. Bilateral cuneus and the left lingual gyrus were activated in the comparison of aesthetic appreciation of paintings versus photographic analogues. In conclusion, the present findings suggest a possibility of the existence of specific neural correlates associated with the aesthetic appreciation for paintings and that bilateral cuneus and the left lingual gyrus may be involved.

  5. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    Directory of Open Access Journals (Sweden)

    Maarten Walmagh

    2015-06-01

    Full Text Available Trehalose (α-d-glucopyranosyl α-d-glucopyranoside is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals, medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside, offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis.

  6. An Analysis of an Autoclitic Analogue in Pigeons

    Science.gov (United States)

    Kuroda, Toshikazu; Lattal, Kennon A.; García-Penagos, Andrés

    2014-01-01

    Using a conditional discrimination procedure, pigeons were exposed to a nonverbal analogue of qualifying autoclitics such as "definitely" and "maybe." It has been suggested that these autoclitics are similar to tacts except that they are under the control of private discriminative stimuli. Instead of the conventional assumption…

  7. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    Science.gov (United States)

    Walmagh, Maarten; Zhao, Renfei; Desmet, Tom

    2015-01-01

    Trehalose (α-d-glucopyranosyl α-d-glucopyranoside) is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals), medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside) or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside), offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis. PMID:26084050

  8. An azumamide C analogue without the zinc-binding functionality

    DEFF Research Database (Denmark)

    Villadsen, Jesper; Kitir, Betül; Wich, Kathrine

    2014-01-01

    + - coordinating moiety. Herein, we describe the synthesis of an azumamide analogue lacking its native Zn 2+ -binding group and evaluation of its inhibitory activity against recombinant human HDAC1 – 11. Furthermore, kinetic investigation of the inhibitory mechanism of both parent natural product and synthetic...

  9. Evaluation of the antibacterial spectrum of drosocin analogues

    NARCIS (Netherlands)

    Bikker, F.J.; Kaman-van Zanten, W.E.; Vries-van de Ruit, A.M.B.C. de; Voskamp-Visser, I.; Hooft, P.A.V. van; Mars-Groenendijk, R.H.; Visser, P.C. de; Noort, D.

    2006-01-01

    Drosocin is a 19-mer, cationic antimicrobial peptide from Drosophila melanogaster. The aim of the study was to examine the antibacterial spectrum of unglycosylated drosocin analogues. Furthermore, the amino acid sequence of DnaK, drosocin's intracellular target, from susceptible species was aligned

  10. Research on uranium deposits as analogues of radioactive waste repositories

    International Nuclear Information System (INIS)

    Hardy, C.J.

    1987-01-01

    The disposal of highly radioactive waste deep underground in suitable geological formations is proposed by many countries to protect public health and safety. The study of natural analogues of nuclear waste repositories is one method of validating mathematical models and assuring that a proposed repository site and design will be safe. (author)

  11. Scattering matrices and expansion coefficients of martian analogue palagonite particles

    NARCIS (Netherlands)

    Laan, E.C.; Volten, H.; Stam, D.M.; Muñoz, O.; Hovenier, J.W.; Roush, T.L.

    2009-01-01

    We present measurements of ratios of elements of the scattering matrix of martian analogue palagonite particles for scattering angles ranging from 3° to 174° and a wavelength of 632.8 nm. To facilitate the use of these measurements in radiative transfer calculations we have devised a method that

  12. Reasoning by analogy: rational foundation of natural analogue studies

    International Nuclear Information System (INIS)

    Petit, J.-C.

    1992-01-01

    Long-term extrapolations concerning the safety of a nuclear waste repository cannot be satisfactorily made on the sole basis of short-term laboratory investigations. Most nuclear countries have hence developed an approach relying on the following research directions: 1. laboratory experiments; 2. in situ testing; 3. modeling; and 4. natural analogues, which are the only means by which very slow mechanisms can be identified and by which long-term predictions of models can be tested for pertinence (if not truly validated). Although the field of natural analogues has grown very rapidly in recent years, receiving support from varied specialists and institutions involved in radioactive waste disposal, there is not yet a full consensus on their actual usefulness. More problematic is the criticism sometimes made that analogical reasoning is not ''true science'' and that information retrieved from the study of natural analogues will always remain questionable. The present paper gives some clues about the exact status of reasoning by analogy, compared to more ''scientific'' ways of deriving information from investigated systems. It is not a thorough discussion of this very complex, and by far too philosophical issue but we hope, at least, to present to readers of papers devoted to natural analogue studies arguments showing that this approach has some sound foundation. (author)

  13. Using natural analogue studies in the secondary science curriculum

    International Nuclear Information System (INIS)

    Ebert, E.K.

    1995-01-01

    This paper discusses an atomic theory unit of a high school chemistry course taught in Nevada. The unit is based on the application of natural analogues to nuclear waste issues. The paper focuses on the students' reactions to the subject material

  14. A Short Review on Cardiotonic Steroids and Their Aminoguanidine Analogues

    Directory of Open Access Journals (Sweden)

    Arturo San Feliciano

    2000-01-01

    Full Text Available A short review on cardiotonic steroids and their analogues is presented. The natural, semisynthetic and synthetic derivatives, as well as their mechanism of action and structure-activity relationships are shown, with a special reference to aminoguanidine derivatives.

  15. Design and synthesis of epicocconone analogues with improved fluorescence properties.

    Science.gov (United States)

    Peixoto, Philippe A; Boulangé, Agathe; Ball, Malcolm; Naudin, Bertrand; Alle, Thibault; Cosette, Pascal; Karuso, Peter; Franck, Xavier

    2014-10-29

    Epicocconone is a natural latent fluorophore that is widely used in biotechnology because of its large Stokes shift and lack of fluorescence in its unconjugated state. However, the low photostability and quantum yields of epicocconone have limited its wider use, and in the absence of a total synthesis, this limitation has been a long-standing problem. Here we report a general strategy for the synthesis of epicocconone analogues that relies on a 2-iodoxybenzoic acid-mediated dearomatization and on the replacement of the triene tail of the natural product by an aromatic ring. This design element is general and the synthesis is straightforward, providing ready access to libraries of polyfunctional fluorophores with long Stokes shifts based on the epicocconone core. Our structural modifications resulted in analogues with increased photostability and quantum yields compared with the natural product. Staining proteomic gels with these new analogues showed significant lowering of the detection limit and a 30% increase in the number of low-abundance proteins detected. These epiccoconone analogues will substantially improve the discovery rate of biomarker needles in the proteomic haystack.

  16. Evaluative comparison of palm wine analogue and oil palm wine ...

    African Journals Online (AJOL)

    0.05 and P=0.01) in colour, odour, effervescence and general acceptability between palm wine analogue and oil palm wine. While there also was no significant difference in the tastes and balance of sweetness at P=0.01, a slight difference ...

  17. Vitamin E analogues and immune response in cancer treatment

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Neužil, Jiří

    2007-01-01

    Roč. 76, - (2007), s. 463-491 ISSN 0083-6729 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : vitamin E analogues * inducers of apoptosis * immune surveillance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.889, year: 2007

  18. Analogue Building Blocks Based on Digital CMOS Gates

    DEFF Research Database (Denmark)

    Mucha, Igor

    1996-01-01

    Low-performance analogue circuits built of digital MOS gates are presented. Depending on the threshold voltages of the technology used the final circuits can be operated using low supply voltages. The main advantage using the proposed circuits is the simplicity and ultimate compatibility...... with the design of digital circuits....

  19. Brassinosteroids: Synthesis and activity of some fluoro analogues

    Czech Academy of Sciences Publication Activity Database

    Slavíková, Barbora; Kohout, Ladislav; Buděšínský, Miloš; Swaczynová, Jana; Kasal, Alexander

    2008-01-01

    Roč. 51, č. 13 (2008), s. 3979-3984 ISSN 0022-2623 R&D Projects: GA AV ČR IAA400550609 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50380511 Keywords : brassinosteroids * fluor o analogues Subject RIV: CC - Organic Chemistry Impact factor: 4.898, year: 2008

  20. Comparison of overlay metrology with analogue and digital cameras

    Science.gov (United States)

    Rigden, Timothy C.; Soroka, Andrew J.; Binns, Lewis A.

    2005-05-01

    Overlay metrology is a very demanding image processing application; current applications are achieving dynamic precision of one hundredth of a pixel or better. As such it requires an accurate image acquisition system, with minimal distortions. Distortions can be physical (e.g. pixel size / shape) or electronic (e.g. clock skew) in nature. They can also affect the image shape, or the gray level intensity of individual pixels, the former causing severe problems to pattern recognition and measurement algorithms, the latter having an adverse effect primarily on the measurement itself. This paper considers the artifacts that are present in a particular analogue camera, with a discussion on how these artifacts translate into a reduction of overlay metrology performance, in particular their effect on precision and tool induced shift (TIS). The observed effects include, but are not limited to, banding and interlacing. This camera is then compared to two digital cameras. The first of these operates at the same frame rate as the analogue camera, and is found to have fewer distortions than the analogue camera. The second camera operates with a frame rate twice that of the other two. It is observed that this camera does not exhibit the distortions of the analogue camera, but instead has some very specific problems, particularly with regards to noise. The quantitative data on the effect on precision and TIS under a wide variety of conditions, is presented. These show that while it is possible to achieve metrology-capable images using an analogue camera, it is preferable to use a digital camera, both from the perspective of overall system performance, and overall system complexity.

  1. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    Science.gov (United States)

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

  2. Analogue model studies of induction effects at auroral latitudes

    Directory of Open Access Journals (Sweden)

    A. Viljanen

    1995-11-01

    Full Text Available In addition to field observations and numerical models, geomagnetic induction effects can be studied by scaled analogue model experiments. We present here results of analogue model studies of the auroral electrojet with an Earth model simulating the Arctic Ocean and inland conductivity structures in northern Fennoscandia. The main elements of the analogue model used were salt water simulating the host rock, an aluminium plate corresponding to the ocean and graphite pieces producing the inland highly conducting anomalies. The electrojet was a time-harmonic line current flowing at a (simulated height of 100 km above northern Fennoscandia. The period simulated was 9 min. The analogue model results confirmed the well-known rapid increase of the vertical field when the coast is approached from the continent. The increase of the horizontal field due to induced ocean currents was demonstrated above the ocean, as well as the essentially negligible effect of these currents on the horizontal field on the continent. The behaviour of the magnetic field is explained with a simple two-dimensional thin-sheet model. The range, or the adjustment distance, of the ocean effect inland was found to be some hundreds of kilometers, which also agrees with earlier results of the Siebert-Kertz separation of IMAGE magnetometer data. The modelled inland anomalies evidently had too large conductivities, but on the other hand, their influence decayed on scales of only some tens of kilometers. Analogue model results, thin-sheet calculations, and field observations show that the induction effect on the horizontal magnetic field Bx near the electrojet is negligible. On the other hand, the vertical component Bz is clearly affected by induced currents in the ocean. Evidence of this is the shift of the zero point of Bz 0-1° southwards from the maximum of Bx. The importance of these results are discussed, emphasizing the determination of ionospheric currents.

  3. Parallel comparison of Illumina RNA-Seq and Affymetrix microarray platforms on transcriptomic profiles generated from 5-aza-deoxy-cytidine treated HT-29 colon cancer cells and simulated datasets

    Science.gov (United States)

    2013-01-01

    Background High throughput parallel sequencing, RNA-Seq, has recently emerged as an appealing alternative to microarray in identifying differentially expressed genes (DEG) between biological groups. However, there still exists considerable discrepancy on gene expression measurements and DEG results between the two platforms. The objective of this study was to compare parallel paired-end RNA-Seq and microarray data generated on 5-azadeoxy-cytidine (5-Aza) treated HT-29 colon cancer cells with an additional simulation study. Methods We first performed general correlation analysis comparing gene expression profiles on both platforms. An Errors-In-Variables (EIV) regression model was subsequently applied to assess proportional and fixed biases between the two technologies. Then several existing algorithms, designed for DEG identification in RNA-Seq and microarray data, were applied to compare the cross-platform overlaps with respect to DEG lists, which were further validated using qRT-PCR assays on selected genes. Functional analyses were subsequently conducted using Ingenuity Pathway Analysis (IPA). Results Pearson and Spearman correlation coefficients between the RNA-Seq and microarray data each exceeded 0.80, with 66%~68% overlap of genes on both platforms. The EIV regression model indicated the existence of both fixed and proportional biases between the two platforms. The DESeq and baySeq algorithms (RNA-Seq) and the SAM and eBayes algorithms (microarray) achieved the highest cross-platform overlap rate in DEG results from both experimental and simulated datasets. DESeq method exhibited a better control on the false discovery rate than baySeq on the simulated dataset although it performed slightly inferior to baySeq in the sensitivity test. RNA-Seq and qRT-PCR, but not microarray data, confirmed the expected reversal of SPARC gene suppression after treating HT-29 cells with 5-Aza. Thirty-three IPA canonical pathways were identified by both microarray and RNA

  4. Insecticidal action of synthetic girgensohnine analogues and essential oils on Rhodnius prolixus (Hemiptera: Reduviidae

    Directory of Open Access Journals (Sweden)

    Juliana Cuadros

    2017-03-01

    Conclusion: Synthetic girgensohnine analogues, and C. flexuosus and C. sinensis essential oils showed insecticidal activity in R. prolixus. Analogue 3 showed the greatest insecticidal activity among all molecules and oils evaluated under our laboratory conditions.

  5. The impact of watching educational video clips on analogue patients' physiological arousal and information recall

    NARCIS (Netherlands)

    Bruinessen, I.R. van; Ende, I.T. van den; Visser, L.N.; Dulmen, S. van

    2016-01-01

    OBJECTIVE: Investigating the influence of watching three educational patient-provider interactions on analogue patients' emotional arousal and information recall. METHODS: In 75 analogue patients the emotional arousal was measured with physiological responses (electrodermal activity and heart rate)

  6. The impact of watching educational video clips on analogue patients' physiological arousal and information recall

    NARCIS (Netherlands)

    van Bruinessen, I. R.; van den Ende, I. T. A.; Visser, L. N. C.; van Dulmen, S.

    2016-01-01

    Investigating the influence of watching three educational patient-provider interactions on analogue patients' emotional arousal and information recall. In 75 analogue patients the emotional arousal was measured with physiological responses (electrodermal activity and heart rate) and self-reported

  7. Altering the communication networks of multispecies microbial systems using a diverse toolbox of AI-2 analogues.

    Science.gov (United States)

    Gamby, Sonja; Roy, Varnika; Guo, Min; Smith, Jacqueline A I; Wang, Jingxin; Stewart, Jessica E; Wang, Xiao; Bentley, William E; Sintim, Herman O

    2012-06-15

    There have been intensive efforts to find small molecule antagonists for bacterial quorum sensing (QS) mediated by the "universal" QS autoinducer, AI-2. Previous work has shown that linear and branched acyl analogues of AI-2 can selectively modulate AI-2 signaling in bacteria. Additionally, LsrK-dependent phosphorylated analogues have been implicated as the active inhibitory form against AI-2 signaling. We used these observations to synthesize an expanded and diverse array of AI-2 analogues, which included aromatic as well as cyclic C-1-alkyl analogues. Species-specific analogues that disrupted AI-2 signaling in Escherichia coli and Salmonella typhimurium were identified. Similarly, analogues that disrupted QS behaviors in Pseudomonas aeruginosa were found. Moreover, we observed a strong correlation between LsrK-dependent phosphorylation of these acyl analogues and their ability to suppress QS. Significantly, we demonstrate that these analogues can selectively antagonize QS in single bacterial strains in a physiologically relevant polymicrobial culture.

  8. Analogue Electrical Circuit for Simulation of the Duffing-Holmes Equation

    DEFF Research Database (Denmark)

    Tamaseviciute, E.; Tamasevicius, A.; Mykolaitis, G.

    2008-01-01

    An extremely simple second order analogue electrical circuit for simulating the two-well Duffing-Holmes mathematical oscillator is described. Numerical results and analogue electrical simulations are illustrated with the snapshots of chaotic waveforms, phase portraits (Lissajous figures...

  9. The impact of watching educational video clips on analogue patients' physiological arousal and information recall.

    NARCIS (Netherlands)

    Bruinessen, I.R. van; Ende, I.T.A. van den; Visser, I.N.C.; Dulmen, S. van

    2016-01-01

    Objective: Investigating the influence of watching three educational patient–provider interactions on analogue patients’ emotional arousal and information recall. Methods: In 75 analogue patients the emotional arousal was measured with physiological responses (electrodermal activity and heart rate)

  10. Stable Boundary Layer Education (STABLE) Final Campaign Summary

    Energy Technology Data Exchange (ETDEWEB)

    Turner, David D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-03-01

    The properties of, and the processes that occur in, the nocturnal stable boundary layer are not well understood, making it difficult to represent adequately in numerical models. The nocturnal boundary layer often is characterized by a temperature inversion and, in the Southern Great Plains region, a low-level jet. To advance our understanding of the nocturnal stable boundary layer, high temporal and vertical resolution data on the temperature and wind properties are needed, along with both large-eddy simulation and cloud-resolving modeling.

  11. Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue

    NARCIS (Netherlands)

    Fiebrich, H. -B.; van den Berg, G.; Kema, I. P.; Links, T. P.; Kleibeuker, J. H.; van Beek, A. P.; Walenkamp, A. M. E.; Sluiter, W. J.; de Vries, E. G. E.

    2010-01-01

    P>Background Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels

  12. On Using Current Steering Logic in Mixed Analogue-digital Circuits

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    The authors investigate power supply noise in mixed analogue-digital circuits, arising from communication between the analogue and digital parts of the circuit. Current steering techniques and proper buffering are used to show which noise currents can be reduced and which cannot. In addition......, a high-swing current steering buffer for driving analogue switches or external digital signals is proposed....

  13. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    International Nuclear Information System (INIS)

    Skagius, K.; Wingefors, S.

    1992-01-01

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  14. α-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice.

    Directory of Open Access Journals (Sweden)

    Petteri Rinne

    Full Text Available Melanocyte-stimulating hormones, α-, β- and γ-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that α-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of α-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable α-MSH analogue [Nle(4, D-Phe(7]-α-MSH (NDP-α-MSH and investigated whether it has protective effects in deoxycorticosterone acetate (DOCA-salt hypertensive mice. Adult male C57Bl/6N mice were subjected to DOCA-salt treatment and randomized to receive intraperitoneal injections of either saline as vehicle or NDP-α-MSH (0.3 mg/kg/day for 14 days starting 7 days after the DOCA-salt treatment. Systemic hemodynamics, serum and urine electrolytes, and oxidative stress markers were assessed in control sham-operated and DOCA-salt mice. NDP-α-MSH elicited marked diuretic and natriuretic responses that were reversible with the MC3/4 receptor antagonist SHU9119. Chronic NDP-α-MSH treatment attenuated blood pressure elevation in DOCA-salt mice without affecting the blood pressure of normotensive control animals. Owing to the enhanced sodium excretion, NDP-α-MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt treatment mildly increased oxidative stress at the tissue level, but NDP-α-MSH had no significant effects on the oxidative stress markers. In conclusion, treatment with NDP-α-MSH increases urinary sodium excretion and protects against DOCA-salt-induced hypertension. These findings point to the potential future use of α-MSH analogues in the treatment of hypertension.

  15. Prospective Analysis of Behavioral Economic Predictors of Stable Moderation Drinking Among Problem Drinkers Attempting Natural Recovery.

    Science.gov (United States)

    Tucker, Jalie A; Cheong, JeeWon; Chandler, Susan D; Lambert, Brice H; Pietrzak, Brittney; Kwok, Heather; Davies, Susan L

    2016-12-01

    As interventions have expanded beyond clinical treatment to include brief interventions for persons with less severe alcohol problems, predicting who can achieve stable moderation drinking has gained importance. Recent behavioral economic (BE) research on natural recovery has shown that active problem drinkers who allocate their monetary expenditures on alcohol and saving for the future over longer time horizons tend to have better subsequent recovery outcomes, including maintenance of stable moderation drinking. This study compared the predictive utility of this money-based "Alcohol-Savings Discretionary Expenditure" (ASDE) index with multiple BE analogue measures of behavioral impulsivity and self-control, which have seldom been investigated together, to predict outcomes of natural recovery attempts. Community-dwelling problem drinkers, enrolled shortly after stopping abusive drinking without treatment, were followed prospectively for up to a year (N = 175 [75.4% male], M age = 50.65 years). They completed baseline assessments of preresolution drinking practices and problems, analogue behavioral choice tasks (Delay Discounting, Melioration-Maximization, and Alcohol Purchase Tasks), and a Timeline Followback interview including expenditures on alcohol compared to voluntary savings (ASDE index) during the preresolution year. Multinomial logistic regression models showed that, among the BE measures, only the ASDE index predicted stable moderation drinking compared to stable abstinence or unstable resolutions involving relapse. As hypothesized, stable moderation was associated with more balanced preresolution allocations to drinking and savings (odds ratio = 1.77, 95% confidence interval = 1.02 to 3.08, p behavior regulation processes than abstinence. The ASDE's unique predictive utility may rest on its comprehensive representation of contextual elements to support this patterning of behavioral allocation. Stable low-risk drinking, but not abstinence

  16. Phosphorylation of inositol 1,4,5-trisphosphate analogues by 3-kinase and dephosphorylation of inositol 1,3,4,5-tetrakisphosphate analogues by 5-phosphatase

    NARCIS (Netherlands)

    Dijken, Peter van; Lammers, Aleida A.; Ozaki, Shoichiro; Potter, Barry V.L.; Erneux, Christophe; Haastert, Peter J.M. van

    1994-01-01

    A series of P-32-labeled D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P-4] analogues was enzymically prepared from the corresponding D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] analogues using recombinant rat brain Ins(1,4,5)P-3 3-kinase and [gamma-P-32]ATP. Ins(1,4,5)P-3 analogues

  17. Simultaneous quantitative analysis of eight vitamin D analogues in milk using liquid chromatography–tandem mass spectrometry

    International Nuclear Information System (INIS)

    Gomes, Fabio P.; Shaw, P. Nicholas; Whitfield, Karen; Hewavitharana, Amitha K.

    2015-01-01

    Milk is an important source of nutrients for various risk populations, including infants. The accurate measurement of vitamin D in milk is necessary to provide adequate supplementation advice for risk groups and to monitor regulatory compliance. Currently used liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods are capable of measuring only four analogues of vitamin D in unfortified milk. We report here an accurate quantitative analytical method for eight analogues of vitamin D: Vitamin D 2 and D 3 (D 2 and D 3 ), 25-hydroxy D 2 and D 3 , 24,25-dihydroxy D 2 and D 3 , and 1,25-dihydroxyD 2 and D 3 . In this study, we compared saponification and protein precipitation for the extraction of vitamin D from milk and found the latter to be more effective. We also optimised the pre-column derivatisation using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD), to achieve the highest sensitivity and accuracy for all major vitamin D forms in milk. Chromatography was optimised to reduce matrix effects such as ion-suppression, and the matrix effects were eliminated using co-eluting stable isotope labelled internal standards for the calibration of each analogue. The analogues, 25-hydroxyD 3 (25(OH)D 3 ) and its epimer (3-epi-25(OH)D 3 ) were chromatographically resolved, to prevent over-estimation of 25(OH)D 3 . The method was validated and subsequently applied for the measurement of total vitamin D levels in human, cow, mare, goat and sheep milk samples. The detection limits, repeatability standard deviations, and recovery ranges were from 0.2 to 0.4 femtomols, 6.30–13.5%, and 88.2–105%, respectively. - Highlights: • Simultaneous, femtomole level, quantification of 8 vitamin D analogues in milk. • Optimisation of the PTAD derivatisation as a pre-column method. • Optimisation of the separation to minimise ion suppression effects, and to separate out an inactive form of vitamin D. • Comparison of saponification and protein precipitation for their

  18. Simultaneous quantitative analysis of eight vitamin D analogues in milk using liquid chromatography–tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Fabio P.; Shaw, P. Nicholas; Whitfield, Karen; Hewavitharana, Amitha K., E-mail: a.hewavitharana@pharmacy.uq.edu.au

    2015-09-03

    Milk is an important source of nutrients for various risk populations, including infants. The accurate measurement of vitamin D in milk is necessary to provide adequate supplementation advice for risk groups and to monitor regulatory compliance. Currently used liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods are capable of measuring only four analogues of vitamin D in unfortified milk. We report here an accurate quantitative analytical method for eight analogues of vitamin D: Vitamin D{sub 2} and D{sub 3} (D{sub 2} and D{sub 3}), 25-hydroxy D{sub 2} and D{sub 3}, 24,25-dihydroxy D{sub 2} and D{sub 3}, and 1,25-dihydroxyD{sub 2} and D{sub 3}. In this study, we compared saponification and protein precipitation for the extraction of vitamin D from milk and found the latter to be more effective. We also optimised the pre-column derivatisation using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD), to achieve the highest sensitivity and accuracy for all major vitamin D forms in milk. Chromatography was optimised to reduce matrix effects such as ion-suppression, and the matrix effects were eliminated using co-eluting stable isotope labelled internal standards for the calibration of each analogue. The analogues, 25-hydroxyD{sub 3} (25(OH)D{sub 3}) and its epimer (3-epi-25(OH)D{sub 3}) were chromatographically resolved, to prevent over-estimation of 25(OH)D{sub 3}. The method was validated and subsequently applied for the measurement of total vitamin D levels in human, cow, mare, goat and sheep milk samples. The detection limits, repeatability standard deviations, and recovery ranges were from 0.2 to 0.4 femtomols, 6.30–13.5%, and 88.2–105%, respectively. - Highlights: • Simultaneous, femtomole level, quantification of 8 vitamin D analogues in milk. • Optimisation of the PTAD derivatisation as a pre-column method. • Optimisation of the separation to minimise ion suppression effects, and to separate out an inactive form of vitamin D. • Comparison

  19. The analogue method for precipitation prediction: finding better analogue situations at a sub-daily time step

    Science.gov (United States)

    Horton, Pascal; Obled, Charles; Jaboyedoff, Michel

    2017-07-01

    Analogue methods (AMs) predict local weather variables (predictands) such as precipitation by means of a statistical relationship with predictors at a synoptic scale. The analogy is generally assessed on gradients of geopotential heights first to sample days with a similar atmospheric circulation. Other predictors such as moisture variables can also be added in a successive level of analogy. The search for candidate situations similar to a given target day is usually undertaken by comparing the state of the atmosphere at fixed hours of the day for both the target day and the candidate analogues. This is a consequence of using standard daily precipitation time series, which are available over longer periods than sub-daily data. However, it is unlikely for the best analogy to occur at the exact same hour for the target and candidate situations. A better analogue situation may be found with a time shift of several hours since a better fit can occur at different times of the day. In order to assess the potential for finding better analogues at a different hour, a moving time window (MTW) has been introduced. The MTW resulted in a better analogy in terms of the atmospheric circulation and showed improved values of the analogy criterion on the entire distribution of the extracted analogue dates. The improvement was found to increase with the analogue rank due to an accumulation of better analogues in the selection. A seasonal effect has also been identified, with larger improvements shown in winter than in summer. This may be attributed to stronger diurnal cycles in summer that favour predictors taken at the same hour for the target and analogue days. The impact of the MTW on the precipitation prediction skill has been assessed by means of a sub-daily precipitation series transformed into moving 24 h totals at 12, 6, and 3 h time steps. The prediction skill was improved by the MTW, as was the reliability of the prediction. Moreover, the improvements were greater for days

  20. Radiation-stable polyolefin compositions

    International Nuclear Information System (INIS)

    Rekers, J.W.

