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Sample records for elimination par catalyse

  1. ParTIES: a toolbox for Paramecium interspersed DNA elimination studies.

    PubMed

    Denby Wilkes, Cyril; Arnaiz, Olivier; Sperling, Linda

    2016-02-15

    Developmental DNA elimination occurs in a wide variety of multicellular organisms, but ciliates are the only single-celled eukaryotes in which this phenomenon has been reported. Despite considerable interest in ciliates as models for DNA elimination, no standard methods for identification and characterization of the eliminated sequences are currently available. We present the Paramecium Toolbox for Interspersed DNA Elimination Studies (ParTIES), designed for Paramecium species, that (i) identifies eliminated sequences, (ii) measures their presence in a sequencing sample and (iii) detects rare elimination polymorphisms. ParTIES is multi-threaded Perl software available at https://github.com/oarnaiz/ParTIES. ParTIES is distributed under the GNU General Public Licence v3. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. [Investigation of a measles outbreak in Pará State, Brazil, in the age of elimination of the disease].

    PubMed

    Jesus, Hiane Santos de; Nascimento, Gilmara Lima; Rosa, Fabiano Marques; Santos, Deise Aparecida dos

    2015-10-01

    In July 27th, 2010, witnessed the late notification of a positive test result for measles IgM antibodies in Belém, Pará State, Brazil, sparking an epidemiological investigation and control and preventive measures. Two more confirmed cases were identified, both of whom were siblings of the index case, with clinical signs and symptoms and incubation period consistent with measles. We conducted a retrospective search in hospitals and laboratories for suspected cases that lived in or had visited Pará State from May 1st to August 4th, 2010, and had presented fever and exanthema accompanied by cough and/or sneezing and/or conjunctivitis. All identified cases were investigated by telephone contact and/or home visits. We reviewed 183,854 consultation forms and identified 56 (0.03%) suspected cases. We applied 2,535 doses of triple viral vaccine distributed between blockades vaccination intensifications. A household measles outbreak occurred in Belém with the detection and isolation of a viral genotype imported from Europe. Timely and sensitive epidemiological surveillance is recommended for the detection of suspected cases of measles and maintenance of high immunization coverage.

  3. Borinic acid catalysed peptide synthesis.

    PubMed

    El Dine, Tharwat Mohy; Rouden, Jacques; Blanchet, Jérôme

    2015-11-18

    The catalytic synthesis of peptides is a major challenge in the modern organic chemistry hindered by the well-established use of stoichiometric coupling reagents. Herein, we describe for the first time that borinic acid is able to catalyse this reaction under mild conditions with an improved activity compared to our recently developed thiophene-based boronic acid. This catalyst is particularly efficient for peptide bond synthesis affording dipeptides in good yields without detectable racemization.

  4. A study on the AMACR catalysed elimination reaction and its application to inhibitor testing† †Electronic supplementary information (ESI) available: 1H NMR spectra of synthesised compounds; details of X-ray crystal structure determination of compound 35; original data for Table 1; plots of fluorescence resulting from reaction of sensors 33 and 34 with fluoride solutions. CCDC 1408401. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ob01541c Click here for additional data file. Click here for additional data file.

    PubMed Central

    Yevglevskis, Maksims; Lee, Guat L.; Sun, Jenny; Zhou, Shiyi; Sun, Xiaolong; Kociok-Köhn, Gabriele; James, Tony D.; Woodman, Timothy J.

    2016-01-01

    α-Methylacyl-CoA racemase (AMACR; P504S) catalyses a key step in the degradation of branched-chain fatty acids and is important for the pharmacological activation of Ibuprofen and related drugs. Levels of AMACR are increased in prostate and other cancers, and it is a drug target. Development of AMACR as a drug target is hampered by lack of a convenient assay. AMACR irreversibly catalyses the elimination of HF from 3-fluoro-2-methylacyl-CoA substrates, and this reaction was investigated for use as an assay. Several known inhibitors and alternative substrates reduced conversion of 3-fluoro-2-methyldecanoyl-CoA by AMACR, as determined by 1H NMR. The greatest reduction of activity was observed with known potent inhibitors. A series of novel acyl-CoA esters with aromatic side chains were synthesised for testing as chromophoric substrates. These acyl-CoA esters were converted to unsaturated products by AMACR, but their use was limited by non-enzymatic elimination. Fluoride sensors were also investigated as a method of quantifying released fluoride and thus AMACR activity. These sensors generally suffered from high background signal and lacked reproducibility under the assay conditions. In summary, the elimination reaction can be used to characterise inhibitors, but it was not possible to develop a convenient colorimetric or fluorescent assay using 3-fluoro-2-methylacyl-CoA substrates. PMID:26537174

  5. THE MEASURES PAR PROJECT

    NASA Astrophysics Data System (ADS)

    Frouin, R. J.; Franz, B.

    2009-12-01

    The solar energy available for photosynthesis, known as PAR, controls the growth of phytoplankton and, therefore, regulates the composition and evolution of marine ecosystems. Knowing the spatial and temporal distribution of PAR over the oceans is critical to understanding biogeochemical cycles of carbon, nutrients, and oxygen, and to address important climate and global change issues such as the fate of anthropogenic atmospheric carbon dioxide. In view of this, a 12-year time series of PAR at the ocean surface, starting in September 1997, is being produced by the NASA Ocean Biology Processing Group from SeaWiFS, MODIS-Terra, and MODIS-Aqua data. The product covers the global oceans, with a spatial resolution of about 9.3x9.3 km (equal area grid) and a temporal resolution of one day. PAR is computed as the difference between the 400-700 nm solar flux incident on the top of the atmosphere (known) and reflected back to space by the atmosphere and surface (derived from satellite radiance), taking into account atmospheric absorption (modeled). Knowledge of pixel composition is not required, eliminating the need for cloud screening and arbitrary assumptions about sub-pixel cloudiness. Combining data from satellite sensors with different equatorial crossing times accounts for the diurnal variability of clouds and, therefore, increases accuracy on a daily time scale. The processing system, including routine check of accuracy and control of quality, is designed to operate during the entire lifetime of SeaWiFS and MODIS, and to accommodate future sensors with ocean-color capabilities. Maps of daily, weekly, and monthly PAR obtained from individual sensors are presented, as well as merged products. Accuracy is quantified in comparisons with other satellite estimates, the National Centers for Environmental Prediction reanalysis product, and in-situ measurements from fixed buoys and platforms. The good statistical performance makes the satellite PAR product suitable for large

  6. Eliminating Bias

    EPA Pesticide Factsheets

    Learn how to eliminate bias from monitoring systems by instituting appropriate installation, operation, and quality assurance procedures. Provides links to download An Operator's Guide to Eliminating Bias in CEM Systems.

  7. Microfabricated components for heterogeneously catalysed reactions

    NASA Astrophysics Data System (ADS)

    Wießmeier, Georg; Hönicke, Dieter

    1996-06-01

    Microsystems offer considerable industrial potential for unit operations, e.g. heat transfer, mass transport, and mixing of gases and liquids. The development of techniques for performing chemical reactions in microsystems has high priority. Only a few examples are known of using microreactors for performing homogeneous chemical reactions and heterogeneously catalysed liquid-phase enzyme reactions. However, heterogeneously catalysed gas-phase reactions in microreactors have not been reported at all. This is due to the lack of surfaces having enough catalytically active sites. The present article describes a method for treating the surfaces of channels in a microreactor in order to achieve adequate numbers of catalytically active and selective sites - which is the main prerequisite for the performance of heterogeneously catalysed reactions. The experimental procedure and the measurements of characteristic parameters are described. An envisaged scheme for a chemical microsystem similar to a chemical microplant is presented, and its scaling up via replication is addressed.

  8. Metal‐Catalysed Azidation of Organic Molecules

    PubMed Central

    Goswami, Monalisa

    2016-01-01

    The azide moiety is a desirable functionality in organic molecules, useful in a variety of transformations such as olefin aziridination, C–H bond amination, isocyanate synthesis, the Staudinger reaction and the formation of azo compounds. To harness the versatility of the azide functionality fully it is important that these compounds be easy to prepare, in a clean and cost‐effective manner. Conventional (non‐catalysed) methods to synthesise azides generally require quite harsh reaction conditions that are often not tolerant of functional groups. In the last decade, several metal‐catalysed azidations have been developed in attempts to circumvent this problem. These methods are generally faster, cleaner and more functional‐group‐tolerant than conventional methods to prepare azides, and can sometimes even be conveniently combined with one‐pot follow‐up transformations of the installed azide moiety. This review highlights metal‐catalysed approaches to azide synthesis, with a focus on the substrate scopes and mechanisms, as well as on advantages and disadvantages of the methods. Overall, metal‐catalysed azidation reactions provide shorter routes to a variety of potentially useful organic molecules containing the azide moiety. PMID:28344503

  9. Evidence that the mechanism of antibody-catalysed hydrolysis of arylcarbamates can be determined by the structure of the immunogen used to elicit the catalytic antibody

    PubMed Central

    Boucher, Guillaume; Said, Bilal; Ostler, Elizabeth L.; Resmini, Marina; Brocklehurst, Keith; Gallacher, Gerard

    2006-01-01

    A kinetically homogeneous anti-phosphate catalytic antibody preparation was shown to catalyse the hydrolysis of a series of O-aryl N-methyl carbamates containing various substituents in the 4-position of the O-phenyl group. The specific nature of the antibody catalysis was demonstrated by the adherence of these reactions to the Michaelis–Menten equation, the complete inhibition by a hapten analogue, and the failure of the antibody to catalyse the hydrolysis of the 2-nitrophenyl analogue of the 4-nitrophenylcarbamate substrate. Hammett σ–ρ analysis suggests that both the non-catalysed and antibody-catalysed reactions proceed by mechanisms in which development of the aryloxyanion of the leaving group is well advanced in the transition state of the rate-determining step. This is probably the ElcB (elimination–addition) mechanism for the non-catalysed reaction, but for the antibody-catalysed reaction might be either ElcB or BAc2 (addition–elimination), in which the elimination of the aryloxy group from the tetrahedral intermediate has become rate-determining. This result provides evidence of the dominance of recognition of phenolate ion character in the phosphate hapten in the elicitation process, and is discussed in connection with data from the literature that suggest a BAc2 mechanism, with rate-determining formation of the tetrahedral intermediate for the hydrolysis of carbamate substrates catalysed by an antibody elicited by a phosphonamidate hapten in which phenolate anion character is minimized. The present paper contributes to the growing awareness that small differences in the structure of haptens can produce large differences in catalytic characteristics. PMID:17020536

  10. RNA-catalysed synthesis of complementary-strand RNA

    NASA Astrophysics Data System (ADS)

    Doudna, Jennifer A.; Szostak, Jack W.

    1989-06-01

    The Tetrahymena ribozyme can splice together multiple oligonucleotides aligned on a template strand to yield a fully complementary product strand. This reaction demonstrates the feasibility of RNA-catalysed RNA replications.

  11. A convergent rhodium-catalysed asymmetric synthesis of tetrahydroquinolines.

    PubMed

    Li, Ho Yin; Horn, Joachim; Campbell, Amanda; House, David; Nelson, Adam; Marsden, Stephen P

    2014-09-14

    Rh-catalysed conjugate additions of 2-aminophenyl boronic acid derivatives were exploited in diastereoselective and asymmetric syntheses of tetrahydroquinolines. In both cases, combinatorial variation of the substitution of the tetrahydroquinoline ring system was possible.

  12. Enzyme-catalysed conjugations of glutathione with unsaturated compounds

    PubMed Central

    Boyland, E.; Chasseaud, L. F.

    1967-01-01

    1. Rat-liver supernatant catalyses the reaction of diethyl maleate with glutathione. 2. Evidence is presented that the enzyme involved is different from the known glutathione-conjugating enzymes, glutathione S-alkyltransferase, S-aryltransferase and S-epoxidetransferase. 3. Rat-liver supernatant catalyses the reaction of a number of other αβ-unsaturated compounds, including aldehydes, ketones, lactones, nitriles and nitro compounds, with glutathione: separate enzymes may be responsible for these reactions. PMID:6035529

  13. Gravity waves catalysed by ageostrophic baroclinic instability

    NASA Astrophysics Data System (ADS)

    Chouksey, Manita; Eden, Carsten; Brüggemann, Nils

    2017-04-01

    Internal gravity waves are ubiquitous in the ocean interior and are significantly important for the ocean's energy budget. Most ocean models do not resolve gravity waves explicitly and thus they need to be parametrized. For parameterization of gravity waves the specification and understanding of their sources is important. This includes the energy pathway(s) from balanced flows down to scales where energy is finally dissipated. We discuss if the balanced motions, for instance mesoscale flows, can generate unbalanced motions, i.e. gravity waves, during baroclinic instability in ageostrophic to quasi-geostrophic regimes. Previous results (Brüggemann and Eden, JPO, 2015) show a dominant forward energy cascade for a large Rossby number (Ro) in an idealized channel model, while for Ro<<1 the inverse energy cascade dominates. We discuss the role of gravity waves for the forward cascade of energy. A spectral analysis of energy in frequency-wavenumber space for different regimes characterized by a range of Ro, shows that energy contained in the super-inertial frequencies corresponding to gravity waves is much higher for an ageostrophic regime than for a quasi-geostrophic regime. A modal decomposition into geostrophic and gravity wave modes indicates that the energy associated with the super-inertial frequencies is indeed related to gravity waves. Hence, gravity wave emission could be catalysed by ageostrophic baroclinic instability. A modal decomposition of the spectral fluxes of energy in wavenumber space provides more insight about how much energy is contained in which mode.

  14. Iron-catalysed tritiation of pharmaceuticals

    NASA Astrophysics Data System (ADS)

    Pony Yu, Renyuan; Hesk, David; Rivera, Nelo; Pelczer, István; Chirik, Paul J.

    2016-01-01

    A thorough understanding of the pharmacokinetic and pharmacodynamic properties of a drug in animal models is a critical component of drug discovery and development. Such studies are performed in vivo and in vitro at various stages of the development process—ranging from preclinical absorption, distribution, metabolism and excretion (ADME) studies to late-stage human clinical trials—to elucidate a drug molecule’s metabolic profile and to assess its toxicity. Radiolabelled compounds, typically those that contain 14C or 3H isotopes, are one of the most powerful and widely deployed diagnostics for these studies. The introduction of radiolabels using synthetic chemistry enables the direct tracing of the drug molecule without substantially altering its structure or function. The ubiquity of C-H bonds in drugs and the relative ease and low cost associated with tritium (3H) make it an ideal radioisotope with which to conduct ADME studies early in the drug development process. Here we describe an iron-catalysed method for the direct 3H labelling of pharmaceuticals by hydrogen isotope exchange, using tritium gas as the source of the radioisotope. The site selectivity of the iron catalyst is orthogonal to currently used iridium catalysts and allows isotopic labelling of complementary positions in drug molecules, providing a new diagnostic tool in drug development.

  15. Iron-catalysed tritiation of pharmaceuticals.

    PubMed

    Yu, Renyuan Pony; Hesk, David; Rivera, Nelo; Pelczer, István; Chirik, Paul J

    2016-01-14

    A thorough understanding of the pharmacokinetic and pharmacodynamic properties of a drug in animal models is a critical component of drug discovery and development. Such studies are performed in vivo and in vitro at various stages of the development process--ranging from preclinical absorption, distribution, metabolism and excretion (ADME) studies to late-stage human clinical trials--to elucidate a drug molecule's metabolic profile and to assess its toxicity. Radiolabelled compounds, typically those that contain (14)C or (3)H isotopes, are one of the most powerful and widely deployed diagnostics for these studies. The introduction of radiolabels using synthetic chemistry enables the direct tracing of the drug molecule without substantially altering its structure or function. The ubiquity of C-H bonds in drugs and the relative ease and low cost associated with tritium ((3)H) make it an ideal radioisotope with which to conduct ADME studies early in the drug development process. Here we describe an iron-catalysed method for the direct (3)H labelling of pharmaceuticals by hydrogen isotope exchange, using tritium gas as the source of the radioisotope. The site selectivity of the iron catalyst is orthogonal to currently used iridium catalysts and allows isotopic labelling of complementary positions in drug molecules, providing a new diagnostic tool in drug development.

  16. Dynamics of Radical-Mediated Enzyme Catalyses

    NASA Astrophysics Data System (ADS)

    Warncke, Kurt

    1997-11-01

    An emergent class of enzymes harnesses the extreme reactivity of electron-deficient free radical species to perform some of the most difficult reactions in biology. The regio- and stereo-selectivity achieved by these enzymes defies long-held ideas that radical reactions are non-specific. The common primary step in these catalyses is metal- or metallocenter-assisted generation of an electron-deficient organic "initiator radical". The initiator radical abstracts a hydrogen atom from the substrate, opening a new reaction channel for rearrangement to the product. Our aim is to elucidate the detailed molecular mechanisms of the radical pair separation and radical rearrangement steps. Radical pair separation and substrate radical rearrangement are tracked by using time-resolved (10-7 to 10-3 s) techniques of pulsed-electron paramagnetic resonance spectroscopy (FT-EPR, ESEEM). Synchronous time-evolution of the reactions is attained by triggering with a visible laser pulse. Transient non-Boltzmann population of the states of the spin-coupled systems, and resultant electron spin polarization, facilitates study at or near room temperature under conditions where the enzymes are operative. The systems examined include ethanolamine deaminase, a vitamin B12 coenzyme-dependent enzyme, ribonucleotide reductase and photosynthetic reaction centers. The electronic and nuclear structural and kinetic information obtained from the pulsed-EPR studies is used to address how the initiator radicals are stabilized against deleterious recombination with the metal, and to distinguish the participation of concerted versus sequential rearrangement pathways.

  17. Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

    SciTech Connect

    Bai, Da -Chang; Yu, Fei -Le; Wang, Wan -Ying; Chen, Di; Li, Hao; Liu, Qing -Rong; Ding, Chang -Hua; Chen, Bo; Hou, Xue -Long

    2016-06-10

    The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of beta-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. As a result, mechanistic studies by both experiments and density functional theory ( DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination.

  18. Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

    PubMed Central

    Bai, Da-Chang; Yu, Fei-Le; Wang, Wan-Ying; Chen, Di; Li, Hao; Liu, Qing-Rong; Ding, Chang-Hua; Chen, Bo; Hou, Xue-Long

    2016-01-01

    The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of β-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. Mechanistic studies by both experiments and density functional theory (DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism—nucleophilic attack of enolate oxygen on Palladium followed by C–C bond-forming [3,3']-reductive elimination. PMID:27283477

  19. Biohydrogen production from kitchen based vegetable waste: effect of pyrolysis temperature and time on catalysed and non-catalysed operation.

    PubMed

    Agarwal, Manu; Tardio, James; Mohan, S Venkata

    2013-02-01

    Pyrolysis of kitchen based vegetable waste (KVW) was studied in a designed packed bed reactor. The effect of process parameters like temperature, time and catalyst on bio-gas yield and its composition was studied. The total bio-gas yield was found to be maximum with non-catalysed operation (260ml/g) at 1073K (180min). Higher hydrogen (H(2)) yield with non-catalysed operation (32.68%) was observed at 1073K (180min) while with catalysed operation the requisite temperature (873K) and time (120min) reduced with both silica gel (33.34%) and sand (41.82%) thus, saving energy input. Methane (CH(4)) yield was found to be highest (4.44times than non-catalysed and 1.42 with silica gel) in presence of sand (71.485ml/g) at medium temperature (873K) and time (60min). The catalyst operation reduced the carbondioxide (CO(2)) share from 47.29% to 41.30% (silica gel catalysed) and 21.91% (sand catalysed) at 873K.

  20. A practical guide to modelling enzyme-catalysed reactions

    PubMed Central

    Lonsdale, Richard; Harvey, Jeremy N.; Mulholland, Adrian J.

    2012-01-01

    Molecular modelling and simulation methods are increasingly at the forefront of elucidating mechanisms of enzyme-catalysed reactions, and shedding light on the determinants of specificity and efficiency of catalysis. These methods have the potential to assist in drug discovery and the design of novel protein catalysts. This Tutorial Review highlights some of the most widely used modelling methods and some successful applications. Modelling protocols commonly applied in studying enzyme-catalysed reactions are outlined here, and some practical implications are considered, with cytochrome P450 enzymes used as a specific example. PMID:22278388

  1. Palladium-catalysed synthesis of triaryl(heteroaryl)methanes

    NASA Astrophysics Data System (ADS)

    Zhang, Shuguang; Kim, Byeong-Seon; Wu, Chen; Mao, Jianyou; Walsh, Patrick J.

    2017-03-01

    Tetraarylmethane derivatives are desirable for a variety of applications, but difficult to access with modern C-C bond-forming reactions. Here we report a straightforward method for palladium-catalysed arylation of aryl(heteroaryl)methanes and diaryl(heteroaryl)methanes with aryl chlorides. This reaction enables introduction of various aryl groups to construct triaryl(heteroaryl)methanes via a C-H functionalization in good to excellent yield, and represents the first step towards a general transition metal catalysed synthesis of tetraarylmethanes.

  2. Palladium-catalysed synthesis of triaryl(heteroaryl)methanes

    PubMed Central

    Zhang, Shuguang; Kim, Byeong-Seon; Wu, Chen; Mao, Jianyou; Walsh, Patrick J.

    2017-01-01

    Tetraarylmethane derivatives are desirable for a variety of applications, but difficult to access with modern C–C bond-forming reactions. Here we report a straightforward method for palladium-catalysed arylation of aryl(heteroaryl)methanes and diaryl(heteroaryl)methanes with aryl chlorides. This reaction enables introduction of various aryl groups to construct triaryl(heteroaryl)methanes via a C–H functionalization in good to excellent yield, and represents the first step towards a general transition metal catalysed synthesis of tetraarylmethanes. PMID:28290445

  3. Asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with a new trifluoromethoxylation reagent

    NASA Astrophysics Data System (ADS)

    Guo, Shuo; Cong, Fei; Guo, Rui; Wang, Liang; Tang, Pingping

    2017-06-01

    Fluorinated organic compounds are becoming increasingly important in pharmaceuticals, agrochemicals and materials science. The introduction of trifluoromethoxy groups into new drugs and agrochemicals has attracted much attention due to their strongly electron-withdrawing nature and high lipophilicity. However, synthesis of trifluoromethoxylated organic molecules is difficult owing to the decomposition of trifluoromethoxide anion and β-fluoride elimination from transition-metal-trifluoromethoxide complexes, and no catalytic enantioselective trifluoromethoxylation reaction has been reported until now. Here, we present an example of an asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with trifluoromethyl arylsulfonate (TFMS) as a new trifluoromethoxylation reagent. Compared to other trifluoromethoxylation reagents, TFMS is easily prepared and thermally stable with good reactivity. In addition, this reaction is operationally simple, scalable and proceeds under mild reaction conditions. Furthermore, broad scope and good functional group compatibility has been demonstrated by application of the method to the bromotrifluoromethoxylation of double bonds in natural products and natural product derivatives.

  4. Gold-catalysed cascade rearrangements of ynamide propargyl esters.

    PubMed

    Heffernan, Stephen J; Beddoes, James M; Mahon, Mary F; Hennessy, Alan J; Carbery, David R

    2013-03-21

    The Au(I)-catalysed rearrangement of propargylic esters formed from an ynamide has been studied. The reaction is facile, and when conducted in the presence of a reactive indole nucleophile, leads to a cascade process whereby γ-indolyl α-acyloxyenamides are formed in good yield and excellent E-stereoselectivity.

  5. Enzyme-catalysed assembly of DNA hydrogel

    NASA Astrophysics Data System (ADS)

    Um, Soong Ho; Lee, Jong Bum; Park, Nokyoung; Kwon, Sang Yeon; Umbach, Christopher C.; Luo, Dan

    2006-10-01

    DNA is a remarkable polymer that can be manipulated by a large number of molecular tools including enzymes. A variety of geometric objects, periodic arrays and nanoscale devices have been constructed. Previously we synthesized dendrimer-like DNA and DNA nanobarcodes from branched DNA via ligases. Here we report the construction of a hydrogel entirely from branched DNA that are three-dimensional and can be crosslinked in nature. These DNA hydrogels were biocompatible, biodegradable, inexpensive to fabricate and easily moulded into desired shapes and sizes. The distinct difference of the DNA hydrogel to other bio-inspired hydrogels (including peptide-based, alginate-based and DNA (linear)-polyacrylamide hydrogels) is that the crosslinking is realized via efficient, ligase-mediated reactions. The advantage is that the gelling processes are achieved under physiological conditions and the encapsulations are accomplished in situ-drugs including proteins and even live mammalian cells can be encapsulated in the liquid phase eliminating the drug-loading step and also avoiding denaturing conditions. Fine tuning of these hydrogels is easily accomplished by adjusting the initial concentrations and types of branched DNA monomers, thus allowing the hydrogels to be tailored for specific applications such as controlled drug delivery, tissue engineering, 3D cell culture, cell transplant therapy and other biomedical applications.

  6. Hydrogen storage and evolution catalysed by metal hydride complexes.

    PubMed

    Fukuzumi, Shunichi; Suenobu, Tomoyoshi

    2013-01-07

    The storage and evolution of hydrogen are catalysed by appropriate metal hydride complexes. Hydrogenation of carbon dioxide by hydrogen is catalysed by a [C,N] cyclometalated organoiridium complex, [Ir(III)(Cp*)(4-(1H-pyrazol-1-yl-κN(2))benzoic acid-κC(3))(OH(2))](2)SO(4) [Ir-OH(2)](2)SO(4), under atmospheric pressure of H(2) and CO(2) in weakly basic water (pH 7.5) at room temperature. The reverse reaction, i.e., hydrogen evolution from formate, is also catalysed by [Ir-OH(2)](+) in acidic water (pH 2.8) at room temperature. Thus, interconversion between hydrogen and formic acid in water at ambient temperature and pressure has been achieved by using [Ir-OH(2)](+) as an efficient catalyst in both directions depending on pH. The Ir complex [Ir-OH(2)](+) also catalyses regioselective hydrogenation of the oxidised form of β-nicotinamide adenine dinucleotide (NAD(+)) to produce the 1,4-reduced form (NADH) under atmospheric pressure of H(2) at room temperature in weakly basic water. In weakly acidic water, the complex [Ir-OH(2)](+) also catalyses the reverse reaction, i.e., hydrogen evolution from NADH to produce NAD(+) at room temperature. Thus, interconversion between NADH (and H(+)) and NAD(+) (and H(2)) has also been achieved by using [Ir-OH(2)](+) as an efficient catalyst and by changing pH. The iridium hydride complex formed by the reduction of [Ir-OH(2)](+) by H(2) and NADH is responsible for the hydrogen evolution. Photoirradiation (λ > 330 nm) of an aqueous solution of the Ir-hydride complex produced by the reduction of [Ir-OH(2)](+) with alcohols resulted in the quantitative conversion to a unique [C,C] cyclometalated Ir-hydride complex, which can catalyse hydrogen evolution from alcohols in a basic aqueous solution (pH 11.9). The catalytic mechanisms of the hydrogen storage and evolution are discussed by focusing on the reactivity of Ir-hydride complexes.

  7. Reconsidering the energetics of ribonuclease catalysed RNA hydrolysis.

    PubMed

    Loverix, S; Laus, G; Martins, J C; Wyns, L; Steyaert, J

    1998-10-01

    In principle, all biochemical reactions are reversible, though some are more reversible than others. The classical ribonuclease mechanism involves a reversible transphosphorylation step, followed by quasi irreversible hydrolysis of the cyclic intermediate. We performed isotope-exchange and intermediate-trapping experiments showing that the second hydrolysis step is readily reversible in the presence of RNase A or RNase T1. As a consequence, the equilibrium between a phosphodiester and a 2',3'-cyclophosphate accounts for all catalysed reactions, even if the leaving/attacking group is a water molecule. Therefore, ribonucleases are transferases rather than hydrolases. The equilibrium constant for the catalysed interconversion is close to 1 M. From this result, we estimate the effective concentration of the 2'-hydroxyl nucleophile in the cyclization step to be 10(7) M. The high effective concentration of the vicinal hydroxyl group balances the strain-associated and solvation-associated instability of the pentacyclic phosphodiester.

  8. Nickel-catalysed Suzuki-Miyaura coupling of amides

    NASA Astrophysics Data System (ADS)

    Weires, Nicholas A.; Baker, Emma L.; Garg, Neil K.

    2016-01-01

    The Suzuki-Miyaura coupling has become one of the most important and prevalent methods for the construction of C-C bonds. Although palladium catalysis has historically dominated the field, the use of nickel catalysis has become increasingly widespread because of its unique ability to cleave carbon-heteroatom bonds that are unreactive towards other transition metals. We report the first nickel-catalysed Suzuki-Miyaura coupling of amides, which proceeds by an uncommon cleavage of the amide C-N bond after N-tert-butoxycarbonyl activation. The methodology is mild, functional-group tolerant and can be strategically employed in sequential transition-metal-catalysed cross-coupling sequences to unite heterocyclic fragments. These studies demonstrate that amides, despite classically considered inert substrates, can be harnessed as synthons for use in reactions that form C-C bonds through cleavage of the C-N bond using non-precious metal catalysis.

  9. Ultrasonic enhancement of lipase-catalysed transesterification for biodiesel synthesis.

    PubMed

    Bhangu, Sukhvir Kaur; Gupta, Shweta; Ashokkumar, Muthupandian

    2017-01-01

    The production of biodiesel was carried out from canola oil and methanol catalysed by lipase from Candida rugosa under different ultrasonic experimental conditions using horn (20kHz) and plate (22, 44, 98 and 300kHz) transducers. The effects of experimental conditions such as horn tip diameter, ultrasonic power, ultrasonic frequency and enzyme concentrations on biodiesel yield were investigated. The results showed that the application of ultrasound decreased the reaction time from 22-24h to 1.5h with the use of 3.5cm ultrasonic horn, an applied power of 40W, methanol to oil molar ratio of 5:1 and enzyme concentration of 0.23wt/wt% of oil. Low intensity ultrasound is efficient and a promising tool for the enzyme catalysed biodiesel synthesis as higher intensities tend to inactivate the enzyme and reduce its efficiency.

  10. Soluble transition-metal nanoparticles-catalysed hydrogenation of arenes.

    PubMed

    Gual, Aitor; Godard, Cyril; Castillón, Sergio; Claver, Carmen

    2010-12-28

    Over the last decade, the hydrogenation of arenes catalysed by soluble nanoparticles has attracted much interest from both academic and industrial research groups due to the milder conditions and the interesting selectivities achieved when compared to those obtained with classical heterogeneous catalysts. When substituted arenes are used as substrates in this reaction, the stereoselectivity is a key objective, and high levels of enantioselectivity are yet to be achieved.

  11. Formamide Synthesis through Borinic Acid Catalysed Transamidation under Mild Conditions.

    PubMed

    Dine, Tharwat Mohy El; Evans, David; Rouden, Jacques; Blanchet, Jérôme

    2016-04-18

    A highly efficient and mild transamidation of amides with amines co-catalysed by borinic acid and acetic acid has been reported. A wide range of functionalised formamides was synthesized in excellent yields, including important chiral α-amino acid derivatives, with minor racemisation being observed. Experiments suggested that the reaction rely on a cooperative catalysis involving an enhanced boron-derived Lewis acidity rather than an improved Brønsted acidity of acetic acid.

  12. Degradation of C-hordein by metal-catalysed oxidation.

    PubMed

    Huang, Xin; Kanerva, Päivi; Salovaara, Hannu; Sontag-Strohm, Tuula

    2016-04-01

    C-hordein is a monomeric prolamin protein in barley. The unusual primary structure of C-hordein has highly repetitive sequences and forms a secondary structure of beta-turns. C-hordein structure is similar to that of collagen protein, whose degradation by metal-catalysed oxidation has been intensively studied. No information exists on the metal catalysed oxidation of C-hordein, however. In this study, copper-catalysed hydrogen peroxide induced oxidation of C-hordein caused substantial degradation and formed some insoluble compounds. The use of a gliadin standard in R5 ELISA determinations causes an overestimation of hordeins in a sample. A C-hordein standard was therefore directly used as a standard, thus allowing the C-hordein to be analysed as its oxidised prolamin product. After 48 h of oxidation, the prolamin concentration of oxidised C-hordein decreased to 20% of its original amount for competitive ELISA, and to 3% for sandwich ELISA methods. Carbonyl groups were formed during the oxidation. Backbone fragmentation and side-chain modification suggested structural changes of R5 epitopes in C-hordein. Oxidation is an alternative to enzymatic hydrolysis when degrading and modifying C-hordein.

  13. Microbially induced and microbially catalysed precipitation: two different carbonate factories

    NASA Astrophysics Data System (ADS)

    Meister, Patrick

    2016-04-01

    The landmark paper by Schlager (2003) has revealed three types of benthic carbonate production referred to as "carbonate factories", operative at different locations at different times in Earth history. The tropical or T-factory comprises the classical platforms and fringing reefs and is dominated by carbonate precipitation by autotrophic calcifying metazoans ("biotically controlled" precipitation). The cool or C-factory is also biotically controlled but via heterotrophic, calcifying metazoans in cold and deep waters at the continental margins. A further type is the mud-mound or M-factory, where carbonate precipitation is supported by microorganisms but not controlled by a specific enzymatic pathway ("biotically induced" precipitation). How exactly the microbes influence precipitation is still poorly understood. Based on recent experimental and field studies, the microbial influence on modern mud mound and microbialite growth includes two fundamentally different processes: (1) Metabolic activity of microbes may increase the saturation state with respect to a particular mineral phase, thereby indirectly driving the precipitation of the mineral phase: microbially induced precipitation. (2) In a situation, where a solution is already supersaturated but precipitation of the mineral is inhibited by a kinetic barrier, microbes may act as a catalyser, i.e. they lower the kinetic barrier: microbially catalysed precipitation. Such a catalytic effect can occur e.g. via secreted polymeric substances or specific chemical groups on the cell surface, at which the minerals nucleate or which facilitate mechanistically the bonding of new ions to the mineral surface. Based on these latest developments in microbialite formation, I propose to extend the scheme of benthic carbonate factories of Schlager et al. (2003) by introducing an additional branch distinguishing microbially induced from microbially catalysed precipitation. Although both mechanisms could be operative in a M

  14. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre l’épidémiologie, la pathogenèse, l’histologie et l’approche clinique au diagnostic de la pelade par plaques. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant la pathogenèse, le diagnostic et le pronostic de la pelade par plaques. Message principal La pelade par plaques est une forme de perte pileuse auto-immune dont la prévalence durant une vie est d’environ 2 %. Des antécédents personnels ou familiaux de troubles auto-immuns concomitants, comme le vitiligo ou une maladie de la thyroïde, peuvent être observés dans un petit sous-groupe de patients. Le diagnostic peut souvent être posé de manière clinique en se fondant sur la perte de cheveux non cicatricielle et circulaire caractéristique, accompagnée de cheveux en « point d’exclamation » en périphérie chez ceux dont le problème en est aux premiers stades. Le diagnostic des cas plus complexes ou des présentations inhabituelles peut être facilité par une biopsie et un examen histologique. Le pronostic varie largement et de mauvais résultats sont associés à une apparition à un âge précoce, une perte importante, la variante ophiasis, des changements aux ongles, des antécédents familiaux ou des troubles auto-immuns concomitants. Conclusion La pelade par plaques est une forme auto-immune de perte de cheveux périodiquement observée en soins primaires. Les médecins de famille sont bien placés pour identifier la pelade par plaques, déterminer la gravité de la maladie et poser le diagnostic différentiel approprié. De plus, ils sont en mesure de renseigner leurs patients à propos de l’évolution clinique de la maladie ainsi que du pronostic général selon le sous-type de patients.

  15. Slanted baffle mist eliminator

    DOEpatents

    Vance, Richard F.

    1995-11-07

    An apparatus for the elimination of mist from off-gas during vitrification f nuclear waste, where baffles are installed on a slant toward the flow of the off-gasses eliminating the need to expand the cross-sectional area of the duct size.

  16. Slanted baffle mist eliminator

    DOEpatents

    Vance, Richard F.

    1995-01-01

    An apparatus for the elimination of mist from off-gas during vitrification f nuclear waste, where baffles are installed on a slant toward the flow of the off-gasses eliminating the need to expand the cross-sectional area of the duct size.

  17. Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

    DOE PAGES

    Bai, Da -Chang; Yu, Fei -Le; Wang, Wan -Ying; ...

    2016-06-10

    The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of beta-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. As a result, mechanistic studiesmore » by both experiments and density functional theory ( DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination.« less

  18. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre les schémas thérapeutiques et les résultats des traitements pour la pelade par plaques, de même que les aider à identifier les patients pour qui une demande de consultation en dermatologie pourrait s’imposer. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant le traitement de la pelade par plaques. Message principal La pelade par plaques est une forme auto-immune de perte pileuse qui touche à la fois les enfants et les adultes. Même s’il n’y a pas de mortalité associée à la maladie, la morbidité découlant des effets psychologiques de la perte des cheveux peut être dévastatrice. Lorsque la pelade par plaques et le sous-type de la maladie sont identifiés, un schéma thérapeutique approprié peut être amorcé pour aider à arrêter la chute des cheveux et possiblement faire commencer la repousse. Les traitements de première intention sont la triamcinolone intralésionnelle avec des corticostéroïdes topiques ou du minoxidil ou les 2. Les médecins de famille peuvent prescrire ces traitements en toute sécurité et amorcer ces thérapies. Les cas plus avancés ou réfractaires pourraient avoir besoin de diphénylcyclopropénone topique ou d’anthraline topique. On peut traiter la perte de cils avec des analogues de la prostaglandine. Les personnes ayant subi une perte de cheveux abondante peuvent recourir à des options de camouflage ou à des prothèses capillaires. Il est important de surveiller les troubles psychiatriques en raison des effets psychologiques profonds de la perte de cheveux. Conclusion Les médecins de famille verront de nombreux patients qui perdent leurs cheveux. La reconnaissance de la pelade par plaques et la compréhension du processus pathologique sous-jacent permettent d’amorcer un schéma thérapeutique approprié. Les cas plus graves ou r

  19. Peroxidase-catalysed interfacial adhesion of aquatic caddisworm silk

    PubMed Central

    Wang, Ching-Shuen; Pan, Huaizhong; Weerasekare, G. Mahika; Stewart, Russell J.

    2015-01-01

    Casemaker caddisfly (Hesperophylax occidentalis) larvae use adhesive silk fibres to construct protective shelters under water. The silk comprises a distinct peripheral coating on a viscoelastic fibre core. Caddisworm silk peroxinectin (csPxt), a haem-peroxidase, was shown to be glycosylated by lectin affinity chromatography and tandem mass spectrometry. Using high-resolution H2O2 and peroxidase-dependent silver ion reduction and nanoparticle deposition, imaged by electron microscopy, csPxt activity was shown to be localized in the peripheral layer of drawn silk fibres. CsPxt catalyses dityrosine cross-linking within the adhesive peripheral layer post-draw, initiated perhaps by H2O2 generated by a silk gland-specific superoxide dismutase 3 (csSOD3) from environmental reactive oxygen species present in natural water. CsSOD3 was also shown to be a glycoprotein and is likely localized in the peripheral layer. Using a synthetic fluorescent phenolic copolymer and confocal microscopy, it was shown that csPxt catalyses oxidative cross-linking to external polyphenolic compounds capable of diffusive interpenetration into the fuzzy peripheral coating, including humic acid, a natural surface-active polyphenol. The results provide evidence of enzyme-mediated covalent cross-linking of a natural bioadhesive to polyphenol conditioned interfaces as a mechanism of permanent adhesion underwater. PMID:26490632

  20. Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium

    NASA Astrophysics Data System (ADS)

    Feng, Zhang; Min, Qiao-Qiao; Fu, Xia-Ping; An, Lun; Zhang, Xingang

    2017-09-01

    Difluoromethylated aromatic compounds are of increasing importance in pharmaceuticals, agrochemicals and materials. Chlorodifluoromethane (ClCF2H), an inexpensive, abundant and widely used industrial raw material, represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF2H) from ClCF2H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF2H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate scope, including heteroarylboronic acids, and was used for difluoromethylation of a range of pharmaceuticals and biologically active compounds. Preliminary mechanistic studies revealed that a palladium difluorocarbene intermediate is involved in the reaction. Although numerous metal-difluorocarbene complexes have been prepared, the catalytic synthesis of difluoromethylated or difluoromethylenated compounds involving metal-difluorocarbene complexes has not received much attention. This new reaction therefore also opens the door to understand metal-difluorocarbene complex catalysed reactions.