    1986-01-01

    This invention relates to compositions of olefinic polymers suitable for high energy radiation treatment. In particular, the invention relates to olefinic polymer compositions that are stable to sterilizing dosages of high energy radiation such as a gamma radiation. Stabilizers are described that include benzhydrol and benzhydrol derivatives; these stabilizers may be used alone or in combination with secondary antioxidants or synergists

  1. Monitoring of stable glaucoma patients

    NARCIS (Netherlands)

    K.M. Holtzer-Goor (Kim); N.S. Klazinga (Niek); M.A. Koopmanschap (Marc); H.G. Lemij (Hans); T. Plochg; E. van Sprundel (Esther)

    2010-01-01

    textabstractA high workload for ophthalmologists and long waiting lists for patients challenge the organization of ophthalmic care. Tasks that require less specialized skills, like the monitoring of stable (well controlled) glaucoma patients could be substituted from ophthalmologists to other

  2. Optoelectronic analogue signal transfer for LHC detectors, 1991

    CERN Document Server

    Dowell, John D; Homer, R J; Jovanovic, P; Kenyon, I; Staley, R; Webster, K; Da Via, C; Feyt, J; Nappey, P; Stefanini, G; Dwir, B; Reinhart, F K; Davies, J; Green, N; Stewart, W; Young, T; Hall, G; Akesson, T; Jarlskog, G; Kröll, S; Nickerson, R; Jaroslawski, S; CERN. Geneva. Detector Research and Development Committee

    1991-01-01

    We propose to study and develop opto-electronic analogue front-ends based on electro-optic intensity modulators. These devices translate the detector electrical analogue signals into optical signals which are then transferred via optical fibres to photodetector receivers at the remote readout. In comparison with conventional solutions based on copper cables, this technique offers the advantages of high speed, very low power dissipation and transmission losses, compactness and immunity to electromagnetic interference. The linearity and dynamic range that can be obtained are more than adequate for central tracking detectors, and the proposed devices have considerable radiation- hardness capabilities. The large bandwidth and short transit times offer possibilities for improved triggering schemes. The proposed R&D programme is aimed at producing multi-channel "demonstrator" units for evaluation both in laboratory and beam tests. This will allow the choice of the most effective technology. A detailed study wil...

  3. Ribosome-catalyzed formation of an abnormal peptide analogue

    International Nuclear Information System (INIS)

    Roesser, J.R.; Chorghade, M.S.; Hecht, S.M.

    1986-01-01

    The peptidyl-tRNA analogue N-(chloracetyl) phenylalanyl-tRNA/sup Phe/ was prepared by chemical aminoacylation and prebound to the P site of Escherichia coli ribosomes in response to poly(uridylic acid). Admixture of phenylalanyl-tRNA/sup Phe/ to the A site resulted in the formation of two dipeptides, one of which was found by displacement of chloride ion from the peptidyl-tRNA. This constitutes the first example of ribosome-mediated formation of a peptide of altered connectivity and suggests a need for revision of the current model of peptide bond formation. Also suggested by the present finding is the feasibility of utilizing tRNAs to prepare polypeptides of altered connectivity in an in vitro protein biosynthesizing system. [ 32 P]-oligo(rA), [ 3 H]- and [ 14 C] phenylalanines were used in the assay of the peptidye-tRNA analogue

  4. Concentration and second-gas effects in the water analogue.

    Science.gov (United States)

    Mapleson, W W; Korman, B

    1998-12-01

    The water analogue provides a visual model of the process of anaesthetic exchange. In the standard version, a single pipe connects the mouth container to the lung container and the conductance of this mouth-lung pipe is proportional to alveolar ventilation. This implies that inspired and expired ventilations are equal. In fact, with high inspired concentrations of nitrous oxide, early rapid uptake of gas by solution leads to a substantial difference between inspired and expired ventilation which in turn leads to concentration and second-gas effects. It is shown that by representing inspired and expired ventilations separately, and keeping one of them constant while varying the other to compensate for rapid uptake, concentration and second-gas effects are reproduced in the water analogue. Other means of reproducing the effects are reported but we believe that the first method is the most realistic and the most appropriate for teaching.

  5. A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

    Science.gov (United States)

    Jameson, Bradford A.; McDonnell, James M.; Marini, Joseph C.; Korngold, Robert

    1994-04-01

    EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS)1,2. The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset3-5. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents6-9, and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4+ subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

  6. From the Canadian High Arctic to Mars by Analogue

    Science.gov (United States)

    Soare, R. J.; Pollard, W. H.

    2002-12-01

    Planetary scientists are limited in their understanding of physical bodies in the solar system by the lack of primary data or knowledge. Analogue science is science practised in absentia, precisely in those instances when a non-terrestrial physical environment lies beyond one's direct, empirical grasp. Recognising that some environments on Earth may mirror present or past conditions on Mars, planetary scientists have invoked terrestrial analogues with increasing regularity over the last thirty years as fonts of putative understanding. Notwithstanding its ubiquity in planetary science, analogical reasoning has stood, by and large, unconstrained by rules or guidelines of usage. In order to redress this imbalance we propose to take two steps: 1. introduce primary data on newly discovered pingos at Axel Heiberg Island in the Canadian High Arctic, and 2. coalesce these and related data on Martian glacial, peri-glacial and fluvio-glacial landforms as a model with which to evaluate the meaningfulness of analogical reasoning in planetary science.

  7. Optical analogue of relativistic Dirac solitons in binary waveguide arrays

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Truong X., E-mail: truong.tran@mpl.mpg.de [Department of Physics, Le Quy Don University, 236 Hoang Quoc Viet str., 10000 Hanoi (Viet Nam); Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); Longhi, Stefano [Department of Physics, Politecnico di Milano and Istituto di Fotonica e Nanotecnologie del Consiglio Nazionale delle Ricerche, Piazza L. da Vinci 32, I-20133 Milano (Italy); Biancalana, Fabio [Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); School of Engineering and Physical Sciences, Heriot-Watt University, EH14 4AS Edinburgh (United Kingdom)

    2014-01-15

    We study analytically and numerically an optical analogue of Dirac solitons in binary waveguide arrays in the presence of Kerr nonlinearity. Pseudo-relativistic soliton solutions of the coupled-mode equations describing dynamics in the array are analytically derived. We demonstrate that with the found soliton solutions, the coupled mode equations can be converted into the nonlinear relativistic 1D Dirac equation. This paves the way for using binary waveguide arrays as a classical simulator of quantum nonlinear effects arising from the Dirac equation, something that is thought to be impossible to achieve in conventional (i.e. linear) quantum field theory. -- Highlights: •An optical analogue of Dirac solitons in nonlinear binary waveguide arrays is suggested. •Analytical solutions to pseudo-relativistic solitons are presented. •A correspondence of optical coupled-mode equations with the nonlinear relativistic Dirac equation is established.

  8. Somatostatin analogues labelled with 99mTc

    International Nuclear Information System (INIS)

    Obenaus, Esteban R.; Crudo, Jose L.; Edreira, Martin M.; Castiglia, Silvia G.

    1999-01-01

    Biological and radiochemical studies have been carried out on two labelled somatostatin analogues, the peptide RC-150 and the Tyr 3 -Octreotide. Both analogues have been labelled with 99m Tc using the direct and the indirect method and MAG-3 and HYNIC as chelating agents. By the direct method RC-150 was labelled using sodium ascorbate and dithionite as reducing agents. The radiochemical purity was 70%. By the indirect method, in the case of RC-160 with MAG-3 a radiochemical purity higher than 70% was attained while a purity of 100% was reached in the case of Tyr 3 -Octreotide with HYNIC. The biological distribution of HYNIC-Tyr 3 -Octreotide has been studied in rats. (author)

  9. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  10. Solid-phase synthesis of polyamine toxin analogues

    DEFF Research Database (Denmark)

    Kromann, Hasse; Krikstolaityte, Sonata; Andersen, Anne J

    2002-01-01

    The wasp toxin philanthotoxin-433 (PhTX-433) is a nonselective and noncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are extensively used for the characterization of subtypes of ionotropic glutamate...... receptors, in particular Ca(2+)-permeable AMPA and kainate receptors. We have previously shown that an analogue of PhTX-433 with one of the amino groups replaced by a methylene group, philanthotoxin-83 (PhTX-83) is a selective and potent antagonist of AMPA receptors. We now describe the solid...... of analogues, the acyl moiety of PhTX-83 was replaced by acids of different size and lipophilicity. Using electrophysiological techniques, PhTX-56 was shown to be a highly potent (K(i) = 3.3 +/- 0.78 nM) and voltage-dependent antagonist of homomeric GluR1 receptors and was more than 1000-fold less potent when...

  11. New Immunosuppressive Sphingoid Base and Ceramide Analogues in Wild Cordyceps

    Science.gov (United States)

    Mi, Jia-Ning; Han, Yuwei; Xu, Yingqiong; Kou, Junping; Wang, Jing-Rong; Jiang, Zhi-Hong

    2016-01-01

    A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps. PMID:27966660

  12. Higher-dimensional analogues of Donaldson-Witten theory

    International Nuclear Information System (INIS)

    Acharya, B.S.; Spence, B.

    1997-01-01

    We present a Donaldson-Witten-type field theory in eight dimensions on manifolds with Spin(7) holonomy. We prove that the stress tensor is BRST exact for metric variations preserving the holonomy and we give the invariants for this class of variations. In six and seven dimensions we propose similar theories on Calabi-Yau threefolds and manifolds of G 2 holonomy, respectively. We point out that these theories arise by considering supersymmetric Yang-Mills theory defined on such manifolds. The theories are invariant under metric variations preserving the holonomy structure without the need for twisting. This statement is a higher-dimensional analogue of the fact that Donaldson-Witten field theory on hyper-Kaehler 4-manifolds is topological without twisting. Higher-dimensional analogues of Floer cohomology are briefly outlined. All of these theories arise naturally within the context of string theory. (orig.)

  13. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  14. Rubrene analogues with the aggregation-induced emission enhancement behaviour

    DEFF Research Database (Denmark)

    Zhang, Xiaoxu; Sørensen, Jakob Kryger; Fu, Xiaowei

    2014-01-01

    In the light of the principle of aggregation-induced emission enhancement (AIEE), the rubrene analogue with orange light-emitting properties is designed and synthesized by substituting the phenyl side groups of rubrene with thienyl groups. To the best of our knowledge, this is the first report on...... on the synthesis of rubrene with AIEE behaviour, thus paving the way for the development of light-emitting rubrene derivatives. This journal is...

  15. Synthetic analogues of natural semiochemicals as promising insect control agents

    International Nuclear Information System (INIS)

    Ujvary, Istvan; Toth, Miklos; Guerin, Patrick

    2000-01-01

    After decades of research and development, insect pheromones and other semiochemicals became indispensable tools of ecologically based agricultural pest and disease vector management programmes with main uses as: 1) detection and population monitoring of emerging and migrating insects, 2) mass trapping of insects, 3) combined formulation of semiochemicals and insecticides ('lure-and-kill'), and 4) mating disruption with specially formulated pheromone components. In spite of their demonstrated safety and biodegradability, the direct application of these semiochemicals for pest control has not fulfilled initial expectations. Nonetheless considerable field experience has been accumulated (Carde and Minks 1995). Evidently, two important factors limit the practical potential of these substances: 1) inherent in their particular mode of action, semiochemicals, especially pheromones, are effectively cleared by specific enzymes in the insect antennae, and 2) some of these compounds contain labile functional moieties that are prone to degradation (oxidation, isomerisation and polymerisation) under field conditions. Appropriate chemical modifications of these natural compounds, however, can circumvent these problems by providing synthetic analogues (sometimes also called parapheromones or antipheromones; for early studies, see Roelofs and Comeau 1971, Payne et al. 1973) which in ideal cases are not only more potent and environmentally acceptable but more economical as well. It should also be mentioned that many effective attractants have been discovered through the empirical screening of synthetic chemicals, some of which have actually turned out to be structural relatives of natural semiochemicals of the particular insect. In this paper, selected case studies of analogues of sex pheromones and kairomones will be presented. The examples from our work include nitrile bioisosteres of labile aldehyde pheromone components of the cranberry girdler moth, Chrysoteuchia topiaria

  16. Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P.; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-01

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

  17. Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-02

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. The Two-Dimensional Analogue of General Relativity

    OpenAIRE

    Lemos, José P. S.; Sá, Paulo M.

    1993-01-01

    General Relativity in three or more dimensions can be obtained by taking the limit $\\omega\\rightarrow\\infty$ in the Brans-Dicke theory. In two dimensions General Relativity is an unacceptable theory. We show that the two-dimensional closest analogue of General Relativity is a theory that also arises in the limit $\\omega\\rightarrow\\infty$ of the two-dimensional Brans-Dicke theory.

  19. Matrix diffusion model. In situ tests using natural analogues

    International Nuclear Information System (INIS)

    Rasilainen, K.

    1997-11-01

    Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories

  20. Matrix diffusion model. In situ tests using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rasilainen, K. [VTT Energy, Espoo (Finland)

    1997-11-01

    Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories. 98 refs. The thesis includes also eight previous publications by author.

  1. (18)F-labelled metomidate analogues as adrenocortical imaging agents.

    Science.gov (United States)

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Långström, Bengt

    2009-05-01

    Two- and one-step syntheses of (18)F-labelled analogues of metomidate, such as 2-[(18)F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[(18)F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[(18)F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[(18)F]fluoroethyl 4-methylbenzenesulfonate or 3-[(18)F]fluoropropyl 4-methylbenzenesulfonate. These were used as (18)F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46+/-3% and 79+/-30%, respectively. Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  2. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  3. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry...... including MSNT-mediated esterification of both support-bound alcohols and carboxylic acids has been implemented successfully. Copyright (C) 1996 Elsevier Science Ltd....

  4. Alkaloids of family Amaryllidaceae and their analogues as potential drugs

    OpenAIRE

    Kavková, Zuzana

    2016-01-01

    Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Zuzana Kavková Supervisor: doc. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Alkaloids of family Amaryllidaceae and their analogues as potential drugs The object of this diploma thesis was to prepare derivatives of alkaloids of Amaryllidaceae family and to deal with their biological activity. These alkaloids are famous for their antibacterial, antiinfectives, a...

  5. Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer

    Science.gov (United States)

    2006-06-01

    product analogs. J Am Chem Soc 1978; 100: 2551–2553. 39 Burri C, Brun R. Eflornithine for the treatment of human African trypanosomiasis . Parasitol Res...ototoxicity) at high therapeutic doses [29]. Currently, DFMO is the front-line agent in the treatment of African trypanosomiasis and is undergoing...Polyamine Analogues in Human Breast Cancer. PRINCIPAL INVESTIGATOR: Yi Huang, M.D., Ph.D. CONTRACTING ORGANIZATION: Johns

  6. Bisphenol A and Its Analogues Activate Human Pregnane X Receptor

    OpenAIRE

    Sui, Yipeng; Ai, Ni; Park, Se-Hyung; Rios-Pilier, Jennifer; Perkins, Jordan T.; Welsh, William J.; Zhou, Changcheng

    2012-01-01

    Background: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA and its analogues are present in environmental and human samples. Many endocrine-disrupting chemicals, including BPA, have been shown to activate the pregnane X receptor (PXR), a nuclear receptor that functions as a master regulator of xenobiotic metabolism. However, the detailed mechanism by which these chemicals activate PXR remains unknown. Objective: We investigated the mechanism by which BPA ...

  7. Manipulating lightcone fluctuations in an analogue cosmic string

    Directory of Open Access Journals (Sweden)

    Jiawei Hu

    2018-02-01

    Full Text Available We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

  8. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  9. Degludec: the new ultra-long insulin analogue.

    Science.gov (United States)

    Tambascia, Marcos Antonio; Eliaschewitz, Freddy Goldberg

    2015-01-01

    The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, "De") and the attachment, via a glutamic acid linker ("glu"), of a 16-carbon fatty diacid (hexadecanoic diacid, "dec") to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26-52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia.

  10. Natural analogue studies as supplements to biomineralization research

    International Nuclear Information System (INIS)

    McNeil, M.B.

    1995-01-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu 4 SO 4 (OH) 6· H 2 O] and mineral morphologies unusual in corrosion [malachite, Cu 2 CO 3 (OH) 2 , rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena

  11. Do film soundtracks contain nonlinear analogues to influence emotion?

    Science.gov (United States)

    Blumstein, Daniel T.; Davitian, Richard; Kaye, Peter D.

    2010-01-01

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly regarded films to generate a set of highly ranked action/adventure, dramatic, horror and war films. We then scored the presence of a variety of nonlinear analogues in these film soundtracks. Dramatic films suppressed noise of all types, contained more abrupt frequency transitions and musical sidebands, and fewer noisy screams than expected. Horror films suppressed abrupt frequency transitions and musical sidebands, but had more non-musical sidebands, and noisy screams than expected. Adventure films had more male screams than expected. Together, our results suggest that film-makers manipulate sounds to create nonlinear analogues in order to manipulate our emotional responses. PMID:20504815

  12. Design and synthesis of biotin analogues reversibly binding with streptavidin.

    Science.gov (United States)

    Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

    2015-04-01

    Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G. Saulnier and W. Statham

    2006-04-16

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

  14. Manipulating lightcone fluctuations in an analogue cosmic string

    Science.gov (United States)

    Hu, Jiawei; Yu, Hongwei

    2018-02-01

    We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

  15. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis.

    Science.gov (United States)

    Branis, Natalia M; Wittlin, Steven D

    2015-01-01

    Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA) after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35-7.45), bicarbonate 16 mmol/L (22-29 mmol/L), and anion gap 19 mmol/L (8-16 mmol/L). Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA) availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  16. On the Use of the Analogue Transformation Acoustics in Aeroacoustics

    Directory of Open Access Journals (Sweden)

    Umberto Iemma

    2017-01-01

    Full Text Available The objective of the paper is the assessment of the Analogue Transformation Acoustics (ATA in the design of acoustic metamaterial for aeronautical applications. The work focuses on the consistency of the background flow resulting from the application of the ATA with the equations governing the potential aerodynamics. Indeed, in case of acoustic perturbations propagating within moving media, the convective terms in the governing equations are responsible for the failure of formal invariance under the action of conformal mappings. The ATA approach overcomes this limitation, introducing the possibility of handling the convective form of the wave equation in a straightforward and elegant way. It is based on the concept of analogue space-time and fully relies on the analytical tools of Lorentzian differential geometry. The present paper analyses the relationship between the analogue velocity field with a realistic potential flow. The method is validated through numerical simulations using two widely assessed acoustic cloaking problems. The preliminary results obtained show that the use of numerical, quasi-conformal mappings can lead to transformed streamlines negligibly deviating from those of the potential velocity field satisfying the fluid-dynamic conservation laws, but with incompatible intensity of the local velocity.

  17. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    International Nuclear Information System (INIS)

    G.J. Saulnier Jr; W. Statham

    2006-01-01

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO 2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 ± 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory analysis

  18. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

  19. Toward Practical Secure Stable Matching

    Directory of Open Access Journals (Sweden)

    Riazi M. Sadegh

    2017-01-01

    Full Text Available The Stable Matching (SM algorithm has been deployed in many real-world scenarios including the National Residency Matching Program (NRMP and financial applications such as matching of suppliers and consumers in capital markets. Since these applications typically involve highly sensitive information such as the underlying preference lists, their current implementations rely on trusted third parties. This paper introduces the first provably secure and scalable implementation of SM based on Yao’s garbled circuit protocol and Oblivious RAM (ORAM. Our scheme can securely compute a stable match for 8k pairs four orders of magnitude faster than the previously best known method. We achieve this by introducing a compact and efficient sub-linear size circuit. We even further decrease the computation cost by three orders of magnitude by proposing a novel technique to avoid unnecessary iterations in the SM algorithm. We evaluate our implementation for several problem sizes and plan to publish it as open-source.

  20. Towards stable acceleration in LINACS

    CERN Document Server

    Dubrovskiy, A D

    2014-01-01

    Ultra-stable and -reproducible high-energy particle beams with short bunches are needed in novel linear accelerators and, in particular, in the Compact Linear Collider CLIC. A passive beam phase stabilization system based on a bunch compression with a negative transfer matrix element R56 and acceleration at a positive off-crest phase is proposed. The motivation and expected advantages of the proposed scheme are outlined.

  1. Benchmarking the Sandbox: Quantitative Comparisons of Numerical and Analogue Models of Brittle Wedge Dynamics (Invited)

    Science.gov (United States)

    Buiter, S.; Schreurs, G.; Geomod2008 Team

    2010-12-01

    When numerical and analogue models are used to investigate the evolution of deformation processes in crust and lithosphere, they face specific challenges related to, among others, large contrasts in material properties, the heterogeneous character of continental lithosphere, the presence of a free surface, the occurrence of large deformations including viscous flow and offset on shear zones, and the observation that several deformation mechanisms may be active simultaneously. These pose specific demands on numerical software and laboratory models. By combining the two techniques, we can utilize the strengths of each individual method and test the model-independence of our results. We can perhaps even consider our findings to be more robust if we find similar-to-same results irrespective of the modeling method that was used. To assess the role of modeling method and to quantify the variability among models with identical setups, we have performed a direct comparison of results of 11 numerical codes and 15 analogue experiments. We present three experiments that describe shortening of brittle wedges and that resemble setups frequently used by especially analogue modelers. Our first experiment translates a non-accreting wedge with a stable surface slope. In agreement with critical wedge theory, all models maintain their surface slope and do not show internal deformation. This experiment serves as a reference that allows for testing against analytical solutions for taper angle, root-mean-square velocity and gravitational rate of work. The next two experiments investigate an unstable wedge, which deforms by inward translation of a mobile wall. The models accommodate shortening by formation of forward and backward shear zones. We compare surface slope, rate of dissipation of energy, root-mean-square velocity, and the location, dip angle and spacing of shear zones. All models show similar cross-sectional evolutions that demonstrate reproducibility to first order. However

  2. Is the pain visual analogue scale linear and responsive to change? An exploration using Rasch analysis.

    Directory of Open Access Journals (Sweden)

    Paula Kersten

    Full Text Available OBJECTIVES: Pain visual analogue scales (VAS are commonly used in clinical trials and are often treated as an interval level scale without evidence that this is appropriate. This paper examines the internal construct validity and responsiveness of the pain VAS using Rasch analysis. METHODS: Patients (n = 221, mean age 67, 58% female with chronic stable joint pain (hip 40% or knee 60% of mechanical origin waiting for joint replacement were included. Pain was scored on seven daily VASs. Rasch analysis was used to examine fit to the Rasch model. Responsiveness (Standardized Response Means, SRM was examined on the raw ordinal data and the interval data generated from the Rasch analysis. RESULTS: Baseline pain VAS scores fitted the Rasch model, although 15 aberrant cases impacted on unidimensionality. There was some local dependency between items but this did not significantly affect the person estimates of pain. Daily pain (item difficulty was stable, suggesting that single measures can be used. Overall, the SRMs derived from ordinal data overestimated the true responsiveness by 59%. Changes over time at the lower and higher end of the scale were represented by large jumps in interval equivalent data points; in the middle of the scale the reverse was seen. CONCLUSIONS: The pain VAS is a valid tool for measuring pain at one point in time. However, the pain VAS does not behave linearly and SRMs vary along the trait of pain. Consequently, Minimum Clinically Important Differences using raw data, or change scores in general, are invalid as these will either under- or overestimate true change; raw pain VAS data should not be used as a primary outcome measure or to inform parametric-based Randomised Controlled Trial power calculations in research studies; and Rasch analysis should be used to convert ordinal data to interval data prior to data interpretation.

  3. Is the Pain Visual Analogue Scale Linear and Responsive to Change? An Exploration Using Rasch Analysis

    Science.gov (United States)

    Kersten, Paula; White, Peter J.; Tennant, Alan

    2014-01-01

    Objectives Pain visual analogue scales (VAS) are commonly used in clinical trials and are often treated as an interval level scale without evidence that this is appropriate. This paper examines the internal construct validity and responsiveness of the pain VAS using Rasch analysis. Methods Patients (n = 221, mean age 67, 58% female) with chronic stable joint pain (hip 40% or knee 60%) of mechanical origin waiting for joint replacement were included. Pain was scored on seven daily VASs. Rasch analysis was used to examine fit to the Rasch model. Responsiveness (Standardized Response Means, SRM) was examined on the raw ordinal data and the interval data generated from the Rasch analysis. Results Baseline pain VAS scores fitted the Rasch model, although 15 aberrant cases impacted on unidimensionality. There was some local dependency between items but this did not significantly affect the person estimates of pain. Daily pain (item difficulty) was stable, suggesting that single measures can be used. Overall, the SRMs derived from ordinal data overestimated the true responsiveness by 59%. Changes over time at the lower and higher end of the scale were represented by large jumps in interval equivalent data points; in the middle of the scale the reverse was seen. Conclusions The pain VAS is a valid tool for measuring pain at one point in time. However, the pain VAS does not behave linearly and SRMs vary along the trait of pain. Consequently, Minimum Clinically Important Differences using raw data, or change scores in general, are invalid as these will either under- or overestimate true change; raw pain VAS data should not be used as a primary outcome measure or to inform parametric-based Randomised Controlled Trial power calculations in research studies; and Rasch analysis should be used to convert ordinal data to interval data prior to data interpretation. PMID:24921952

  4. Quantum Analogues: From Phase Transitions to Black Holes and Cosmology

    International Nuclear Information System (INIS)

    Liberati, Stefano

    2008-01-01

    'And I cherish more than anything else the analogies, my most trustworthy masters. They know all the secrets of nature, and they ought to be least neglected in geometry.' These words of the great astronomer Johannes Kepler embody the philosophy behind the research recounted in this interesting book-a book composed of nine selected lectures (and a nice introduction by Bill Unruh) from the international workshop on 'Quantum Simulations via Analogues', which was held in the Max Planck Institute for the Physics of Complex Systems in Dresden during the summer of 2005. Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. However the last decade has seen a remarkable and steady development of analogue gravity models based on condensed matter systems, leading to some hundreds of published articles, numerous workshops, and several books. While the main driver for this booming field has definitely been the puzzling physics associated with quantum effects in black holes, more recently much attention has also been devoted to other interesting issues-such as cosmological particle production or the cosmological constant problem. Moreover, together with these new themes there has been a persistent interest in the possibility of simulating cosmic topological defects in the laboratory (although it should be said that momentum for this line of research has been somewhat weakened by the progressive decrease of interest in cosmological topological defects as an alternative to inflationary scenarios). All these aspects are faithfully accounted for in this book, which does a good job at presenting a vivid snapshot of many (if not quite all) of the most interesting lines of research in the field. All the articles have a self-consistent structure-which allows one to read them in arbitrary order and appreciate the full richness of each topic. However, when considered together I would say that they also provide a

  5. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  6. Alligator Rivers Analogue Project. Final Report - Volume 1

    International Nuclear Information System (INIS)

    Duerden, P.; Lever, D.A.; Sverjensky, D.A.; Townley, L.R.