  1. Carbohydrate-binding module assisting glycosynthase-catalysed polymerizations.

    PubMed

    Codera, Victoria; Gilbert, Harry J; Faijes, Magda; Planas, Antoni

    2015-08-15

    Carbohydrate-binding modules (CBMs) are found within multi-modular polysaccharide degrading enzymes [glycoside hydrolases (GHs)]. CBMs play a critical role in the recognition of plant cell-wall polysaccharides and enhance the hydrolase activity of their cognate catalytic domains by increasing enzyme substrate proximity. Mimicking their role in Nature, we, in the present study, propose that CBMs may assist in vitro glycosynthase-catalysed polymerization reactions to produce artificial polysaccharides. Glycosynthases are GHs that have been engineered to catalyse glycoside bond formation for the synthesis of oligosaccharides, glycoconjugates and glycans. The degree of polymerization (DP) of the glycans generated is limited by the solubility of the polymeric product. In the present study, we have targeted the synthesis of artificial 1,3-1,4-β-glucans with a regular sequence using the glycosynthase E(134)S derived from a Bacillus licheniformis lichenase. We show that the addition of CBM11, which binds mixed-linked β-glucans, either as an isolated protein or fused to the glycosynthase E(134)S, has an effect on the DP of the polysaccharide products that is dependent on the rate of polymerization. The mechanism by which CBM influences the DP of the synthesized glycans is discussed.

  2. Cobalt-Catalysed Asymmetric Hydrovinylation of 1,3-Dienes

    PubMed Central

    Timsina, Yam N.; Sharma, Rakesh K.

    2015-01-01

    In the presence of bidentate 1,n-bis-diphenylphosphinoalkane-CoCl2 complexes {Cl2Co[P~P]} and Me3Al or methylaluminoxane, acyclic (E)-1,3-dienes react with ethylene (1 atmosphere) to give excellent yields of hydrovinylation products. The regioselectivity (1,4- or 1,2-addition) and the alkene configuration (E- or Z-) of the resulting product depend on the nature of the ligand and temperature at which the reaction is carried out. Cobalt(II)-complexes of 1,1-diphenylphosphinomethane and similar ligands with narrow bite angles give mostly 1,2-addition, retaining the E-geometry of the original diene. Complexes of most other ligands at low temperature (−40 °C) give almost exclusively a single branched product, (Z)-3-alkylhexa-1,4-diene, which arises from a 1,4-hydrovinylation reaction. A minor product is the linear adduct, a 5-alkyl-hexa-1,4-diene, also arising from a 1,4-addition of ethylene. As the temperature is increased, a higher proportion of the major 1,4-adduct appears as the (E)-isomer. The unexpectedly high selectivity seen in the Co-catalysed reaction as compared to the corresponding Ni-catalysed reaction can be rationalized by invoking the intermediacy of an η4-[(diene)[P~P]CoH]+-complex and its subsequent reactions. The enhanced reactivity of terminal E-1,3-dienes over the corresponding Z-dienes can also be explained on the basis of the ease of formation of this η4-complex in the former case. The lack of reactivity of the X2Co(dppb) (X = Cl, Br) complexes in the presence of Zn/ZnI2 makes the Me3Al-mediated reaction different from the previously reported hydroalkenylation of dienes. Electron-rich phospholanes, bis-oxazolines and N-heterocyclic carbenes appear to be poor ligands for the Co(II)-catalysed hydrovinylation of 1,3-dienes. An extensive survey of chiral ligands reveals that complexes of DIOP, BDDP and Josiphos ligands are quite effective for these reactions even at −45 °C and enantioselectivities in the range of 90–99 % ee can be realized

  3. Ag-catalysed cutting of multi-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    La Torre, A.; Rance, G. A.; Miners, S. A.; Herreros Lucas, C.; Smith, E. F.; Fay, M. W.; Zoberbier, T.; Giménez-López, M. C.; Kaiser, U.; Brown, P. D.; Khlobystov, A. N.

    2016-04-01

    In this work, the cutting of carbon nanotubes is investigated using silver nanoparticles deposited on arc discharge multi-walled carbon nanotubes. The composite is subsequently heated in air to fabricate shortened multi-walled nanotubes. Complementary transmission electron microscopy and spectroscopy techniques shed light on the cutting mechanism. The nanotube cutting is catalysed by the fundamental mechanism based on the coordination of the silver atoms to the π-bonds of carbon nanotubes. As a result of the metal coordination, the strength of the carbon-carbon bond is reduced, promoting the oxidation of carbon at lower temperature when heated in air, or lowering the activation energy required for the removal of carbon atoms by electron beam irradiation, assuring in both cases the cutting of the nanotubes.

  4. Phase-transfer-catalysed asymmetric synthesis of tetrasubstituted allenes.

    PubMed

    Hashimoto, Takuya; Sakata, Kazuki; Tamakuni, Fumiko; Dutton, Mark J; Maruoka, Keiji

    2013-03-01

    Allenes are molecules based on three carbons connected by two cumulated carbon-carbon double bonds. Given their axially chiral nature and unique reactivity, substituted allenes have a variety of applications in organic chemistry as key synthetic intermediates and directly as part of biologically active compounds. Although the demands for these motivated many endeavours to make axially chiral, substituted allenes by exercising asymmetric catalysis, the catalytic asymmetric synthesis of fully substituted ones (tetrasubstituted allenes) remained largely an unsolved issue. The fundamental obstacle to solving this conundrum is the lack of a simple synthetic transformation that provides tetrasubstituted allenes in the action of catalysis. We report herein a strategy to overcome this issue by the use of a phase-transfer-catalysed asymmetric functionalization of 1-alkylallene-1,3-dicarboxylates with N-arylsulfonyl imines and benzylic and allylic bromides.

  5. Ag-catalysed cutting of multi-walled carbon nanotubes.

    PubMed

    La Torre, A; Rance, G A; Miners, S A; Herreros Lucas, C; Smith, E F; Fay, M W; Zoberbier, T; Giménez-López, M C; Kaiser, U; Brown, P D; Khlobystov, A N

    2016-04-29

    In this work, the cutting of carbon nanotubes is investigated using silver nanoparticles deposited on arc discharge multi-walled carbon nanotubes. The composite is subsequently heated in air to fabricate shortened multi-walled nanotubes. Complementary transmission electron microscopy and spectroscopy techniques shed light on the cutting mechanism. The nanotube cutting is catalysed by the fundamental mechanism based on the coordination of the silver atoms to the π-bonds of carbon nanotubes. As a result of the metal coordination, the strength of the carbon-carbon bond is reduced, promoting the oxidation of carbon at lower temperature when heated in air, or lowering the activation energy required for the removal of carbon atoms by electron beam irradiation, assuring in both cases the cutting of the nanotubes.

  6. Rhenium-catalysed hydroboration of aldehydes and aldimines.

    PubMed

    Arévalo, Rebeca; Vogels, Christopher M; MacNeil, Gregory A; Riera, Lucía; Pérez, Julio; Westcott, Stephen A

    2017-06-28

    The first examples for the rhenium-catalysed hydroboration of aldehydes, ketones and aldimines, including heteroaromatic quinoline, are reported herein. Reactions are remarkably chemoselective and tolerant of several functional groups. A wide array of rhenium complexes were efficient pre-catalysts for these hydroborations, including new low-valent complexes of the formula [Re(N-N)(CO)3(L)]X (N-N = bipy derivative, L = labile ligand/solvent, and X = [BAr(F)4](-) and [B(3,5-di-tBu-cat)2](-)), which have been characterized fully including an X-ray diffraction study for [Re(bipy)(CO)3(quin)][BAr(F)4] (2). A new silver spiroboronate ester Ag[B(3,5-di-tBu-cat)2](NCCH3)3 (3) was prepared and characterized fully, including an X-ray diffraction study, and used to make one of the new rhenium complexes.

  7. Carbon–heteroatom bond formation catalysed by organometallic complexes

    PubMed Central

    Hartwig, John F.

    2010-01-01

    At one time the synthetic chemist’s last resort, reactions catalysed by transition metals are now the preferred method for synthesizing many types of organic molecule. A recent success in this type of catalysis is the discovery of reactions that form bonds between carbon and heteroatoms (such as nitrogen, oxygen, sulphur, silicon and boron) via complexes of transition metals with amides, alkoxides, thiolates, silyl groups or boryl groups. The development of these catalytic processes has been supported by the discovery of new elementary reactions that occur at metal–heteroatom bonds and by the identification of factors that control these reactions. Together, these findings have led to new synthetic processes that are in daily use and have formed a foundation for the development of processes that are likely to be central to synthetic chemistry in the future. PMID:18800130

  8. Ceramic microreactors for heterogeneously catalysed gas-phase reactions.

    PubMed

    Knitter, Regina; Liauw, Marcel A

    2004-08-01

    The high surface to volume ratio of microchannel components offers many advantages in micro chemical engineering. It is obvious, however, that the reactor material and corrosion phenomena play an important role when applying these components. For chemical reactions at very high temperatures or/and with corrosive reactants involved, microchannel components made of metals or polymers are not suited. Hence, a modular microreactor system made of alumina was developed and fabricated using a rapid prototyping process chain. With exchangeable inserts the system can be adapted to the requirements of various reactions. Two heterogeneously catalysed gas-phase reactions (oxidative coupling of methane, isoprene selective oxidation to citraconic anhydride) were investigated to check the suitability of the system at temperatures of up to 1000 degrees C. Apart from the high thermal and chemical resistance, the lack of any blind activity was found to be another advantage of ceramic components.

  9. Brulures par Diluant

    PubMed Central

    Benbrahim, A.; Jerrah, H.; Diouri, M.; Bahechar, N.; Boukind, E.H.

    2009-01-01

    Summary La flamme de diluant est une cause non rare de brûlure dans le contexte marocain. Nous avons jugé intéressant de faire une étude épidémiologique sur la brûlure par flamme de diluant (BFD) au centre national des brûlés (CNB) du CHU Ibn-Rochd de Casablanca. Ce travail a été réalisé sur une période de 10 mois (septembre 2007/juin 2008). Le but du travail est de montrer les caractéristiques de ce type de brûlures pour les prévenir et ce par l'information sur le diluant, produit causant ces brûlures, et ses différents dangers, la brûlure notamment. Durant cette période, nous avons colligé 17 cas de BFD sur un total de 356 patients admis au CNB pour brûlures aiguës toute étiologie confondue. La moyenne d'age des patients concernés est de 32 ans. Ils sont presque tous de sexe masculin (16 hommes/1 femme) et ont des antécédents de toxicomanie et/ou de délinquance. Tous nos patients sont de bas niveau socio-économique et habitent dans des bidonvilles pour la plupart. La brûlure est souvent secondaire à une agression dans la rue (92% des cas). Concernant les caractéristiques de la brûlure, la surface cutanée brûlée moyenne est de 23%; elle est souvent profonde et siège surtout au niveau des membres supérieurs et du tronc. PMID:21991179

  10. Minding Rachlin's Eliminative Materialism

    ERIC Educational Resources Information Center

    McDowell, J. J.

    2012-01-01

    Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist…

  11. Elimination chemistry in asphalt

    SciTech Connect

    Boucher, J.L.; Ihsiung Wang; Martinez, D.F. )

    1990-07-01

    Elimination chemistry provides important information, not only about the chemical properties of asphalt, but also the chemical modification method of asphalt. The chemical reactions which use the natural abundance of radicals are important for free-radical halogenation reaction. Spectral data demonstrates the formation of halogenated asphalt. The utility of dehydrohalogenation modified asphalt is limited. However, the resulting dehydrohalogenation modified asphalt does produce a significant unsaturated intermediate, which can incorporate elastomeric polymers (and monomers) via condensation or addition process. The second chemical modification method is the Hofmann elimination reaction, which was performed by reaction of methyl iodide with asphalt, followed by treatment of base. Spectroscopic data shows that a methyl group attached to nitrogen or sulfur in asphalt after Hofmann elimination reaction. Physical data shows that the Hofmann elimination modification improved the quality of asphalt, such as low temperature susceptibility measured by PVN. The modified asphalt also studied by HP-GPC in order to correlate their physical properties. The result shows that the molecular size distribution has changed and reduced the amount of LMS. The amount of decreasing LMS is also dependent on the content of nitrogen and sulfur in asphalts.

  12. Elimination of Social Rules.

    ERIC Educational Resources Information Center

    O'Toole, Teddy

    The thesis of this document is that arbitrary social rules must be eliminated. Chapters cover: (1) what it is like to be a student whose personal activities are controlled; (2) the necessity of environmental freedom as a prerequisite to successful educational reform; (3) the question of environmental control; (4) the legal history of environmental…

  13. Modeling disease elimination.

    PubMed

    Somerville, Kevin; Francombe, Paula

    2005-01-01

    The effect of the elimination of mortality from heart disease and cancer was modelled mathematically to allow for the effect of other competing causes of death. The model allows for potential dependence between heart disease or cancer and other causes of death by using cupola functions, which analyse the individual risk itself and the dependence structure between causes of death by using correlation coefficients. As the strength of these risk associations is unknown, the study investigated both full positive and negative dependence and compared this with no dependence. Depending upon the degree and type of correlation assumed, positive or negative, the life expectancy at birth is increased by between 3 months and 6.5 years if cancer mortality was eliminated, and between 5 months and 7.5 years in the case of heart disease. In addition, estimates of these effects on life insurance premia can be made with the greatest reduction for women with the elimination of cancer mortality. These figures provide a range of improvements in life expectancy and the consequent effect on life insurance risk premium rates which elimination of either of these important diseases would produce.

  14. Minding Rachlin's Eliminative Materialism

    ERIC Educational Resources Information Center

    McDowell, J. J.

    2012-01-01

    Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist…

  15. Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

    PubMed Central

    Palík, Miroslav; Kožíšek, Jozef; Koóš, Peter

    2014-01-01

    Summary The study of Pd-catalysed cyclisation reactions of alkenols using different catalytic systems is reported. These transformations affect the stereoselective construction of mono- and/or bicyclic oxaheterocyclic derivatives depending on a starting alkenol. The substrate scope and proposed mechanism of Pd-catalysed cyclisation reactions are also discussed. Moreover, the diastereoselective Pd-catalysed cyclisation of appropriate alkenols to tetrahydrofurans and subsequent cyclisation provided properly substituted 2,5-dioxabicyclo[2.2.1]heptane and 2,6-dioxabicyclo[3.2.1]octane, respectively. Such bicyclic ring subunits are found in many natural products including ocellenynes and aurovertines. PMID:25246967

  16. Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds.

    PubMed

    Palík, Miroslav; Kožíšek, Jozef; Koóš, Peter; Gracza, Tibor

    2014-01-01

    The study of Pd-catalysed cyclisation reactions of alkenols using different catalytic systems is reported. These transformations affect the stereoselective construction of mono- and/or bicyclic oxaheterocyclic derivatives depending on a starting alkenol. The substrate scope and proposed mechanism of Pd-catalysed cyclisation reactions are also discussed. Moreover, the diastereoselective Pd-catalysed cyclisation of appropriate alkenols to tetrahydrofurans and subsequent cyclisation provided properly substituted 2,5-dioxabicyclo[2.2.1]heptane and 2,6-dioxabicyclo[3.2.1]octane, respectively. Such bicyclic ring subunits are found in many natural products including ocellenynes and aurovertines.

  17. Triphos derivatives and diphosphines as ligands in the ruthenium-catalysed alcohol amination with NH3.

    PubMed

    Nakagawa, N; Derrah, E J; Schelwies, M; Rominger, F; Trapp, O; Schaub, T

    2016-04-28

    The ruthenium-triphos and diphosphine-catalysed amination of alcohols with ammonia is reported. Various types of triphos derivatives with electron-donating functional group were synthesized and used as ligands in the Ru-catalysed alcohol amination with NH3. The triphos derivatives are effective for the formation of primary amines. On the other hand, if hemilabile diphosphines as tridentate ligands are used, mixtures of secondary-along with primary amines are obtained. It was found that even simple diphosphines can be used as ligands for the selective formation of the secondary amines. The diphosphine system allows a new entry to the Ru-catalysed formation of secondary amines.

  18. Minding Rachlin's Eliminative Materialism

    PubMed Central

    McDowell, J.J

    2012-01-01

    Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist ontology of science, but without eliminating the phenomenology of consciousness. This view implies that to be judged human, machines not only must exhibit complicated temporally structured patterns of behavior, but also must have first-person conscious experience. Although confirming machine sentience is likely to be problematic, extended contact with a machine that results in a person interacting with it as if it were conscious could reasonably lead to the conclusion that for all intents and purposes it is. PMID:22942531

  19. Minding Rachlin's eliminative materialism.

    PubMed

    McDowell, J J

    2012-01-01

    Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist ontology of science, but without eliminating the phenomenology of consciousness. This view implies that to be judged human, machines not only must exhibit complicated temporally structured patterns of behavior, but also must have first-person conscious experience. Although confirming machine sentience is likely to be problematic, extended contact with a machine that results in a person interacting with it as if it were conscious could reasonably lead to the conclusion that for all intents and purposes it is.

  20. Automobile dirty smoke eliminator

    SciTech Connect

    Chen, H.

    1981-08-04

    An automobile dirty smoke eliminator is disclosed which mainly consists of two oval tin plates externally, and upper and lower exhaust pipes , left and right support plates, a blade, a discharge chamber, a discharge pipe, etc. internally. The principle of the present invention mainly consists in making use of the effect of mixing water and gas to entirely eliminate automobile dirty smoke. When the dirty smoke (exhaust gas) of automobile enters into the lower exhaust pipe of the present invention, the blade at the outlet of said lower exhaust pipe submerged in water is impacted by the compression force derived from the engine exhaust stroke so as to generate a mixture of said water and exhaust gas and to form a whirlpool having many buddles. The effect of walls of left and right support plates promote the toxin in the said dirty smoke (Exhaust gas) automatically to deposit in the said water. The surplus toxin is discharged through the upper exhaust pipe and then mixed with the water to form a colorless, odorless nontoxious fog-like vapor which exhausts through the discharge pipe in order to achieve the best result of eliminating the said dirty smoke (Exhaust gas).

  1. Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates.

    PubMed

    Ackerman, Laura K G; Lovell, Matthew M; Weix, Daniel J

    2015-08-27

    The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis--can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross-coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this

  2. Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates

    NASA Astrophysics Data System (ADS)

    Ackerman, Laura K. G.; Lovell, Matthew M.; Weix, Daniel J.

    2015-08-01

    The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis--can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross-coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this

  3. Metallaphotoredox-catalysed sp3-sp3 cross-coupling of carboxylic acids with alkyl halides

    NASA Astrophysics Data System (ADS)

    Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.

    2016-08-01

    In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp3-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3-sp3 bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp3-sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp3-sp3 coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3-sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for

  4. Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

    PubMed Central

    Menon, Rajeev S; Biju, Akkattu T

    2016-01-01

    Summary N-Heterocyclic carbenes (NHCs) have emerged as a powerful class of organocatalysts that mediate a variety of organic transformations. The Benzoin reaction constitutes one of the earliest known carbon–carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented. PMID:27340440

  5. A Cu‐Catalysed Radical Cross‐Dehydrogenative Coupling Approach to Acridanes and Related Heterocycles

    PubMed Central

    2017-01-01

    The synthesis of acridanes and related compounds through a Cu‐catalysed radical cross‐dehydrogenative coupling of simple 2‐[2‐(arylamino)aryl]malonates is reported. This method can be further streamlined to a one‐pot protocol involving the in situ fomation of the 2‐[2‐(arylamino)aryl]malonate by α‐arylation of diethyl malonate with 2‐bromodiarylamines under Pd catalysis, followed by Cu‐catalysed cyclisation. PMID:28479872

  6. Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols

    NASA Astrophysics Data System (ADS)

    Shi, Shi-Liang; Wong, Zackary L.; Buchwald, Stephen L.

    2016-04-01

    The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.

  7. 'Impact hunters' catalyse cooperative hunting in two wild chimpanzee communities.

    PubMed

    Gilby, Ian C; Machanda, Zarin P; Mjungu, Deus C; Rosen, Jeremiah; Muller, Martin N; Pusey, Anne E; Wrangham, Richard W

    2015-12-05

    Even when hunting in groups is mutually beneficial, it is unclear how communal hunts are initiated. If it is costly to be the only hunter, individuals should be reluctant to hunt unless others already are. We used 70 years of data from three communities to examine how male chimpanzees 'solve' this apparent collective action problem. The 'impact hunter' hypothesis proposes that group hunts are sometimes catalysed by certain individuals that hunt more readily than others. In two communities (Kasekela and Kanyawara), we identified a total of five males that exhibited high hunt participation rates for their age, and whose presence at an encounter with red colobus monkeys increased group hunting probability. Critically, these impact hunters were observed to hunt first more often than expected by chance. We argue that by hunting first, these males dilute prey defences and create opportunities for previously reluctant participants. This by-product mutualism can explain variation in group hunting rates within and between social groups. Hunting rates declined after the death of impact hunter FG in Kasekela and after impact hunter MS stopped hunting frequently in Kanyawara. There were no impact hunters in the third, smaller community (Mitumba), where, unlike the others, hunting probability increased with the number of females present at an encounter with prey.

  8. Aldolase-catalysed stereoselective synthesis of fluorinated small molecules.

    PubMed

    Windle, Claire L; Berry, Alan; Nelson, Adam

    2017-04-01

    The introduction of fluorine has been widely exploited to tune the biological functions of small molecules. Indeed, around 20% of leading drugs contain at least one fluorine atom. Yet, despite profound effects of fluorination on conformation, there is only a limited toolkit of reactions that enable stereoselective synthesis of fluorinated compounds. Aldolases are useful catalysts for the stereoselective synthesis of bioactive small molecules; however, despite fluoropyruvate being a viable nucleophile for some aldolases, the potential of aldolases to control the formation of fluorine-bearing stereocentres has largely been untapped. Very recently, it has been shown that aldolase-catalysed stereoselective carboncarbon bond formation with fluoropyruvate as nucleophile enable the synthesis of many α-fluoro β-hydroxy carboxyl derivatives. Furthermore, an understanding of the structural basis for the stereocontrol observed in these reactions is beginning to emerge. Here, we review the application of aldolase catalysis in the stereocontrolled synthesis of chiral fluorinated small molecules, and highlight likely areas for future developments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Laccase-catalysed iodide oxidation in presence of methyl syringate.

    PubMed

    Kulys, Juozas; Bratkovskaja, Irina; Vidziunaite, Regina

    2005-10-05

    The kinetics of potassium triiodide (KI(3)) formation during fungal laccase action was investigated in presence of methyl syringate (MS). The recombinant forms of Polyporus pinsitus (rPpL), Myceliophthora thermophila (rMtL), Coprinus cinereus (rCcL), and Rhizoctonia solani (rRsL) laccases were used. The triiodide formation rate reached 6.1, 5.5, 6.0, and 2.1 microM/min at saturated rPpL, rCcL, rRsL, and rMtL concentration, respectively, in acetate buffer solution pH 5.5 and in presence of 10 microM of MS and 1 mM of potassium iodide. The triiodide formation rate increased if pH decreased from 6.5 to 4.5. The scheme of laccase-catalysed iodide oxidation includes stadium of MS interaction with oxidized laccase with concomitant production of MS(ox). The reaction of MS(ox) with iodide produced triiodide. The turnover number of MS was 93 and 44 at pH 5.5 for rPpL and rMtL, respectively. The scheme also contained a stadium of reversible reduction of laccase active centre with the mediator explaining the different saturation rate of triiodide production. The fitting kinetic data revealed that the reversibility of the reaction increased for laccases containing lower redox potential of copper type I.

  10. Switchable regioselectivity in amine-catalysed asymmetric cycloadditions

    NASA Astrophysics Data System (ADS)

    Zhou, Zhi; Wang, Zhou-Xiang; Zhou, Yuan-Chun; Xiao, Wei; Ouyang, Qin; Du, Wei; Chen, Ying-Chun

    2017-06-01

    Building small-molecule libraries with structural and stereogenic diversity plays an important role in drug discovery. The development of switchable intermolecular cycloaddition reactions from identical substrates in different regioselective fashions would provide an attractive protocol. However, this also represents a challenge in organic chemistry, because it is difficult to control regioselectivity to afford the products exclusively and at the same time achieve high levels of stereoselectivity. Here, we report the diversified cycloadditions of α‧-alkylidene-2-cyclopentenones catalysed by cinchona-derived primary amines. An asymmetric γ,β‧-regioselective intermolecular [6+2] cycloaddition reaction with 3-olefinic (7-aza)oxindoles is realized through the in situ generation of formal 4-aminofulvenes, while a different β,γ-regioselective [2+2] cycloaddition reaction with maleimides to access fused cyclobutanes is disclosed. In contrast, an intriguing α,γ-regioselective [4+2] cycloaddition reaction is uncovered with the same set of substrates, by employing an unprecedented dual small-molecule catalysis of amines and thiols. All of the cycloaddition reactions exhibit excellent regio- and stereoselectivity, producing a broad spectrum of chiral architectures with high structural diversity and molecular complexity.

  11. Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols.

    PubMed

    Shi, Shi-Liang; Wong, Zackary L; Buchwald, Stephen L

    2016-04-21

    The chirality, or 'handedness', of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.

  12. Protease-activated receptor-2 (PAR-2): structure-function study of receptor activation by diverse peptides related to tethered-ligand epitopes.

    PubMed

    Maryanoff, B E; Santulli, R J; McComsey, D F; Hoekstra, W J; Hoey, K; Smith, C E; Addo, M; Darrow, A L; Andrade-Gordon, P

    2001-02-15

    Protease-activated receptor-2 (PAR-2) is a tethered-ligand, G-protein-coupled receptor that is activated by proteolytic cleavage or by small peptides derived from its cleaved N-terminal sequence, such as SLIGRL-NH2. To assess specific PAR activity, we developed an immortalized murine PAR-1 (-/-) cell line transfected with either human PAR-2 or PAR-1. A "directed" library of more than 100 PAR agonist peptide analogues was synthesized and evaluated for PAR-2 and PAR-1 activity to establish an in-depth structure-function profile for specific action on PAR-2. The most potent agonist peptides (EC50 = 2-4 microM) had Lys at position 6, Ala at position 4, and pFPhe at position 2; however, these also exhibited potent PAR-1 activity (EC50 = 0.05-0.35 microM). We identified SLIARK-NH2 and SL-Cha-ARL-NH2 as relatively potent, highly selective PAR-2 agonists with EC50 values of 4 microM. Position 1 did not tolerate basic, acidic, or large hydrophobic amino acids. N-Terminal capping by acetyl eliminated PAR-2 activity, although removal of the amino group reduced potency by just 4-fold. At position 2, substitution of Leu by Cha or Phe gave equivalent PAR-2 potency, but this modification also activated PAR-1, whereas Ala, Asp, Lys, or Gln abolished PAR-2 activity; at position 3, Ile and Cha were optimal, although various amino acids were tolerated; at position 4, Ala or Cha increased PAR-2 potency 2-fold, although Cha introduced PAR-1 activity; at position 5, Arg or Lys could be replaced successfully by large hydrophobic amino acids. These results with hexapeptide C-terminal amides that mimic the native PAR-2 ligand indicate structural modes for obtaining optimal PAR-2 activity, which could be useful for the design of PAR-2 antagonists.

  13. Par Pond vegetation status 1996

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1996-12-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995, and into the early spring and late summer of 1996. Communities similar to the pre-drawdown, Par Pond aquatic plant communities continue to become re-established. Emergent beds of maidencane, lotus, waterlily, watershield, and Pontederia are extensive and well developed. Measures of percent cover, width of beds, and estimates of area of coverage with satellite data indicate regrowth within two years of from 40 to 60% of levels prior to the draw down. Cattail occurrence continued to increase during the summer of 1996, especially in the former warm arm of Par Pond, but large beds common to Par Pond prior to the draw down still have not formed. Lotus has invaded and occupies many of the areas formerly dominated by cattail beds. To track the continued development of macrophytes in Par Pond, future surveys through the summer and early fall of 1997, along with the evaluation of satellite data to map the extent of the macrophyte beds of Par Pond, are planned.

  14. Phased array ghost elimination

    PubMed Central

    Kellman, Peter; McVeigh, Elliot R.

    2007-01-01

    Parallel imaging may be applied to cancel ghosts caused by a variety of distortion mechanisms, including distortions such as off-resonance or local flow, which are space variant. Phased array combining coefficients may be calculated that null ghost artifacts at known locations based on a constrained optimization, which optimizes SNR subject to the nulling constraint. The resultant phased array ghost elimination (PAGE) technique is similar to the method known as sensitivity encoding (SENSE) used for accelerated imaging; however, in this formulation is applied to full field-of-view (FOV) images. The phased array method for ghost elimination may result in greater flexibility in designing acquisition strategies. For example, in multi-shot EPI applications ghosts are typically mitigated by the use of an interleaved phase encode acquisition order. An alternative strategy is to use a sequential, non-interleaved phase encode order and cancel the resultant ghosts using PAGE parallel imaging. Cancellation of ghosts by means of phased array processing makes sequential, non-interleaved phase encode acquisition order practical, and permits a reduction in repetition time, TR, by eliminating the need for echo-shifting. Sequential, non-interleaved phase encode order has benefits of reduced distortion due to off-resonance, in-plane flow and EPI delay misalignment. Furthermore, the use of EPI with PAGE has inherent fat-water separation and has been used to provide off-resonance correction using a technique referred to as lipid elimination with an echo-shifting N/2-ghost acquisition (LEENA), and may further generalized using the multi-point Dixon method. Other applications of PAGE include cancelling ghosts which arise due to amplitude or phase variation during the approach to steady state. Parallel imaging requires estimates of the complex coil sensitivities. In vivo estimates may be derived by temporally varying the phase encode ordering to obtain a full k-space dataset in a scheme

  15. Cyclic carbonate synthesis catalysed by bimetallic aluminium-salen complexes.

    PubMed

    Clegg, William; Harrington, Ross W; North, Michael; Pasquale, Riccardo

    2010-06-18

    The development of bimetallic aluminium-salen complexes [{Al(salen)}(2)O] as catalysts for the synthesis of cyclic carbonates (including the commercially important ethylene and propylene carbonates) from a wide range of terminal epoxides in the presence of tetrabutylammonium bromide as a cocatalyst is reported. The bimetallic structure of one complex was confirmed by X-ray crystallography. The bimetallic complexes displayed exceptionally high catalytic activity and in the presence of tetrabutylammonium bromide could catalyse cyclic carbonate synthesis at atmospheric pressure and room temperature. Catalyst-reuse experiments demonstrated that one bimetallic complex was stable for over 60 reactions, though the tetrabutylammonium bromide decomposed in situ by a retro-Menschutkin reaction to form tributylamine and had to be regularly replaced. The mild reaction conditions allowed a full analysis of the reaction kinetics to be carried out and this showed that the reaction was first order in aluminium complex concentration, first order in epoxide concentration, first order in carbon dioxide concentration (except when used in excess) and unexpectedly second order in tetrabutylammonium bromide concentration. Further kinetic experiments demonstrated that the tributylamine formed in situ was involved in the catalysis and that addition of butyl bromide to reconvert the tributylamine into tetrabutylammonium bromide resulted in inhibition of the reaction. The reaction kinetics also indicated that no kinetic resolution of racemic epoxides was possible with this class of catalysts, even when the catalyst was derived from a chiral salen ligand. However, it was shown that if enantiomerically pure styrene oxide was used as substrate, then enantiomerically pure styrene carbonate was formed. On the basis of the kinetic and other experimental data, a catalytic cycle that explains why the bimetallic complexes display such high catalytic activity has been developed.

  16. Horseradish peroxidase-catalysed in situ-forming hydrogels for tissue-engineering applications.

    PubMed

    Bae, Jin Woo; Choi, Jong Hoon; Lee, Yunki; Park, Ki Dong

    2015-11-01

    In situ-forming hydrogels are an attractive class of implantable biomaterials that are used for biomedical applications. These injectable hydrogels are versatile and provide a convenient platform for delivering cells and drugs via minimally invasive surgery. Although several crosslinking methods for preparing in situ forming hydrogels have been developed over the past two decades, most hydrogels are not sufficiently versatile for use in a wide variety of tissue-engineering applications. In recent years, enzyme-catalysed crosslinking approaches have been emerged as a new approach for developing in situ-forming hydrogels. In particular, the horseradish peroxidase (HRP)-catalysed crosslinking approach has received increasing interest, due to its highly improved and tunable capacity to obtain hydrogels with desirable properties. The HRP-catalysed crosslinking reaction immediately occurs upon mixing phenol-rich polymers with HRP and hydrogen peroxide (H2O2) in aqueous media. Based on this unique gel-forming feature, recent studies have shown that various properties of formed hydrogels, such as gelation time, stiffness and degradation rate, can be easily manipulated by varying the concentrations of HRP and H2O2. In this review, we outline the versatile properties of HRP-catalysed in situ-forming hydrogels, with a brief introduction to the crosslinking mechanisms involved. In addition, the recent biomedical applications of HRP-catalysed in situ-forming hydrogels for tissue regeneration are described.

  17. Exploration of locomotion in the ParA/ParB system

    NASA Astrophysics Data System (ADS)

    Jindal, Lavisha; Emberly, Eldon

    2015-03-01

    In many bacteria the ParA/ParB system is responsible for actively segregating DNA during replication. ParB precessively moves by hydrolyzing DNA bound ParA-ATP forming a depleted ParA region in its wake. Recent in-vitro experiments have shown that a ParB covered bead can traverse a ParA bound DNA substrate. It has been suggested that the formation of a gradient in ParA leads to diffusion-ratchet like motion of the ParB bead but its origin and potential consequences requires investigation. We have developed a deterministic model for the in-vitro ParA/ParB system and show that any amount of spatial noise in ParA can lead to the spontaneous formation of its gradient. The velocity of the bead is independent of this noise but depends on the scale over which ParA exerts a force on the bead and the scale over which ParB hydrolyzes ParA from the substrate. There is a particular ratio of these scales at which the velocity is a maximum. We also explore the effects of cooperative vs independent rebinding of ParA to the substrate. Our model shows how the driving force for ParB originates and highlights necessary conditions for directed motion in the in-vitro system that may provide insight into the in-vivo behaviour of the ParA/ParB system.

  18. Oxygen-dependent conjugation of dopa with cysteine catalysed by iron-EDTA complex.

    PubMed

    Ito, S; Fujita, K

    1984-07-15

    Cytotoxicity of catechols has been ascribed to their binding with proteins through sulfhydryl groups. The possibility that iron-protein complexes catalyse this type of covalent binding was studied with a model system. Reaction of dopa and cysteine catalysed by iron-EDTA complexes at physiological pH resulted in the formation of not only cystine but also conjugation products, cysteinyldopas among which 5-S-cysteinyldopa was the major product. The reaction required iron ion, EDTA, and molecular oxygen. Fe3+ and Fe2+ were equally effective, while other transition metal ions examined had no effect on the formation of cysteinyldopas. Catalase, superoxide dismutase, and scavengers of hydroxyl radical inhibited to some extents the formation of 5-S-cysteinyldopa. Addition of both catalase and superoxide dismutase resulted in approximately 60% inhibition. These results indicated that the iron-EDTA-catalysed conjugation of dopa with cysteine was mainly mediated by hydroxyl radical.

  19. Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons

    PubMed Central

    Wu, Xuesong; Yang, Ke; Zhao, Yan; Sun, Hao; Li, Guigen; Ge, Haibo

    2015-01-01

    Cobalt-catalysed sp2 C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. In comparison, much less efforts have been devoted to the sp3 carbons. Here we report the cobalt-catalysed site-selective dehydrogenative cyclization of aliphatic amides via a C–H bond functionalization process on unactivated sp3 carbons with the assistance of a bidentate directing group. This method provides a straightforward synthesis of monocyclic and spiro β- or γ-lactams with good to excellent stereoselectivity and functional group tolerance. In addition, a new procedure has been developed to selectively remove the directing group, which enables the synthesis of free β- or γ-lactam compounds. Furthermore, the first cobalt-catalysed intermolecular dehydrogenative amination of unactivated sp3 carbons is also realized. PMID:25753366

  20. Ferric sulphate catalysed esterification of free fatty acids in waste cooking oil.

    PubMed

    Gan, Suyin; Ng, Hoon Kiat; Ooi, Chun Weng; Motala, Nafisa Osman; Ismail, Mohd Anas Farhan

    2010-10-01

    In this work, the esterification of free fatty acids (FFA) in waste cooking oil catalysed by ferric sulphate was studied as a pre-treatment step for biodiesel production. The effects of reaction time, methanol to oil ratio, catalyst concentration and temperature on the conversion of FFA were investigated on a laboratory scale. The results showed that the conversion of FFA reached equilibrium after an hour, and was positively dependent on the methanol to oil molar ratio and temperature. An optimum catalyst concentration of 2 wt.% gave maximum FFA conversion of 59.2%. For catalyst loadings of 2 wt.% and below, this catalysed esterification was proposed to follow a pseudo-homogeneous pathway akin to mineral acid-catalysed esterification, driven by the H(+) ions produced through the hydrolysis of metal complex [Fe(H(2)O)(6)](3+) (aq).

  1. USA supports measles elimination.

    PubMed

    1996-06-01

    The United States, through the United States Agency for International Development (USAID), has approved an $8 million grant in support of the Pan American Health Organization (PAHO) goal to eliminate measles in the Americas by the year 2000. From 1996 to 2001, the grant will complement regional efforts to stop the disease. Mrs. Hillary Clinton had pledged the support on World Health Day 1995. Although record low levels of measles cases were reported in 1995 for the region, the virus could be imported from elsewhere in the world. A major obstacle is the accumulation of susceptible preschool-aged children. As the proportion of susceptibles expands, the risk of a measles outbreak increases, if the virus is reintroduced. To prevent this, follow-up campaigns are being conducted throughout the region, focusing on all children aged 1-4 years, regardless of previous vaccination or disease history. PAHO recommends follow-up whenever the number of susceptible preschool children approaches the size of an average birth cohort. The interval between these campaigns and the specific age group targeted will depend on the vaccination coverage obtained through routine services since the last campaign. Follow-up campaigns were conducted in Cuba in 1993; in Belize, Brazil, Columbia, and Jamaica in 1995; and in Chile and the countries of Central America during April 1996. 19 million children were reached. Follow-up campaigns are planned for the remaining countries of the English-speaking Caribbean later in 1996. USAID played a key role in the successful completion of the 1994 poliomyelitis eradication initiative; the agency contributed approximately 60% of the external costs associated with the hemispheric campaign.

  2. Eliminating Rabies in Estonia

    PubMed Central

    Cliquet, Florence; Robardet, Emmanuelle; Must, Kylli; Laine, Marjana; Peik, Katrin; Picard-Meyer, Evelyne; Guiot, Anne-Laure; Niin, Enel

    2012-01-01

    The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV) campaigns were conducted twice a year using Rabigen® SAG2 baits, beginning in autumn 2005 in North Estonia. They were then extended to the whole territory from spring 2006. Following the vaccination campaigns, the incidence of rabies cases dramatically decreased, with 266 cases in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies cases have been detected in Estonia other than three cases reported in summer 2009 and one case in January 2011, all in areas close to the South-Eastern border with Russia. The bait uptake was satisfactory, with tetracycline positivity rates ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs. Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from 38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that of the other two Baltic States, Latvia and Lithuania. Despite regular OV campaigns conducted throughout their territory since 2006, and an improvement in the epidemiological situation, rabies has still not been eradicated in these countries. An analysis of the number of baits distributed and the funding allocated by the European Commission showed that the strategy for rabies control is more cost-effective in Estonia than in Latvia and Lithuania. PMID:22393461

  3. Eliminating rabies in Estonia.

    PubMed

    Cliquet, Florence; Robardet, Emmanuelle; Must, Kylli; Laine, Marjana; Peik, Katrin; Picard-Meyer, Evelyne; Guiot, Anne-Laure; Niin, Enel

    2012-01-01

    The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV) campaigns were conducted twice a year using Rabigen® SAG2 baits, beginning in autumn 2005 in North Estonia. They were then extended to the whole territory from spring 2006. Following the vaccination campaigns, the incidence of rabies cases dramatically decreased, with 266 cases in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies cases have been detected in Estonia other than three cases reported in summer 2009 and one case in January 2011, all in areas close to the South-Eastern border with Russia. The bait uptake was satisfactory, with tetracycline positivity rates ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs. Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from 38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that of the other two Baltic States, Latvia and Lithuania. Despite regular OV campaigns conducted throughout their territory since 2006, and an improvement in the epidemiological situation, rabies has still not been eradicated in these countries. An analysis of the number of baits distributed and the funding allocated by the European Commission showed that the strategy for rabies control is more cost-effective in Estonia than in Latvia and Lithuania.