    1992-01-01

    This summary report, which highlights the work and findings of the Alligator Rivers Analogue Project (ARAP) is one of a series of 16 volumes, listed below. Detailed descriptions and results are provided in Volumes 2 to 16. Full acknowledgment to individual contributions is provided in the individual reports, and in Appendix I of this report. The findings from the technical studies are discussed in the context of assessments of the long-term performance of geological repositories for radioactive wastes, which are being undertaken in many countries. They are also considered in an integrated 'Scenario Development' approach, aimed to understand the formation of the ore deposit. Despite their inherent uncertainties, the findings provide a basis for assessing the way in which radionuclides will migrate in environments with a variety of geologic settings and over a range of different geologic timescales. Thus, section 2 of this report discusses the concept of using uranium deposits as natural analogues and refers to a number of such studies, including those at the Koongarra deposit in the Alligator Rivers Region of the Northern Territory of Australia. Section 3 reviews early scientific work in the Alligator Rivers Region and summarises the results of the analogue studies undertaken between 1981 and 1987 that were funded by the US Nuclear Regulatory Commission (USNRC) and the UK Department of the Environment (UKDoE). Section 4 describes the objectives of ARAP and the manner in which the study was conducted and provides a general outline of the project and a summary of the findings. A general description of the Koongarra ore deposit, the focus of ARAP, is provided in Section 5, with Sections 6-13 providing summaries of the work carried out to characterise the site in detail and provide data for modelling. Sections 14-18 discuss how this data was used in modelling and how the results may be applied for performance assessment studies. Finally, Section 19 considers the

  7. Stable Hemiaminals: 2-Aminopyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Anna Kwiecień

    2015-08-01

    Full Text Available Stable hemiaminals can be obtained in the one-pot reaction between 2-aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents on the phenyl ring and pyrimidine ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess a tetrahedral carbon atom constituting a stereogenic centre. As the result of crystallisation in centrosymmetric space groups both enantiomers are present in the crystal structure.

  8. Organic synthesis with stable isotopes

    International Nuclear Information System (INIS)

    Daub, G.H.; Kerr, V.N.; Williams, D.L.; Whaley, T.W.

    1978-01-01

    Some general considerations concerning organic synthesis with stable isotopes are presented. Illustrative examples are described and discussed. The examples include DL-2-amino-3-methyl- 13 C-butanoic-3,4- 13 C 2 acid (DL-valine- 13 C 3 ); methyl oleate-1- 13 C; thymine-2,6- 13 C 2 ; 2-aminoethanesulfonic- 13 C acid (taurine- 13 C); D-glucose-6- 13 C; DL-2-amino-3-methylpentanoic-3,4- 13 C 2 acid (DL-isoleucine- 13 C 2 ); benzidine- 15 N 2 ; and 4-ethylsulfonyl-1-naphthalene-sulfonamide- 15 N

  9. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  10. Pena Blanca Natural Analogue Project: Summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-02-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  11. Application of FPGA's in Flexible Analogue Electronic Image Generator Design

    Directory of Open Access Journals (Sweden)

    Peter Kulla

    2006-01-01

    Full Text Available This paper focuses on usage of the FPGAs (Field Programmable Gate Arrays Xilinx as a part of our more complex workdedicated to design of flexible analogue electronic images generator for application in TV measurement technique or/and TV servicetechnique or/and education process. The FPGAs performs here the role of component colour R, G, B, synchronization and blanking signals source. These signals are next processed and amplified in other parts of the generator as NTSC/PAL source encoder and RF modulator. The main aim of this paper is to show the possibilities how with suitable development software use a FPGAs in analog TV technology.

  12. Captopril analogues as metallo-β-lactamase inhibitors.

    Science.gov (United States)

    Yusof, Yusralina; Tan, Daniel T C; Arjomandi, Omid Khalili; Schenk, Gerhard; McGeary, Ross P

    2016-03-15

    A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure-activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Synthesis, Preliminary Bioevaluation and Computational Analysis of Caffeic Acid Analogues

    Directory of Open Access Journals (Sweden)

    Zhiqian Liu

    2014-05-01

    Full Text Available A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.

  14. Optical analogues of nanostructures with Rashba–Dresselhaus interactions

    International Nuclear Information System (INIS)

    Dragoman, Daniela

    2014-01-01

    We demonstrate that light propagation through uniaxial crystals with suitably oriented optical axes is quantitatively analogous to electron propagation in a two-dimensional electron gas in the presence of Rashba and/or Dresselhaus effects. It is shown that, through an appropriate shaping of light beams and a rigorous control of their incidence angle on properly oriented uniaxial crystals, it is possible to investigate independently the effects of angular divergence and energy broadening on electron wavefunction evolution. Such optical analogues could be useful in designing spintronic devices, in particular those relying on the equality of Rashba and Dresselhaus coefficients. (paper)

  15. A high speed digital-to-analogue converter

    International Nuclear Information System (INIS)

    Hallgren, B.I.

    1974-02-01

    An 8-bit Digital-to-Analogue converter of the current-weighting type has been constructed using 8 monolithic integrated circuit transistor arrays -one for each bit. The D/A-converter has a voltage output within the range 0 to -2V. The settling time to within half of the least significant bit is about 50 nsec. The temperature dependence and transient response of the converter has been analysed using computer aided design techniques. A comparison is made between the experimental and simulated transient performance. (Auth.)

  16. Pena blanca natural analogue project: summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

    2010-12-08

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  17. Isosteric phosphonate pyrrolidine-based dinucleoside monophosphate analogues

    Czech Academy of Sciences Publication Activity Database

    Vaněk, Václav; Buděšínský, Miloš; Kavenová, Ivana; Rinnová, Markéta; Rosenberg, Ivan

    2003-01-01

    Roč. 22, 5/8 (2003), s. 1065-1067 ISSN 1525-7770. [International Roundtable Nucleosides, Nucleotides and Nucleic Acids /15./. Leuven, 10.09.2002-14.09.2002] R&D Projects: GA ČR GA203/01/1166; GA AV ČR IAA4055101 Institutional research plan: CEZ:AV0Z4055905 Keywords : pyrrolidine-based phosphonate nucleotides * ApA analogues * triplex Subject RIV: CC - Organic Chemistry Impact factor: 0.813, year: 2003

  18. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    Directory of Open Access Journals (Sweden)

    B S Jackson

    2017-04-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA. To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  19. Are Structural Analogues to Bisphenol A Safe Alternatives?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Mikael

    2014-01-01

    Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives......, there is a risk of effects similar to BPA.Objectives: The aim was to elucidate and compare the hazards of bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), bisphenol S (BPS) and 4-cumylphenol (HPP) to BPA.Methods: In vitro studies on steroidogenesis, receptor activity, and biomarkers of effect, as well...

  20. Synthesis of Analogues of Thyroid Hormones: Nuclear Receptor Modulators

    Directory of Open Access Journals (Sweden)

    Guilherme Vieira de Castro

    2015-09-01

    Full Text Available Thyroid hormones are essential for the development and differentiation of all cells of the human body. This work reports the synthesis of some synthetic structural analogues of thyroid hormones, which may be modulators of the thyroid hormone receptor. The known compounds GC-1 (Sobetirome and CG-24 were successfully prepared and two novel analogous molecules were also synthesized by a new and efficient synthetic methodology. DOI: http://dx.doi.org/10.17807/orbital.v7i3.739  

  1. Tidal regimes and salt marshes - the River Hamble analogue

    International Nuclear Information System (INIS)

    Gray, A.J.; Moy, I.L.; Warman, E.A.; Dawson, F.H.; Henville, P.

    1993-01-01

    Construction of estuarine tidal-energy barrages has a potentially major effect on the tidal regime of the estuary, particularly upstream of a barrage. Because tidal regime largely controls the distribution and species composition of intertidal plant and animal communities, it is important to understand how barrages may affect such communities. The main objectives of the research described in this report were to relate recent changes in tidal regime within an embanked area of salt marsh and mudflat to changes in the distribution of plant species. This was to test predictions about tidal control of species' range and to assess the site's suitability as an analogue of post-barrage conditions. (author)

  2. Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond.

    Science.gov (United States)

    Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei

    2016-06-08

    Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.

  3. Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond

    OpenAIRE

    Ling-Na Wang; Wei Wang; Masao Hattori; Mohsen Daneshtalab; Chao-Mei Ma

    2016-01-01

    Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylq...

  4. Excited state properties of 2‧-hydroxychalcone analogues functionalized with a diene moiety studied by steady state and laser flash photolysis

    Science.gov (United States)

    Shinozaki, Yukino; Yamaji, Minoru; Arai, Tatsuo

    2018-01-01

    2‧-Hydroxychalcone (HC) analogues 1 and 2 having a diene part tethering the phenyl and naphthyl chromophores, respectively, were prepared, and their photochemical and photophysical properties were studied. Fluorescence from these compounds was absent in solution and the solid state. Based on the results obtained upon steady state and laser flash photolyses, compound 2 was found to be substantially stable on photoirradiation without undergoing intersystem crossing to the triplet state whereas compounds 1 showed transient absorption due to the triplet tautomer. The deactivation processes in the excited states were discussed by considering energetic reaction diagrams for the corresponding tautomers and isomers.

  5. The arsonomethyl analogue of adenosine 5'-phosphate. An uncoupler of adenylate kinase.

    Science.gov (United States)

    Adams, S R; Sparkes, M J; Dixon, H B

    1984-01-01

    Adenosine was converted into the arsonomethyl analogue of AMP. The reactions used provide a general route for converting an alcohol, R-CH2-OH, into the arsonomethyl analogue, R-CH2-CH2-AsO3H2, of its phosphate, R-CH2-O-PO3H2. The analogue of AMP proves to be a substrate for rabbit adenylate kinase, which shows a limiting velocity with it of 1/17 that with AMP, a Michaelis constant raised 70-fold to about 10 mM, and hence a specificity constant lowered about 1200-fold. The product of transfer of a phospho group from ATP to the analogue is, like all anhydrides of arsonic acids, unstable to hydrolysis, and so breaks down to yield orthophosphate and regenerate the analogue. Hence adenylate kinase is converted into an ATPase by the presence of the analogue. PMID:6089748

  6. Stable cosmology in chameleon bigravity

    Science.gov (United States)

    De Felice, Antonio; Mukohyama, Shinji; Oliosi, Michele; Watanabe, Yota

    2018-02-01

    The recently proposed chameleonic extension of bigravity theory, by including a scalar field dependence in the graviton potential, avoids several fine-tunings found to be necessary in usual massive bigravity. In particular it ensures that the Higuchi bound is satisfied at all scales, that no Vainshtein mechanism is needed to satisfy Solar System experiments, and that the strong coupling scale is always above the scale of cosmological interest all the way up to the early Universe. This paper extends the previous work by presenting a stable example of cosmology in the chameleon bigravity model. We find a set of initial conditions and parameters such that the derived stability conditions on general flat Friedmann background are satisfied at all times. The evolution goes through radiation-dominated, matter-dominated, and de Sitter eras. We argue that the parameter space allowing for such a stable evolution may be large enough to encompass an observationally viable evolution. We also argue that our model satisfies all known constraints due to gravitational wave observations so far and thus can be considered as a unique testing ground of gravitational wave phenomenologies in bimetric theories of gravity.

  7. Synthesis of phosphono analogues of dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

    Science.gov (United States)

    Page, P; Blonski, C; Périé, J

    1999-07-01

    The present paper describes the synthetic routes of six phosphono analogues of dihydroxyacetone phosphate and five phosphono analogues of glyceraldehyde 3-phosphate through alpha-, beta- and gamma-hydroxyphosphonate esters precursors containing a protected carbonyl group. In some situations, depending on the sequence used for the deprotection of the phosphonate and carbonyl groups, the aldol/ketol rearrangement allowed the synthesis of either dihydroxyacetone phosphate or glyceraldehyde 3-phosphate analogues from the same precursors. All these analogues are of interest both as active-site probes and as potential substrates for glycolytic enzymes such as fructose 1,6-diphosphate aldolases (EC 4.1.2.13).

  8. Applications of natural analogue studies to Yucca Mountain as a potential high level radioactive waste repository

    International Nuclear Information System (INIS)

    1995-02-01

    The 5-member group convened in Las Vegas, Nov. 11-13, 1991, to clarify the extent to which studies of natural analogues can assist the Yucca Mountain site characterization (SC) project. This document is to provide guidance and recommendations to DOE for the implementation of natural analogue studies in the SC program. Performance assessment, integrity of engineered barriers, and communication to the public and the scientific community are stressed. The reference design being developed by Babcock ampersand Wilcox Fuel Company are reviewed. Guidelines for selecting natural analogues are given. Quality assurance is discussed. Recommendations are given for developing an effective natural analogue program within the SC program

  9. Isolation and structural identification of a novel minoxidil analogue in an illegal dietary supplement: triaminodil.

    Science.gov (United States)

    Lee, Ji Hyun; Park, Han Na; Park, Hyoung Joon; Kim, Nam Sook; Park, Sung-Kwan; Lee, Jongkook; Baek, Sun Young

    2018-01-01

    A new minoxidil analogue was detected in an illegal dietary supplement advertised as a hair-growth treatment. The analogue was identified using ultra-performance liquid chromatography (UPLC), high-resolution mass spectrometry (LC-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound was structurally elucidated as a minoxidil analogue in which the piperidinyl group of minoxidil was replaced with a pyrrolidinyl group corresponding to a molecular formula of C 8 H 13 N 5 O. The new analogue has been named triaminodil. As this is the first report of the compound, there are no chemical, toxicology or pharmacological data available.

  10. Martian analogue test site - pilbara craton, western Australia

    Science.gov (United States)

    Brown, A.; Allwood, A.; Walter, M. R.; van Kranendonk, M.

    All exploration for life elsewhere depends on extrapolation from our knowledge of Earth. If the target is former microbial life, for example on Mars, there is no better analogue on Earth than the 3.5 billion year old rocks of the Pilbara region, Western Australia. This area is home to signs of the earliest life on Earth in the form of microbe, many famous stromatolitic horizons and carbon isotope biosignatures. These occur in a volcanic terrain, with weathering and hydrothermal alteration, which also has some similarity to Mars. The geology of this region is known in detail after decades of mapping and other studies. Current work includes studies to resolve disputes about the biogenicity of the microfossils and stromatolites. On balance, biological origins are most likely. In any event, problems of demonstrating biogenicity on other planets will be far more severe, and the work on the Pilbara materials will illuminate those problems. Also underway is mineral mapping of the volcanic, hydrothermal and fossiliferous units using both airborne and hand-held short-wave infrared spectrometers, We are able to map the fossiliferous units using this technique and contend that it would be a powerful exploration technique on Mars and elsewhere. Using the Pilbara as an analogue for other bodies in the Solar System can extend to using it as a place to test instrument packages under realistic conditions. The region has good air and road access, and good supporting infrastructure.

  11. Integrating TEMPO and Its Analogues with Visible-Light Photocatalysis.

    Science.gov (United States)

    Lang, Xianjun; Zhao, Jincai

    2018-01-16

    Visible light has risen to become a very important facilitator for selective radical reactions enabled by well-cognized photocatalysts. The renaissance of visible-light photocatalysis on this matter partly relies on integrating it with other fields of catalysis. In parallel, 2,2,6,6-tetramethylpiperidin N-oxide (TEMPO), a quintessential persistent radical, has a wide range of uses owing to its exceptional redox behavior, which gives rise to its latest prominence in catalysis. Therefore, integrating the catalysis of TEMPO with photocatalysis to perform visible-light-induced selective reactions becomes a very convenient marriage of merits. In this context, the integration of different types of photocatalysts, including metal complexes, metal-free organic dyes, and semiconductors, with TEMPO for outstanding organic transformations will be summarized. To expand further the catalytic repertoire, the integration of TEMPOH analogues such as NHPI (N-hydroxyphthalimide) and NHS (N-hydroxysuccinimide) with photocatalysis will also be discussed. Hopefully, these advances will pave the way for more breakthroughs by integrating TEMPO and its analogues with photocatalysis to lead to a valuable blueprint for visible-light-induced selective organic transformations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. A Bosonic Analogue of a Topological Dirac Semi-Metal

    Science.gov (United States)

    Lapa, Matthew; Cho, Gil Young; Hughes, Taylor

    We construct a bosonic analogue of a two-dimensional topological Dirac Semi-Metal (DSM). The low-energy description of the most basic 2D DSM model consists of two Dirac cones at positions +/-k0 in momentum space. The local stability of the Dirac cones is guaranteed by a composite symmetry Z2, where  is time-reversal and  is inversion. This model also exhibits interesting time-reversal and inversion symmetry breaking electromagnetic responses. In this work we construct a bosonic analogue of a DSM by replacing each Dirac cone with a copy of the O (4) Nonlinear Sigma Model (NLSM) with topological theta term and theta angle θ = +/- π . One copy of this NLSM also describes the gapless surface termination of the 3D Bosonic Topological Insulator (BTI). We compute the time-reversal and inversion symmetry breaking electromagnetic responses for our model and show that they are twice the value one gets in the DSM case. We also investigate the local stability of the individual O (4) NLSM's in the BSM model. Along the way we clarify many aspects of the surface theory of the BTI including the electromagnetic response, the charges of vortex excitations, and the stability to symmetry-allowed perturbations. Nsf CAREER DMR-1351895.

  13. Classical analogue of an interstellar travel through a hydrodynamic wormhole

    Science.gov (United States)

    Euvé, L.-P.; Rousseaux, G.

    2017-09-01

    The classical theory of space-time, namely general relativity, suggests but does not demonstrate the existence of so-called wormholes allowing for interstellar journeys. Alternative proposals such as quantum gravity theories are developed nowadays to allow for wormhole travels by assuming hypothetical trans-Planckian effects at tiny scales. Here we show experimentally that analogue traversable and bidirectional wormholes exist in hydrodynamics following a suggestion by Wheeler. Using a water channel, we sent free surface waves on a countercurrent in an analogue gravity setup aiming at showing that hydrodynamic wormhole travels are controlled by a cascade of dispersive scales including surface tension effects: the capillary wavelength plays the role of a Planckian scale below which long gravity waves are transformed into short capillary waves that are able to move at speeds higher than the "flow" of space-time. Whereas our results do not apply to putative astrophysical wormholes per se, we anticipate that they will trigger new ideas to explore quantum gravity physics.

  14. Limonene hydroperoxide analogues show specific patch test reactions.

    Science.gov (United States)

    Christensson, Johanna Bråred; Hellsén, Staffan; Börje, Anna; Karlberg, Ann-Therese

    2014-05-01

    The fragrance terpene R-limonene is a very weak sensitizer, but forms allergenic oxidation products upon contact with air. The primary oxidation products of oxidized limonene, the hydroperoxides, have an important impact on the sensitizing potency of the oxidation mixture. One analogue, limonene-1-hydroperoxide, was experimentally shown to be a significantly more potent sensitizer than limonene-2-hydroperoxide in the local lymph node assay with non-pooled lymph nodes. To investigate the pattern of reactivity among consecutive dermatitis patients to two structurally closely related limonene hydroperoxides, limonene-1-hydroperoxide and limonene-2-hydroperoxide. Limonene-1-hydroperoxide, limonene-2-hydroperoxide, at 0.5% in petrolatum, and oxidized limonene 3.0% pet. were tested in 763 consecutive dermatitis patients. Of the tested materials, limonene-1-hydroperoxide gave most reactions, with 2.4% of the patients showing positive patch test reactions. Limonene-2-hydroperoxide and oxidized R-limonene gave 1.7% and 1.2% positive patch test reactions, respectively. Concomitant positive patch test reactions to other fragrance markers in the baseline series were frequently noted. The results are in accordance with the experimental studies, as limonene-1-hydroperoxide gave more positive patch test reactions in the tested patients than limonene-2-hydroperoxide. Furthermore, the results support the specificity of the allergenic activity of the limonene hydroperoxide analogues and the importance of oxidized limonene as a cause of contact allergy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Metabolites of saxitoxin analogues in bivalves contaminated by Gymnodinium catenatum.

    Science.gov (United States)

    Vale, Paulo

    2010-01-01

    Bivalve metabolites of saxitoxin analogues, not present in microalgae, were recently described as an important toxin fraction in mussels contaminated by Alexandrium tamarense. These possess very low fluorescence, and require mass spectrometry detection. HILIC-MS was implemented to look for these metabolites in bivalves contaminated during Gymnodinium catenatum blooms at the Portuguese coast. The presence of M1 was tentatively identified in several bivalves, ranging from estuarine (Mytilus galloprovinciallis, Cerastoderma edule and Ruditapes decussatus) to oceanic habitat (Donax trunculus and Ensis spp.). It was hypothesized that M1 could contribute to an important fraction of the profile of STX analogues. M1 was more abundant in estuarine bivalves that retain longer PSP toxins, in the following order: mussels>cockles>clams. These data highlight that the study by fluorimetry alone of the carbamoyl, N-sulfocarbamoyl, and decarbamoyl families is manifestly insufficient to fully understand toxin dynamics in bivalves feeding on G. catenatum without a proper study of hydroxybenzoate and hydroxylated M-toxins.

  16. Parabolic flights as Earth analogue for surface processes on Mars

    Science.gov (United States)

    Kuhn, Nikolaus J.

    2017-04-01

    The interpretation of landforms and environmental archives on Mars with regards to habitability and preservation of traces of life requires a quantitative understanding of the processes that shaped them. Commonly, qualitative similarities in sedimentary rocks between Earth and Mars are used as an analogue to reconstruct the environments in which they formed on Mars. However, flow hydraulics and sedimentation differ between Earth and Mars, requiring a recalibration of models describing runoff, erosion, transport and deposition. Simulation of these processes on Earth is limited because gravity cannot be changed and the trade-off between adjusting e.g. fluid or particle density generates other mismatches, such as fluid viscosity. Computational Fluid Dynamics offer an alternative, but would also require a certain degree of calibration or testing. Parabolic flights offer a possibility to amend the shortcomings of these approaches. Parabolas with reduced gravity last up to 30 seconds, which allows the simulation of sedimentation processes and the measurement of flow hydraulics. This study summarizes the experience gathered during four campaigns of parabolic flights, aimed at identifying potential and limitations of their use as an Earth analogue for surface processes on Mars.

  17. The role of natural analogues in safety assessment and acceptability

    International Nuclear Information System (INIS)

    Papp, Toenis

    1987-01-01

    The safety assessment must evaluate the level of safety for a repository, the confidence that can be placed on the assessment and how well the repository can meet the acceptance criteria of the society. Many of the processes and phenomena that govern the long term performance of a deep geologic repository for radioactive waste also take place in nature. To investigate these natural analogues and try to validate the models on which the safety assessment are based is a main task in the effort to build of confidence in the safety assessments. The assessment of the safety of a repository can, however, not only be based on good models. The possible role of natural analogues or natural evidence in other parts of the safety assessment is discussed. Specially with regard to - the need to demonstrate that all relevant processes have been taken into account, and that the important ones have been validated to an acceptable level for relevant parameters spans, -the definition and analysis of external scenarios for the safety assessment and for the claim that all reasonable scenarios have been addressed, - the public confidence in the long-term relevance of the acceptance criteria. (author)

  18. Historical space psychology: Early terrestrial explorations as Mars analogues

    Science.gov (United States)

    Suedfeld, Peter

    2010-03-01

    The simulation and analogue environments used by psychologists to circumvent the difficulties of conducting research in space lack many of the unique characteristics of future explorations, especially the mission to Mars. This paper suggests that appropriate additional analogues would be the multi-year maritime and terrestrial explorations that mapped the surface of the Earth in previous centuries. These, like Mars, often involved a hazardous trek through unknown territory, flanked by extended, dangerous voyages to and from the exploration sites. Characteristic issues included interpersonal relationships under prolonged stress, stretches of boredom interspersed with intense work demands, the impossibility of rescue, resupply, or other help from home, chronic danger, physical discomfort and lack of privacy, and the crucial role of the leader. Illustrative examples of one important factor, leadership style, are discussed. The examination of such expeditions can help to identify the psychological stressors that are likely to be experienced by Mars explorers, and can also indicate countermeasures to reduce the damaging impact of those stressors.

  19. A low-dimensional analogue of holographic baryons

    Science.gov (United States)

    Bolognesi, Stefano; Sutcliffe, Paul

    2014-04-01

    Baryons in holographic QCD correspond to topological solitons in the bulk. The most prominent example is the Sakai-Sugimoto model, where the bulk soliton in the five-dimensional spacetime of AdS-type can be approximated by the flat space self-dual Yang-Mills instanton with a small size. Recently, the validity of this approximation has been verified by comparison with the numerical field theory solution. However, multi-solitons and solitons with finite density are currently beyond numerical field theory computations. Various approximations have been applied to investigate these important issues and have led to proposals for finite density configurations that include dyonic salt and baryonic popcorn. Here we introduce and investigate a low-dimensional analogue of the Sakai-Sugimoto model, in which the bulk soliton can be approximated by a flat space sigma model instanton. The bulk theory is a baby Skyrme model in a three-dimensional spacetime with negative curvature. The advantage of the lower-dimensional theory is that numerical simulations of multi-solitons and finite density solutions can be performed and compared with flat space instanton approximations. In particular, analogues of dyonic salt and baryonic popcorn configurations are found and analysed.

  20. Stable isotope mass spectrometry in petroleum exploration

    International Nuclear Information System (INIS)

    Mathur, Manju

    1997-01-01

    The stable isotope mass spectrometry plays an important role to evaluate the stable isotopic composition of hydrocarbons. The isotopic ratios of certain elements in petroleum samples reflect certain characteristics which are useful for petroleum exploration

  1. Difluorothromboxane A2 and stereoisomers: Stable derivatives of thromboxane A2 with differential effects on platelets and blood vessels

    International Nuclear Information System (INIS)

    Morinelli, T.A.; Okwu, A.K.; Mais, D.E.; Halushka, P.V.; John, V.; Chen, Chienkuang; Fried, J.

    1989-01-01

    The present study reports on the selective effects on human platelets and canine saphenous veins of four stable difluorinated analogues and thromboxane A 2 (TXA 2 ), in which the characteristic 2,6-dioxa[3.1.1]bicycloheptane structure of TXA 2 has been retained. The four compounds differ in their stereochemistry of the 5,6 double bond and/or the 15-hydroxyl group. Only 10,10-difluoro-TXA 2 (compound I) with the natural stereochemistry of TXA 2 was an agonist in both platelets and canine saphenous veins. (15R)-10,10-Difluoro-TXA 2 (compound II), (5E)-10,10-difluoro-TXA 2 (compound III), and (5E,15R)-10,10-difluoro-TXA 2 (compound IV) were antagonists of platelet aggregation stimulated by compound I. However, compounds II, III, and IV stimulated contraction of canine saphenous veins. All four compounds could displace the TXA 2 /prostaglandin H 2 antagonist 9,11-dimethylmethano-11,12-methano-16-(3- 125 I-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-ω-tetranor-TXA 2 from its platelet receptor. These results support the existence of two subtypes of TXA 2 /prostaglandin H 2 receptors and emphasize the importance of the stereochemical requirements of these TXA 2 analogues for interaction with these receptors. These stable fluorinated TXA 2 analogues should prove useful tools for the further characterization of these and other TXA 2 /prostaglandin H 2 receptors

  2. The costal landslide from analogue experiments: perspectives and limitation

    Science.gov (United States)

    Del Ventisette, C.; Nolesini, T.; Moretti, S.; Fanti, R.