  4. Synthesis of functionalised diarylmethanes via a cobalt-catalysed cross-coupling of arylzinc species with benzyl chlorides.

    PubMed

    Amatore, Muriel; Gosmini, Corinne

    2008-10-28

    A new cobalt-catalysed reductive coupling of aryl halides with benzyl chlorides is reported; a variety of diarylmethanes can be prepared in good to excellent yields under mild reaction conditions using CoBr(2) as catalyst and Zn dust; this new cobalt-catalysed coupling represents a practical and interesting alternative to previously known methods for the synthesis diarylmethanes.

  5. Rhenium-catalysed dehydrogenative borylation of primary and secondary C(sp3)-H bonds adjacent to a nitrogen atom.

    PubMed

    Murai, Masahito; Omura, Tetsuya; Kuninobu, Yoichiro; Takai, Kazuhiko

    2015-03-18

    Rhenium-catalysed C(sp(3))-H bond borylation in the absence of any oxidant, hydrogen acceptor, or external ligand, with the generation of H2 as the sole byproduct is described. The transformation, which represents a rare example of rhenium-catalysed C(sp(3))-H bond functionalisation, features high atom efficiency and simple reaction conditions.

  6. Vesicoureteral reflux and elimination disorders.

    PubMed

    Alova, I; Lottmann, H B

    2008-03-01

    Two kinds of elimination disorders can be associated with Vesico Ureteral Reflux (VUR): pure bladder elimination disorders or combination of bladder and bowel elimination disorders. An elimination disorder is always a factor which worsens the prognosis of VUR, as it increases the risk of infectious complications and thus presents a threat for the upper urinary tract. Regarding pure bladder elimination disorders, a chronic urine residue is observed in four clinical situations: the syndrome megacystis-mega ureter; the mega bladder without mega ureter, but with VUR; high grade massive VUR without a mega bladder; organic obstructions of the urethra (such as posterior urethral valves.). VUR associated with urine and fecal elimination disorders cover functional pelvi perineal dyscoordination, bladder sphincter dysynergia, disturbances of visceral motricity and anal sphincter function. The most characteristic type is represented by the neuropathic detrusor-sphincter dysfunction; also enter in this category neurogenic non-neurogenic bladders (Hinman's syndrome); However the vast majority of urine and fecal elimination disorders is represented by non neuropathic perineal dyscoordination associating at various degrees: voiding postponement, lack of sphincter relaxation during micturation, interrupted voiding, and constipation. The diagnosis of elimination disorders associated with VUR is based on non invasive investigations such as anamnesis and drinking/voiding chart in children and adolescents, and "four observation test" in infants. Ultrasound and uroflowmetry are also useful tools. Invasive investigations include mainly voiding cystourethrography and urodynamics, ideally combined in video urodynamic studies. The management of urinary and intestinal elimination disorders is based on the prevention of infections, the suppression of the post voiding residual urine and the treatment of an associated constipation. If surgical treatment of VUR is needed, it must be associated

  7. Par Pond Fish, Water, and Sediment Chemistry

    SciTech Connect

    Paller, M.H.; Wike, L.D.

    1996-06-01

    The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond.

  8. Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage

    PubMed Central

    Kang, Ho Chul; Lee, Yun-Il; Shin, Joo-Ho; Andrabi, Shaida A.; Chi, Zhikai; Gagné, Jean-Philippe; Lee, Yunjong; Ko, Han Seok; Lee, Byoung Dae; Poirier, Guy G.; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Ubiquitin mediated protein degradation is crucial for regulation of cell signaling and protein quality control. Poly(ADP-ribose) (PAR) is a cell-signaling molecule that mediates changes in protein function through binding at PAR binding sites. Here we characterize the PAR binding protein, Iduna, and show that it is a PAR-dependent ubiquitin E3 ligase. Iduna’s E3 ligase activity requires PAR binding because point mutations at Y156A and R157A eliminate Iduna’s PAR binding and Iduna’s E3 ligase activity. Iduna’s E3 ligase activity also requires an intact really interesting new gene (RING) domain because Iduna possessing point mutations at either H54A or C60A is devoid of ubiquitination activity. Tandem affinity purification reveals that Iduna binds to a number of proteins that are either PARsylated or bind PAR including PAR polymerase-1, 2 (PARP1, 2), nucleolin, DNA ligase III, KU70, KU86, XRCC1, and histones. PAR binding to Iduna activates its E3 ligase function, and PAR binding is required for Iduna ubiquitination of PARP1, XRCC1, DNA ligase III, and KU70. Iduna’s PAR-dependent ubiquitination of PARP1 targets it for proteasomal degradation. Via PAR binding and ubiquitin E3 ligase activity, Iduna protects against cell death induced by the DNA damaging agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest and promotes cell survival after γ-irradiation. Moreover, Iduna facilitates DNA repair by reducing apurinic/apyrimidinic (AP) sites after MNNG exposure and facilitates DNA repair following γ-irradiation as assessed by the comet assay. These results define Iduna as a PAR-dependent E3 ligase that regulates cell survival and DNA repair. PMID:21825151

  9. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

    NASA Astrophysics Data System (ADS)

    Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

    The segregation of DNA prior to cell division is essential for faithful genetic inheritance. In many bacteria, segregation of the low-copy-number plasmids involves an active partition system composed of ParA ATPase and its stimulator protein ParB. Recent experiments suggest that ParA/ParB system motility is driven by a diffusion-ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. We develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB bound cargo. Paradoxically, the resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work sheds light on a new emergent phenomenon in which non-motor proteins work collectively via mechanochemical coupling to propel cargos -- an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

  10. Efficient preparation of carbamates by Rh-catalysed oxidative carbonylation: unveiling the role of the oxidant.

    PubMed

    Iturmendi, Amaia; Iglesias, Manuel; Munárriz, Julen; Polo, Victor; Pérez-Torrente, Jesús J; Oro, Luis A

    2016-12-22

    The synthesis of a wide variety of carbamates from amines, alcohols and carbon monoxide has been achieved by means of a Rh-catalysed oxidative carbonylation reaction that uses Oxone as a stoichiometric oxidant. In-depth studies on the reaction mechanism shed light on the intimate role of Oxone in the catalytic cycle.

  11. Structure sensitivity in the nonscalable regime explored via catalysed ethylene hydrogenation on supported platinum nanoclusters

    SciTech Connect

    Crampton, Andrew S.; Rötzer, Marian D.; Ridge, Claron J.; Schweinberger, Florian F.; Heiz, Ueli; Yoon, Bokwon; Landman, Uzi

    2016-01-28

    The sensitivity, or insensitivity, of catalysed reactions to catalyst structure is a commonly employed fundamental concept. Here we report on the nature of nano-catalysed ethylene hydrogenation, investigated through experiments on size-selected Ptn (n=8-15) clusters soft-landed on magnesia and first-principles simulations, yielding benchmark information about the validity of structure sensitivity/insensitivity at the bottom of the catalyst size range. Both ethylene-hydrogenation-to-ethane and the parallel hydrogenation–dehydrogenation ethylidyne-producing route are considered, uncovering that at the <1 nm size-scale the reaction exhibits characteristics consistent with structure sensitivity, in contrast to structure insensitivity found for larger particles. The onset of catalysed hydrogenation occurs for Ptn (n≥10) clusters at T>150 K, with maximum room temperature reactivity observed for Pt13. Structure insensitivity, inherent for specific cluster sizes, is induced in the more active Pt13 by a temperature increase up to 400 K leading to ethylidyne formation. As a result, control of sub-nanometre particle size may be used for tuning catalysed hydrogenation activity and selectivity.

  12. Structure sensitivity in the nonscalable regime explored via catalysed ethylene hydrogenation on supported platinum nanoclusters

    DOE PAGES

    Crampton, Andrew S.; Rötzer, Marian D.; Ridge, Claron J.; ...

    2016-01-28

    The sensitivity, or insensitivity, of catalysed reactions to catalyst structure is a commonly employed fundamental concept. Here we report on the nature of nano-catalysed ethylene hydrogenation, investigated through experiments on size-selected Ptn (n=8-15) clusters soft-landed on magnesia and first-principles simulations, yielding benchmark information about the validity of structure sensitivity/insensitivity at the bottom of the catalyst size range. Both ethylene-hydrogenation-to-ethane and the parallel hydrogenation–dehydrogenation ethylidyne-producing route are considered, uncovering that at the <1 nm size-scale the reaction exhibits characteristics consistent with structure sensitivity, in contrast to structure insensitivity found for larger particles. The onset of catalysed hydrogenation occurs for Ptn (n≥10)more » clusters at T>150 K, with maximum room temperature reactivity observed for Pt13. Structure insensitivity, inherent for specific cluster sizes, is induced in the more active Pt13 by a temperature increase up to 400 K leading to ethylidyne formation. As a result, control of sub-nanometre particle size may be used for tuning catalysed hydrogenation activity and selectivity.« less

  13. Kinetic resolution of alkyne-substituted quaternary oxindoles via copper catalysed azide-alkyne cycloadditions.

    PubMed

    Brittain, William D G; Buckley, Benjamin R; Fossey, John S

    2015-12-18

    The synthesis and kinetic resolution of quaternary oxindoles through copper catalysed azide-alkyne cycloadditions is presented. Selectivity factors (s) up to 22.1 ± 0.5 are reported. Enantioenriched alkynes and triazoles were obtained in ≥80% enantiomeric excess (e.e.).

  14. Structure sensitivity in the nonscalable regime explored via catalysed ethylene hydrogenation on supported platinum nanoclusters

    PubMed Central

    Crampton, Andrew S.; Rötzer, Marian D.; Ridge, Claron J.; Schweinberger, Florian F.; Heiz, Ueli; Yoon, Bokwon; Landman, Uzi

    2016-01-01

    The sensitivity, or insensitivity, of catalysed reactions to catalyst structure is a commonly employed fundamental concept. Here we report on the nature of nano-catalysed ethylene hydrogenation, investigated through experiments on size-selected Ptn (n=8–15) clusters soft-landed on magnesia and first-principles simulations, yielding benchmark information about the validity of structure sensitivity/insensitivity at the bottom of the catalyst size range. Both ethylene-hydrogenation-to-ethane and the parallel hydrogenation–dehydrogenation ethylidyne-producing route are considered, uncovering that at the <1 nm size-scale the reaction exhibits characteristics consistent with structure sensitivity, in contrast to structure insensitivity found for larger particles. The onset of catalysed hydrogenation occurs for Ptn (n≥10) clusters at T>150 K, with maximum room temperature reactivity observed for Pt13. Structure insensitivity, inherent for specific cluster sizes, is induced in the more active Pt13 by a temperature increase up to 400 K leading to ethylidyne formation. Control of sub-nanometre particle size may be used for tuning catalysed hydrogenation activity and selectivity. PMID:26817713

  15. Direct, efficient NHC-catalysed aldehyde oxidative amidation: in situ formed benzils as unconventional acylating agents.

    PubMed

    Kumar, Vikas; Connon, Stephen J

    2017-09-01

    A new N-heterocyclic carbene-catalysed oxidative amidation of aldehydes has been developed which converts the aldehyde to a benzil acylating agent in situ. The process uses an air-recyclable oxidant and a nucleophilic co-catalyst and does not require the use of a large excess of either one coupling partner or catalyst.

  16. Ancillary ligand-free copper catalysed hydrohydrazination of terminal alkynes with NH2NH2.

    PubMed

    Peltier, Jesse L; Jazzar, Rodolphe; Melaimi, Mohand; Bertrand, Guy

    2016-02-14

    An efficient and selective Cu-catalysed hydrohydrazination of terminal alkynes with parent hydrazine is reported. The methodology tolerates a broad range of functional groups, allows for the synthesis of symmetrical and unsymmetrical azines, and can be extended to hydrazine derivatives and amines.

  17. MINDO Forces Study of the Uncatalysed and Acid-Catalysed Friedel-Crafts Reactions Between CH3F and CH4

    NASA Astrophysics Data System (ADS)

    Abed, Amel G.; Khalil, Salim M.

    1999-04-01

    MINDO-forces calculations have been performed on the uncatalysed and acid-catalysed Friedel-Crafts reaction between CH3F and CH4 . It has been found that the catalysed reaction is exothermic, spontaneous and has a smaller potential-energy barrier than the uncatalysed reaction. The mechanisms for uncatalysed and catalysed reactions are discussed.

  18. Parallel Climate Analysis Toolkit (ParCAT)

    SciTech Connect

    Smith, Brian Edward

    2013-06-30

    The parallel analysis toolkit (ParCAT) provides parallel statistical processing of large climate model simulation datasets. ParCAT provides parallel point-wise average calculations, frequency distributions, sum/differences of two datasets, and difference-of-average and average-of-difference for two datasets for arbitrary subsets of simulation time. ParCAT is a command-line utility that can be easily integrated in scripts or embedded in other application. ParCAT supports CMIP5 post-processed datasets as well as non-CMIP5 post-processed datasets. ParCAT reads and writes standard netCDF files.

  19. Overproduction and localization of Mycobacterium tuberculosis ParA and ParB proteins

    PubMed Central

    Maloney, Erin; Madiraju, Murty; Rajagopalan, Malini

    2011-01-01

    SUMMARY The ParA and ParB family proteins are required for accurate partitioning of replicated chromosomes. The Mycobacterium tuberculosis genome contains parB, parA and two parA homologs, Rv1708 and Rv3213c. It is unknown if parA and its homologs are functionally related. To understand the roles of ParA and ParB proteins in M. tuberculosis cell cycle, we have evaluated the consequences of their overproduction and visualized their localization patterns in M. smegmatis. We show that cells overproducing of ParA, Rv1708 and Rv3213c and ParB are filamentous and multinucleoidal indicating defects in cell cycle progression. Visualization of green-fluorescent protein fusions of ParA and its homologues showed similar localization patterns with foci at poles, quarter-cell, midcell positions and spiral-like structures indicating that they are functionally related. On the other hand, the ParBGFP fusion protein localized only to the cell poles. The cyan and yellow fluorescent fusion proteins of ParA and ParB, respectively, colocalized at the cell poles indicating that these proteins interact and possibly associate with the chromosomal origin of replication. Collectively our results suggest that the M. tuberculosis Par proteins play important roles in cell cycle progression. PMID:20006309

  20. suPAR: The Molecular Crystal Ball

    PubMed Central

    Thunø, Maria; Macho, Betina; Eugen-Olsen, Jesper

    2009-01-01

    soluble urokinase Plasminogen Activator Receptor (suPAR) levels reflect inflammation and elevated suPAR levels are found in several infectious diseases and cancer. suPAR exists in three forms; suPARI-III, suPARII-III and suPARI which show different properties due to structural differences. Studies suggest that full-length suPAR is a regulator of uPAR/uPA by acting as uPA-scavenger, whereas the cleaved suPARII-III act as a chemotactic agent promoting the immune response via the SRSRY sequence in the linker-region. This review focus on the various suPAR fragments and their involvement in inflammation and pathogenic processes. We focus on the molecular mechanisms of the suPAR fragments and the link to the inflammatory process, as this could lead to medical applications in infectious and pathological conditions. PMID:19893210

  1. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

    PubMed Central

    Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

    2015-01-01

    The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA–nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos—an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria. PMID:26647183

  2. [Ambroise Paré, landlord].

    PubMed

    Pion-Graff, Joëlle; Bonnichon, Philippe

    2010-01-01

    Paré is well-known through many papers. His incomes allowed him to have a middle-class Parisian living. It is impossible to have an accurate knowledge of his fortune before his death but we have a good idea of his landed property. In fact as a Parishioner of Saint-Andre-des-Arts Church he probably was a landlord only in Paris and its vicinity with a building (rue de l'Hirondelle), two houses (rue Garancière), Meudon, Cormeille-en-Parisis and La-Ville-Du-Bois which the authors describe the present state of.

  3. Measles - The epidemiology of elimination.

    PubMed

    Durrheim, David N; Crowcroft, Natasha S; Strebel, Peter M

    2014-12-05

    Tremendous progress has been made globally to reduce the contribution of measles to the burden of childhood deaths and measles cases have dramatically decreased with increased two dose measles-containing vaccine coverage. As a result the Global Vaccine Action Plan, endorsed by the World Health Assembly, has targeted measles elimination in at least five of the six World Health Organisation Regions by 2020. This is an ambitious goal, since measles control requires the highest immunisation coverage of any vaccine preventable disease, which means that the health system must be able to reach every community. Further, while measles remains endemic in any country, importations will result in local transmission and outbreaks in countries and Regions that have interrupted local endemic measles circulation. One of the lines of evidence that countries and Regions must address to confirm measles elimination is a detailed description of measles epidemiology over an extended period. This information is incredibly valuable as predictable epidemiological patterns emerge as measles elimination is approached and achieved. These critical features, including the source, size and duration of outbreaks, the seasonality and age-distribution of cases, genotyping pointers and effective reproduction rate estimates, are discussed with illustrative examples from the Region of the Americas, which eliminated measles in 2002, and the Western Pacific Region, which has established a Regional Verification Commission to review progress towards elimination in all member countries.

  4. Microcystin elimination during sediment contact.

    PubMed

    Grützmacher, Gesche; Wessel, Gabriele; Klitzke, Sondra; Chorus, Ingrid

    2010-01-15

    Microcystins (MCYSTs) are a group of structurally similar toxic peptides produced by cyanobacteria ("blue-green algae") which occur frequently in surface waters worldwide. Reliable elimination is necessary when using these waters as drinking water sources. Bank filtration and artificial groundwater recharge utilize adsorption and degradation processes in the subsurface, commonly through sand and gravel aquifers, for the elimination of a wide range of substances during drinking water (pre-) treatment. To obtain parameters for estimating whether MCYST breakthrough is likely in field settings, we tested MCYST elimination in laboratory experiments (batch experiments, column experiments) under a range of conditions. Adsorption coefficients (k(d)-values) obtained from batch studies ranged from 0.2 mL/g for filter sand to 11.6 mL/g for fine grained aquifer materials with 2% fine grains (<63 microm) and 0.8% organic matter. First order degradation rates in column studies reached 1.87 d(-1) under aerobic conditions and showed high variations under anoxic conditions (<0.01-1.35 d(-1)). These results show that, next to sediment texture, redox conditions play an important role for MCYST elimination during sediment passage. Biodegradation was identified as the dominating process for MCYST elimination in sandy aquifer material.

  5. Cytochrome c catalyses the formation of pentyl radical and octanoic acid radical from linoleic acid hydroperoxide.

    PubMed Central

    Iwahashi, Hideo; Nishizaki, Koji; Takagi, Ichiro

    2002-01-01

    A reaction of 13-hydroperoxide octadecadienoic acid (13-HPODE) with cytochrome c was analysed using ESR, HPLC-ESR and HPLC-ESR-MS by the combined use of the spin-trapping technique. The ESR, HPLC-ESR and HPLC-ESR-MS analyses showed that cytochrome c catalyses formation of pentyl and octanoic acid radicals from 13-HPODE. On the other hand, only the alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone/octanoic acid radical adduct was detected in the elution profile of HPLC-ESR for a mixture of 13-HPODE with haematin, indicating that haematin catalyses the formation of octanoic acid radical. In addition, the reaction of 13-HPODE with cytochrome c was inhibited by chlorogenic acid, caffeic acid and ferulic acid via two possible mechanisms, i.e. reducing cytochrome c (chlorogenic acid and caffeic acid) and scavenging the radical intermediates (chlorogenic acid, caffeic acid and ferulic acid). PMID:11742529

  6. Screening test for rapid food safety evaluation by menadione-catalysed chemiluminescent assay.

    PubMed

    Yamashoji, Shiro; Yoshikawa, Naoko; Kirihara, Masayuki; Tsuneyoshi, Toshihiro

    2013-06-15

    The chemiluminescent assay of menadione-catalysed H2O2 production by living mammalian cells was proposed to be useful for rapid food safety evaluation. The tested foods were extracted with water, ethanol and dimethylsulfoxide, and each extract was incubated with NIH3T3, Neuro-2a and HepG2 cells for 4h. Menadione-catalysed H2O2 production by living mammalian cells exposed to each extract was determined by the chemiluminescent assay requiring only 10 min, and the viability of the cells was estimated as percentage based on H2O2 production by intact cells. In this study the cytotoxicity of food was rated in order of inhibitory effect on H2O2 production by intact cells. The well known natural toxins such as Fusarium mycotoxin, tomato toxin tomatine, potato toxin solanine and marine toxins terodotoxin and brevetoxin could be detected by the above chemiluminescent assay.

  7. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols.

    PubMed

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  8. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols

    NASA Astrophysics Data System (ADS)

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W.; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J.

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  9. Alkene Cleavage Catalysed by Heme and Nonheme Enzymes: Reaction Mechanisms and Biocatalytic Applications

    PubMed Central

    Mutti, Francesco G.

    2012-01-01

    The oxidative cleavage of alkenes is classically performed by chemical methods, although they display several drawbacks. Ozonolysis requires harsh conditions (−78°C, for a safe process) and reducing reagents in a molar amount, whereas the use of poisonous heavy metals such as Cr, Os, or Ru as catalysts is additionally plagued by low yield and selectivity. Conversely, heme and nonheme enzymes can catalyse the oxidative alkene cleavage at ambient temperature and atmospheric pressure in an aqueous buffer, showing excellent chemo- and regioselectivities in certain cases. This paper focuses on the alkene cleavage catalysed by iron cofactor-dependent enzymes encompassing the reaction mechanisms (in case where it is known) and the application of these enzymes in biocatalysis. PMID:22811656

  10. Borane catalysed ring opening and closing cascades of furans leading to silicon functionalized synthetic intermediates

    PubMed Central

    Hazra, Chinmoy K.; Gandhamsetty, Narasimhulu; Park, Sehoon; Chang, Sukbok

    2016-01-01

    The conversion of renewable biomass resources to synthetically valuable chemicals is highly desirable, but remains a formidable challenge in regards to the substrate scope and reaction conditions. Here we present the development of tris(pentafluorophenyl)borane–catalysed conversion of furans via ring-opening and closing cascade processes to afford silicon-functionalized synthetic chemicals under transition metal-free conditions. The furan ring-opening with hydrosilanes is highly efficient (TON up to 2,000) and atom-economical without forming any byproduct to give rise to α-silyloxy-(Z)-alkenyl silanes. Additional equivalents of silane smoothly induce a subsequent B(C6F5)3-catalysed cyclization of initially formed olefinic silane compounds to produce anti-(2-alkyl)cyclopropyl silanes, another versatile synthon being potentially applicable in the synthesis of natural products and pharmacophores. PMID:27892459

  11. Sulphuric acid-catalysed formation of hemiacetal from glyoxal and ethanol

    NASA Astrophysics Data System (ADS)

    Sarrami, Farzaneh; Yu, Li-Juan; Wan, Wenchao; Karton, Amir

    2017-05-01

    We examine the reaction of ethanol with glyoxal to form hemiacetal by means of the high-level G4(MP2) procedure. In this reaction, an intermolecular proton transfer is coupled with the formation of a covalent Csbnd O bond between the two molecules. We find a novel catalytic reaction mechanism in which an H2SO4 catalyst reduces the barrier height from ∆H‡298 = 140.2 to 16.3 kJ mol-1. It is well established that H2SO4 can effectively catalyse intramolecular proton transfers. This letter shows that H2SO4 can catalyse an intermolecular proton transfer that is coupled with a covalent bond formation.

  12. Iron-catalysed cross-coupling of organolithium compounds with organic halides

    PubMed Central

    Jia, Zhenhua; Liu, Qiang; Peng, Xiao-Shui; Wong, Henry N. C.

    2016-01-01

    In past decades, catalytic cross-coupling reactions between organic halides and organometallic reagents to construct carbon–carbon bond have achieved a tremendous progress. However, organolithium reagents have rarely been used in cross-coupling reactions, due mainly to their high reactivity. Another limitation of this transformation using organolithium reagents is how to control reactivity with excellent selectivity. Although palladium catalysis has been applied in this field recently, the development of an approach to replace catalytic systems of noble metals with nonprecious metals is currently in high demand. Herein, we report an efficient synthetic protocol involving iron-catalysed cross-coupling reactions employing organolithium compounds as key coupling partners to unite aryl, alkyl and benzyl fragments and also disclose an efficient iron-catalysed release-capture ethylene coupling with isopropyllithium. PMID:26847602

  13. Enzyme catalysed Pictet-Spengler formation of chiral 1,1'-disubstituted- and spiro-tetrahydroisoquinolines

    NASA Astrophysics Data System (ADS)

    Lichman, Benjamin R.; Zhao, Jianxiong; Hailes, Helen C.; Ward, John M.

    2017-04-01

    The Pictet-Spengler reaction (PSR) involves the condensation and ring closure between a β-arylethylamine and a carbonyl compound. The combination of dopamine and ketones in a PSR leads to the formation of 1,1'-disubstituted tetrahydroisoquinolines (THIQs), structures that are challenging to synthesize and yet are present in a number of bioactive natural products and synthetic pharmaceuticals. Here we have discovered that norcoclaurine synthase from Thalictrum flavum (TfNCS) can catalyse the PSR between dopamine and unactivated ketones, thus facilitating the facile biocatalytic generation of 1,1'-disubstituted THIQs. Variants of TfNCS showing improved conversions have been identified and used to synthesize novel chiral 1,1'-disubstituted and spiro-THIQs. Enzyme catalysed PSRs with unactivated ketones are unprecedented, and, furthermore, there are no equivalent stereoselective chemical methods for these transformations. This discovery advances the utility of enzymes for the generation of diverse THIQs in vitro and in vivo.

  14. Brønsted acid-catalysed enantioselective construction of axially chiral arylquinazolinones

    NASA Astrophysics Data System (ADS)

    Wang, Yong-Bin; Zheng, Sheng-Cai; Hu, Yu-Mei; Tan, Bin

    2017-05-01

    The axially chiral arylquinazolinone acts as a privileged structural scaffold, which is present in a large number of natural products and biologically active compounds as well as in chiral ligands. However, a direct catalytic enantioselective approach to access optically pure arylquinazolinones has been underexplored. Here we show a general and efficient approach to access enantiomerically pure arylquinazolinones in one-pot fashion catalysed by chiral phosphoric acids. A variety of axially chiral arylquinazolinones were obtained in high yields with good to excellent enantioselectivities under mild condition. Furthermore, we disclosed a method for atroposelective synthesis of alkyl-substituted arylquinazolinones involving Brønsted acid-catalysed carbon-carbon bond cleavage strategy. Finally, the asymmetric total synthesis of eupolyphagin bearing a cyclic arylquinazolinone skeleton was accomplished with an overall yield of 32% in six steps by utilizing the aforementioned methodology.

  15. Borane catalysed ring opening and closing cascades of furans leading to silicon functionalized synthetic intermediates

    NASA Astrophysics Data System (ADS)

    Hazra, Chinmoy K.; Gandhamsetty, Narasimhulu; Park, Sehoon; Chang, Sukbok

    2016-11-01

    The conversion of renewable biomass resources to synthetically valuable chemicals is highly desirable, but remains a formidable challenge in regards to the substrate scope and reaction conditions. Here we present the development of tris(pentafluorophenyl)borane-catalysed conversion of furans via ring-opening and closing cascade processes to afford silicon-functionalized synthetic chemicals under transition metal-free conditions. The furan ring-opening with hydrosilanes is highly efficient (TON up to 2,000) and atom-economical without forming any byproduct to give rise to α-silyloxy-(Z)-alkenyl silanes. Additional equivalents of silane smoothly induce a subsequent B(C6F5)3-catalysed cyclization of initially formed olefinic silane compounds to produce anti-(2-alkyl)cyclopropyl silanes, another versatile synthon being potentially applicable in the synthesis of natural products and pharmacophores.

  16. Asymmetric hydrogenation of quinazolinium salts catalysed by halide-bridged dinuclear iridium complexes bearing chiral diphosphine ligands.

    PubMed

    Kita, Yusuke; Higashida, Kosuke; Yamaji, Kenta; Iimuro, Atsuhiro; Mashima, Kazushi

    2015-03-14

    Asymmetric hydrogenation of quinazolinium salts was catalysed by halogen-bridged dinuclear iridium complexes bearing chiral diphosphine ligands, yielding tetrahydroquinazoline and 3,4-dihydroquinazoline with high enantioselectivity. A derivative of chiral dihydroquinazoline was used as a chiral NHC ligand.

  17. Pd-catalysed decarboxylative Suzuki reactions and orthogonal Cu-based O-arylation of aromatic carboxylic acids.

    PubMed

    Dai, Jian-Jun; Liu, Jing-Hui; Luo, Dong-Fen; Liu, Lei

    2011-01-14

    Pd-catalysed decarboxylative Suzuki reactions and orthogonal Cu-based O-arylation reactions of aromatic carboxylic acids are reported. The new reactions may provide alternative routes for the synthesis of some biaryls and aromatic carboxylic esters.

  18. Enantioselective synthesis of 3-hydroxy oxindoles by ytterbium-catalysed decarboxylative addition of β-ketoacids to isatins.

    PubMed

    Duan, Zhiqiang; Han, Jianlin; Qian, Ping; Zhang, Zirui; Wang, Yi; Pan, Yi

    2013-10-14

    A ytterbium(III)-indapybox catalysed enantioselective decarboxylative addition reaction of β-ketoacids to isatins is described. The biologically important 3-hydroxy oxindoles were obtained in high yields and excellent enantioselectivities.

  19. Synthesis of oxazoles by silver catalysed oxidative decarboxylation-cyclization of α-oxocarboxylates and isocyanides.

    PubMed

    Ma, Yiyang; Yan, Zhiyuan; Bian, Changliang; Li, Ke; Zhang, Xiaowen; Wang, Mengfan; Gao, Xinlong; Zhang, Heng; Lei, Aiwen

    2015-07-04

    A silver catalysed synthesis of oxazoles by the oxidative decarboxylation-cyclization of α-oxocarboxylates and isocyanides was developed. This method provided a novel strategy to construct oxazole rings compared to traditional methods. Mechanistic investigations such as operando IR, EPR and radical inhibition experiments were carefully done and confirmed the acyl cation and Ag(II) as the intermediates in this transformation, and the involvement of a radical decarboxylative process.

  20. Chiral Co(III)(salen)-catalysed hydrolytic kinetic resolution of racemic epoxides in ionic liquids.

    PubMed

    Oh, Chun Rim; Choo, Dong Joon; Shim, Woo Ho; Lee, Dong Hoon; Roh, Eun Joo; Lee, Sang-gi; Song, Choong Eui

    2003-05-07

    In the chiral Co(III)(salen)-catalysed HKR of racemic epoxides, in the presence of ionic liquids, Co(II)(salen) complex is oxidised without acetic acid to catalytically active Co(III)(salen) complex during reaction and, moreover, this oxidation state is stabilised against reduction to Co(II) complex which enables the reuse of the recovered catalyst for consecutive reactions without extra reoxidation.

  1. Nitrene transfer reactions catalysed by copper(I) complexes in ionic liquid using chloramine-T.

    PubMed

    Cano, Israel; Nicasio, M Carmen; Pérez, Pedro J

    2009-01-28

    The complex [Tpm(*,Br)Cu(NCMe)]BF4 (Tpm(*,Br) = HC(3,5-Me2-4-Br-pyrazolyl)3) catalyses the aziridination of alkenes and the amidation of cyclic ethers with chloramine-T as the nitrene source and the ionic liquid [bmim]PF6 as the reaction medium (bmim = 1-n-butyl-3-methylimidazolium). High conversions have been obtained over several cycles of catalyst recovery and reuse.

  2. Kinetic and solvent deuterium isotope effects in the oxidation of putrescine catalysed by enzyme diamine oxidase.

    PubMed

    Pałka, Katarzyna; Szymańska, Jolanta; Kańska, Marianna

    2013-01-01

    In this study, the kinetic isotope effects and solvent isotope effects in the reaction of the deamination of [(1R)-(2)H ] putrescine--catalysed by enzyme diamine oxidase (EC 1.4.3.6)--were determined using a non-competitive spectroscopic method. Putrescine, stereospecifically labelled with deuterium, was obtained by enzymatic decarboxylation of l-ornithine that was carried out in a fully deuteriated incubation medium.

  3. Iron-catalysed carbon-heteroatom and heteroatom-heteroatom bond forming processes.

    PubMed

    Correa, Arkaitz; García Mancheño, Olga; Bolm, Carsten

    2008-06-01

    Given its ready availability, low price and environmentally friendly character, iron is an attractive and often advantageous alternative to other transition metals in the field of catalysis. This tutorial review summarises recent progress in the development of novel and practical iron-catalysed reactions with a particular focus on those which provide access to new carbon-heteroatom and heteroatom-heteroatom linkages. It shall be of interest for both the academic as well as the industrial community.

  4. Potentiation effect of choline esters on choline-catalysed decarbamoylation of dimethylcarbamoyl-acetylcholinesterase.

    PubMed Central

    Kim, Y B; Jung, C H; Choi, S J; Seo, W J; Cha, S H; Sok, D E

    1992-01-01

    The choline esters potentiated the choline-catalysed decarbamoylation of dimethylcarbamoyl-acetylcholinesterase in proportion to the length of acyl group, although esters containing an acyl chain longer than the hexanoyl group exhibited a corresponding decrease in the potentiation. In structural requirement analysis it was found that both the quaternary ammonium moiety and the ester bond were important for the effective acceleration of choline-catalysed decarbamoylation. In general, the respective thiocholine ester was found to be more effective than the corresponding choline ester. Whereas the binding affinity (Ka) of choline in the decarbamoylation was not significantly altered, the maximum decarbamoylation rate (kr(max.)) of choline was greatly enhanced in the presence of choline esters or thiocholine esters. Along with the above observation, the isotope solvent effect, the effect of ionic strength and the antagonism studies demonstrate that the choline esters or thiocholine esters may interact with one of peripheral anionic sites, and thereby make the choline-catalysed decarbamoylation more favourable. PMID:1599395

  5. Mechanistic investigation of the reaction of epoxides with heterocumulenes catalysed by a bimetallic aluminium salen complex.

    PubMed

    Beattie, Christopher; North, Michael

    2014-06-23

    The bimetallic aluminium(salen) complex [(Al(salen))2O] is known to catalyse the reaction between epoxides and heterocumulenes (carbon dioxide, carbon disulfide and isocyanates) leading to five-membered ring heterocycles. Despite their apparent similarities, these three reactions have very different mechanistic features, and a kinetic study of oxazolidinone synthesis combined with previous kinetic work on cyclic carbonate and cyclic dithiocarbonate synthesis showed that all three reactions follow different rate equations. An NMR study of [Al(salen)]2O and phenylisocyanate provided evidence for an interaction between them, consistent with the rate equation data. A variable-temperature kinetics study on all three reactions showed that cyclic carbonate synthesis had a lower enthalpy of activation and a more negative entropy of activation than the other two heterocycle syntheses. The kinetic study was extended to oxazolidinone synthesis catalysed by the monometallic complex Al(salen)Cl, and this reaction was found to have a much less negative entropy of activation than any reaction catalysed by [Al(salen)]2O, a result that can be explained by the partial dissociation of an oligomeric Al(salen)Cl complex. A mechanistic rationale for all of the results is presented in terms of [Al(salen)]2O being able to function as a Lewis acid and/or a Lewis base, depending upon the susceptibility of the heterocumulene to reaction with nucleophiles.

  6. Enzyme-catalysed synthesis and reactions of benzene oxide/oxepine derivatives of methyl benzoates.

    PubMed

    Boyd, Derek R; Sharma, Narain D; Harrison, John S; Malone, John F; McRoberts, W Colin; Hamilton, John T G; Harper, David B

    2008-04-07

    A series of twelve benzoate esters was metabolised, by species of the Phellinus genus of wood-rotting fungi, to yield the corresponding benzyl alcohol derivatives and eight salicylates. The isolation of a stable oxepine metabolite, from methyl benzoate, allied to evidence of the migration and retention of a carbomethoxy group (the NIH Shift), during enzyme-catalysed ortho-hydroxylation of alkyl benzoates to form salicylates, is consistent with a mechanism involving an initial arene epoxidation step. This mechanism was confirmed by the isolation of a remarkably stable, optically active, substituted benzene oxide metabolite of methyl 2-(trifluoromethyl)benzoate, which slowly converted into the racemic form. The arene oxide was found to undergo a cycloaddition reaction with 4-phenyl-1,2,4-triazoline-3,5-dione to yield a crystalline cycloadduct whose structure and racemic nature was established by X-ray crystallography. The metabolite was also found to undergo some novel benzene oxide reactions, including epoxidation to give an anti-diepoxide, base-catalysed hydrolysis to form a trans-dihydrodiol and acid-catalysed aromatisation to yield a salicylate derivative via the NIH Shift of a carbomethoxy group.

  7. PAR for the Course: A Congruent Pedagogical Approach for a PAR Methods Class

    ERIC Educational Resources Information Center

    Hammond, Joyce D.; Hicks, Maria; Kalman, Rowenn; Miller, Jason

    2005-01-01

    In the past two years, three graduate students and a senior faculty member have co-taught a participatory action research (PAR) course to undergraduate and graduate students. In this article the co-teachers advocate a set of pedagogical principles and practices in a PAR-oriented classroom that establishes congruency with community PAR projects in…

  8. Eliminating Racism in Educational Settings.

    ERIC Educational Resources Information Center

    Sedlacek, William E.; Brooks, Glenwood C., Jr.

    The Cultural Study Center at the University of Maryland, College Park, has developed an approach for eliminating racism in white-oriented educational institutions by changing the attitudes and behaviors of those who control the system. The model is designed to be implemented as a conference consisting of six stages, each with its own particular…

  9. Reducing Crime by Eliminating Cash.

    ERIC Educational Resources Information Center

    Warwick, David R.

    Ending the use of cash in the United States can provide substantial social and economic gain while requiring only modest levels of investment. One primary benefit is the reduction of cash-related crimes. Because most street crime is committed to obtain cash or uses cash as a transaction medium, elimination of cash will dramatically reduce crime.…

  10. Measles elimination: progress and challenges.

    PubMed

    Cutts, F T; Henao-Restrepo, A; Olivé, J M

    1999-10-29

    The accelerating progress in reducing measles incidence and mortality in many parts of the world has led to calls for its global eradication during the next 10-15 years. Three regions have established goals of elimination of indigenous transmission of measles. The strategy used in the Americas of a mass 'catchup' campaign of children 9 months to 15 years of age, high coverage through routine vaccination of infants, intensive surveillance and follow-up campaigns to prevent excessive build-up of susceptibles has had great success in reducing measles transmission close to zero. However, while these developments are impressive, much remains to be done to reduce measles-associated mortality in western and central Africa, where less than half of children are currently receiving measles vaccine and half a million children die from measles each year. The obstacles to global measles eradication are perceived to be predominantly political and financial. There are also technical questions, however. These include the refinement of measles elimination strategies in the light of recent outbreaks in the Americas; the implications of the HIV epidemic for measles elimination, issues around injection safety, and concerns about the possibility that secondary vaccine failures will contribute in sustaining transmission in highly vaccinated populations. The global priorities are to improve measles control in low income countries, increase awareness among industrialized countries of the importance of measles, and conduct studies to answer the technical questions about measles elimination strategies.

  11. Par Pond vegetation status Summer 1995 -- Summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1996-01-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar to the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  12. Renal elimination of perfluorocarboxylates (PFCAs).

    PubMed

    Han, Xing; Nabb, Diane L; Russell, Mark H; Kennedy, Gerald L; Rickard, Robert W

    2012-01-13

    Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasis on their relevance to renal elimination. PFCAs vary in their affinities to bind to serum albumins in plasma, which is an important factor in determining the renal clearance of PFCAs. PFCA-albumin binding has been well characterized and is summarized in this review. The mechanism of the sex-, species-, and chain length-dependent renal PFCA elimination is a research area that has gained continuous interest since the beginning of toxicological studies of PFCAs. It is now recognized that organic anion transport proteins play a key role in PFCA renal tubular reabsorption, a process that is sex-, species-, and chain length-dependent. Recent studies on the identification of PFCA renal transport proteins and characterization of their transport kinetics have greatly improved our understanding of the PFCA renal transport mechanism at the molecular level. A mathematical representation of this renal tubular reabsorption mechanism has been incorporated in physiologically based pharmacokinetic (PBPK) modeling of perfluorooctanoate (PFOA). Improvement of PBPK models in the future will require more accurate and quantitative characterization of renal transport pathways of PFCAs. To that end, a basolateral membrane efflux pathway for the reabsorption of PFCAs in the kidney is discussed in this review, which could provide a future research direction toward a better understanding of the mechanisms of PFCA renal elimination.