    2010-12-01

    Understanding the triggering mechanism of coastal landslides (triggered and/or developed at air-water interface) and their evolution is fundamental to evaluate their hazard and, predicting the energy, the associated tsunami risk. The aim of this work is to verify the suitability of analogue modelling to understand the triggering mechanism and the evolution of landslide along the costal line. As a starting case study the Sciara del Fuoco (SdF), northwest flank of the volcanic island of Stromboli (Italy), was chosen. The analogue modelling technique has been proven to represent an useful tool to understand many geological processes, as it allows studying the progressive deformation, providing also useful indications about the role of distinct factors controlling the final deformation pattern. The models simulated at a first approximation the geological geometries observed at Stromboli, a composite volcano forming the northernmost island of the Aeolian Archipelago (Tyrrhenian Sea). The activity of Stromboli volcano is characterized by a persistent mild explosive activity at the summit craters sporadically interrupted by episodes of lava effusion and violent paroxysmal explosions as in 2002-2003 and in 2007. During the 2002 effusion a large landslide occurred on the SdF. The landslide caused a tsunami, which produced severe damages along the island shores. A series of analogue models was performed to investigate the influence of two different types of triggering mechanism and the behaviour of landslides both in air and air-water interface: 1) surface bulging due to the intrusion of a dike; 2) accumulation of material due to an uppermost landslide or due to opening of a new vent. The models, constructed in a Plexiglas tank, were scaled to the natural prototype following the geometrical, rheological, kinematical and dynamical similarities (e.g. Hubbert, 1937; Ramberg, 1981). The modelling material (Fontainbleau sand and rice) was sieved on a slope, inclination of which

  3. Stable rotating dipole solitons in nonlocal media

    DEFF Research Database (Denmark)

    Lopez-Aguayo, Servando; Skupin, Stefan; Desyatnikov, Anton S.

    2006-01-01

    We present the first example of stable rotating two-soliton bound states in nonlinear optical media with nonlocal response. We show that, in contrast to media with local response, nonlocality opens possibilities to generate stable azimuthons.......We present the first example of stable rotating two-soliton bound states in nonlinear optical media with nonlocal response. We show that, in contrast to media with local response, nonlocality opens possibilities to generate stable azimuthons....

  4. Uses of stable isotopes in fish ecology

    Science.gov (United States)

    Analyses of fish tissues (other than otoliths) for stable isotope ratios can provide substantial information on fish ecology, including physiological ecology. Stable isotopes of nitrogen and carbon frequently are used to determine the mix of diet sources for consumers. Stable i...

  5. Periodicity of the stable isotopes

    CERN Document Server

    Boeyens, J C A

    2003-01-01

    It is demonstrated that all stable (non-radioactive) isotopes are formally interrelated as the products of systematically adding alpha particles to four elementary units. The region of stability against radioactive decay is shown to obey a general trend based on number theory and contains the periodic law of the elements as a special case. This general law restricts the number of what may be considered as natural elements to 100 and is based on a proton:neutron ratio that matches the golden ratio, characteristic of biological and crystal growth structures. Different forms of the periodic table inferred at other proton:neutron ratios indicate that the electronic configuration of atoms is variable and may be a function of environmental pressure. Cosmic consequences of this postulate are examined. (author)

  6. Stable States of Biological Organisms

    Science.gov (United States)

    Yukalov, V. I.; Sornette, D.; Yukalova, E. P.; Henry, J.-Y.; Cobb, J. P.

    2009-04-01

    A novel model of biological organisms is advanced, treating an organism as a self-consistent system subject to a pathogen flux. The principal novelty of the model is that it describes not some parts, but a biological organism as a whole. The organism is modeled by a five-dimensional dynamical system. The organism homeostasis is described by the evolution equations for five interacting components: healthy cells, ill cells, innate immune cells, specific immune cells, and pathogens. The stability analysis demonstrates that, in a wide domain of the parameter space, the system exhibits robust structural stability. There always exist four stable stationary solutions characterizing four qualitatively differing states of the organism: alive state, boundary state, critical state, and dead state.

  7. Theory of stable allocations II

    Directory of Open Access Journals (Sweden)

    Pantelić Svetlana

    2015-01-01

    Full Text Available The Swedish Royal Academy awarded the 2012 Nobel Prize in Economics to Lloyd Shapley and Alvin Roth, for the theory of stable allocations and the practice of market design. These two American researchers worked independently from each other, combining basic theory and empirical investigations. Through their experiments and practical design they generated a flourishing field of research and improved the performance of many markets. Shapley provided the fundamental theoretical contribution to this field of research, whereas Roth, a professor at the Harvard University in Boston, developed and upgraded these theoretical investigations by applying them to the American market of medical doctors. Namely, their research helps explain the market processes at work, for instance, when doctors are assigned to hospitals, students to schools and human organs for transplant to recipients.

  8. Stable massive particles at colliders

    Energy Technology Data Exchange (ETDEWEB)

    Fairbairn, M.; /Stockholm U.; Kraan, A.C.; /Pennsylvania U.; Milstead, D.A.; /Stockholm U.; Sjostrand, T.; /Lund U.; Skands, P.; /Fermilab; Sloan, T.; /Lancaster U.

    2006-11-01

    We review the theoretical motivations and experimental status of searches for stable massive particles (SMPs) which could be sufficiently long-lived as to be directly detected at collider experiments. The discovery of such particles would address a number of important questions in modern physics including the origin and composition of dark matter in the universe and the unification of the fundamental forces. This review describes the techniques used in SMP-searches at collider experiments and the limits so far obtained on the production of SMPs which possess various colour, electric and magnetic charge quantum numbers. We also describe theoretical scenarios which predict SMPs, the phenomenology needed to model their production at colliders and interactions with matter. In addition, the interplay between collider searches and open questions in cosmology such as dark matter composition are addressed.

  9. Gut peptide GLP-1 and its analogue, Exendin-4, decrease alcohol intake and reward.

    Directory of Open Access Journals (Sweden)

    Rozita H Shirazi

    Full Text Available Glucagon-like-peptide-1 (GLP-1 is a gut- and neuro-peptide with an important role in the regulation of food intake and glucose metabolism. Interestingly, GLP-1 receptors (GLP-1R are expressed in key mesolimbic reward areas (including the ventral tegmental area, VTA, innervated by hindbrain GLP-1 neurons. Recently GLP-1 has emerged as a potential regulator of food reward behavior, an effect driven by the mesolimbic GLP-1Rs. Its role in other reward behaviors remains largely unexplored. Since a considerable overlap has been suggested for circuitry controlling reward behavior derived from food and alcohol we hypothesized that GLP-1 and GLP-1Rs could regulate alcohol intake and alcohol reward. We sought to determine whether GLP-1 or its clinically safe stable analogue, Exendin-4, reduce alcohol intake and reward. To determine the potential role of the endogenous GLP-1 in alcohol intake we evaluated whether GLP-1R antagonist, Exendin 9-39, can increase alcohol intake. Furthermore, we set out to evaluate whether VTA GLP-1R activation is sufficient to reduce alcohol intake. Male Wistar rats injected peripherally with GLP-1 or Exendin-4 reduced their alcohol intake in an intermittent access two bottle free choice drinking model. Importantly, a contribution of endogenously released GLP-1 is highlighted by our observation that blockade of GLP-1 receptors alone resulted in an increased alcohol intake. Furthermore, GLP-1 injection reduced alcohol reward in the alcohol conditioned place preference test in mice. To evaluate the neuroanatomical substrate linking GLP-1 with alcohol intake/reward, we selectively microinjected GLP-1 or Exendin 4 into the VTA. This direct stimulation of the VTA GLP-1 receptors potently reduced alcohol intake. Our findings implicate GLP-1R signaling as a novel modulator of alcohol intake and reward. We show for the first time that VTA GLP-1R stimulation leads to reduced alcohol intake. Considering that GLP-1 analogues are already

  10. Climate Analogues for agricultural impact projection and adaptation – a reliability test

    Directory of Open Access Journals (Sweden)

    Swen P.M. Bos

    2015-10-01

    Full Text Available The climate analogue approach is often considered a valuable tool for climate change impact projection and adaptation planning, especially for complex systems that cannot be modelled reliably. Important examples are smallholder farming systems using agroforestry or other mixed-cropping approaches. For the projected climate at a particular site of interest, the analogue approach identifies locations where the current climate is similar to these projected conditions. By comparing baseline-analogue site pairs, information on climate impacts and opportunities for adaptation can be obtained. However, the climate analogue approach is only meaningful, if climate is a dominant driver of differences between baseline and analogue site pairs. For a smallholder farming setting on Mt. Elgon in Kenya, we tested this requirement by comparing yield potentials of maize and coffee (obtained from the IIASA Global Agro-ecological Zones dataset among 50 close analogue sites for different future climate scenarios and models, and by comparing local ecological knowledge and farm characteristics for one baseline-analogue pair.Yield potentials among the 50 closest analogue locations varied strongly within all climate scenarios, hinting at factors other than climate as major drivers of what the analogue approach might interpret as climate effects. However, on average future climatic conditions seemed more favourable to maize and coffee cultivation than current conditions. The detailed site comparison revealed substantial differences between farms in important characteristics, such as farm size and presence of cash crops, casting doubt on the usefulness of the comparison for climate change analysis. Climatic constraints were similar between sites, so that no apparent lessons for adaptation could be derived. Pests and diseases were also similar, indicating that climate change may not lead to strong changes in biotic constraints at the baseline site in the near future. From

  11. Na-smectite s in the Cala de Tomate bentonite deposit (Spain): a natural analogue of the salinity effect on the bentonite barrier of a rad waste disposal

    Energy Technology Data Exchange (ETDEWEB)

    Perez del Villar, L.; Pelayo, M.; Fernandez, A.M.; Cozar, J.S. [CIEMAT - Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT/DIRE/CEAGP), Madrid (Spain); Delgado, A.; Reyes, E. [Ciencias de la Tierra y Quimica Ambiental Estacion Experimental del Zaidin Dpt., Granada (Spain); Fernandez-Soler, J.M. [Granada Univ., Dpt. de Mineralogia y Petrologia (Spain); Tsige, M. [Facultad de Ciencias Geologicas, Dpt. de Geodinamica, Madrid (Spain)

    2005-07-01

    Within the framework of the ENRESA programme for the assessment of the long-term behaviour of the bentonite-engineered barrier for a deep radwaste geological repository, analogue studies on several bentonite deposits are conducted at CIEMAT. Among these analogue studies, the thermal effect induced by volcanic intrusions on bentonite deposits is highlighted. In the Cabo de Gata volcanic region, there are several analogue scenarios where these studies have been performed, such as the Cala de Tomate bentonite deposit that was intruded by a pyroxene andesite volcanic dome. However, geological, mineralogical, physicochemical, geochemical and stable isotopic data obtained from the smectites do not allow to establish any analogy with the thermal effect expected on the bentonite-engineered barrier of a deep geological repository after burial. Thus, the bentonitisation processes took place after the intrusion of the dome, as a result of meteoric diagenesis intensively developed on faulting zone affecting the parent pyroclastic acid tuffs. This faulting process occurred after the dome intrusion. However, the physicochemical characteristics of these smectites, specially the exchangeable cations, allow to consider this bentonite deposit as a natural analogue of the saline effect on the clayey barrier. This analogy has been established because Na-smectites are present in this deposit and, up to our present knowledge, it is the first time that these smectites occur naturally in the Cabo de Gata-La Serrata de Nijar volcanic region. As a consequence, the main objectives of this work are: i) to characterise these smectites; ii) to establish their genesis and processes affecting them after their formation and iii) to identify the effects on the bentonite-engineered barrier should it were affected by a Na-rich saline waterfront. (authors)

  12. Cyprus natural analogue project (CNAP). Phase II Final Report

    International Nuclear Information System (INIS)

    Alexander, W.R.; Milodowski, A.E.

    2011-02-01

    Due to the extremely slow kinetics of bentonite reaction in low alkali cement leachates, natural analogues would appear to be the only viable method of studying bentonite reaction. As a result of a review of the available literature, several sites in Cyprus were selected as particularly promising for this purpose. This report presents the results of two short field campaigns in Cyprus in November/December, 2008 and February, 2009. The main aim of these campaigns was to establish if appropriate sites existed for a natural analogue study of bentonite-low alkali cement leachate reaction. Focus is on mineralogical changes and not changes in physical properties (such as porosity and permeability) of bentonite as the industrially-processed bentonite used in a repository will be completely different in terms of its engineering and hydrogeological properties to the unprocessed natural bentonite or analogue smectite-rich materials. The first campaign was in the form of a reconnaissance study to identify sites of likely interest and the second, follow-up, campaign focussed on obtaining preliminary groundwater and solid phase (bentonites/clay-rich sediments/altered igneous rocks/soils) samples which would allow a more detailed assessment of several of the potential sites. A large amount of information was collected during these short field campaigns and subsequent laboratory analysis of the collected samples so, to keep the main report down to a digestible size, much of the supporting information has been collated in seven appendices. These include full details of all 30 sites visited during both campaigns along with sample details, information on the analytical techniques, the analytical raw data and numerous photographs of the sites. The intention is that this report will provide full supporting information for a potential Phase III and a detailed database for our colleagues at the Geological Survey Department (GSD) in Cyprus. Consequently, all the information acquired

  13. Synthesis and antimicrobial activity of cholic acid hydrazone analogues.

    Science.gov (United States)

    Rasras, Anas J M; Al-Tel, Taleb H; Al-Aboudi, Amal F; Al-Qawasmeh, Raed A

    2010-06-01

    Synthesis and antimicrobial activity of cholic acid analogues 4a-t are reported. The synthesis of 4a-t was accomplished from ethylcholate 2. The hydrazone moiety was introduced via coupling of the cholic acid hydrazide (3) with appropriately functionalized aldehyde utilizing acetic acid as a catalyst. Quiet of interest in relation to the synthesized hydrazones is the formation of two rotamers s-cis.E and s-trans.E. Most compounds showed stronger antimicrobial activity against Gram-positive bacteria than Cefaclor and Cefixime. Compounds 4d, 4i and 4j indicated 15-fold stronger antimicrobial activities against Enterobacter faecalis compared to Cefaclor and Cefixime. Some of the synthesized compounds (e.g. 4a, 4c, 4d, 4i, and 4l) reflected two-folds less activity against Escherichia coli relative to Cefixime. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  14. Quasi-particle creation by analogue black holes

    Science.gov (United States)

    Barceló, Carlos; Liberati, Stefano; Sonego, Sebastiano; Visser, Matt

    2006-09-01

    We discuss the issue of quasi-particle production by 'analogue black holes' with particular attention to the possibility of reproducing Hawking radiation in a laboratory. By constructing simple geometric acoustic models, we obtain a somewhat unexpected result: we show that in order to obtain a stationary and Planckian emission of quasi-particles, it is not necessary to create an ergoregion in the acoustic spacetime (corresponding to a supersonic regime in the flow). It is sufficient to set up a suitable dynamically changing flow. For instance, either a flow that eventually generates an arbitrarily small sonic region v = c, but without any ergoregion, or even a flow that just asymptotically, in laboratory time, approaches a sonic regime with sufficient rapidity.

  15. Quasi-particle creation by analogue black holes

    Energy Technology Data Exchange (ETDEWEB)

    Barcelo, Carlos [Instituto de AstrofIsica de AndalucIa, CSIC, Camino Bajo de Huetor 50, 18008 Granada (Spain); Liberati, Stefano [International School for Advanced Studies, Via Beirut 2-4, 34014 Trieste (Italy); Sonego, Sebastiano [Universita di Udine, Via delle Scienze 208, 33100 Udine (Italy); Visser, Matt [School of Mathematics, Statistics, and Computer Science, Victoria University of Wellington, Wellington (New Zealand)

    2006-09-07

    We discuss the issue of quasi-particle production by 'analogue black holes' with particular attention to the possibility of reproducing Hawking radiation in a laboratory. By constructing simple geometric acoustic models, we obtain a somewhat unexpected result: we show that in order to obtain a stationary and Planckian emission of quasi-particles, it is not necessary to create an ergoregion in the acoustic spacetime (corresponding to a supersonic regime in the flow). It is sufficient to set up a suitable dynamically changing flow. For instance, either a flow that eventually generates an arbitrarily small sonic region v = c, but without any ergoregion, or even a flow that just asymptotically, in laboratory time, approaches a sonic regime with sufficient rapidity.

  16. The Mojave vadose zone: a subsurface biosphere analogue for Mars.

    Science.gov (United States)

    Abbey, William; Salas, Everett; Bhartia, Rohit; Beegle, Luther W

    2013-07-01

    If life ever evolved on the surface of Mars, it is unlikely that it would still survive there today, but as Mars evolved from a wet planet to an arid one, the subsurface environment may have presented a refuge from increasingly hostile surface conditions. Since the last glacial maximum, the Mojave Desert has experienced a similar shift from a wet to a dry environment, giving us the opportunity to study here on Earth how subsurface ecosystems in an arid environment adapt to increasingly barren surface conditions. In this paper, we advocate studying the vadose zone ecosystem of the Mojave Desert as an analogue for possible subsurface biospheres on Mars. We also describe several examples of Mars-like terrain found in the Mojave region and discuss ecological insights that might be gained by a thorough examination of the vadose zone in these specific terrains. Examples described include distributary fans (deltas, alluvial fans, etc.), paleosols overlain by basaltic lava flows, and evaporite deposits.

  17. An IMS-IMS Analogue of MS-MS

    Energy Technology Data Exchange (ETDEWEB)

    Koeniger, Stormy L.; Merenbloom, Samuel I.; Valentine, Stephen J.; Jarrold, Martin F.; Udseth, Harold R.; Smith, Richard D.; Clemmer, David E.

    2006-06-15

    The development of a new ion mobility/mass spectrometry instrument that incorporates a multifield drift tube/ion funnel design is described. In this instrument, individual components from a mixture of ions can be resolved and selected on the basis of mobility differences prior to collisional activation inside the drift tube. The fragment ions that are produced can be dispersed again in a second ion mobility spectrometry (IMS) region prior to additional collisional activation and MS analysis. The result is an IMS-IMS analogue of MS-MS. Here, we describe the preliminary instrumental design and experimental approach. We illustrate the approach by examining the highly characterized bradykinin and ubiquitin systems. Mobility-resolved fragment ions of bradykinin show that b-type ions are readily discernible fragments, because they exist as two easily resolvable structural types. Current limitations and future directions are briefly discussed.

  18. Thermal environment and sleep in winter shelter-analogue settings

    Science.gov (United States)

    Mochizuki, Yosuke; Maeda, Kazuki; Nabeshima, Yuki; Tsuzuki, Kazuyo

    2017-10-01

    We aimed to examine sleep in shelter-analogue settings in winter to determine the sleep and environmental conditions in evacuation shelters. Twelve young healthy students took part in the sleep study of two nights for seven hours from 0 AM to 7 AM in a gymnasium. One night the subject used a pair of futons and on the other the subject used emergency supplies consisting of four blankets and a set of portable partitions. Air temperature, humidity were measured around the sleeping subjects through the night. Sleep parameters, skin temperature, microclimate temperature, rectal temperature, and heart rate of the subjects were continuously measured and recorded during the sleeping period. The subjects completed questionnaires relating to thermal comfort and subjective sleep before and after sleep. The sleep efficiency indices were lower when the subjects slept using the blankets. As the microclimate temperature between the human body and blanket was lower, mean skin temperature was significantly lower in the case of blankets.

  19. Pheophytin analogues from the medicinal lichen Usnea diffracta.

    Science.gov (United States)

    Xu, Hong-Bo; Yang, Tong-Hua; Xie, Pei; Liu, Shi-Jun; Liang, Yan-Ni; Zhang, Yu; Song, Zhong-Xing; Tang, Zhi-Shu

    2018-05-01

    A new pheophytin, (13 2 S, 17S, 18S)-13 2 -hydroxy-20-chloro-ethylpheophorbide a (3), along with two known analogues (1-2) were isolated from the lichen Usnea diffracta Vainio (Parmeliaceae). Among them, compound 3 was a rare C-20-chloro type pheophytin obtained from lichens. Their structures were elucidated by extensive spectroscopic analysis, and all the compounds were obtained for the first time from U. diffracta. Compounds (1-3) were evaluated for their xanthine oxidase (XO) inhibitory activities in vitro, and the results showed that 1-3 possessed significant enzyme inhibitory actions with IC 50 values of 46.9 ± 3.8, 75.9 ± 7.4 and 42.1 ± 1.7 μg/mL, respectively.

  20. Synthesis and antifungal evaluation of PCA amide analogues.

    Science.gov (United States)

    Qin, Chuan; Yu, Di-Ya; Zhou, Xu-Dong; Zhang, Min; Wu, Qing-Lai; Li, Jun-Kai

    2018-04-18

    To improve the physical and chemical properties of phenazine-1-carboxylic acid (PCA) and find higher antifungal compounds, a series of PCA amide analogues were designed and synthesized and their structures were confirmed by 1 H NMR, HRMS, and X-ray. Most compounds showed some antifungal activities in vitro. Particularly, compound 3d exhibited inhibition effect against Pyriculariaoryzac Cavgra with EC 50 value of 28.7 μM and compound 3q exhibited effect against Rhizoctonia solani with EC 50 value of 24.5 μM, more potently active than that of the positive control PCA with its EC 50 values of 37.3 μM (Pyriculariaoryzac Cavgra) and 33.2 μM (Rhizoctonia solani), respectively.

  1. Determination of micro amounts of praseodymium by analogue derivative spectrophotometry

    International Nuclear Information System (INIS)

    Ishii, Hajime; Satoh, Katsuhiko.

    1986-01-01

    Derivative spectrophotometry using the analogue differentiation circuit was applied to the determination of praseodymium at the ppm level. By the proposed method, in which the second or fourth derivative spectrum of the characteristic absorption band of praseodymium(III) at 444 nm is measured, as little as 3 ppm of praseodymium can be determined directly and easily even in the presence of large amounts of other rare earths without any prior separation. Interferences from neodymium, samarium, dysprosium, holmium and erbium ions which have characteristic absorption bands around 444 nm can easily be removed by utilizing the isosbestic point in the derivative spectra of praseodymium(III) and the interfering rare earth(III). (author)

  2. A green multicomponent synthesis of tocopherol analogues with antiproliferative activities.

    Science.gov (United States)

    Ingold, Mariana; Dapueto, Rosina; Victoria, Sabina; Galliusi, Germán; Batthyàny, Carlos; Bollati-Fogolín, Mariela; Tejedor, David; García-Tellado, Fernando; Padrón, José M; Porcal, Williams; López, Gloria V

    2018-01-01

    A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI 50 values between 1 and 5 μM. A structure-activity relationship is also discussed. One of the studied compounds comes up as a future candidate for the development of potent tocopherol-mimetic therapeutic agents for cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Pocos de Caldas, Minas Gerais, Brazil: a natural analogue study

    International Nuclear Information System (INIS)

    Smellie, J.

    1989-01-01

    The Pocos de Caldas natural analogue project is an internationally funded project hosted by Brazil; the contributary organizations are SKB (Sweden), NAGRA (Switzerland), DOE (United Kingdom) and the DOE (United States). The Project is a multidisciplinary study of two mineralized areas within an alkaline igneous caldera complex located near the town of Pocos de Caldas in the state of Minas Gerais. One area, the Osamu Utsumi mine, is characterized by redox deposits of secondary remobilized pitchblende, and the other area, Morro do Ferro, comprises a highly weathered deposit of thorium and REE with subordinate uranium. The project, scheduled for three years (1986-1989), is now entering its third and final year. The pilot and feasibility studies, which characterized the first year, helped to establish the major drilling programme and the sampling protocols for both rock and groundwater studies which constituted the major part of the second year. The latest status of the investigations are briefly reported

  4. Quasinormal modes and classical wave propagation in analogue black holes

    International Nuclear Information System (INIS)

    Berti, Emanuele; Cardoso, Vitor; Lemos, Jose P.S.

    2004-01-01

    Many properties of black holes can be studied using acoustic analogues in the laboratory through the propagation of sound waves. We investigate in detail sound wave propagation in a rotating acoustic (2+1)-dimensional black hole, which corresponds to the 'draining bathtub' fluid flow. We compute the quasinormal mode frequencies of this system and discuss late-time power-law tails. Because of the presence of an ergoregion, waves in a rotating acoustic black hole can be superradiantly amplified. We also compute superradiant reflection coefficients and instability time scales for the acoustic black hole bomb, the equivalent of the Press-Teukolsky black hole bomb. Finally we discuss quasinormal modes and late-time tails in a nonrotating canonical acoustic black hole, corresponding to an incompressible, spherically symmetric (3+1)-dimensional fluid flow

  5. Synthesis and Biological Evaluation of 7-Deoxy-Epothilone Analogues

    Directory of Open Access Journals (Sweden)

    Laura M. Woods

    2017-03-01

    Full Text Available The synthesis of two deoxygenated analogues of potent epothilones is reported in an effort to analyze the relative importance of molecular conformation and ligand–target interactions to biological activity. 7-deoxy-epothilone D and 7-deoxy-(S-14-methoxy-epothilone D were prepared through total synthesis and shown to maintain the conformational preferences of their biologically active parent congeners through computer modeling and nuclear magnetic resonance (NMR studies. The significant decrease in observed potency for each compound suggests that a hydrogen bond between the C7-hydroxyl group and the tubulin binding site plays a critical role in the energetics of binding in the epothilone class of polyketides.

  6. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

    Directory of Open Access Journals (Sweden)

    Bryan L Roth

    Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

  7. Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes

    DEFF Research Database (Denmark)

    Frølund, Sidsel; Bella, Angelo; Kristensen, Anders Skov

    2010-01-01

    -electrode voltage-clamp electrophysiology employing Xenopus laevis oocytes expressing GluA1(i) AMPA or GluN1/2A NMDA receptors. Several of the analogues showed significantly increased inhibition of the GluN1/2A NMDA receptor. Thus, an analogue containing N-(1-naphtyl)acetyl group showed an IC(50) value of 47 n...

  8. How Analogue Research Can Advance Descriptive Evaluation Theory: Understanding (and Improving) Stakeholder Dialogue

    Science.gov (United States)

    Campbell, Bernadette; Mark, Melvin M.

    2015-01-01

    Evaluation theories can be tested in various ways. One approach, the experimental analogue study, is described and illustrated in this article. The approach is presented as a method worthy to use in the pursuit of what Alkin and others have called descriptive evaluation theory. Drawing on analogue studies conducted by the first author, we…

  9. New analogues of ACPD with selective activity for group II metabotropic glutamate receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Madsen, U; Mikiciuk-Olasik, E

    1997-01-01

    In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-hom...

  10. Insulin analogues in pregnancy and specific congenital anomalies; a literature review

    NARCIS (Netherlands)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-01-01

    BACKGROUND: Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. METHODS: We performed a literature search for

  11. Rational design of a-conotoxin analogues targeting a7 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Armishaw, Christopher; Jensen, Anders Asbjørn; Balle, Thomas

    2009-01-01

    ], by introducing a range of substituents on the Pro6 residue in these toxins to probe the importance of this residue for their binding to the nAChRs. Pharmacological characterization of the toxin analogues at the alpha(7) nAChR show that while polar and charged groups on Pro6 result in analogues with significantly...

  12. Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors

    NARCIS (Netherlands)

    Mooney, Caitlin A.; Johnson, Stuart A.; 'T Hart, Peter; Quarles Van Ufford, Linda; De Haan, Cornelis A M; Moret, Ed E.; Martin, Nathaniel I.

    2014-01-01

    A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza the two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display

  13. Synthesis of new 4,6-disubstituted-1,3-oxazinan-2-one analogues

    Indian Academy of Sciences (India)

    Abstract. 1,3-Oxazinan-2-one analogues are important heterocyclic compounds having significant biologi- cal activities. This study reports the synthesis of eight new 4,6-disubstituted -1,3-oxazinan-2-one analogues from corresponding homoallylic carbamates. Homoallylic carbamates were synthesized via a three- ...

  14. Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile.

    Science.gov (United States)

    Coney, Leigh D; Maier, Larissa J; Ferris, Jason A; Winstock, Adam R; Barratt, Monica J

    2017-05-01

    This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them. An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues. Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD. LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement. Copyright © 2017 John Wiley & Sons, Ltd.

  15. State selective reactions of cosmic dust analogues at cryogenic temperatures

    International Nuclear Information System (INIS)

    Perry, James Samuel Anthony

    2001-01-01

    Molecular hydrogen (H 2 ) is the most abundant molecule in interstellar space. It is crucial for initiating all of the chemistry in the Interstellar Medium (ISM) and consequently plays an important role in star formation. However, the amount of H 2 believed to exist in the ISM cannot be accounted for by formation through gas-phase reactions alone. The current, widely accepted theory, is that H 2 forms on the surface of cosmic dust grains. These grains are thought to be composed of amorphous forms of carbon or silicates with temperatures of around 10 K. This thesis describes a new experiment that has been constructed to study H 2 formation on the surface of cosmic dust analogues and presents the initial experimental results. The experiment simulates, through ultra-high vacuum and the use of cryogenics, the conditions of the ISM where cosmic dust grains and H 2 molecules exist. During the experiment, a beam of atomic hydrogen is aimed at a cosmic dust analogue target. H 2 formed on the target's surface is ionised using a laser spectroscopy technique known as Resonance Enhanced Multiphoton lonisation (REMPI) and detected using time-of-flight mass spectrometry. The sensitivity of REMPI is such that H 2 molecules can be ionised in selective internal energy states. This allows the rovibrational populations of the H 2 molecules desorbing from the cosmic dust targets to be determined, providing information on the energy budget of the H 2 formation process in the ISM. Preliminary results from the experiment show that H 2 molecules formed on a diamond-like-carbon surface have a significant non-thermal population of excited vibrational and rotational energy states. (author)

  16. Natural analogues of bitumen and bituminized radioactive waste

    International Nuclear Information System (INIS)

    Hellmuth, K.-H.

    1989-07-01

    Occurrences of natural bitumen provide possibilities to identify and assess materials, processes, phenomena and conditions in nature which can serve as model cases valid also with respect to a final repository. Natural bitumens meet the basic requirements for use as natural analogues. In natural sites, processes of bitumen formation and degradation often work simultaneously. The major processes are thermal alteration, evaporation, reaction with water, biodegradation, oxidation, weathering and radiation degradation. Progress in analytical organic geochemistry made during recent years has enabled a deeper understanding of the structural and compositional effects of these processes on bitumen. This is necessary in natural analogue applications. The time scales involved in degradation processes, as observed in natural occurrences, exceed the time scales dictated by the half-lives of most important fission products in low and medium level waste by orders of magnitude. Only exposure to the weather at the surface leads to a more rapid destruction of bitumen. Trace metals in bitumen arenot released until the matrix is completely destroyed. Products of radiation degradation and weathering of bitumen are able, to a certain degree, to delay migration of the metal ions released. Impregnation with bitumen may effectively reduce the microbial decomposition of easily destructable organic waste components, as can be deduced on the basis of the excellent preservation of fossils observed in bitumen. The complexity of all the natural sites described requires extensive understanding of the origin and kind of organic material in bitumen, its maturation, migration, alteration and degradation and of the geological and tectonic evolution of the site. The latter is used for establishing the time scale

  17. A novel nucleic acid analogue shows strong angiogenic activity

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Ikuko, E-mail: tukamoto@med.kagawa-u.ac.jp [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Sakakibara, Norikazu; Maruyama, Tokumi [Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193 (Japan); Igarashi, Junsuke; Kosaka, Hiroaki [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Kubota, Yasuo [Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Tokuda, Masaaki [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Ashino, Hiromi [The Tokyo Metropolitan Institute of Medical Science, 1-6 Kamikitazawa2-chome, Setagaya-ku, Tokyo 156-8506 (Japan); Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro [Teikoku Seiyaku Co., Ltd., Sanbonmatsu, Higashikagawa, Kagawa 769-2695 (Japan); Konishi, Ryoji [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan)

    2010-09-03

    Research highlights: {yields} A novel nucleic acid analogue (2Cl-C.OXT-A, m.w. 284) showed angiogenic potency. {yields} It stimulated the tube formation, proliferation and migration of HUVEC in vitro. {yields} 2Cl-C.OXT-A induced the activation of ERK1/2 and MEK in HUVEC. {yields} Angiogenic potency in vivo was confirmed in CAM assay and rabbit cornea assay. {yields} A synthesized small angiogenic agent would have great clinical therapeutic value. -- Abstract: A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 {mu}M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.

  18. Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled octreotide analogue for radiotherapy of somatostatin receptor-positive tumours

    International Nuclear Information System (INIS)

    Smith-Jones, Peter M.; Stolz, Barbara; Albert, Rainer; Ruser, Gerd; Briner, Ulrich; Maecke, Helmut R.; Bruns, Christian

    1998-01-01

    An investigation into the in vitro behaviour of two yttrium-90-labelled somatostatin analogues was performed. Further in vivo characterisation was performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA-oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal amine of the D-Phe 1 of Tyr 3 -octreotide. This new SRIF analogue and DTPA-octreotide (OctreoScan) were radiolabelled with 90 Y prior to serum stability being evaluated. Receptor binding assays were also performed on the two radioligands using rat cortex membranes. The [ 90 Y]-Bz-DTPA-oct was further evaluated in vivo using tumour-bearing rats. The first conjugate (DTPA-octreotide) bound with a high affinity to SRIF receptors and the 90 Y complex was relatively stable in human serum (t 1/2 3.8 d for 90 Y lost to serum proteins). The second conjugate (Bz-DTPA-oct) also exhibited a high binding affinity to SRIF receptors, but it demonstrated an even slower loss of 90 Y to serum proteins (t 1/2 12.1 d). The in vivo evaluation of the more stable [ 90 Y]-Bz-DTPA-oct showed a very rapid and high accumulation in somatostatin receptor-positive tumours, which after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood, muscle, and liver, respectively). These tumour/nontumour ratios increased, and were by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and liver). Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accumulated in somatostatin receptor-positive tissue. Octadentate Bz-DTPA-oct could be ligand for 90 Y radiotherapy of somatostatin receptor-positive tumours and their metastases

  19. Stable Treemaps via Local Moves.

    Science.gov (United States)

    Sondag, Max; Speckmann, Bettina; Verbeek, Kevin

    2018-01-01

    Treemaps are a popular tool to visualize hierarchical data: items are represented by nested rectangles and the area of each rectangle corresponds to the data being visualized for this item. The visual quality of a treemap is commonly measured via the aspect ratio of the rectangles. If the data changes, then a second important quality criterion is the stability of the treemap: how much does the treemap change as the data changes. We present a novel stable treemapping algorithm that has very high visual quality. Whereas existing treemapping algorithms generally recompute the treemap every time the input changes, our algorithm changes the layout of the treemap using only local modifications. This approach not only gives us direct control over stability, but it also allows us to use a larger set of possible layouts, thus provably resulting in treemaps of higher visual quality compared to existing algorithms. We further prove that we can reach all possible treemap layouts using only our local modifications. Furthermore, we introduce a new measure for stability that better captures the relative positions of rectangles. We finally show via experiments on real-world data that our algorithm outperforms existing treemapping algorithms also in practice on either visual quality and/or stability. Our algorithm scores high on stability regardless of whether we use an existing stability measure or our new measure.

  20. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century.

    Science.gov (United States)

    Montag, Christian; Kannen, Christopher; Lachmann, Bernd; Sariyska, Rayna; Duke, Éilish; Reuter, Martin; Markowetz, Alexander

    2015-12-01

    Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution - particularly since the advent of the smartphone - mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based applications). Of N = 3084 participants, 45% reported wearing a wristwatch and 67% used an analogue alarm clock. We observed that participants who reported using analogue zeitgebers used their mobile-/smartphone significantly less. Use of analogue zeitgebers may prove a practical tool for therapeutic and preventative interventions for problematic Internet use in an increasingly digital age.

  1. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century

    Directory of Open Access Journals (Sweden)

    Christian Montag

    2015-12-01

    Full Text Available Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution – particularly since the advent of the smartphone – mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based applications. Of N = 3084 participants, 45% reported wearing a wristwatch and 67% used an analogue alarm clock. We observed that participants who reported using analogue zeitgebers used their mobile-/smartphone significantly less. Use of analogue zeitgebers may prove a practical tool for therapeutic and preventative interventions for problematic Internet use in an increasingly digital age.

  2. Advanced thermally stable jet fuels

    Energy Technology Data Exchange (ETDEWEB)

    Schobert, H.H.

    1999-01-31

    The Pennsylvania State University program in advanced thermally stable coal-based jet fuels has five broad objectives: (1) Development of mechanisms of degradation and solids formation; (2) Quantitative measurement of growth of sub-micrometer and micrometer-sized particles suspended in fuels during thermal stressing; (3) Characterization of carbonaceous deposits by various instrumental and microscopic methods; (4) Elucidation of the role of additives in retarding the formation of carbonaceous solids; (5) Assessment of the potential of production of high yields of cycloalkanes by direct liquefaction of coal. Future high-Mach aircraft will place severe thermal demands on jet fuels, requiring the development of novel, hybrid fuel mixtures capable of withstanding temperatures in the range of 400--500 C. In the new aircraft, jet fuel will serve as both an energy source and a heat sink for cooling the airframe, engine, and system components. The ultimate development of such advanced fuels requires a thorough understanding of the thermal decomposition behavior of jet fuels under supercritical conditions. Considering that jet fuels consist of hundreds of compounds, this task must begin with a study of the thermal degradation behavior of select model compounds under supercritical conditions. The research performed by The Pennsylvania State University was focused on five major tasks that reflect the objectives stated above: Task 1: Investigation of the Quantitative Degradation of Fuels; Task 2: Investigation of Incipient Deposition; Task 3: Characterization of Solid Gums, Sediments, and Carbonaceous Deposits; Task 4: Coal-Based Fuel Stabilization Studies; and Task 5: Exploratory Studies on the Direct Conversion of Coal to High Quality Jet Fuels. The major findings of each of these tasks are presented in this executive summary. A description of the sub-tasks performed under each of these tasks and the findings of those studies are provided in the remainder of this volume

  3. Population Games, Stable Games, and Passivity

    Directory of Open Access Journals (Sweden)

    Michael J. Fox

    2013-10-01

    Full Text Available The class of “stable games”, introduced by Hofbauer and Sandholm in 2009, has the attractive property of admitting global convergence to equilibria under many evolutionary dynamics. We show that stable games can be identified as a special case of the feedback-system-theoretic notion of a “passive” dynamical system. Motivated by this observation, we develop a notion of passivity for evolutionary dynamics that complements the definition of the class of stable games. Since interconnections of passive dynamical systems exhibit stable behavior, we can make conclusions about passive evolutionary dynamics coupled with stable games. We show how established evolutionary dynamics qualify as passive dynamical systems. Moreover, we exploit the flexibility of the definition of passive dynamical systems to analyze generalizations of stable games and evolutionary dynamics that include forecasting heuristics as well as certain games with memory.

  4. Recurrent high-grade meningioma: a phase II trial with somatostatin analogue therapy.

    Science.gov (United States)

    Simó, Marta; Argyriou, Andreas A; Macià, Miquel; Plans, Gerard; Majós, Carles; Vidal, Noemi; Gil, Miguel; Bruna, Jordi

    2014-05-01

    A prospective, two-stage phase II trial with octreotide in patients with recurrent high-grade meningioma was conducted. The radiographic partial response (RPR) was set as the primary study endpoint, whereas progression-free survival at 6 months (PFS6) was defined as the secondary endpoint. Nine patients (eight men; median age 65) with histological high-grade meningioma (five with grade II and four with grade III) and progression after prior surgery and radiotherapy were included. All had positive brain octreotide SPECT scanning. Octreotide was administered intramuscularly once every 28 days at a dose of 30 mg for the first two cycles and 40 mg for subsequent cycles until progression. Magnetic resonance imaging was performed every 3 months. Progression and RPR were defined as an increase of ≥25 % and as a decrease of ≥50 % in two-dimensional maximum diameters, respectively. Patients received a median of three octreotide cycles (range 1-8) without grade ≥2 toxicities. No RPRs were observed. Stable disease was the best response in 33.3 % (n = 3). All patients had progressive disease at 10 months of follow-up. Median time to progression was 4.23 months (range 1-9.4), and the PFS6 was 44.4 % (n = 4). Our study failed to provide evidence to support the use of monthly long-acting somatostatin analogue schedule in recurrent high-grade meningiomas, as none of our patients demonstrated RPR. The modest median PFS of 4-5 months along with the unknown natural history of recurrent meningiomas render the use of this therapy against these aggressive brain tumors uncertain.

  5. Purine nucleoside analogues inhibit the repair of radiation-induced potentially lethal damage in mammalian cells in culture

    International Nuclear Information System (INIS)

    Nakatsugawa, S.; Kumar, A.

    1982-01-01

    Three purine nucleoside analogues were found to be much more effective than pyrimidine nucleoside analogues in the screening of PLD repair inhibitors using X-irradiated Chinese hamster HA-1 cells. Among the three purine nucleoside analogues, 3'-dG was the most effective at a non-toxic concentration. (author)

  6. Biphasic Insulin Analogues in Type 2 Diabetes: Expert Panel Recommendations

    Directory of Open Access Journals (Sweden)

    Sema Akalın

    2011-09-01

    Full Text Available Recently, the prevalence of type 2 diabetes has reached pandemic levels all over the world, and the problem is still growing. Type 2 diabetes is a progressive disease, in which insulin resistance and decrease in beta cell function accompany obesity. Early disorder, which ensues in clinical progression of the disease, is the defect of early phase insulin secretion. Patients have already lost approximately half of their beta cell reserve at the time of diagnosis. Aims of type 2 diabetes treatment are to eliminate hyperglycemia caused by insufficient insulin secretion and/or insulin resistance, to slow down beta cell destruction/depletion, to improve concomitant metabolic problems and to prevent complications. In treatment algorithms, insulin is evaluated as a replacement therapy at the following stage after life style changes (medical nutrition therapy, exercise and oral anti-diabetic drugs (OADs options. Since beta cell depletion is present at initial stages of the disease, it transforms insulin therapy into an earlier approach in treatment stages. Premixed insulin forms are one of the proposed treatment options in patients with hyperglycemia that is not controlled by OADs. These types of insulins are developed to meet both basal and postprandial insulin requirements of patients. Currently, premixed human insulin forms are replaced by analogue insulin forms, which can mimic the physiological secretion in more acceptable manner. Biphasic analogue insulin is one of the readily available pre-mixed analogue insulin forms, an example of this, Biphasic Insulin aspart 30 which is the one of the premixed analoge insulin forms, contains 30% insulin aspart and 70% protaminated insulin aspart. Consensus recommending the individualized approach in insulin therapy implies that physicians should have more detailed information about the use of different insulin forms. Although a global consensus report about initiation, titration and intensification and the use

  7. Rough Precipitation Forecasts based on Analogue Method: an Operational System

    Science.gov (United States)

    Raffa, Mario; Mercogliano, Paola; Lacressonnière, Gwendoline; Guillaume, Bruno; Deandreis, Céline; Castanier, Pierre

    2017-04-01

    In the framework of the Climate KIC partnership, has been funded the project Wat-Ener-Cast (WEC), coordinated by ARIA Technologies, having the goal to adapt, through tailored weather-related forecast, the water and energy operations to the increased weather fluctuation and to climate change. The WEC products allow providing high quality forecast suited in risk and opportunities assessment dashboard for water and energy operational decisions and addressing the needs of sewage/water distribution operators, energy transport & distribution system operators, energy manager and wind energy producers. A common "energy water" web platform, able to interface with newest smart water-energy IT network have been developed. The main benefit by sharing resources through the "WEC platform" is the possibility to optimize the cost and the procedures of safety and maintenance team, in case of alerts and, finally to reduce overflows. Among the different services implemented on the WEC platform, ARIA have developed a product having the goal to support sewage/water distribution operators, based on a gradual forecast information system ( at 48hrs/24hrs/12hrs horizons) of heavy precipitation. For each fixed deadline different type of operation are implemented: 1) 48hour horizon, organisation of "on call team", 2) 24 hour horizon, update and confirm the "on call team", 3) 12 hour horizon, secure human resources and equipment (emptying storage basins, pipes manipulations …). More specifically CMCC have provided a statistical downscaling method in order to provide a "rough" daily local precipitation at 24 hours, especially when high precipitation values are expected. This statistical technique consists of an adaptation of analogue method based on ECMWF data (analysis and forecast at 24 hours). One of the most advantages of this technique concerns a lower computational burden and budget compared to running a Numerical Weather Prediction (NWP) model, also if, of course it provides only this

  8. Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

    Science.gov (United States)

    Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

    2017-06-02

    Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI -tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr 83 and Glu 73 , respectively. When Glu 73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr 62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu 73 residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. [Pb2F2](SeO4): a heavier analogue of grandreefite, the first layered fluoride selenate

    Science.gov (United States)

    Charkin, Dmitri O.; Plokhikh, Igor V.; Zadoya, Anastasiya I.; Kazakov, Sergey M.; Zaloga, Alexander N.; Kozin, Michael S.; Depmeier, Wulf; Siidra, Oleg I.

    2018-01-01

    Co-precipitation of PbF2 and PbSeO4 in weakly acidic media results in the formation of [Pb2F2](SeO4), the selenate analogue of the naturally occurring mineral grandreefite, [Pb2F2](SO4). The new compound is monoclinic, C2/ c, a = 14.0784(2) Å, b = 4.6267(1) Å, c = 8.8628(1) Å, β = 108.98(1)°, V = 545.93(1) Å3. Its structure has been refined from powder data to R B = 1.55%. From thermal studies, it is established that the compound is stable in air up to about 300 °C, after which it gradually converts into a single phase with composition [Pb2O](SeO4), space group C2/ m, and lattice parameters a = 14.0332(1) Å, b = 5.7532(1) Å, c = 7.2113(1) Å, β = 115.07(1)°, V = 527.37(1) Å3. It is the selenate analogue of lanarkite, [Pb2O](SO4), and phoenicochroite, [Pb2O](CrO4), and its crystal structure was refined to R B = 1.21%. The formation of a single decomposition product upon heating in air suggests that this happens by a thermal hydrolysis mechanism, i.e., Pb2F2SeO4 + H2O (vapor) → Pb2OSeO4 + 2HF↑. This relatively low-temperature process involves complete rearrangement of the crystal structure—from a 2D architecture featuring slabs [Pb2F2]2+ formed by fluorine-centered tetrahedra into a structure characterized by 1D motifs based on [OPb2]2+ chains of oxocentered tetrahedra. The comparative crystal chemistry of the obtained anion-centered structural architectures is discussed.

  10. Rheological and physical characteristics of crustal-scaled materials for centrifuge analogue modelling

    Science.gov (United States)

    Waffle, Lindsay; Godin, Laurent; Harris, Lyal B.; Kontopoulou, M.

    2016-05-01

    We characterize a set of analogue materials used for centrifuge analogue modelling simulating deformation at different levels in the crust simultaneously. Specifically, we improve the rheological characterization in the linear viscoelastic region of materials for the lower and middle crust, and cohesive synthetic sands without petroleum-binding agents for the upper crust. Viscoelastic materials used in centrifuge analogue modelling demonstrate complex dynamic behaviour, so viscosity alone is insufficient to determine if a material will be an effective analogue. Two series of experiments were conducted using an oscillating bi-conical plate rheometer to measure the storage and loss moduli and complex viscosities of several modelling clays and silicone putties. Tested materials exhibited viscoelastic and shear-thinning behaviour. The silicone putties and some modelling clays demonstrated viscous-dominant behaviour and reached Newtonian plateaus at strain rates centrifuge test models. These synthetic sands are recommended as analogues for the brittle upper crust. These new results increase the accuracy of scaling analogue models to prototype. Additionally, with the characterization of three new materials, we propose a complete lithospheric profile of analogue materials for centrifuge modelling, allowing future studies to replicate a broader range of crustal deformation behaviours.

  11. Labelling and evaluation of new stabilised neurotensin (8-13) analogues for SPET

    International Nuclear Information System (INIS)

    Chavatte, K.; Terriere, D.; Jeannin, L.

    1998-01-01

    Neurotensin (8-13) analogues were biologically stabilised by replacement of the peptide bond between amino acids 8 and 9 by the reduced ψ(CH 2 -NH) isostere. DTPA analogues for In-111 labelling and 2-bromo-phenyl-acetyl analogues for radioiodination, showed receptor affinities in the low nanomolar range in combination with a biological half live in human plasma up to 275 minutes. Biodistribution studies in male Wistar rats of metabolically stabilised and non-stabilised 111 In-DTPA-NT(8-13) analogues showed a major clearance from the blood through the kidneys. 125 I-labelled Neurotensin (8-13) analogues showed accumulation up to 2.2% of the injected dose per g tissue in the liver which might be an important disadvantage when diagnosis of tumours in the gut is aimed. It is strongly suggested that stabilised neurotensin (8-13) analogues whether labelled with In-111, I-123 and the near future with Tc-99m, may act as new potential peptidergic radiopharmaceuticals for SPET diagnosis of different NT-receptor positive tumours like non-endocrine pancreas carcinoma, small cell lung carcinoma or colon adeno carcinoma. It is enticing to speculate that metabolically stabilised Neurotensin (8-13) analogues labelled with an appropriate isotope might be useful in therapy of different human cancers. (author)

  12. Large seismic source imaging from old analogue seismograms

    Science.gov (United States)

    Caldeira, Bento; Buforn, Elisa; Borges, José; Bezzeghoud, Mourad

    2017-04-01

    In this work we present a procedure to recover the ground motions by a proper digital structure, from old seismograms in analogue physical support (paper or microfilm) to study the source rupture process, by application of modern finite source inversion tools. Despite the quality that the analog data and the digitizing technologies available may have, recover the ground motions with the accurate metrics from old seismograms, is often an intricate procedure. Frequently the general parameters of the analogue instruments response that allow recover the shape of the ground motions (free periods and damping) are known, but the magnification that allow recover the metric of these motions is dubious. It is in these situations that the procedure applies. The procedure is based on assign of the moment magnitude value to the integral of the apparent Source Time Function (STF), estimated by deconvolution of a synthetic elementary seismogram from the related observed seismogram, corrected with an instrument response affected by improper magnification. Two delicate issues in the process are 1) the calculus of the synthetic elementary seismograms that must consider later phases if applied to large earthquakes (the portions of signal should be 3 or 4 times larger than the rupture time) and 2) the deconvolution to calculate the apparent STF. In present version of the procedure was used the Direct Solution Method to compute the elementary seismograms and the deconvolution was processed in time domain by an iterative algorithm that allow constrains the STF to stay positive and time limited. The method was examined using synthetic data to test the accuracy and robustness. Finally, a set of 17 real old analog seismograms from the Santa Maria (Azores) 1939 earthquake (Mw=7.1) was used in order to recover the waveforms in the required digital structure, from which by inversion allows compute the finite source rupture model (slip distribution). Acknowledgements: This work is co

  13. Meglitinide analogues in the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Landgraf, R

    2000-11-01

    Type 2 diabetes mellitus is a complex heterogenous metabolic disorder in which peripheral insulin resistance and impaired insulin release are the main pathogenetic factors. The rapid response of the pancreatic beta-cells to glucose is already markedly disturbed in the early stages of type 2 diabetes mellitus. The consequence is often postprandial hyperglycaemia, which seems to be extremely important in the development of secondary complications, especially macrovascular disease. Therefore one of the main aims of treatment is to minimise blood glucose oscillations and attain near-normal glycosylated haemoglobin levels. Meglitinide analogues belong to a new family of insulin secretagogues which stimulate insulin release by inhibiting ATP-sensitive potassium channels of the beta-cell membrane via binding to a receptor distinct from that of sulphonylureas (SUR1/KIR 6.2). The pharmacokinetic and pharmacodynamic properties of repaglinide, the first drug of these new antihyperglycaemic agents on the market, and of nateglinide, which will be available soon, differ markedly from the currently used sulphonylureas [mainly glibenclamide (glyburide) and glimepiride]. Repaglinide and nateglinide are absorbed rapidly, stimulate insulin release within a few minutes, are rapidly metabolised in the liver and are mainly excreted in the bile. Therefore, following preprandial administration of these drugs, insulin is more readily available during and just after the meal. This leads to a significant reduction in postprandial hyperglycaemia without the danger of hypoglycaemia between meals. The short action of these compounds and biliary elimination makes repaglinide and nateglinide especially suitable for patients with type 2 diabetes mellitus who would like to have a more flexible lifestyle, need more flexibility because of unplanned eating behaviour (e.g. geriatric patients) or in whom one of the other first-line antidiabetic drugs, i.e. metformin, is strictly contraindicated (e

  14. The Greenland Analogue Project (GAP). Literature review of hydrogeology/ hydrogeochemistry

    International Nuclear Information System (INIS)

    Wallroth, Thomas; Lokrantz, Hanna; Rimsa, Andrius

    2010-09-01

    This report is produced as part of the Greenland Analogue Project (GAP), carried out as a collaboration project with the Canadian Nuclear Waste Management Organization (NWMO), Posiva Oy and the Swedish Nuclear Fuel and Waste Management Co (SKB). The overall aim of the project is to improve the current understanding of hydrogeological and hydrogeochemical processes associated with continental-scale glacial periods including with the presence of permafrost and the advance/retreat of ice sheets. The project will focus on studying how an ice sheet affects groundwater flow and water chemistry around a deep geological repository in crystalline bedrock. The Greenland Analogue Project consists of three active sub-projects (A-C) with individual objectives. Field studies are conducted in the Kangerlussuaq region, in central Western Greenland. Sub-projects A and B collectively aim at improving the understanding of ice sheet hydrology by combining investigations on surface water processes with ice sheet drilling and instrumentation. In sub-project C, the penetration of glacial melt water into the bedrock, groundwater flow and the chemical composition of water will be studied. Main planned activities in sub-project C include drilling of a deep borehole in front of the ice sheet, in which different downhole surveys, sampling and monitoring will be carried out. The primary aim of this report is to review available information about hydrogeology and hydrogeochemistry in central Western Greenland, with special emphasis on the area around Kangerlussuaq. The relevant information about this area is however very limited, and it was decided to extend the review to briefly include studies made in other regions with similar conditions in terms of geology, climate and glaciology. The number of published studies made in other areas with glaciers, ice sheets or permafrost is very large, and the review and list of references in this report is far from complete. It is also obvious that both