  13. How To Eliminate Narcissism Overnight

    PubMed Central

    2011-01-01

    The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition appears likely to eliminate the diagnosis of narcissistic personality disorder. There are significant problems with the discriminant validity of the current narcissistic personality disorder critiera set; furthermore, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition's narrow focus on “grandiosity” probably contributes to the wide disparity between low narcissistic personality disorder prevalence rates in epidemiological studies and high rates of narcissistic personality disorder in clinical practice. Nevertheless, the best course of action may be to refine the narcissistic personality disorder criteria, followed by careful field testing and a search for biomarkers, rather than wholesale elimination of the narcissistic personality disorder category. The construct of “malignant narcissism” is also worthy of more intense empirical investigation. PMID:21468294

  14. THE RENAL ELIMINATION OF BILIRUBIN

    PubMed Central

    Haessler, Herbert; Rous, Peyton; Broun, G. O.

    1922-01-01

    The elimination of bile pigment during jaundice is, for practical purposes, unincreased by diuresis from water by mouth. Possibly, though, the flushing of the kidneys tends to lessen pigment accumulation within these organs and thus to diminish a serious potential source of trouble in long continued jaundice. Flood diuresis from intravenous injections of salt solution markedly increases the output of bile pigment. It is important to know the effect of variations in the urinary output on the elimination of bile salts, but methods for the purpose are not available at present. The passage of bile pigment into the kidney cells during jaundice is attested by the presence in the freshly voided urine of desquamated renal elements specifically stained, stippled, or granulated with bilirubin. Pigmentation of this sort is readily to be distinguished from the indiscriminate staining of cellular debris that occurs in icteric urines on standing. It has clinical significance, furnishing direct evidence on the degree of renal change. PMID:19868627

  15. A surprising observation that oxygen can affect the product enantiopurity of an enzyme-catalysed reaction.

    PubMed

    Fryszkowska, Anna; Toogood, Helen S; Mansell, David; Stephens, Gill; Gardiner, John M; Scrutton, Nigel S

    2012-11-01

    Enzymes are natural catalysts, controlling reactions with typically high stereospecificity and enantiospecificity in substrate selection and/or product formation. This makes them useful in the synthesis of industrially relevant compounds, particularly where highly enantiopure products are required. The flavoprotein pentaerythritol tetranitrate (PETN) reductase is a member of the Old Yellow Enzyme family, and catalyses the asymmetric reduction of β-alkyl-β-arylnitroalkenes. Under aerobic conditions, it additionally undergoes futile cycles of NAD(P)H reduction of flavin, followed by reoxidation by oxygen, which generates the reactive oxygen species (ROS) hydrogen peroxide and superoxide. Prior studies have shown that not all reactions catalysed by PETN reductase yield enantiopure products, such as the reduction of (E)-2-phenyl-1-nitroprop-1-ene (PNE) to produce (S)-2-phenyl-1-nitropropane (PNA) with variable enantiomeric excess (ee). Recent independent studies of (E)-PNE reduction by PETN reductase showed that the major product formed could be switched to (R)-PNA, depending on the reaction conditions. We investigated this phenomenon, and found that the presence of oxygen and ROS influenced the overall product enantiopurity. Anaerobic reactions produced consistently higher nitroalkane (S)-PNA product yields than aerobic reactions (64% versus 28%). The presence of oxygen dramatically increased the preference for (R)-PNA formation (up to 52% ee). Conversely, the presence of the ROS superoxide and hydrogen peroxide switched the preference to (S)-PNA product formation. Given that oxygen has no role in the natural catalytic cycle, these findings demonstrate a remarkable ability to manipulate product enantiopurity of this enzyme-catalysed reaction by simple manipulation of reaction conditions. Potential mechanisms of this unusual behaviour are discussed. © 2012 The Authors Journal compilation © 2012 FEBS.

  16. Abilities of peroxidases to catalyse peroxidase-oxidase oxidation of thiols.

    PubMed Central

    Svensson, B E

    1988-01-01

    The abilities of various peroxidases to catalyse the peroxidase-oxidase oxidation of seven aminothiols were studied. Cysteamine and cysteine esters were found to be peroxidase-oxidase substrates for eosinophil peroxidase and myeloperoxidase, whereas other thiols tested were inactive or poorly active with these peroxidases. With lactoperoxidase and horseradish peroxidase, all the tested thiols were inactive or poorly active as peroxidase-oxidase substrates. These studies suggest that a main reason for thiols being poor peroxidase-oxidase substrates is because these thiols are poor peroxidatic substrates. PMID:2852004

  17. Unprecedented Carbonato Intermediates in Cyclic Carbonate Synthesis Catalysed by Bimetallic Aluminium(Salen) Complexes.

    PubMed

    Castro-Osma, José A; North, Michael; Offermans, Willem K; Leitner, Walter; Müller, Thomas E

    2016-04-21

    The mechanism by which [Al(salen)]2 O complexes catalyse the synthesis of cyclic carbonates from epoxides and carbon dioxide in the absence of a halide cocatalyst has been investigated. Density functional theory (DFT) studies, mass spectrometry and (1) H NMR, (13) C NMR and infrared spectroscopies provide evidence for the formation of an unprecedented carbonato bridged bimetallic aluminium complex which is shown to be a key intermediate for the halide-free synthesis of cyclic carbonates from epoxides and carbon dioxide. Deuterated and enantiomerically-pure epoxides were used to study the reaction pathway. Based on the experimental and theoretical results, a catalytic cycle is proposed.

  18. Palladium-catalysed mono-α-alkenylation of ketones with alkenyl tosylates.

    PubMed

    Wu, Yong; Fu, Wai Chung; Chiang, Chien-Wei; Choy, Pui Ying; Kwong, Fuk Yee; Lei, Aiwen

    2017-01-16

    The first example of palladium-catalysed selective mono-α-alkenylation of ketones with alkenyl tosylates is described. In the presence of a Pd/XPhos catalyst system (0.1-1.0 mol%), the reaction provides mono-α-alkenylated ketones in good yields and exhibits excellent substrate tolerance. Highly congested, tri- and tetra-substituted alkenyl tosylates react smoothly and even problematic heteroaryl and aliphatic ketones are applicable substrates. Notably, small β,γ-unsaturated ketones are successfully prepared using acetone as a simple three-carbon feedstock.

  19. Practically convenient and industrially-aligned methods for iridium-catalysed hydrogen isotope exchange processes.

    PubMed

    Cochrane, A R; Idziak, C; Kerr, W J; Mondal, B; Paterson, L C; Tuttle, T; Andersson, S; Nilsson, G N

    2014-06-14

    The use of alternative solvents in the iridium-catalysed hydrogen isotope exchange reaction with developing phosphine/NHC Ir(I) complexes has identified reaction media which are more widely applicable and industrially acceptable than the commonly employed chlorinated solvent, dichloromethane. Deuterium incorporation into a variety of substrates has proceeded to deliver high levels of labelling (and regioselectivity) in the presence of low catalyst loadings and over short reaction times. The preparative outputs have been complemented by DFT studies to explore ligand orientation, as well as solvent and substrate binding energies within the catalyst system.

  20. Accumulation of acyl-enzyme in DD-peptidase-catalysed reactions with analogues of peptide substrates.

    PubMed Central

    Jamin, M; Adam, M; Damblon, C; Christiaens, L; Frère, J M

    1991-01-01

    Thioester substrates can be used to study the hydrolysis and transfer reactions catalysed by beta-lactamases and DD-peptidases. With the latter enzymes, accumulation of the acyl-enzyme can be detected directly. The efficiency of various amines as acceptor substrates was in excellent agreement with previous results obtained with peptide substrates of the DD-peptidases. The results indicated the presence of a specific binding site for the acceptor substrates. Although most of the results agreed well with a simple partition model, more elaborate hypotheses will be needed to account for all the data presented. PMID:1747125

  1. Gold(I)-catalysed cycloisomerisation of 1,6-cyclopropene-enes.

    PubMed

    Miege, Frédéric; Meyer, Christophe; Cossy, Janine

    2012-06-18

    The gold(I)-catalysed cycloisomerisation of appropriately substituted 1,6-cyclopropene-enes proceeds through regioselective electrophilic ring opening of the three-membered ring to generate an alkenyl gold carbenoid that achieves the intramolecular cyclopropanation of the remote olefin. This strategy allows straightforward, highly efficient and diastereoselective access to a variety of substituted 3-oxa- and 3-azabicyclo[4.1.0]heptanes, as well as to bicyclo[4.1.0]heptan-3-ol derivatives. Since the isopropylidene group in the resulting cycloisomerisation products can be subjected to ozonolysis, 3,3-dimethylcyclopropenes behave as interesting surrogates for α-diazoketones.

  2. A quenched-flow study of the reaction catalysed by creatine kinase.

    PubMed Central

    Engelborghs, Y; Marsh, A; Gutfreund, H

    1975-01-01

    The reaction catalysed by creatine kinase was studied in both directions by quenched-flow techniques to follow the initial product formation in the millisecond range. In both directions the amount of product formed increases linearly with time, and the turnover number corresponds to the steady-state value. Extrapolation to zero time indicates the absence of either a large transient phase or a large lag phase in both directions. This indicates that the actual chemical reaction is rate-limiting, and that all possible isomerizations before or after the chemical step must be much more rapid. PMID:1212215

  3. Unprecedented Access to β-Arylated Selenophenes through Palladium-Catalysed Direct Arylation.

    PubMed

    Skhiri, Aymen; Salem, Ridha Ben; Soulé, Jean-François; Doucet, Henri

    2017-02-24

    Several reported methods allow access to α-arylated selenophenes, whereas the synthesis of β-arylated selenophenes remains very challenging. Here, the Pd-catalysed coupling of benzenesulfonyl chlorides with selenophenes affording regiospecific β-arylated selenophenes is reported. The reaction proceeds with easily accessible catalyst, base and substrates, and tolerates a variety of substituents both on the benzene and selenophene moieties. This transformation allows the programmed synthesis of polyarylated selenophenes with potential applications in pharmaceutical and materials chemistry, as the installation of aryl groups at the desired positions can be achieved.

  4. Stochastic elimination of cancer cells.

    PubMed Central

    Michor, Franziska; Nowak, Martin A; Frank, Steven A; Iwasa, Yoh

    2003-01-01

    Tissues of multicellular organisms consist of stem cells and differentiated cells. Stem cells divide to produce new stem cells or differentiated cells. Differentiated cells divide to produce new differentiated cells. We show that such a tissue design can reduce the rate of fixation of mutations that increase the net proliferation rate of cells. It has, however, no consequence for the rate of fixation of neutral mutations. We calculate the optimum relative abundance of stem cells that minimizes the rate of generating cancer cells. There is a critical fraction of stem cell divisions that is required for a stochastic elimination ('wash out') of cancer cells. PMID:14561289

  5. Comparative cactus architecture and par interception

    SciTech Connect

    Geller, G.N.; Nobel, P.S. )

    1987-07-01

    Because CO{sup 2} uptake by cacti can be limited by low levels of photosynthetically active radiation (PAR) and because plant form affects PAR interception, various cactus forms were studied using a computer model, field measurements, and laboratory phototropic studies. Model predictions indicated that CO{sub 2} uptake by individual stems at an equinox was greatest when the stem were vertical, but at the summer and the winter solstice CO{sub 2} uptake was greatest for stems titled 30{degree} away from the equator. Stem tilting depended on form and taxonomic group. Not only can the shape of cacti be affected by PAR, but also shape influences PAR interception and hence CO{sub 2} uptake.

  6. Effect of V/III ratio on the structural and optical properties of self-catalysed GaAs nanowires

    NASA Astrophysics Data System (ADS)

    Ahtapodov, L.; Munshi, A. M.; Nilsen, J. S.; Reinertsen, J. F.; Dheeraj, D. L.; Fimland, B. O.; van Helvoort, A. T. J.; Weman, H.

    2016-11-01

    The performance of GaAs nanowire (NW) devices depends critically on the presence of crystallographic defects in the NWs such as twinning planes and stacking faults, and considerable effort has been devoted to understanding and preventing the occurrence of these. For self-catalysed GaAs NWs grown by molecular beam epitaxy (MBE) in particular, there are in addition other types of defects that may be just as important for NW-based optoelectronic devices. These are the point defects such as the As vacancy and the Ga antisite occurring due to the inherently Ga-rich conditions of the self-catalysed growth. Here we demonstrate experimentally the effects of these point defects on the optical properties of GaAs/AlGaAs core-shell NWs grown by self-catalysed MBE. The present results enable insight into the role of the point defects both on their own and in conjunction with crystallographic planar defects.

  7. The feasibility of eliminating podoconiosis

    PubMed Central

    Wanji, Samuel; Shafi, Oumer; M Tukahebwa, Edrida; Umulisa, Irenee; Molyneux, David H; Davey, Gail

    2015-01-01

    Abstract Podoconiosis is an inflammatory disease caused by prolonged contact with irritant minerals in soil. Major symptoms include swelling of the lower limb (lymphoedema) and acute pain. The disease has major social and economic consequences through stigma and loss of productivity. In the last five years there has been good progress in podoconiosis research and control. Addressing poverty at household level and infrastructure development such as roads, water and urbanization can all help to reduce podoconiosis incidence. Specific control methods include the use of footwear, regular foot hygiene and floor coverings. Secondary and tertiary prevention are based on the management of the lymphoedema-related morbidity and include foot hygiene, foot care, wound care, compression, exercises, elevation of the legs and treatment of acute infections. Certain endemic countries are taking the initiative to include podoconiosis in their national plans for the control of neglected tropical diseases and to scale up interventions against the disease. Advocacy is needed for provision of shoes as a health intervention. We suggest case definitions and elimination targets as a starting point for elimination of the disease. PMID:26600613

  8. Surveillance considerations for malaria elimination.

    PubMed

    Barclay, Victoria C; Smith, Rachel A; Findeis, Jill L

    2012-08-31

    Constant malaria monitoring and surveillance systems have been highlighted as critical for malaria elimination. The absence of robust monitoring and surveillance systems able to respond to outbreaks in a timely manner undeniably contributed to the failure of the last global attempt to eradicate malaria. Today, technological advances could allow for rapid detection of focal outbreaks and improved deployment of diagnostic and treatment supplies to areas needing support. However, optimizing diffusion activities (e.g., distributing vector controls and medicines, as well as deploying behaviour change campaigns) requires networks of diverse scholars to monitor, learn, and evaluate data and multiple organizations to coordinate their intervention activities. Surveillance systems that can gather, store and process information, from communities to national levels, in a centralized, widely accessible system will allow tailoring of surveillance and intervention efforts. Different systems and, thus reactions, will be effective in different endemic, geographical or socio-cultural contexts. Investing in carefully designed monitoring technologies, built for a multiple-acter, dynamic system, will help to improve malaria elimination efforts by improving the coordination, timing, coverage, and deployment of malaria technologies.

  9. The feasibility of eliminating podoconiosis.

    PubMed

    Deribe, Kebede; Wanji, Samuel; Shafi, Oumer; M Tukahebwa, Edrida; Umulisa, Irenee; Molyneux, David H; Davey, Gail

    2015-10-01

    Podoconiosis is an inflammatory disease caused by prolonged contact with irritant minerals in soil. Major symptoms include swelling of the lower limb (lymphoedema) and acute pain. The disease has major social and economic consequences through stigma and loss of productivity. In the last five years there has been good progress in podoconiosis research and control. Addressing poverty at household level and infrastructure development such as roads, water and urbanization can all help to reduce podoconiosis incidence. Specific control methods include the use of footwear, regular foot hygiene and floor coverings. Secondary and tertiary prevention are based on the management of the lymphoedema-related morbidity and include foot hygiene, foot care, wound care, compression, exercises, elevation of the legs and treatment of acute infections. Certain endemic countries are taking the initiative to include podoconiosis in their national plans for the control of neglected tropical diseases and to scale up interventions against the disease. Advocacy is needed for provision of shoes as a health intervention. We suggest case definitions and elimination targets as a starting point for elimination of the disease.

  10. Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation

    NASA Astrophysics Data System (ADS)

    You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P.

    2015-01-01

    The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of >=50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.

  11. A two-step chemical mechanism for ribosome-catalysed peptide bond formation.

    PubMed

    Hiller, David A; Singh, Vipender; Zhong, Minghong; Strobel, Scott A

    2011-07-17

    The chemical step of natural protein synthesis, peptide bond formation, is catalysed by the large subunit of the ribosome. Crystal structures have shown that the active site for peptide bond formation is composed entirely of RNA. Recent work has focused on how an RNA active site is able to catalyse this fundamental biological reaction at a suitable rate for protein synthesis. On the basis of the absence of important ribosomal functional groups, lack of a dependence on pH, and the dominant contribution of entropy to catalysis, it has been suggested that the role of the ribosome is limited to bringing the substrates into close proximity. Alternatively, the importance of the 2'-hydroxyl of the peptidyl-transfer RNA and a Brønsted coefficient near zero have been taken as evidence that the ribosome coordinates a proton-transfer network. Here we report the transition state of peptide bond formation, based on analysis of the kinetic isotope effect at five positions within the reaction centre of a peptidyl-transfer RNA mimic. Our results indicate that in contrast to the uncatalysed reaction, formation of the tetrahedral intermediate and proton transfer from the nucleophilic nitrogen both occur in the rate-limiting step. Unlike in previous proposals, the reaction is not fully concerted; instead, breakdown of the tetrahedral intermediate occurs in a separate fast step. This suggests that in addition to substrate positioning, the ribosome is contributing to chemical catalysis by changing the rate-limiting transition state.

  12. Challenging nickel-catalysed amine arylations enabled by tailored ancillary ligand design

    PubMed Central

    Lavoie, Christopher M.; MacQueen, Preston M.; Rotta-Loria, Nicolas L.; Sawatzky, Ryan S.; Borzenko, Andrey; Chisholm, Alicia J.; Hargreaves, Breanna K. V.; McDonald, Robert; Ferguson, Michael J.; Stradiotto, Mark

    2016-01-01

    Palladium-catalysed C(sp2)–N cross-coupling (that is, Buchwald–Hartwig amination) is employed widely in synthetic chemistry, including in the pharmaceutical industry, for the synthesis of (hetero)aniline derivatives. However, the cost and relative scarcity of palladium provides motivation for the development of alternative, more Earth-abundant catalysts for such transformations. Here we disclose an operationally simple and air-stable ligand/nickel(II) pre-catalyst that accommodates the broadest combination of C(sp2)–N coupling partners reported to date for any single nickel catalyst, without the need for a precious-metal co-catalyst. Key to the unprecedented performance of this pre-catalyst is the application of the new, sterically demanding yet electron-poor bisphosphine PAd-DalPhos. Featured are the first reports of nickel-catalysed room temperature reactions involving challenging primary alkylamine and ammonia reaction partners employing an unprecedented scope of electrophiles, including transformations involving sought-after (hetero)aryl mesylates for which no capable catalyst system is known. PMID:27004442

  13. EtfA catalyses the formation of dipicolinic acid in Clostridium perfringens.

    PubMed

    Orsburn, Benjamin C; Melville, Stephen B; Popham, David L

    2010-01-01

    Dipicolinic acid (DPA) is a major component of bacterial endospores, comprising 5-15% of the spore dry weight, and is important for spore stability and resistance properties. The biosynthetic precursor to DPA, dihydro-dipicolinic acid (DHDPA), is produced by DHDPA synthase within the lysine biosynthesis pathway. In Bacillus subtilis, and most other bacilli and clostridia, DHDPA is oxidized to DPA by the products of the spoVF operon. Analysis of the genomes of the clostridia in Cluster I, including the pathogens Clostridium perfringens, Clostridium botulinum and Clostridium tetani, has shown that no spoVF orthologues exist in these organisms. DPA synthase was purified from extracts of sporulating C. perfringens cells. Peptide sequencing identified an electron transfer flavoprotein, EtfA, in this purified protein fraction. A C. perfringens strain with etfA inactivated is blocked in late stage sporulation and produces < or = 11% of wild-type DPA levels. C. perfringens EtfA was expressed in and purified from Escherichia coli, and this protein catalysed DPA formation in vitro. The sequential production of DHDPA and DPA in C. perfringens appears to be catalysed by DHDPA synthase followed by EtfA. Genome sequence data and the taxonomy of spore-forming species suggest that this may be the ancestral mechanism for DPA synthesis.