  15. The Greenland Analogue Project (GAP). Literature review of hydrogeology/ hydrogeochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Wallroth, Thomas; Lokrantz, Hanna; Rimsa, Andrius (Bergab Consulting Geologists, Goeteborg (Sweden))

    2010-09-15

    This report is produced as part of the Greenland Analogue Project (GAP), carried out as a collaboration project with the Canadian Nuclear Waste Management Organization (NWMO), Posiva Oy and the Swedish Nuclear Fuel and Waste Management Co (SKB). The overall aim of the project is to improve the current understanding of hydrogeological and hydrogeochemical processes associated with continental-scale glacial periods including with the presence of permafrost and the advance/retreat of ice sheets. The project will focus on studying how an ice sheet affects groundwater flow and water chemistry around a deep geological repository in crystalline bedrock. The Greenland Analogue Project consists of three active sub-projects (A-C) with individual objectives. Field studies are conducted in the Kangerlussuaq region, in central Western Greenland. Sub-projects A and B collectively aim at improving the understanding of ice sheet hydrology by combining investigations on surface water processes with ice sheet drilling and instrumentation. In sub-project C, the penetration of glacial melt water into the bedrock, groundwater flow and the chemical composition of water will be studied. Main planned activities in sub-project C include drilling of a deep borehole in front of the ice sheet, in which different downhole surveys, sampling and monitoring will be carried out. The primary aim of this report is to review available information about hydrogeology and hydrogeochemistry in central Western Greenland, with special emphasis on the area around Kangerlussuaq. The relevant information about this area is however very limited, and it was decided to extend the review to briefly include studies made in other regions with similar conditions in terms of geology, climate and glaciology. The number of published studies made in other areas with glaciers, ice sheets or permafrost is very large, and the review and list of references in this report is far from complete. It is also obvious that both

  16. Efficacy of Antimicrobials on Bacteria Cultured in a Spaceflight Analogue

    Science.gov (United States)

    Nickerson, CA; Wotring, Virginia; Barrila, Jennifer; Crabbe, Aurelie; Castro, Sarah; Davis, Richard; Rideout, April; McCarthy, Breanne; Ott, C. Mark

    2014-01-01

    As humans travel in space, they will interact with microbial flora from themselves, other crewmembers, their food, and the environment. While evaluations of microbial ecology aboard the Mir and ISS suggest a predominance of common environmental flora, the presence of (and potential for) infectious agents has been well documented. Likewise, pathogens have been detected during preflight monitoring of spaceflight food, resulting in the disqualification of that production lot from flight. These environmental and food organisms range from the obligate pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium), which has been responsible for disqualification and removal of food destined for ISS and has previously been reported from Shuttle crew refuse, to the opportunistic pathogen Staphylococcus aureus, isolated numerous times from ISS habitable compartments and the crew. Infectious disease events have affected spaceflight missions, including an upper respiratory infection that delayed the launch of STS-36 and an incapacitating Pseudomonas aeruginosa urinary tract infection of a crewmember during Apollo 13. These observations indicate that the crew has the potential to be exposed to obligate and opportunistic pathogens. This risk of exposure is expected to increase with longer mission durations and increased use of regenerative life support systems. As antibiotics are the primary countermeasure after infection, determining if their efficacy during spaceflight missions is comparable to terrestrial application is of critical importance. The NASA Rotating Wall Vessel (RWV) culture system has been successfully used as a spaceflight culture analogue to identify potential alterations in several key microbial characteristics, such as virulence and gene regulation, in response to spaceflight culture. We hypothesized that bacteria cultured in the low fluid shear RWV environment would demonstrate changes in efficacy of antibiotics compared to higher fluid shear controls

  17. How stakeholders view the use of analogues in safety cases: PAMINA

    International Nuclear Information System (INIS)

    Atherton, Elizabeth; Bailey, Lucy

    2008-01-01

    The aim of this presentation is to provide an overview of some research that has been undertaken in the UK to investigate stakeholders' views of analogues. There are various reasons for using analogues including: to try and explain difficult concepts; to compare disposal facility features with familiar and/or natural systems; to provide an alternative, non-numerical line of reasoning to support the Safety Case conclusions; to provide evidence of behaviour over very long timescales, that cannot be achieved in the laboratory. There are some dangers when using analogues that people should be aware of: the analogue conditions may not be the same as those found in a disposal facility, so the analogue may have limited application. Some analogues may have negative implications, for example artefacts that have corroded. Analogues can be taken too far and used in inappropriate ways to try and support an assumption. So it is important to find out how stakeholders view the use of analogues in a safety case. NDA is involved in an EC funded project called Pamina (Performance Assessment Methodologies in Application). The project involves 26 partners from 11 European countries, plus other associated members and runs for 3 years from October 2006 to October 2009. The NDA is involved in several parts of the project: Exploring issues of modelling uncertainty; Evaluating effectiveness of approaches for communicating safety cases with stakeholders. NDA ran a workshop in October 2007 in Manchester. The aims of the workshop were to explore how different methods of communicating aspects of a safety case were received by stakeholders. The workshop presented stakeholders with: Examples of different repository concepts; Descriptions of barrier performance; Different ways of presenting numerical results; Use of natural analogues

  18. Gas phase thermal diffusion of stable isotopes

    International Nuclear Information System (INIS)

    Eck, C.F.

    1979-01-01

    The separation of stable isotopes at Mound Facility is reviewed from a historical perspective. The historical development of thermal diffusion from a laboratory process to a separation facility that handles all the noble gases is described. In addition, elementary thermal diffusion theory and elementary cascade theory are presented along with a brief review of the uses of stable isotopes

  19. physico-chemical and stable isotopes

    African Journals Online (AJOL)

    This paper details the mineralogical, chemical and stable isotope abundances of calcrete in the Letlhakeng fossil valley. The stable isotope abundances (O and C) of calcretes yielded some values which were tested against the nature of the calcretes – pedogenic or groundwater type. The Kgalagadi (Kalahari) is a vast ...

  20. Modelling stable atmospheric boundary layers over snow

    NARCIS (Netherlands)

    Sterk, H.A.M.

    2015-01-01

    Thesis entitled:

    Modelling Stable Atmospheric Boundary Layers over Snow

    H.A.M. Sterk

    Wageningen, 29th of April, 2015

    Summary

    The emphasis of this thesis is on the understanding and forecasting of the Stable Boundary Layer (SBL) over snow-covered surfaces. SBLs

  1. Modelling stable atmospheric boundary layers over snow

    NARCIS (Netherlands)

    Sterk, H.A.M.

    2015-01-01

    Thesis entitled: Modelling Stable Atmospheric Boundary Layers over Snow H.A.M. Sterk Wageningen, 29th of April, 2015 Summary The emphasis of this thesis is on the understanding and forecasting of the Stable Boundary Layer (SBL) over snow-covered surfaces. SBLs typically form at night and in polar

  2. Stable isotopes and biomarkers in microbial ecology

    NARCIS (Netherlands)

    Boschker, H.T.S.; Middelburg, J.J.

    2002-01-01

    The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

  3. Stable Agrobacterium -mediated transformation of the halophytic ...

    African Journals Online (AJOL)

    Stable Agrobacterium-mediated transformation of the halophytic Leymus chinensis (Trin.) Yan-Lin Sun, Soon-Kwan Hong. Abstract. In this study, an efficient procedure for stable Agrobacterium-mediated transformation of Leymus chinensis (Trin.) was established. Agrobacterium tumefaciens strain EHA105, harboring a ...

  4. Serotonin receptor binding affinities of several hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues.

    Science.gov (United States)

    Glennon, R A; Liebowitz, S M; Mack, E C

    1978-08-01

    Hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues are known to affect serotonergic systems both in vivo and in vitro. Using a rat stomach fundus model, the 5-HT receptor binding affinities of several of these analogues were determined and compared. The most behaviorally potent analogues examined, DOB, DOM, and 5-methoxy-N,N-dimethyltryptamine, were found to possess rather high affirmities (pA2 = 7.35, 7.12, and 7.08, respectively) for the 5-HT receptors of the model system.

  5. New analogues of Cucurbita maxima trypsin inhibitor III (CMTI III) with simplified structure.

    Science.gov (United States)

    Rolka, K; Kupryszewski, G; Rózycki, J; Ragnarsson, U; Zbyryt, T; Otlewski, J

    1992-10-01

    Seven new analogues of trypsin inhibitor CMTI III were obtained by solid-phase peptide synthesis. Three analogues contained only two, instead of three, disulfide bridges, whereas the molecules of the next four analogues were shortened at the N- and/or C-terminus. The elimination of one disulfide bridge in CMTI III induces a decrease in the association equilibrium constants by 6-7 orders of magnitude, whereas the removal of one, two or three amino-acid residues at the N- and/or C-terminus does not significantly affect the activity.

  6. Canangalias C-H, juvenile hormone III analogues from the roots of Cananga latifolia.

    Science.gov (United States)

    Phatchana, Ratchanee; Thongsri, Yordhathai; Yenjai, Chavi

    2016-10-01

    Chemical investigation of the roots of Cananga latifolia led to the isolation and purification of thirteen juvenile hormone III analogues. Six new analogues, canangalias C-H (1-6) and a new natural product, (2E,6E,10R)-10-acetoxy-11-hydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid methyl ester (7), were isolated. In addition, six known juvenile hormone III analogues were isolated. Their structures were established by spectroscopic methods including 1D and 2D NMR, IR and mass spectrometry. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

    DEFF Research Database (Denmark)

    Rabe, Patrick; Klapschinski, Tim A.; Brock, Nelson L.

    2014-01-01

    aureus and Vibrio anguillarum for a structure-activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues......Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus...... is presented and the bioactivity of the synthetic compounds is discussed....

  8. Structure of acid-stable carmine.

    Science.gov (United States)

    Sugimoto, Naoki; Kawasaki, Yoko; Sato, Kyoko; Aoki, Hiromitsu; Ichi, Takahito; Koda, Takatoshi; Yamazaki, Takeshi; Maitani, Tamio

    2002-02-01

    Acid-stable carmine has recently been distributed in the U.S. market because of its good acid stability, but it is not permitted in Japan. We analyzed and determined the structure of the major pigment in acid-stable carmine, in order to establish an analytical method for it. Carminic acid was transformed into a different type of pigment, named acid-stable carmine, through amination when heated in ammonia solution. The features of the structure were clarified using a model compound, purpurin, in which the orientation of hydroxyl groups on the A ring of the anthraquinone skeleton is the same as that of carminic acid. By spectroscopic means and the synthesis of acid-stable carmine and purpurin derivatives, the structure of the major pigment in acid-stable carmine was established as 4-aminocarminic acid, a novel compound.

  9. Stable Fly, (L., Dispersal and Governing Factors

    Directory of Open Access Journals (Sweden)

    Allan T. Showler

    2015-01-01

    Full Text Available Although the movement of stable fly, Stomoxys calcitrans (L., has been studied, its extent and significance has been uncertain. On a local scale (13 km is mainly wind-driven by weather fronts that carry stable flies from inland farm areas for up to 225 km to beaches of northwestern Florida and Lake Superior. Stable flies can reproduce for a short time each year in washed-up sea grass, but the beaches are not conducive to establishment. Such movement is passive and does not appear to be advantageous to stable fly's survival. On a regional scale, stable flies exhibit little genetic differentiation, and on the global scale, while there might be more than one “lineage”, the species is nevertheless considered to be panmictic. Population expansion across much of the globe likely occurred from the late Pleistocene to the early Holocene in association with the spread of domesticated nomad livestock and particularly with more sedentary, penned livestock.

  10. Detecting Pyrolysis Products from Bacteria in a Mars Soil Analogue

    Science.gov (United States)

    Glavin, D. P.; Cleaves, H. J.; Schubert, M.; Aubrey, A.; Buch, A.; Mahaffy, P. R.; Bada, J. L.

    2004-01-01

    One of the primary objectives of the 1976 Viking missions was to determine whether organic compounds, possibly of biological origin, were present in the Martian surface soils. The Viking gas chromatography mass spectrometry (GCMS) instruments found no evidence for any organic compounds of Martian origin above a few parts per billion in the upper 10 cm of surface soil, suggesting the absence of a widely distributed Martian biota. However, it is now known that key organic compounds important to biology, such as amino acids, carboxylic acids and nucleobases, would likely have been missed by the Viking GCMS instruments. In this study, a Mars soil analogue that was inoculated with approx. 10 billion Escherichia coli cells was heated at 500 C under Martian ambient pressure to release volatile organic compounds from the sample. The pyrolysis products were then analyzed for amino acids and nucleobases using high performance liquid chromatography (HPLC) and GCMS. Our experimental results indicate that at the part per billion level, the degradation products generated from several million bacterial cells per gram of Martian soil would not have been detected by the Viking GCMS instruments. Upcoming strategies for Mars exploration will require in-situ analyses by instruments that can assess whether any organic compounds, especially those that might be associated with life, are present in Martian surface samples.

  11. Cetalox and analogues: synthesis via acid-mediated polyene cyclizations.

    Science.gov (United States)

    Snowden, Roger L

    2008-06-01

    Using a novel, acid-mediated cyclization methodology, a direct access to Cetalox ((+/-)-1; a commercially important ambergris-type odorant) and various structurally related didehydro (i.e., 19, 26, and 30) and tetradehydro (i.e., 28 and 37/38) analogues is described. Treatment of either (E,E)-14 or (E)-15 with an excess of FSO(3)H in 2-nitropropane at -90 degrees stereospecifically afforded (+/-)-1 in 40 and 42% yield, respectively. Under similar conditions, cyclization of (E)-18 or 20 furnished 19 in 60 and 64% yield, respectively. Analogously, using an excess of ClSO(3)H in CH(2)Cl(2) at -80 degrees, 26 is formed with high stereoselectivity by cyclization of either (E)-24 or (Z)-25 (52 and 31% yield, resp.); in the same manner, 28 was prepared from 27 (22% yield). The same principle was applied to the synthesis of racemic Superambrox (30), via cyclization of 35, but only with poor selectivity (22%) and low yield (7%). Another approach via cyclization of (E)-40 under solvolysis conditions (excess TFA in CH(2)Cl(2) at -10 degrees) gave a higher yield (15%) with improved selectivity (43%). Finally, cyclization of 34 (1:1 diastereoisomer mixture) afforded 37/38 (10:1) in 27% yield. The qualitative organoleptic properties of 19, 26, 28, 30, and 37/38 (10:1) are briefly discussed.

  12. ENDOCRINE EVALUATION OF ATHLETE FOR TESTOSTERONE OR ITS ANALOGUES ABUSE

    Directory of Open Access Journals (Sweden)

    Joško Osredkar

    2003-12-01

    Full Text Available Background. Doping involves the use of substances and methods prohibited by international and national sports institutions. The use of certain substances and methods is harmful to the human organism, so all sports organisations are trying to protect athletes from the harmful side effects of such substances and methods.Methods. The article deals with special protocol, which is used in the case, when the testosterone/epitestosterone ratio in urine is higher than 6 and less then 10. When establishing the use of testosterone or analogues, ketoconazol is used. If after the application the presence of a testosterone (T to epitestosterone (E ratio is greater than six (6 to one (1, there is an evidence of doping offence.Conclusions. In the case of T/E greater than 6, it is mandatory that the relevant medical authority conducts an investigation before the sample is declared positive. A full report should be written and should include a review of previous tests, subsequent tests and any results of endocrine investigations.

  13. Effects of cognitive and pharmacologic strategies on analogued labor pain.

    Science.gov (United States)

    Geden, E A; Beck, N C; Anderson, J S; Kennish, M E; Mueller-Heinze, M

    1986-01-01

    Using an analogued labor pain procedure, the efficacy of combinations of five cognitive and one pharmacologic approach to pain management was examined. Nulliparous undergraduates (N = 120) were randomly assigned to 1 of 12 groups. Cognitive groups included: systematic desensitization (SYS DENS); sensory description (SEN DESC); sensory transformation (ST); modeling (M); and relaxation (R); combined groups: SYS DENS, SEN DESC, and ST; SEN DESC, ST, and R; SEN DESC, R, ST, and Demerol. Pharmacologic groups included expected Demerol, did not expect Demerol, placebo, and no treatment control. Subjects assigned to a cognitive group received two 1-hour training sessions 1 week apart. Remaining subjects were given the assigned pharmacologic treatment one-half hour prior to the exposure to the painful stimulus. Assessment of the cognitive and pharmacologic approaches were made in a 1-hour session involving twenty 80-second exposures to a laboratory pain stimulus patterned to resemble labor contractions. Dependent variables included self-reported pain, blood pressure, frontalis electromyograph, heart rate, and respiratory rate. Significant treatment by trials and treatment effects were found for self-reported pain. No other effects achieved statistical significance.

  14. Superconducting Analogue of the Parafermion Fractional Quantum Hall States

    Directory of Open Access Journals (Sweden)

    Abolhassan Vaezi

    2014-07-01

    Full Text Available Read-Rezayi Z_{k} parafermion wave functions describe ν=2+(k/kM+2 fractional quantum Hall (FQH states. These states support non-Abelian excitations from which protected quantum gates can be designed. However, there is no experimental evidence for these non-Abelian anyons to date. In this paper, we study the ν=2/k FQH-superconductor heterostructure and find the superconducting analogue of the Z_{k} parafermion FQH state. Our main tool is the mapping of the FQH into coupled one-dimensional chains, each with a pair of counterpropagating modes. We show that by inducing intrachain pairing and charge preserving backscattering with identical couplings, the one-dimensional chains flow into gapless Z_{k} parafermions when k<4. By studying the effect of interchain coupling, we show that every parafermion mode becomes massive except for the two outermost ones. Thus, we achieve a fractional topological superconductor whose chiral edge state is described by a Z_{k} parafermion conformal field theory. For instance, we find that a ν=2/3 FQH in proximity to a superconductor produces a Z_{3} parafermion superconducting state. This state is topologically indistinguishable from the non-Abelian part of the ν=12/5 Read-Rezayi state. Both of these systems can host Fibonacci anyons capable of performing universal quantum computation through braiding operations.

  15. Nontoxic piperamides and their synthetic analogues as novel antifouling reagents

    KAUST Repository

    Huang, Xiang-Zhong

    2014-03-25

    Bioassay-guided isolation of an acetone extract from a terrestrial plant Piper betle produced four known piperamides with potent antifouling (AF) activities, as evidenced by inhibition of settlement of barnacle cypris larvae. The AF activities of the four piperamides and 15 synthesized analogues were compared and their structure-activity relationships were probed. Among the compounds, piperoleine B and 1-[1-oxo-7-(3′,4′-methylenedioxyphenyl)-6E-heptenyl]-piperidine (MPHP) showed strong activity against settlement of cyprids of the barnacle Balanus amphitrite, having EC50 values of 1.1 ± 0.3 and 0.5 ± 0.2 μg ml-1, respectively. No toxicity against zebra fish was observed following incubation with these two compounds. Besides being non-toxic, 91% of piperoleine B-treated cyprids and 84% of MPHP-treated cyprids at a concentration of 100 μM completed normal metamorphosis in recovery bioassays, indicating that the anti-settlement effect of these two compounds was reversible. Hydrolysis and photolysis experiments indicated that MPHP could be decomposed in the marine environment. It is concluded that piperamides are promising compounds for use in marine AF coatings. © 2014 © 2014 Taylor & Francis.

  16. Phospholipid analogue distributions of Iranian isolates of candida

    International Nuclear Information System (INIS)

    Zarei Mahmoudabadi, A.; Brucker, D.B.

    2004-01-01

    The aim of this study was to analyse polar lipids of candida species isolated from Ahwas (Iran) by fast Atom bombardment mass spectrometry . Nine isolates of Candida Sp. were identified by growth at 45 d ig c , production of chlamydoconidia on cornmeal agar, colonial colour on CHROMagar Candida, germ tube production and ID 32 C kits. Then polar lipids were extracted from freeze-dried cultures and analysed using Fast Atom Bombardment Mass Spectrometry. The most intense carboxylate and phospholipid molecular species anions were of m/z 281 (C 1 8 : 1 ) and m/z 515 (PA 23:2). However, the most intense carboxylate and phospholipid analogues in Candida Parapsilosis were 292 (Un) and 555 (PA 26:3), which differed from other yeasts. Isolates were grouped by single linkage clustering based on correlation coefficient for strain pairs calculated with carboxylate and phospholipid molecular species distributions. Fast Atom Bombardment Mass Spectrometry can differentiate the C. albicans based on analysis of polar lipid distributions.These findings support that differentiation between C. albicans and other species is possible based on polar lipids

  17. Implementation of Power Efficient Flash Analogue-to-Digital Converter

    Directory of Open Access Journals (Sweden)

    Taninki Sai Lakshmi

    2014-01-01

    Full Text Available An efficient low power high speed 5-bit 5-GS/s flash analogue-to-digital converter (ADC is proposed in this paper. The designing of a thermometer code to binary code is one of the exacting issues of low power flash ADC. The embodiment consists of two main blocks, a comparator and a digital encoder. To reduce the metastability and the effect of bubble errors, the thermometer code is converted into the gray code and there after translated to binary code through encoder. The proposed encoder is thus implemented by using differential cascade voltage switch logic (DCVSL to maintain high speed and low power dissipation. The proposed 5-bit flash ADC is designed using Cadence 180 nm CMOS technology with a supply rail voltage typically ±0.85 V. The simulation results include a total power dissipation of 46.69 mW, integral nonlinearity (INL value of −0.30 LSB and differential nonlinearity (DNL value of −0.24 LSB, of the flash ADC.

  18. Potential of carbon nanotube field effect transistors for analogue circuits

    Directory of Open Access Journals (Sweden)

    Khizar Hayat

    2013-11-01

    Full Text Available This Letter presents a detailed comparison of carbon nanotube field effect transistors (CNFETs and metal oxide semiconductor field effect transistors (MOSFETs with special focus on carbon nanotube FET's potential for implementing analogue circuits in the mm-wave and sub-terahertz range. The latest CNFET lithographic dimensions place it at-par with complementary metal oxide semiconductor in terms of current handling capability, whereas the forecasted improvement in the lithography enables the CNFETs to handle more than twice the current of MOSFETs. The comparison of RF parameters shows superior performance of CNFETs with a g(m, f(T and f(max of 2.7, 2.6 and 4.5 times higher, respectively. MOSFET- and CNFET-based inverter, three-stage ring oscillator and LC oscillator have been designed and compared as well. The CNFET-based inverters are found to be ten times faster, the ring oscillator demonstrates three times higher oscillation frequency and CNFET-based LC oscillator also shows improved performance than its MOSFET counterpart.

  19. Antifolate resistance and its circumvention by new analogues.

    Science.gov (United States)

    Takemura, Y; Kobayashi, H; Miyachi, H

    2001-09-01

    We have established human leukemia cell lines made resistant to various antifolate drugs and analyzed resistance mechanisms developed in these cells at the cellular and molecular levels. The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Each resistance mechanism was not necessarily induced at random, but appeared to relate to the biochemical and pharmacological properties of the drug exposed, biological dispositions of the cells, drug-exposure manners to, or culture conditions of the cells. Since it has been shown that a minor modification at the specified position of the folate structure resulted in a drastic change in its pharmacological properties, many new compounds have been rationally designed on the basis of the knowledge of relationships between structure modifications and pharmacological properties. The step-by-step approach to the development of new analogues led to the discoveries of several promising antifolate drugs such as trimetrexate and raltitrexed, which can overcome the acquired and natural resistance to methotrexate, a classical antifolate, and clinical trials of these newer classes of antifolate compounds are currently underway.

  20. Pyrazine analogues from wolf urine induced unlearned fear in rats.

    Science.gov (United States)

    Kashiwayanagi, Makoto; Miyazono, Sadaharu; Osada, Kazumi

    2017-08-01

    Urine excreted from the common grey wolf ( Canis lupus ) contains a kairomone, inducing fear-related behaviors in various mammals. Numerous fear-inducing substances activate neurons at the main and/or accessory olfactory bulb (AOB), medial and central amygdala, and hypothalamus. Our previous study showed that the mixture of pyrazine analogues (P-mix) contained in wolf urine induced avoidance and fear-related behaviors in laboratory mice and Hokkaido deer ( Cervus nippon yesoensis ), a species native to Japan. Exposure to wolf urine or P-mix induced expression of Fos, a marker of neuronal excitation, in the AOB of mice. In the present study, we explored the effects of P-mix on fear-related behaviors and Fos-expression in rats. Exposure to P-mix induced avoidance and immobilization in rats, while that to a mixture of i -amyl acetate, linalool and R(+)-limonene (O-mix), which generate floral and fruity odors, induced avoidance but not immobilization. P-mix but not O-mix increased Fos-immunoreactivity of the AOB, medial and central amygdala, and hypothalamus of rats. The present results suggest that P-mix odor induces unlearned fear-related behaviors in rats.

  1. Pyrazine analogues from wolf urine induced unlearned fear in rats

    Directory of Open Access Journals (Sweden)

    Makoto Kashiwayanagi

    2017-08-01

    Full Text Available Urine excreted from the common grey wolf (Canis lupus contains a kairomone, inducing fear-related behaviors in various mammals. Numerous fear-inducing substances activate neurons at the main and/or accessory olfactory bulb (AOB, medial and central amygdala, and hypothalamus. Our previous study showed that the mixture of pyrazine analogues (P-mix contained in wolf urine induced avoidance and fear-related behaviors in laboratory mice and Hokkaido deer (Cervus nippon yesoensis, a species native to Japan. Exposure to wolf urine or P-mix induced expression of Fos, a marker of neuronal excitation, in the AOB of mice. In the present study, we explored the effects of P-mix on fear-related behaviors and Fos-expression in rats. Exposure to P-mix induced avoidance and immobilization in rats, while that to a mixture of i-amyl acetate, linalool and R(+-limonene (O-mix, which generate floral and fruity odors, induced avoidance but not immobilization. P-mix but not O-mix increased Fos-immunoreactivity of the AOB, medial and central amygdala, and hypothalamus of rats. The present results suggest that P-mix odor induces unlearned fear-related behaviors in rats.

  2. Synthesis and metabolism of pheromones and pheromone analogues

    International Nuclear Information System (INIS)

    Ding, Y.S.

    1987-01-01

    [9, 10- 3 H 2 ]Z9-14:Ac was synthesized at high specific activity ( 3 H, 58 Ci/mmole) by partial tritiation of the corresponding alkyne and was converted to the labeled Z9-14:OH and Z9-14:Al to study tissue specificity of acetate esterase (E), alcohol oxidase (OX), and aldehyde dehydrogenase (ALDH) in male and female Heliothis virescens. Soluble and membrane-associated enzyme activities were determined by radio-TLC assays. Compounds of the tritium-labeled Z11-16 series were synthesized and their in vitro fates examined as well. In order to achieve an alternative approach in which (1) pheromone receptor proteins would be stoichiometrically and irreversibly modified, or (2) pheromone-catabolizing enzymes are inactivated by tight-binding or irreversible inhibitors, we have designed analogues of pheromones of lepidopterous insect pests and assayed their biological activity in vitro and in vivo. Various fluorinated molecules such as acyl fluorides, fluoroolefins, 2-fluoro aldehydes, 2,2-difluoro aldehydes and trifluoromethyl ketones were synthesized. The synthesis of some other functional groups such as cyclopropanones, cyclopropanols, cyclopropyl carbinols, cyclopropyl aldehydes and Michael acceptors will also be discussed

  3. JACoW Lightweight acquisition system for analogue signals

    CERN Document Server

    Bielawski, Bartosz

    2018-01-01

    In a complex machine such as a particle accelerator there are thousands of analogue signals that need monitoring and even more signals that could be used for debugging or as a tool for detecting symptoms of potentially avoidable problems. Usually it is not feasible to acquire and monitor all of these signals not only because of the cost but also because of cabling and space required. The Radio Frequency system in the Large Hadron Collider (LHC) is protected by multiple hardware interlocks that ensure safe operation of klystrons, superconducting cavities and all the other equipment. In parallel, a diagnostic system has been deployed to monitor the health of the klystrons. Due to the limited amount of space and the moderate number of signals to be monitored, a standard approach with a full VME or Compact PCI crate has not been selected. Instead, small embedded industrial computers with Universal Serial Bus (USB) oscilloscopes chosen for the specific application have been installed. This cost effective, rapidly ...

  4. Neurotoxicity Caused by the Treatment with Platinum Analogues

    Directory of Open Access Journals (Sweden)

    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  5. Potential of carbon nanotube field effect transistors for analogue circuits

    KAUST Repository

    Hayat, Khizar

    2013-05-11

    This Letter presents a detailed comparison of carbon nanotube field effect transistors (CNFETs) and metal oxide semiconductor field effect transistors (MOSFETs) with special focus on carbon nanotube FET\\'s potential for implementing analogue circuits in the mm-wave and sub-terahertz range. The latest CNFET lithographic dimensions place it at-par with complementary metal oxide semiconductor in terms of current handling capability, whereas the forecasted improvement in the lithography enables the CNFETs to handle more than twice the current of MOSFETs. The comparison of RF parameters shows superior performance of CNFETs with a g m , f T and f max of 2.7, 2.6 and 4.5 times higher, respectively. MOSFET- and CNFET-based inverter, three-stage ring oscillator and LC oscillator have been designed and compared as well. The CNFET-based inverters are found to be ten times faster, the ring oscillator demonstrates three times higher oscillation frequency and CNFET-based LC oscillator also shows improved performance than its MOSFET counterpart.

  6. Robenidine Analogues as Gram-Positive Antibacterial Agents.

    Science.gov (United States)

    Abraham, Rebecca J; Stevens, Andrew J; Young, Kelly A; Russell, Cecilia; Qvist, Anastasia; Khazandi, Manouchehr; Wong, Hui San; Abraham, Sam; Ogunniyi, Abiodun D; Page, Stephen W; O'Handley, Ryan; McCluskey, Adam; Trott, Darren J

    2016-03-10

    Robenidine, 1 (2,2'-bis[(4-chlorophenyl)methylene]carbonimidic dihydrazide), was active against MRSA and VRE with MIC's of 8.1 and 4.7 μM, respectively. SAR revealed tolerance for 4-Cl isosteres with 4-F (8), 3-F (9), 3-CH3 (22), and 4-C(CH3)3 (27) (23.7-71 μM) and with 3-Cl (3), 4-CH3 (21), and 4-CH(CH3)2 (26) (8.1-13.0 μM). Imine carbon alkylation identified a methyl/ethyl binding pocket that also accommodated a CH2OH moiety (75; 2,2'-bis[1-(4-chlorophenyl)-2-hydroxyethylidene]carbonimidic dihydrazide). Analogues 1, 27 (2,2'-bis{[4-(1,1-dimethylethyl)phenyl]methylene}carbonimidic dihydrazide), and 69 (2,2'-bis[1-(4-chlorophenyl)ethylidene]carbonimidic dihydrazide hydrochloride) were active against 24 clinical MRSA and MSSA isolates. No dose-limiting cytotoxicity at ≥2× MIC or hemolysis at ≥8× MIC was observed. Polymyxin B addition engendered Escherichia coli and Pseudomonas aeruginosa Gram-negative activity MIC's of 4.2-21.6 μM. 1 and 75 displayed excellent microsomal stability, intrinsic clearance, and hepatic extraction ratios with T1/2 > 247 min, CLint < 7 μL/min/mg protein, and EH < 0.22 in both human and mouse liposomes for 1 and in human liposomes for 75.

  7. Synthesis and Properties of Group IV Graphane Analogues

    Science.gov (United States)

    Goldberger, Joshua

    Similar to how carbon networks can be sculpted into low-dimensional allotropes such as fullerenes, nanotubes, and graphene with fundamentally different properties, it is possible to create similar ligand terminated sp3-hybridized honeycomb graphane derivatives containing Ge or Sn that feature unique and tunable properties. Here, we will describe our recent success in the creation of hydrogen and organic-terminated group IV graphane analogues, from the topochemical deintercalation of precursor Zintl phases, such as CaGe2. We will discuss how the optical, electronic, and thermal properties of these materials can be systematically controlled by substituting either the surface ligand or via alloying with other Group IV elements. Additionally, we have also developed an epitopotaxial approach for integrating precise thicknesses of germanane layers onto Ge wafers that combines the epitaxial deposition of CaGe2 precursor phases with the topotactic interconversion into the 2D material. Finally, we will describe our recent efforts on the synthesis and crystal structures of Sn-containing graphane alloys in order to access novel topological phenomena predicted to occur in these graphanes.

  8. Human sperm swimming in a high viscosity mucus analogue.

    Science.gov (United States)

    Ishimoto, Kenta; Gadêlha, Hermes; Gaffney, Eamonn A; Smith, David J; Kirkman-Brown, Jackson

    2018-02-17

    Remarkably, mammalian sperm maintain a substantive proportion of their progressive swimming speed within highly viscous fluids, including those of the female reproductive tract. Here, we analyse the digital microscopy of a human sperm swimming in a highly viscous, weakly elastic mucus analogue. We exploit principal component analysis to simplify its flagellar beat pattern, from which boundary element calculations are used to determine the time-dependent flow field around the sperm cell. The sperm flow field is further approximated in terms of regularized point forces, and estimates of the mechanical power consumption are determined, for comparison with analogous low viscosity media studies. This highlights extensive differences in the structure of the flows surrounding human sperm in different media, indicating how the cell-cell and cell-boundary hydrodynamic interactions significantly differ with the physical microenvironment. The regularized point force decomposition also provides cell-level information that may ultimately be incorporated into sperm population models. We further observe indications that the core feature in explaining the effectiveness of sperm swimming in high viscosity media is the loss of cell yawing, which is related with a greater density of regularized point force singularities along the axis of symmetry of the flagellar beat to represent the flow field. In turn this implicates a reduction of the wavelength of the distal beat pattern - and hence dynamical wavelength selection of the flagellar beat - as the dominant feature governing the effectiveness of sperm swimming in highly viscous media. Copyright © 2018. Published by Elsevier Ltd.

  9. Bead-Based Microfluidic Sediment Analogues: Fabrication and Colloid Transport.

    Science.gov (United States)

    Guo, Yang; Huang, Jingwei; Xiao, Feng; Yin, Xiaolong; Chun, Jaehun; Um, Wooyong; Neeves, Keith B; Wu, Ning

    2016-09-13

    Mobile colloids can act as carriers for low-solubility contaminants in the environment. However, the dominant mechanism for this colloid-facilitated transport of chemicals is unclear. Therefore, we developed a bead-based microfluidic platform of sediment analogues and measured both single and population transport of model colloids. The porous medium is assembled through a bead-by-bead injection method. This approach has the versatility to build both electrostatically homogeneous and heterogeneous media at the pore scale. A T-junction at the exit also allowed for encapsulation and enumeration of colloids effluent at single particle resolution to give population dynamics. Tortuosity calculated from pore-scale trajectory analysis and its comparison with lattice Boltzmann simulations revealed that transport of colloids was influenced by the size exclusion effect. The porous media packed by positively and negatively charged beads into two layers showed distinctive colloidal particle retention and significant remobilization and re-adsorption of particles during water flushing. We demonstrated the potential of our method to fabricate porous media with surface heterogeneities at the pore scale. With both single and population dynamics measurement, our platform has the potential to connect pore-scale and macroscale colloid transport on a lab scale and to quantify the impact of grain surface heterogeneities that are natural in the subsurface environment.

  10. Hydrogen adsorption in thin films of Prussian blue analogue

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dali [Los Alamos National Laboratory; Ding, Vivian [Los Alamos National Laboratory; Luo, Junhua [Los Alamos National Laboratory; Currier, Robert P [Los Alamos National Laboratory; Obrey, Steve [Los Alamos National Laboratory; Zhao, Yusheng [Los Alamos National Laboratory

    2008-01-01

    Quartz crystal microbalance with dissipation (QCM-D) measurement was used to investigate the kinetics of the molecular hydrogen adsorption into thin films of prussian blue analogues - Cu{sub 3}[Co(CN){sub 6}]{sub 2} at ambient conditions. Although the equilibrium adsorption seems to be independent of the thickness, the adsorption rate substantially decreases with the thickness of the films. In addition, the reversibility of H{sub 2} adsorption into the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films was investigated. The results indicate that the Cu{sub 3}[Co(CN){sub 6}]{sub 2} maily interacts with H{sub 2} molecules physically. The highest H{sub 2} uptake by the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films is obtained when the gas phase is stagnant inside the testing cell. However, the unusual high H{sub 2} uptake obtained from the QCM-D measurement makes us question how reliable this analytic methodology is.

  11. Synthesis and metabolism of pheromones and pheromone analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.

    1987-01-01

    (9, 10-/sup 3/H/sub 2/)Z9-14:Ac was synthesized at high specific activity (/sup 3/H, 58 Ci/mmole) by partial tritiation of the corresponding alkyne and was converted to the labeled Z9-14:OH and Z9-14:Al to study tissue specificity of acetate esterase (E), alcohol oxidase (OX), and aldehyde dehydrogenase (ALDH) in male and female Heliothis virescens. Soluble and membrane-associated enzyme activities were determined by radio-TLC assays. Compounds of the tritium-labeled Z11-16 series were synthesized and their in vitro fates examined as well. In order to achieve an alternative approach in which (1) pheromone receptor proteins would be stoichiometrically and irreversibly modified, or (2) pheromone-catabolizing enzymes are inactivated by tight-binding or irreversible inhibitors, we have designed analogues of pheromones of lepidopterous insect pests and assayed their biological activity in vitro and in vivo. Various fluorinated molecules such as acyl fluorides, fluoroolefins, 2-fluoro aldehydes, 2,2-difluoro aldehydes and trifluoromethyl ketones were synthesized. The synthesis of some other functional groups such as cyclopropanones, cyclopropanols, cyclopropyl carbinols, cyclopropyl aldehydes and Michael acceptors will also be discussed.

  12. Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Science.gov (United States)

    Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

    2017-09-01

    Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  13. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues

    Directory of Open Access Journals (Sweden)

    Monika Stompor

    2016-05-01

    Full Text Available The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus. The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus and Gram-negative (Escherichia coli bacteria, fungi (Alternaria sp., and yeasts (Rhodotorula rubra, Candida albicans revealed that compounds with at least one hydroxyl group—all of them have it at the C-4 position—demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones. The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4’-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4’-methoxychalcones or its replacement by a halogen atom (−Cl, −Br, nitro group (−NO2, ethoxy group (−OCH2CH3, or aliphatic substituent (−CH3, −CH2CH3 resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4-hydroxy-4′-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra.

  14. Of mongooses and mitigation: ecological analogues to geoengineering

    International Nuclear Information System (INIS)

    Matthews, H Damon; Turner, Sarah E

    2009-01-01

    Anthropogenic global warming is a growing environmental problem resulting from unintentional human intervention in the global climate system. If employed as a response strategy, geoengineering would represent an additional intentional human intervention in the climate system, with the intent of decreasing net climate impacts. There is a rich and fascinating history of human intervention in environmental systems, with many specific examples from ecology of deliberate human intervention aimed at correcting or decreasing the impact of previous unintentionally created problems. Additional interventions do not always bring the intended results, and in many cases there is evidence that net impacts have increased with the degree of human intervention. In this letter, we report some of the examples in the scientific literature that have documented such human interventions in environmental systems, which may serve as analogues to geoengineering. We argue that a high degree of system understanding is required for increased intervention to lead to decreased impacts. Given our current level of understanding of the climate system, it is likely that the result of at least some geoengineering efforts would follow previous ecological examples where increased human intervention has led to an overall increase in negative environmental consequences.

  15. Multidisciplinary integrated field campaign to an acidic Martian Earth analogue with astrobiological interest: Rio Tinto

    Czech Academy of Sciences Publication Activity Database

    Gómez, F.; Walter, N.; Amils, R.; Rull, F.; Klingelhöfer, G.; Kvíderová, Jana; Sarrazin, P.; Foing, B.; Behar, A.; Fleischer, I.; Parro, V.; Garcia-Villadangos, M.; Blake, D.; Martin-Ramos, J. D.; Direito, S.; Mahapatra, P.; Stam, C.; Venkateswaran, K.; Voytek, M.

    2011-01-01

    Roč. 10, č. 3 (2011), 291-305 ISSN 1473-5504 Institutional research plan: CEZ:AV0Z60050516 Keywords : astrobiology * extreme environments * Earth analogue Subject RIV: EF - Botanics Impact factor: 1.723, year: 2011

  16. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

  17. Promising Strategy To Improve Charge Separation in Organic Photovoltaics : Installing Permanent Dipoles in PCBM Analogues

    NARCIS (Netherlands)

    de Gier, Hilde D.; Jahani, Fatemeh; Broer, Ria; Hummelen, Jan C.; Havenith, Remco W. A.

    2016-01-01

    A multidisciplinary approach involving organic synthesis and theoretical chemistry was applied to investigate a promising strategy to improve charge separation in organic photovoltaics: installing permanent dipoles in fullerene derivatives. First, a PCBM analogue with a permanent dipole in the side

  18. Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

    DEFF Research Database (Denmark)

    Petersen, Asger Bjørn; Andersen, Nikolaj Sten; Konotop, Gleb

    2017-01-01

    potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve...... the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation...... studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral...

  19. Physical Characterization of Synthetic Phosphatidylinositol Dimannosides and Analogues in Binary Systems with Phosphatidylcholine

    DEFF Research Database (Denmark)

    Hubert, Madlen; Larsen, David S; Hayman, Colin M

    2014-01-01

    Native phosphatidylinositol mannosides (PIMs) from the cell wall of Mycobacterium bovis (M. bovis) and synthetic analogues have been identified to exert immunostimulatory activities. These activities have been investigated using particulate delivery systems containing native mannosylated lipids o...

  20. Transient High-Temperature Processing of Silicates in Fulgurites as Analogues for Meteorite and Impact Melts

    Science.gov (United States)

    Parnell, J.; Thackrey, S.; Muirhead, D. K.; Wright, A. J.

    2008-03-01

    A fulgurite from the Sahara yielded petrographic data valuable as an analogue for highly reduced meteorite and impact melts, including iron silicide formation, devolatilization features, zircon melting and extreme melt heterogeneity.

  1. Testing safety assessment models using natural analogues in high natural-series groundwaters

    International Nuclear Information System (INIS)

    Smellie, J.; Chapman, N.; McKinley, I.; Franca, E.P.; Shea, M.

    1989-01-01

    Progress in the second year of the project is outlined in terms of four analogue objectives. Results of modelling of the preliminary data sets on groundwater chemical speciation of radionuclides, colloids, redox processes, and hydrothermal fluid transport are presented

  2. Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars; Jensen, Simon Skøde

    2009-01-01

    Two lipophilic methotrexate analogues have been synthesized and evaluated for cytotoxicity against KATO III and HT-29 human colon cancer cells. Both analogues contained a C-16-alkyl chain attached to the gamma-carboxylic acid and one of the analogues had an additional benzyl group attached...... cytotoxicity was incorporated into liposomes that were designed to be particularly Susceptible to a liposome degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high concentrations in tumors of several different cancer types. Liposome incorporation was investigated by differential...... of the MTX-liposomes against KATO III and HT-29 cancer cells was found to be independent of sPLA(2) hydrolysis, indicating that the alkylated MTX-analogue was available for cancer cell uptake even in the absence of liposome hydrolysis. Using a DSC based method for assessing the anchoring stability...

  3. Stable Organic Neutral Diradical via Reversible Coordination.

    Science.gov (United States)

    Lu, Zhenpin; Quanz, Henrik; Burghaus, Olaf; Hofmann, Jonas; Logemann, Christian; Beeck, Sebastian; Schreiner, Peter R; Wegner, Hermann A

    2017-12-27

    We report the formation of a stable neutral diboron diradical simply by coordination of an aromatic dinitrogen compound to an ortho-phenyldiborane. This process is reversible upon addition of pyridine. The diradical species is stable above 200 °C. Computations are consistent with an open-shell triplet diradical with a very small open-shell singlet-triplet energy gap that is indicative of the electronic disjointness of the two radical sites. This opens a new way of generating stable radicals with fascinating electronic properties useful for a large variety of applications.

  4. Experiential acceptance and trait-mindfulness as predictors of analogue post-traumatic stress.

    Science.gov (United States)

    Boelen, Paul A; Lenferink, Lonneke I M

    2018-03-01

    Experiential acceptance and trait-mindfulness are associated with post-traumatic stress disorder (PTSD) after traumatic events. This study was a preliminary attempt to examine (1) associations of experiential acceptance and trait-mindfulness with post-traumatic stress (PTS) associated with negative, but not necessarily traumatizing, life events ('analogue' PTS), (2) the role of these variables in the context of neuroticism as well as worry and rumination - two other regulatory strategies associated with PTS, and (3) the impact of pre-trauma tendencies towards experiential acceptance and mindfulness on analogue PTS. Data were obtained from two distinct student samples. A first sample provided cross-sectional data. In a second sample, indices of acceptance, mindfulness, neuroticism, worry, and rumination were tapped at inclusion into the study, and analogue PTS and confrontation with stressful life events were subsequently assessed 1 year later. In the cross-sectional sample, higher acceptance and mindfulness were associated with lower analogue PTS, even when controlling for neuroticism, worry, and rumination. In the prospective sample, pre-trauma mindfulness (but not experiential acceptance, neuroticism, worry, and rumination) assessed at baseline predicted levels of analogue PTS 1 year later. Findings suggest that experiential acceptance and trait-mindfulness are incrementally related to PTS beyond neuroticism, worry, and rumination and that pre-trauma trait-mindfulness may be a resilience factor protecting against severe PTS. We examined associations of experiential acceptance and trait-mindfulness with post-traumatic stress (PTS) associated with negative life events ('analogue' PTS). Experiential acceptance and trait-mindfulness were associated with concurrent analogue PTS, over and above neuroticism, worry, and rumination. Pre-trauma trait-mindfulness (but not pre-trauma experiential acceptance) significantly predicted analogue PTS in prospective analyses

  5. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century

    OpenAIRE

    Christian Montag; Christopher Kannen; Bernd Lachmann; Rayna Sariyska; Éilish Duke; Martin Reuter; Alexander Markowetz

    2015-01-01

    Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution – particularly since the advent of the smartphone – mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based app...

  6. Long-acting lipidated analogue of human pancreatic polypeptide is slowly released into circulation

    DEFF Research Database (Denmark)

    Bellmann-Sickert, Kathrin; Elling, Christian E; Madsen, Andreas N

    2011-01-01

    The main disadvantages of peptide pharmaceuticals are their rapid degradation and excretion, their low hydrophilicity, and low shelf lifes. These bottlenecks can be circumvented by acylation with fatty acids (lipidation) or polyethylene glycol (PEGylation). Here, we describe the modification....... Lipidation resulted in prolonged action of the hPP analogue in respect of reducing food intake in mice after subcutaneous administration. Therefore, the lipidated hPP analogue could constitute a potential new therapeutic agent against obesity....

  7. Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes

    OpenAIRE

    Li Wang; Ping-Ping Shou; Si-Ping Wei; Chun Zhang; Shuang-Xun Li; Ping-Xian Liu; Xi Du; Qin Wang

    2016-01-01

    An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

  8. Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-01-01

    Full Text Available An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

  9. Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes.

    Science.gov (United States)

    Wang, Li; Shou, Ping-Ping; Wei, Si-Ping; Zhang, Chun; Li, Shuang-Xun; Liu, Ping-Xian; Du, Xi; Wang, Qin

    2016-01-19

    An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

  10. Exploring the Patient Experience of Changes in Appetite and Diet with Incretin Analogue Therapy

    OpenAIRE

    Paisey, Rosamund May

    2014-01-01

    Incretin analogue therapies are a valuable recent treatment option for type 2 diabetes (T2D) as they can improve blood glucose control and aid weight loss. The way in which an individual recognises and responds to changes in satiety signals induced by these treatments may explain why individual response is variable. Purposive sampling of individuals with successful outcome of incretin analogue therapy (GLP-1) for T2D gathered a participant cohort 15 people with 37 years (448 months) combined ...

  11. The value of pseudo 3D techniques for the interpretation of analogue archaeological research

    OpenAIRE

    Overmars, G.; Panhuysen, R.; Börner, W.; Uhlirz, S.

    2014-01-01

    The use of virtual 3D techniques as a research tool in the interpretation of analogue archaeological data has gained little attention. The current paper will explore whether the use of 3D techniques can help to understand data from old archaeological excavations. A method is presented which facilitates the translation of analogue data into a pseudo 3D environment. One trench from the famous excavations of the early medieval trading town of Dorestad serves as a case study. This trench was exca...

  12. Decarbonylative thioetherification by nickel catalysis using air- and moisture-stable nickel precatalysts.

    Science.gov (United States)

    Liu, Chengwei; Szostak, Michal

    2018-02-22

    A general, highly selective method for decarbonylative thioetherification of aryl thioesters by C-S cleavage is reported. These reactions are promoted by a commercially-available, user-friendly, inexpensive, air- and moisture-stable nickel precatalyst. The process occurs with broad functional group tolerance, including free anilines, cyanides, ketones, halides and aryl esters, to efficiently generate thioethers using ubiquitous carboxylic acids as ultimate cross-coupling precursors (cf. conventional aryl halides or pseudohalides). Selectivity studies and site-selective orthogonal cross-coupling/thioetherification are described. This thioester activation/coupling has been highlighted in the expedient synthesis of biorelevant drug analogue. In light of the synthetic utility of thioethers and Ni(ii) precatalysts, we anticipate that this user-friendly method will be of broad interest.

  13. 3D Strain Modelling of Tear Fault Analogues

    Science.gov (United States)

    Hindle, D.; Vietor, T.

    2005-12-01

    Tear faults can be described as vertical discontinuities, with near fault parallel displacements terminating on some sort of shallow detachment. As such, they are difficult to study in "cross section" i.e. 2 dimensions as is often the case for fold-thrust systems. Hence, little attempt has been made to model the evolution of strain around tear faults and the processes of strain localisation in such structures due to the necessity of describing these systems in 3 dimensions and the problems this poses for both numerical and analogue modelling. Field studies suggest that strain in such regions can be distributed across broad zones on minor tear systems, which are often not easily mappable. Such strain is probably assumed to be due to distributed strain and to displacement gradients which are themselves necessary for the initiation of the tear itself. We present a numerical study of the effects of a sharp, basal discontinutiy parallel to the transport direction in a shortening wedge of material. The discontinuity is represented by two adjacent basal surfaces with strongly contrasting (0.5 and 0.05) friction coefficient. The material is modelled using PFC3D distinct element software for simulating granular material, whose properties are chosen to simulate upper crustal, sedimentary rock. The model geometry is a rectangular bounding box, 2km x 1km, and 0.35-0.5km deep, with a single, driving wall of constant velocity. We show the evolution of strain in the model in horizontal and vertical sections, and interpret strain localization as showing the spontaneous development of tear fault like features. The strain field in the model is asymmetrical, rotated towards the strong side of the model. Strain increments seem to oscillate in time, suggesting achievement of a steady state. We also note that our model cannot be treated as a critical wedge, since the 3rd dimension and the lateral variations of strength rule out this type of 2D approximation.

  14. Hypocalcemic action of the several types of salicylic acid analogues.

    Science.gov (United States)

    Kato, Y; Nishishita, K; Sakai, H; Tatsumi, M; Yamamoto, K

    1989-02-01

    The present study was performed to see the structure-activity relationships on the aspirin-induced hypocalcemia. Several kinds of salicylic acid (SA) analogues administered orally with a stomach tube. In general, the drugs were suspended in the 2% CMC solution. At the scheduled times after the treatment, 60 microliters of the blood was collected to determine the level of calcium. Aspirin, sodium salt of o-hydroxybenzoic acid (Na-salicylate), sodium salt of m- and p-hydroxybenzoic acid (HBA), 2,5-dihydroxybenzoic acid (DHBA), PAS sodium dihydrate (PAS-Na), salicylamide (SAM) and 2% CMC control were used. Hypocalcemia was induced by aspirin and Na-salicylate but not by m- and p-HBA-Na. In addition, DHBA and PAS caused hypocalcemia when they were administered intravenously but not orally. These results suggest that the carboxyl group must be adjacent to the hydroxyl group on the benzene ring to induce this type of hypocalcemia and that the SA structure would be able to induce hypocalcemia, even in the presence of the additional third substituent on the same ring. On the comparison between aspirin-DL lysine (water soluble aspirin) and SA-DL lysine, SA-DL lysine, which is not an inhibitor of PG synthetase, was more effective on the hypocalcemic action than ASP-DL lysine. The phenomenon was observed at the stage especially immediately after intravenous injection, when the acetyl group may be more responsible to acetylate the PG synthetase in the aspirin-DL lysine group. The present results seems to be consistent with the previous hypothesis that PGs are not involved in the process of aspirin-induced hypocalcemia in the rat.

  15. Design of potent substrate-analogue inhibitors of canine renin

    Science.gov (United States)

    Hui, K. Y.; Siragy, H. M.; Haber, E.

    1992-01-01

    Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.

  16. Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Armaković, Stevan, E-mail: stevan.armakovic@df.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Physics, Trg Dositeja Obradovića 4, 21000, Novi Sad (Serbia); Armaković, Sanja J. [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000, Novi Sad (Serbia); Holodkov, Vladimir [Educons University, Faculty of Sport and Tourism - TIMS, Radnička 30a, 21000, Novi Sad (Serbia); Pelemiš, Svetlana [University of East Sarajevo, Faculty of Technology, Karakaj bb, 75400, Zvornik, Republic of Srpska, Bosnia and Herzegovina (Bosnia and Herzegovina)

    2016-02-15

    We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S{sub 1}−T{sub 1}). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S{sub 1}−T{sub 1}) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S{sub 1}−T{sub 1}), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

  17. Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability.

    Science.gov (United States)

    Petersen, Asger B; Andersen, Nikolaj S; Konotop, Gleb; Hanafiah, Nur Hafzan Md; Raab, Marc S; Krämer, Alwin; Clausen, Mads H

    2017-04-21

    Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral and intravenous administration. Finally, 2'-benzylamine analogue 10 was confirmed to induce G2/M cell cycle arrest in vitro. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues with Improved Water Solubility

    Directory of Open Access Journals (Sweden)

    Ahmed K. Hamdy

    2017-01-01

    Full Text Available Griseofulvin 1 is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Study of SAR of some griseofulvin analogues has led to the identification of 2′-benzyloxy griseofulvin 3, a more potent analogue which retards tumor growth through inhibition of centrosomal clustering. However, similar to griseofulvin 1, compound 3 exhibited poor aqueous solubility. In order to improve the poor water solubility, six new griseofulvin analogues 5–10 were synthesized and tested for their antiproliferative activity and water solubility. The semicarbazone 9 and aminoguanidine 10 analogues were the most potent against HCT116 and MCF-7 cell lines. In combination studies, compound 9 was found to exert synergistic effects with tamoxifen and 5-fluorouracil against MCF-7 and HCT116 cells proliferation, respectively. The flow cytometric analysis of effect of 9 on cell cycle progression revealed G2/M arrest in HCT116. In addition, compound 9 induced apoptosis in MCF-7 cells. Finally, all synthesized analogues revealed higher water solubility than griseofulvin 1 and benzyloxy analogue 3 in pH 1.2 and 6.8 buffer solutions.

  19. From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents

    International Nuclear Information System (INIS)

    Spielvogel, B.F.; Sood, Anup; Duke Univ., Durham, NC; Shaw, B.R.; Hall, I.H.

    1991-01-01

    Isoelectronic and isostructural boron analogues of the α-amino acids ranging from simple glycine analogues such as H 3 NBH 2 COOH and Me 2 NHBH 2 COOH to alanine analogues have been synthesised. A diverse variety of analogues, including precursors and derivatives (such as peptides) have potent pharmacological activity, including anticancer, antiinflammatory, analgesic, and hypolipidemic activity in animal model studies and in vitro cell cultures. Boronated nucleosides and (oligo)nucleotides, synthetic oligonucleotide analogues of ''antisense'' agents interact with a complementary nucleic acid sequence blocking the biological effect of the target sequence. Nucleosides boronated on the pyrimidine and purine bases have been prepared. It has been established that an entirely new class of nucleic acid derivatives is feasible in which one of the non-bridging oxygens in the internucleotide phosphodiester linkage can be replaced by an isoelectronic analogue, the borane group, (BH 3 ). The boronated oligonucleotides can be viewed as hybrids of the normal oxygen oligonucleotides and the methylphosphonate oligonucleotides. (author)

  20. Stable Isotope Group 1983 progress report

    International Nuclear Information System (INIS)

    Stewart, M.K.

    1984-06-01

    The work of the Stable Isotope Group of the Institute of Nuclear Sciences in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and related fields, and mass spectrometer instrumentation, during 1983, is described

  1. Stable Isotope Group 1982 progress report

    International Nuclear Information System (INIS)

    Stewart, M.K.

    1983-06-01

    The work of the Stable Isotope Group of the Institute of Nuclear Sciences during 1982, in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and mass spectrometer instrumentation, is described

  2. Bartolome Island, Galapagos Stable Oxygen Calibration Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Galapagos Coral Stable Oxygen Calibration Data. Sites: Bartolome Island: 0 deg, 17'S, 90 deg 33' W. Champion Island: 1 deg, 15'S, 90 deg, 05' W. Urvina Bay (Isabela...

  3. Allan Hills Stable Water Isotopes, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes stable water isotope values at 10 m resolution along an approximately 5 km transect through the main icefield of the Allan Hills Blue Ice...

  4. Applications of stable isotopes in clinical pharmacology

    Science.gov (United States)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the pharmacokinetic profile or mode of action of a drug substance. Secondly, stable isotopes may be used for the assessment of drug products or drug delivery systems by determination of parameters such as the bioavailability or the release profile. Thirdly, patients may be assessed in relation to patient-specific drug treatment; this concept is often called personalized medicine. In this article, the application of stable isotope technology in the aforementioned three areas is reviewed, with emphasis on developments over the past 25 years. The applications are illustrated with examples from clinical studies in humans. PMID:21801197

  5. Tannaka duality and stable infinity-categories

    OpenAIRE

    Iwanari, Isamu

    2014-01-01

    We introduce the notion of fine tannakian infinity-categories and prove Tannaka duality results for symmetric monoidal stable infinity-categories over a field of characteristic zero. We also discuss several examples.

  6. On Stable Marriages and Greedy Matchings

    Energy Technology Data Exchange (ETDEWEB)

    Manne, Fredrik; Naim, Md; Lerring, Hakon; Halappanavar, Mahantesh

    2016-12-11

    Research on stable marriage problems has a long and mathematically rigorous history, while that of exploiting greedy matchings in combinatorial scientific computing is a younger and less developed research field. In this paper we consider the relationships between these two areas. In particular we show that several problems related to computing greedy matchings can be formulated as stable marriage problems and as a consequence several recently proposed algorithms for computing greedy matchings are in fact special cases of well known algorithms for the stable marriage problem. However, in terms of implementations and practical scalable solutions on modern hardware, the greedy matching community has made considerable progress. We show that due to the strong relationship between these two fields many of these results are also applicable for solving stable marriage problems.

  7. Structures of ceftazidime and its transition-state analogue in complex with AmpC beta-lactamase: Implications for resistance mutations and inhibitor design

    Energy Technology Data Exchange (ETDEWEB)

    Powers, R.A.; Caselli, E.; Focia, P.J.; Prati, F.; Shoichet, B.K.

    2010-03-08

    Third-generation cephalosporins are widely used {beta}-lactam antibiotics that resist hydrolysis by {beta}-lactamases. Recently, mutant {beta}-lactamases that rapidly inactivate these drugs have emerged. To investigate why third-generation cephalosporins are relatively stable to wild-type class C {beta}-lactamases and how mutant enzymes might overcome this, the structures of the class C {beta}-lactamase AmpC in complex with the third-generation cephalosporin ceftazidime and with a transition-state analogue of ceftazidime were determined by X-ray crystallography to 2.0 and 2.3 {angstrom} resolution, respectively. Comparison of the acyl-enzyme structures of ceftazidime and loracarbef, a {beta}-lactam substrate, reveals that the conformation of ceftazidime in the active site differs from that of substrates. Comparison of the structures of the acyl-enzyme intermediate and the transition-state analogue suggests that ceftazidime blocks formation of the tetrahedral transition state, explaining why it is an inhibitor of AmpC. Ceftazidime cannot adopt a conformation competent for catalysis due to steric clashes that would occur with conserved residues Val211 and Tyr221. The X-ray crystal structure of the mutant {beta}-lactamase GC1, which has improved activity against third-generation cephalosporins, suggests that a tandem tripeptide insertion in the {Omega} loop, which contains Val211, has caused a shift of this residue and also of Tyr221 that would allow ceftazidime and other third-generation cephalosporins to adopt a more catalytically competent conformation. These structural differences may explain the extended spectrum activity of GC1 against this class of cephalosporins. In addition, the complexed structure of the transition-state analogue inhibitor (K{sub i} 20 nM) with AmpC reveals potential opportunities for further inhibitor design.

  8. The Reactivity of Stable Metallacyclobutenes and Vinylcarbenes

    OpenAIRE

    Holland, Ryan Lynn

    2016-01-01

    Chapter 1. Historical Development of Stable Metallacyclobutenes Fred Tebbe and co-workers synthesized the first stable metallacyclobutene complexes in the late 1970’s by treatment of an intermediate titanium methylene species – later popularized as the “Tebbe reagent” – with acetylenes. Robert Grubbs at Caltech further studied this system, using it to detail a degenerate metathesis reaction and to isolate a metallacyclobutane complex – which was implicated in the emerging field of alkene meta...

  9. Stable atomic hydrogen: Polarized atomic beam source

    International Nuclear Information System (INIS)

    Niinikoski, T.O.; Penttilae, S.; Rieubland, J.M.; Rijllart, A.

    1984-01-01

    We have carried out experiments with stable atomic hydrogen with a view to possible applications in polarized targets or polarized atomic beam sources. Recent results from the stabilization apparatus are described. The first stable atomic hydrogen beam source based on the microwave extraction method (which is being tested ) is presented. The effect of the stabilized hydrogen gas density on the properties of the source is discussed. (orig.)

  10. A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases

    Science.gov (United States)

    Rashid, M. Harunur; Huq, Redwan; Tanner, Mark R.; Chhabra, Sandeep; Khoo, Keith K.; Estrada, Rosendo; Dhawan, Vikas; Chauhan, Satendra; Pennington, Michael W.; Beeton, Christine; Kuyucak, Serdar; Norton, Raymond S.

    2014-03-01

    HsTX1 toxin, from the scorpion Heterometrus spinnifer, is a 34-residue, C-terminally amidated peptide cross-linked by four disulfide bridges. Here we describe new HsTX1 analogues with an Ala, Phe, Val or Abu substitution at position 14. Complexes of HsTX1 with the voltage-gated potassium channels Kv1.3 and Kv1.1 were created using docking and molecular dynamics simulations, then umbrella sampling simulations were performed to construct the potential of mean force (PMF) of the ligand and calculate the corresponding binding free energy for the most stable configuration. The PMF method predicted that the R14A mutation in HsTX1 would yield a > 2 kcal/mol gain for the Kv1.3/Kv1.1 selectivity free energy relative to the wild-type peptide. Functional assays confirmed the predicted selectivity gain for HsTX1[R14A] and HsTX1[R14Abu], with an affinity for Kv1.3 in the low picomolar range and a selectivity of more than 2,000-fold for Kv1.3 over Kv1.1. This remarkable potency and selectivity for Kv1.3, which is significantly up-regulated in activated effector memory cells in humans, suggest that these analogues represent valuable leads in the development of therapeutics for autoimmune diseases.

  11. FT-IR spectra of the anti-HIV nucleoside analogue d4T (Stavudine). Solid state simulation by DFT methods and scaling by different procedures

    Science.gov (United States)

    Alcolea Palafox, M.; Kattan, D.; Afseth, N. K.

    2018-04-01

    A theoretical and experimental vibrational study of the anti-HIV d4T (stavudine or Zerit) nucleoside analogue was carried out. The predicted spectra in the three most stable conformers in the biological active anti-form of the isolated state were compared. Comparison of the conformers with those of the natural nucleoside thymidine was carried out. The calculated spectra were scaled by using different scaling procedures and three DFT methods. The TLSE procedure leads to the lowest error and is thus recommended for scaling. With the population of these conformers the IR gas-phase spectra were predicted. The crystal unit cell of the different polymorphism forms of d4T were simulated through dimer forms by using DFT methods. The scaled spectra of these dimer forms were compared. The FT-IR spectrum was recorded in the solid state in the 400-4000 cm-1 range. The respective vibrational bands were analyzed and assigned to different normal modes of vibration by comparison with the scaled vibrational values of the different dimer forms. Through this comparison, the polymorphous form of the solid state sample was identified. The study indicates that d4T exist only in the ketonic form in the solid state. The results obtained were in agreement with those determined in related anti-HIV nucleoside analogues.

  12. Local Search Approaches in Stable Matching Problems

    Directory of Open Access Journals (Sweden)

    Toby Walsh

    2013-10-01

    Full Text Available The stable marriage (SM problem has a wide variety of practical applications, ranging from matching resident doctors to hospitals, to matching students to schools or, more generally, to any two-sided market. In the classical formulation, n men and n women express their preferences (via a strict total order over the members of the other sex. Solving an SM problem means finding a stable marriage where stability is an envy-free notion: no man and woman who are not married to each other would both prefer each other to their partners or to being single. We consider both the classical stable marriage problem and one of its useful variations (denoted SMTI (Stable Marriage with Ties and Incomplete lists where the men and women express their preferences in the form of an incomplete preference list with ties over a subset of the members of the other sex. Matchings are permitted only with people who appear in these preference lists, and we try to find a stable matching that marries as many people as possible. Whilst the SM problem is polynomial to solve, the SMTI problem is NP-hard. We propose to tackle both problems via a local search approach, which exploits properties of the problems to reduce the size of the neighborhood and to make local moves efficiently. We empirically evaluate our algorithm for SM problems by measuring its runtime behavior and its ability to sample the lattice of all possible stable marriages. We evaluate our algorithm for SMTI problems in terms of both its runtime behavior and its ability to find a maximum cardinality stable marriage. Experimental results suggest that for SM problems, the number of steps of our algorithm grows only as O(n log(n, and that it samples very well the set of all stable marriages. It is thus a fair and efficient approach to generate stable marriages. Furthermore, our approach for SMTI problems is able to solve large problems, quickly returning stable matchings of large and often optimal size, despite the

  13. Li depletion in solar analogues with exoplanets. Extending the sample

    Science.gov (United States)

    Delgado Mena, E.; Israelian, G.; González Hernández, J. I.; Sousa, S. G.; Mortier, A.; Santos, N. C.; Adibekyan, V. Zh.; Fernandes, J.; Rebolo, R.; Udry, S.; Mayor, M.

    2014-02-01

    Aims: We want to study the effects of the formation of planets and planetary systems on the atmospheric Li abundance of planet host stars. Methods: In this work we present new determinations of lithium abundances for 326 main sequence stars with and without planets in the Teff range 5600-5900 K. The 277 stars come from the HARPS sample, the remaining targets were observed with a variety of high-resolution spectrographs. Results: We confirm significant differences in the Li distribution of solar twins (Teff = T⊙ ± 80 K, log g = log g⊙ ± 0.2 and [Fe/H] = [Fe/H]⊙ ± 0.2): the full sample of planet host stars (22) shows Li average values lower than "single" stars with no detected planets (60). If we focus on subsamples with narrower ranges in metallicity and age, we observe indications of a similar result though it is not so clear for some of the subsamples. Furthermore, we compare the observed spectra of several couples of stars with very similar parameters that show differences in Li abundances up to 1.6 dex. Therefore we show that neither age, mass, nor metallicity of a parent star is the only cause for enhanced Li depletion in solar analogues. Conclusions: We conclude that another variable must account for that difference and suggest that this could be the presence of planets that causes additional rotationally induced mixing in the external layers of planet host stars. Moreover, we find indications that the amount of depletion of Li in planet-host solar-type stars is higher when the planets are more massive than Jupiter. Based on observations collected at the La Silla Observatory, ESO (Chile), with the HARPS spectrograph at the 3.6 m ESO telescope, with CORALIE spectrograph at the 1.2 m Euler Swiss telescope and with the FEROS spectrograph at the 1.52 m ESO telescope; at the Paranal Observatory, ESO (Chile), using the UVES spectrograph at the VLT/UT2 Kueyen telescope, and with the FIES, SARG, and UES spectrographs at the 2.5 m NOT, the 3.6 m TNG and the 4

  14. Alligator Rivers Analogue project. Hydrogeological modelling. Final Report - Volume 6

    Energy Technology Data Exchange (ETDEWEB)

    Townley, L.R.; Trefry, M.G.; Barr, A.D. [CSIRO Div of Water Resources, PO Wembley, WA (Australia); Braumiller, S. [Univ of Arizona, Tucson, AZ (United States). Dept of Hydrology and Water Resources; Kawanishi, M. [Central Research Institute of Electric Power Industry, Abiko-Shi, Chiba-Ken (Japan)] [and others

    1992-12-31

    This volume describes hydrogeological modelling carried out as part of the Alligator Rivers Analogue Project. Hydrogeology has played a key integrating role in the Project, largely because water movement is believed to have controlled the evolution of the Koongarra uranium Orebody and therefore affects field observations of all types at all scales. Aquifer testing described uses the concept of transmissivity in its interpretation of aquifer response to pumping. The concept of an aquifer, a layer transmitting significant quantities of water in a mainly horizontal direction, seems hard to accept in an environment as heterogeneous as that at Koongarra. But modelling of aquifers both in one dimension and two dimensionally in plan has contributed significantly to our understanding of the site. A one-dimensional model with three layers (often described as a quasi two dimensional model) was applied to flow between the Fault and Koongarra Creek. Being a transient model, this model was able to show that reverse flows can indeed occur back towards the Fault, but only if there is distributed recharge over the orebody as well as a mechanism for the Fault, or a region near the Fault, to remove water from the simulated cross-section. The model also showed clearly that the response of the three-layered system, consisting of a highly weathered zone, a fractured transmissive zone and a less conductive lower schist zone, is governed mainly by the transmissivity and storage coefficient of the middle layer. The storage coefficient of the higher layer has little effect. A two-dimensional model in plan used a description of anisotropy to show that reverse flows can also occur even without a conducting Fault. Modelling of a three-dimensional region using discrete fractures showed that it is certainly possible to simulate systems like that observed at Koongarra, but that large amounts of data are probably needed to obtain realistic descriptions of the fracture networks. Inverse modelling

  15. Alligator Rivers Analogue project. Hydrogeological modelling. Final Report - Volume 6

    International Nuclear Information System (INIS)

    Townley, L.R.; Trefry, M.G.; Barr, A.D.; Braumiller, S.

    1992-01-01

    This volume describes hydrogeological modelling carried out as part of the Alligator Rivers Analogue Project. Hydrogeology has played a key integrating role in the Project, largely because water movement is believed to have controlled the evolution of the Koongarra uranium Orebody and therefore affects field observations of all types at all scales. Aquifer testing described uses the concept of transmissivity in its interpretation of aquifer response to pumping. The concept of an aquifer, a layer transmitting significant quantities of water in a mainly horizontal direction, seems hard to accept in an environment as heterogeneous as that at Koongarra. But modelling of aquifers both in one dimension and two dimensionally in plan has contributed significantly to our understanding of the site. A one-dimensional model with three layers (often described as a quasi two dimensional model) was applied to flow between the Fault and Koongarra Creek. Being a transient model, this model was able to show that reverse flows can indeed occur back towards the Fault, but only if there is distributed recharge over the orebody as well as a mechanism for the Fault, or a region near the Fault, to remove water from the simulated cross-section. The model also showed clearly that the response of the three-layered system, consisting of a highly weathered zone, a fractured transmissive zone and a less conductive lower schist zone, is governed mainly by the transmissivity and storage coefficient of the middle layer. The storage coefficient of the higher layer has little effect. A two-dimensional model in plan used a description of anisotropy to show that reverse flows can also occur even without a conducting Fault. Modelling of a three-dimensional region using discrete fractures showed that it is certainly possible to simulate systems like that observed at Koongarra, but that large amounts of data are probably needed to obtain realistic descriptions of the fracture networks. Inverse modelling

  16. Response of Staphylococcus Aureus to a Spaceflight Analogue

    Science.gov (United States)

    Castro, S. L.; Ott, C. M.

    2010-01-01

    The decreased gravity of the spaceflight environment creates quiescent, low fluid shear conditions. This environment can impart considerable effects on the physiology of microorganisms as well as their interactions with potential hosts. Using the rotating wall vessel (RWV), as a spaceflight analogue, the consequence of low fluid shear culture on microbial pathogenesis has provided a better understanding of the risks to the astronaut crew from infectious microorganisms. While the outcome of low fluid shear culture has been investigated for several bacterial pathogens, little has been done to understand how this environmental factor affects Staphylococcus aureus. S. aureus is an opportunistic human pathogen which presents a high level of infection risk to the crew, as it has been isolated from both the space shuttle and International Space Station. Given that approximately forty percent of the population are carriers of the bacteria, eradication of this organism from in flight environments is impractical. These reasons have lead to us to assess the response of S. aureus to a reduced fluid shear environment. Culture in the RWV demonstrated that S. aureus grown under the low-shear condition had lower cell concentrations after 10 hours when compared to the control culture. Furthermore, the low-shear cultured bacteria displayed a reduction in carotenoid production, pigments responsible for their yellow/gold coloration. When exposed to various environmental stressors, post low-shear culture, a decrease in the ability to survive oxidative assault was observed compared to control cultures. The low fluid shear environment also resulted in a decrease in hemolysin secretion, a staphylococcal toxin responsible for red blood cell lysis. When challenged by the immune components present in human whole blood, low-shear cultured S. aureus demonstrated significantly reduced survival rates as compared to the control culture. Assays to determine the duration of these alterations

  17. Interaction between subducting plates: results from numerical and analogue modeling

    Science.gov (United States)

    Kiraly, Agnes; Capitanio, Fabio A.; Funiciello, Francesca; Faccenna, Claudio

    2016-04-01

    The tectonic setting of the Alpine-Mediterranean area is achieved during the late Cenozoic subduction, collision and suturing of several oceanic fragments and continental blocks. In this stage, processes such as interactions among subducting slabs, slab migrations and related mantle flow played a relevant role on the resulting tectonics. Here, we use numerical models to first address the mantle flow characteristic in 3D. During the subduction of a single plate the strength of the return flow strongly depends on the slab pull force, that is on the plate's buoyancy, however the physical properties of the slab, such as density, viscosity or width, do not affect largely the morphology of the toroidal cell. Instead, dramatic effects on the geometry and the dynamics of the toroidal cell result in models where the thickness of the mantle is varied. The vertical component of the vorticity vector is used to define the characteristic size of the toroidal cell, which is ~1.2-1.3 times the mantle depth. This latter defines the range of viscous stress propagation through the mantle and consequent interactions with other slabs. We thus further investigate on this setup where two separate lithospheric plates subduct in opposite sense, developing opposite polarities and convergent slab retreat, and model different initial sideways distance between the plates. The stress profiles in time illustrate that the plates interacts when slabs are at the characteristic distance and the two slabs toroidal cells merge. Increased stress and delayed slab migrations are the results. Analogue models of double-sided subduction show similar maximum distance and allow testing the additional role of stress propagated through the plates. We use a silicon plate subducting on its two opposite margins, which is either homogeneous or comprises oceanic and continental lithospheres, differing in buoyancy. The modeling results show that the double-sided subduction is strongly affected by changes in plate

  18. Prevention of postpartum haemorrhage with the oxytocin analogue carbetocin.

    Science.gov (United States)

    Rath, Werner

    2009-11-01

    Postpartum haemorrhage is the leading cause of maternal mortality worldwide: 67-80% of cases are caused by uterine atony. Preventive measures include prophylactic drug use to aid uterine contraction after delivery, thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin is a synthetic analogue of oxytocin with a half-life approximately 4-10 times longer than that reported for oxytocin. It combines the safety and tolerability profile of oxytocin with the sustained uterotonic activity of injectable ergot alkaloids. Furthermore, carbetocin can be administered as a single dose injection either intravenously or intramuscularly rather than as an infusion over several hours as is the case with oxytocin. Carbetocin is currently indicated for prevention of uterine atony after delivery by caesarean section in spinal or epidural anaesthesia. Data from three randomised controlled trials in caesarean delivery and a meta-analysis indicate that carbetocin significantly reduces the need for additional uterotonic agents or uterine massage to prevent excessive bleeding compared with placebo or oxytocin. The risk of headache, tremor, hypotension, flushing, nausea, abdominal pain, pruritus and feeling of warmth was similar in women who received carbetocin or oxytocin. The findings from two more recent double-blind randomised trials and one retrospective study suggest that carbetocin may also represent a good alternative to conventional uterotonic agents for prevention of postpartum haemorrhage after vaginal deliveries. A reduced need for additional uterotonics was observed with carbetocin vs. oxytocin in high-risk women and carbetocin was at least as effective as syntometrine in low-risk women. In these studies of vaginal deliveries, carbetocin was associated with a low incidence of adverse effects and demonstrated a better tolerability profile than syntometrine. Carbetocin had a long duration of action compared with intravenous oxytocin alone and a

  19. Quantitative determination of sulfur containing wine odorants at sub-ppb levels. 1. Synthesis of the deuterated analogues.

    Science.gov (United States)

    Kotseridis, Y; Ray, J L; Augier, C; Baumes, R

    2000-12-01

    [2H10]-4-Sulfanyl-4-methylpentan-2-one (d10-SMP), [2H2]-3-sulfanylhexan-1-ol (d2-3SH), and [2H5]-3-sulfanylhexyl acetate (d5-3SHAc), the labeled analogues of impact odorants of wines and other foods, were synthesized to be used for the quantitative determination of the natural compounds in white and red wines by stable isotope dilution assay. The sulfidation was achieved by Michael addition, on mesityl oxide or ethyl hex-2-enoate, respectively, of the sulfhydryl anion generated in situ from triphenylsilanethiol and potassium fluoride under phase transfer conditions. The labeling of 4-sulfanyl-4-methylpentan-2-one (SMP) was obtained from the commercial starting material, [2H6]acetone, so that this method could be used to synthesize 13C-labeled SMP from 13C-labeled acetone. The labeling of 3-sulfanylhexan-1-ol (3SH) and 3-sulfanylhexyl acetate (3SHAc) was obtained from reduction with lithium aluminum deuteride of the Michael adduct ethyl 3-sulfanylhexanoate and [2H3]-acetylation. During the synthesis, 3SH and 3SHAc were partially oxidized to their disulfide, which were reduced back to the thiols by an additional reduction step; the tertiary thiol SMP was less sensitive to this oxidation.

  20. Deoxyfluoro-d-trehalose (FDTre) analogues as potential PET probes for imaging mycobacterial infection.

    Science.gov (United States)

    Rundell, Sarah R; Wagar, Zachary L; Meints, Lisa M; Olson, Claire D; O'Neill, Mara K; Piligian, Brent F; Poston, Anne W; Hood, Robin J; Woodruff, Peter J; Swarts, Benjamin M

    2016-09-28

    Mycobacterium tuberculosis, the etiological agent of human tuberculosis, requires the non-mammalian disaccharide trehalose for growth and virulence. Recently, detectable trehalose analogues have gained attention as probes for studying trehalose metabolism and as potential diagnostic imaging agents for mycobacterial infections. Of particular interest are deoxy-[(18)F]fluoro-d-trehalose ((18)F-FDTre) analogues, which have been suggested as possible positron emission tomography (PET) probes for in vivo imaging of M. tuberculosis infection. Here, we report progress toward this objective, including the synthesis and conformational analysis of four non-radioactive deoxy-[(19)F]fluoro-d-trehalose ((19)F-FDTre) analogues, as well as evaluation of their uptake by M. smegmatis. The rapid synthesis and purification of several (19)F-FDTre analogues was accomplished in high yield using a one-step chemoenzymatic method. Conformational analysis of the (19)F-FDTre analogues using NMR and molecular modeling methods showed that fluorine substitution had a negligible effect on the conformation of the native disaccharide, suggesting that fluorinated analogues may be successfully recognized and processed by trehalose metabolic machinery in mycobacteria. To test this hypothesis and to evaluate a possible route for delivery of FDTre probes specifically to mycobacteria, we showed that (19)F-FDTre analogues are actively imported into M. smegmatis via the trehalose-specific transporter SugABC-LpqY. Finally, to demonstrate the applicability of these results to the efficient preparation and use of short-lived (18)F-FDTre PET radiotracers, we carried out (19)F-FDTre synthesis, purification, and administration to M. smegmatis in 1 hour.