  14. Enantioselective amine α-functionalization via palladium-catalysed C-H arylation of thioamides

    NASA Astrophysics Data System (ADS)

    Jain, Pankaj; Verma, Pritha; Xia, Guoqin; Yu, Jin-Quan

    2016-10-01

    Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, the development of methods to functionalize the α-methylene C-H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (-)-sparteine followed by Pd(0) catalysed cross-coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalysed enantioselective α-C-H coupling of a wide range of amines, which include ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C-H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

  15. F-O-G Ring Formation in Glycopeptide Antibiotic Biosynthesis is Catalysed by OxyE

    PubMed Central

    Peschke, Madeleine; Brieke, Clara; Cryle, Max J.

    2016-01-01

    The glycopeptide antibiotics are peptide-based natural products with impressive antibiotic function that derives from their unique three-dimensional structure. Biosynthesis of the glycopeptide antibiotics centres of the combination of peptide synthesis, mediated by a non-ribosomal peptide synthetase, and the crosslinking of aromatic side chains of the peptide, mediated by the action of a cascade of Cytochrome P450s. Here, we report the first example of in vitro activity of OxyE, which catalyses the F-O-G ring formation reaction in teicoplanin biosynthesis. OxyE was found to only act after an initial C-O-D crosslink is installed by OxyB and to require an interaction with the unique NRPS domain from glycopeptide antibiotic – the X-domain – in order to display catalytic activity. We could demonstrate that OxyE displays limited stereoselectivity for the peptide, which mirrors the results from OxyB-catalysed turnover and is in sharp contrast to OxyA. Furthermore, we show that activity of a three-enzyme cascade (OxyB/OxyA/OxyE) in generating tricyclic glycopeptide antibiotic peptides depends upon the order of addition of the OxyA and OxyE enzymes to the reaction. This work demonstrates that complex enzymatic cascades from glycopeptide antibiotic biosynthesis can be reconstituted in vitro and provides new insights into the biosynthesis of these important antibiotics. PMID:27752135

  16. Enzyme catalysed production of sialylated human milk oligosaccharides and galactooligosaccharides by Trypanosoma cruzi trans-sialidase.

    PubMed

    Holck, Jesper; Larsen, Dorte M; Michalak, Malwina; Li, Haiying; Kjærulff, Louise; Kirpekar, Finn; Gotfredsen, Charlotte H; Forssten, Sofia; Ouwehand, Arthur C; Mikkelsen, Jørn D; Meyer, Anne S

    2014-03-25

    A Trypanosoma cruzi trans-sialidase (E.C. 3.2.1.18) was cloned into Pichia pastoris and expressed. The pH and temperature optimum of the enzyme was determined as pH 5.7 and 30°C. Using casein glycomacropeptide (CGMP) and lactose as sialyl-donor and acceptor respectively, the optimal donor/acceptor ratio for the trans-sialidase catalysed 3'-sialyllactose production was found to be 1:4. Quantitative amounts of 3'-sialyllactose were produced from CGMP and lactose at a yield of 40mg/g CGMP. The 3'-sialyllactose obtained exerted a stimulatory effect on selected probiotic strains, including different Bifidobacterium strains in single culture fermentations. The trans-sialidase also catalysed the transfer of sialic acid from CGMP to galacto-oligosaccharides (GOS) and to the human milk oligosaccharide (HMO) backbone lacto-N-tetraose (LNT) to produce 3'-sialyl-GOS, including doubly sialylated GOS products, and 3'-sialyl-LNT, respectively. This work thus provides proof of the concept of producing 3'-sialyllactose and potentially other sialylated HMOs as well as sialylated GOS enzymatically by trans-sialidase activity, while at the same time providing valorisation of CGMP, a co-processing product from cheese manufacture.

  17. Enantioselective amine α-functionalization via palladium-catalysed C-H arylation of thioamides

    NASA Astrophysics Data System (ADS)

    Jain, Pankaj; Verma, Pritha; Xia, Guoqin; Yu, Jin-Quan

    2017-02-01

    Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, the development of methods to functionalize the α-methylene C-H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (-)-sparteine followed by Pd(0) catalysed cross-coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalysed enantioselective α-C-H coupling of a wide range of amines, which include ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C-H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

  18. Atomic scale observation of oxygen delivery during silver-oxygen nanoparticle catalysed oxidation of carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Yue, Yonghai; Yuchi, Datong; Guan, Pengfei; Xu, Jia; Guo, Lin; Liu, Jingyue

    2016-07-01

    To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars-van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes.

  19. Atomic scale observation of oxygen delivery during silver–oxygen nanoparticle catalysed oxidation of carbon nanotubes

    PubMed Central

    Yue, Yonghai; Yuchi, Datong; Guan, Pengfei; Xu, Jia; Guo, Lin; Liu, Jingyue

    2016-01-01

    To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars–van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes. PMID:27406595

  20. Palladium-Catalysed Cross-Coupling Reactions Controlled by Noncovalent Zn⋅⋅⋅N Interactions.

    PubMed

    Kadri, Mohamed; Hou, Jingran; Dorcet, Vincent; Roisnel, Thierry; Bechki, Lazhar; Miloudi, Abdellah; Bruneau, Christian; Gramage-Doria, Rafael

    2017-04-11

    Non-covalent interactions between halopyridine substrates and catalytically inert building blocks, namely zinc(II)-porphyrins and zinc(II)-salphens, influence the catalytic outcome of Suzuki-Miyaura and Mizoroki-Heck palladium-catalysed cross-coupling reactions. The weak Zn⋅⋅⋅N interactions between halopyridine substrates and zinc(II)-containing porphyrins and salphens, respectively, were studied by a combination of (1) H NMR spectroscopy, UV/Vis studies, Job-Plot analysis and, in some cases, X-ray diffraction studies. Additionally, the former studies revealed unique supramolecular polymeric and dimeric rearrangements in the solid state featuring weak Br⋅⋅⋅N (halogen bonding), C-H⋅⋅⋅π, Br⋅⋅⋅π and π⋅⋅⋅π interactions. The reactivity of halopyridine substrates in homogeneous palladium-catalysed cross-coupling reactions was found to correlate with the binding strength between the zinc(II)-containing scaffolds and the corresponding halopyridine. Such observation is explained by the unfavourable formation of inactive over-coordinated halopyridine⋅⋅⋅palladium species. The presented approach is particularly appealing for those cases in which substrates and/or products deactivate (or partially poison) a transition-metal catalyst. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Pd-catalysed reactions of alkynes with model distannanes and poly[di-(n-butyl)]stannane.

    PubMed

    Khan, Aman; Lough, Alan J; Gossage, Robert A; Foucher, Daniel A

    2013-02-21

    A reinvestigation of Pd-catalysed alkyne (R'-C≡CH; R' = H, Ph) insertion chemistry involving R(3)SnSnR(3) (3a: R = Me; 3b: R = n-Bu) was undertaken. Model distannyl ethylenes 4a-b (Me(3)SnCH=CR'SnMe(3)) and 5a-b ((n-Bu)(3)SnCH=CR'Sn(n-Bu)(3)) were reproduced and further characterized by NMR ((119)Sn, (13)C, (1)H) and UV-Vis spectroscopy. In the presence of an excess of phenylacetylene, dimerization-carbostannylation of compound 4b yielded the new conjugated butadiene, (Z,Z)-1,4-bis(trimethylstannyl)-1,4-diphenyl-buta-1,3-diene (9). An X-ray structure determination of 9 reveals a symmetrical double-bond Z confirmation. Compound 9 was further characterized by NMR, UV-Vis spectroscopy, and MS. A DFT analysis of model compounds (4a-b, 5a-b, 9) and the experimental and theoretical λ(max) values from the UV-Vis spectra were also compared. Acetylene and phenylacetylene Pd-catalysed insertion into the backbone of poly[di-(n-butyl)]stannane 12 resulted in new, modest molecular weight, partially inserted alkene tin polymers (13a-b) that were also characterized by GPC, NMR, UV-Vis spectroscopy and elemental analysis.

  2. SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis.

    PubMed

    Ohashi, Masao; Liu, Fang; Hai, Yang; Chen, Mengbin; Tang, Man-Cheng; Yang, Zhongyue; Sato, Michio; Watanabe, Kenji; Houk, K N; Tang, Yi

    2017-09-13

    Pericyclic reactions-which proceed in a concerted fashion through a cyclic transition state-are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-l-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme 'toolboxes'. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

  3. Borane-catalysed postpolymerisation modification of the Si-H bonds in poly(phenylsilane).

    PubMed

    Lee, P T K; Rosenberg, L

    2017-07-11

    B(C6F5)3-catalysed hydrosilation, heterodehydrocoupling, and demethanative coupling reactions of the Si-H bonds in poly(phenylsilane) allow the introduction of 10-40% new sidechains in this polymer. The resulting new polymers contain an unusually wide variety of functionalities including Si-C, Si-O, Si-N, and Si-S bonds, whose presence is confirmed by NMR and IR spectroscopies. Gel permeation chromatography (GPC) and thermogravimetric analysis (TGA) are consistent with conservation of the all-silicon backbones in these modified polymers, a result of the high chemoselectivity of the borane-catalysed reactions for Si-H versus Si-Si bonds. UV-visible spectroscopy is sensitive to the presence of new functional groups in the modified polysilanes, although the high proportion of residual Si-H groups attenuates the changes in the σ-delocalized chromophores. Limitations in substrate scope, arising from issues of borane-substrate complexation or competing catalytic over-reduction chemistry, have been identified, and the potential for achieving greater degrees of sidechain substitution at higher reaction temperatures has been demonstrated for the hydrosilation of 1-hexene.

  4. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis procedures. One man who was well aware of the role of nanostructured catalysts in the progress of material science research was the late Ulrich Gösele, director at the Max-Planck-Institut für Mikrostrukturphysik Halle, who passed away at the age of 60 on 8 November, 2009. Ulrich Gösele published over 750 papers of premium calibre research that have collectively been cited over 20,000 times. His research output includes a cornucopia of excellent work published in Nanotechnology, amongst which are a number of papers detailing the deft manipulation of nanocatalysts to control the quality and structure of nanomaterials [5-8]. Ulrich Gösele was a pioneer in nanoscience. In 1991, when the nanotechnology revolution was little more than a portentous rumble, he published a seminal report examining the effect of quantum confinement on the optical properties of silicon nanowires [9]. While we lament the loss to the community, we have much to celebrate in the insights his legacy has provided for the progress of materials science. It would be unwise to assume that science will or can ultimately advance in such a way as to allow ample means to indulge an unrestrained appetite for consumerism and energy consumption. As with most things, a balanced approach, considering solutions to the problem from many angles, seems sensible. Nonetheless, a browse through the latest literature leaves much cause for optimism for the positive role science can play in improving and sustaining our lifestyle. References [1] Mukherjee P, Roy M, Mandal B P, Dey G K, Mukherjee P K, Ghatak J, Tyagi A K and Kale S P 2008 Nanotechnology 19 075103 [2] Greenham N C and Grätzel M 2008 Nanotechnology 19 420201 [3] Vajo J, Pinkerton F and Stetson N 2009 Nanotechnology 20 200201 [4] Zhong C-J, Luo J, Fang B, Wanjala B N, Njoki P N, Loukrakpam R and Yin J 2010 Nanotechnology 21 062001 [5] Sivakov V A, Scholz A, Syrowatka F, Falk F, Gösele U and Christiansen S H 2009 Nanotechnology 20 405607 [6] Liu L, Lee W, Huang Z, Scholz R and Gösele U 2008 Nanotechnology 19 335604 [7] Fan H J et al 2006 Nanotechnology 17 S231-9 [8] Stelzner Th et al 2006 Nanotechnology 17 2895-8 [9] Lehmann V and Gösele U 1991 Appl. Phys. Lett. 58 856-8

  5. Evaluation of rate constants for enzyme-catalysed reactions by the jackknife technique. Application to liver alcohol dehydrogenase.

    PubMed Central

    Cornish-Bowden, A; Wong, J T

    1978-01-01

    Steady-state measurements of enzyme-catalysed reactions are capable of providing more information about the rate constants of the individual steps than is commonly obtained. We have applied a combination of the jackknife and non-linear regression techniques to measurements of the rate of oxidation of ethanol by NAD+, catalysed by alcohol dehydrogenase from horse liver. This has permitted values and confidence intervals to be assigned to the eight rate constants that characterize the binding of ethanol and NAD+ in random order to the enzyme, and to the net rate constant kcat. for the breakdown of the ternary complex. PMID:743242

  6. Graphic analysis of relaxation times of enzyme-catalysed reactions. An extension of the graphic method of King and Altman.

    PubMed Central

    Zhao, M

    1992-01-01

    An extension of the graphic method of King & Altman (1956) (J. Phys. Chem. 60, 1375-1378) is applied to the analysis of relaxation times of enzyme-catalysed reactions and a simple graphic method is presented. Clear-cut graphs, simple drawing, easy operation (without the need to perform the usual complex mathematical operations), and reliable results are the main characteristics of this kind of graphic method. A system of enzyme-catalysed reactions (E <--> ES <--> EP) is used as the actual example for illustrating the graphic method. PMID:1445198

  7. Multi‐Pathway Consequent Chemoselectivities of CpRuCl(PPh3)2/MeI‐Catalysed Norbornadiene Alkyne Cycloadditions

    PubMed Central

    Fang, De‐Cai; Xia, Shu‐Ya; Cheng, Rui‐Jiao

    2016-01-01

    Abstract Chemoselectivities of five experimentally realised CpRuCl(PPh3)2/MeI‐catalysed couplings of 7‐azabenzo‐norbornadienes with selected alkynes were successfully resolved from multiple reaction pathway models. Density functional theory calculations showed the following mechanistic succession to be energetically plausible: (1) CpRuI catalyst activation; (2) formation of crucial metallacyclopentene intermediate; (3) cyclobutene product (P2) elimination (ΔG Rel(RDS)≈11.9–17.6 kcal mol−1). Alternative formation of dihydrobenzoindole products (P1) by isomerisation to azametalla‐cyclohexene followed by subsequent CpRuI release was much less favourable (ΔG Rel(RDS)≈26.5–29.8 kcal mol−1). Emergent stereoselectivities were in close agreement with experimental results for reactions a, b, e. Consequent investigations employing dispersion corrections similarly support the empirical findings of P1 dominating in reactions c and d through P2→P1 product transformations as being probable (ΔG≈25.3–30.1 kcal mol−1). PMID:27620274

  8. Reductive Elimination from Arylpalladium Cyanide Complexes

    PubMed Central

    Klinkenberg, Jessica L.; Hartwig, John F.

    2012-01-01

    We report the isolation and characterization of arylpalladium cyanide complexes that undergo reductive elimination to form arylnitriles. The rates of reductive elimination from a series of arylpalladium cyanide complexes reveal that the electronic effects on the reductive elimination from arylpalladium cyanide complexes are distinct from those on reductive reductive eliminations from arylpalladium alkoxo, amido, thiolate, and enolate complexes. Arylpalladium cyanide complexes containing aryl ligands with electron-donating substituents undergo faster reductive elimination of aromatic nitriles than complexes containing aryl ligands with electron-withdrawing substituents. In addition, the transition state for the reductive elimination of the aromatic nitrile is much different from that for reductive eliminations that occur from most other arylpalladium complexes. Computational studies indicate that the reductive elimination of an arylnitrile from Pd(II) occurs through a transition state more closely related in structure and electronic distribution to that for the insertion of CO into a palladiumaryl bond. PMID:22352451

  9. Cp*Rh(III) and Cp*Ir(III)-catalysed redox-neutral C-H arylation with quinone diazides: quick and facile synthesis of arylated phenols.

    PubMed

    Zhang, Shang-Shi; Jiang, Chun-Yong; Wu, Jia-Qiang; Liu, Xu-Ge; Li, Qingjiang; Huang, Zhi-Shu; Li, Ding; Wang, Honggen

    2015-06-25

    Cp*Rh(III)- and Cp*Ir(III)-catalysed direct C-H arylation with quinone diazides as efficient coupling partners is disclosed. This redox-neutral protocol offers a facile, operationally simple and environmentally benign access to arylated phenols. The reaction represents the first example of Cp*Ir(III)-catalysed C-H direct arylation reaction.

  10. Elimination communication as colic therapy.

    PubMed

    Jordan, Geraldine J

    2014-09-01

    Colic is generally defined as excessive crying in early infancy and can have negative consequences on the infant as well as on the infant's family life. Excessive crying can result in escalating parental stress levels, abusive caregiver response, increased risk of shaken baby syndrome and parental postpartum depression. In addition to excessive crying, symptoms and descriptors of infant colic include inconsolable crying, screaming, legs drawn up against the abdomen, furrowing of eyebrows, distended abdomen, arched back, passing gas, post-feeding crying and difficulty defecating. There are few well-designed, reproducible, randomized, large-scale studies which demonstrate efficacy of any therapeutic method for colic. An unexplored etiology is that colic is functionally related to a decrease in stooling frequency. Gut distention may periodically result in intensifying discomfort for the infant and in concomitant inconsolable crying. Elimination communication (EC; also known as Natural Infant Hygiene and sometimes referred to as infant potty training, baby-led potty training or assisted infant toilet training) involves the use of cues by which the infant signals to the caregiver that the infant needs to micturate or defecate. Such cues can include types of crying, squirming, straining, wriggling, grimacing, fussing, vocalizing, intent look at caregiver, red face, passing gas and grunting, many of which are the same initial symptoms related to the onset of colicky infant states. A caregiver's attentive and nurturant response to an infant's cues involve uncovering the infant's intergluteal cleft and cradling the infant gently and non-coercively in a supported, secure squatting position. This position will increase the infant's anorectal angle thus facilitating complete defecation. It is hypothesized that effective and timely elimination will cause increased physical comfort for the infant; colic symptoms will concomitantly decrease. Copyright © 2014 Elsevier Ltd. All

  11. Techniques for measuring intercepted and absorbed PAR in corn canopies

    NASA Technical Reports Server (NTRS)

    Gallo, K. P.; Daughtry, C. S. T.

    1984-01-01

    The quantity of radiation potentially available for photosynthesis that is captured by the crop is best described as absorbed photosynthetically active radiation (PAR). Absorbed PAR (APAR) is the difference between descending and ascending fluxes. The four components of APAR were measured above and within two planting densities of corn (Zea mays L.) and several methods of measuring and estimating APAR were examined. A line quantum sensor that spatially averages the photosynthetic photon flux density provided a rapid and portable method of measuring APAR. PAR reflectance from the soil (Typic Argiaquoll) surface decreased from 10% to less than 1% of the incoming PAR as the canopy cover increased. PAR reflectance from the canopy decreased to less than 3% at maximum vegetative cover. Intercepted PAR (1 - transmitted PAR) generally overestimated absorbed PAR by less than 4% throughout most of the growing season. Thus intercepted PAR appears to be a reasonable estimate of absorbed PAR.

  12. Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets.

    PubMed

    Duvernay, Matthew; Young, Summer; Gailani, David; Schoenecker, Jonathan; Hamm, Heidi E; Hamm, Heidi

    2013-04-01

    With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes. PAR4-activating peptide (AP)-stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1-AP-stimulated platelets. PAR4-AP-mediated factor V (FV) association with the platelet surface was 1.6-fold greater than for PAR1-AP. Moreover, PAR4 stimulation resulted in a 3-fold greater release of microparticles, compared with PAR1 stimulation. More robust FV secretion and microparticle generation with PAR4-AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18. Inhibition of Rho-kinase reduced PAR4-AP-mediated FV secretion and microparticle generation to PAR1-AP-mediated levels. Thrombin generation assays measuring prothrombinase complex activity demonstrated 1.5-fold higher peak thrombin levels on PAR4-AP-stimulated platelets, compared with PAR1-AP-stimulated platelets. Rho-kinase inhibition reduced PAR4-AP-mediated peak thrombin generation by 25% but had no significant effect on PAR1-AP-mediated thrombin generation. In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation. The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation. These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders.

  13. Perforating pilomatricoma: transepithelial elimination or not.

    PubMed

    Honda, Yoshihide; Oh-i, Tsunao; Koga, Michiyuki; Tokuda, Yasumoto

    2002-02-01

    We present a 56-year-old woman with a perforating pilomatricoma in the left eyebrow region. Histologically, the tumor consisted mainly of basophilic cells and shadow cells, and the tumor components were being eliminated through an ulcer with damage to the epithelial structures. In past reports of perforating pilomatricoma, this elimination pattern has often been described as transepithelial elimination. In many patients with perforating pilomatricoma, elimination is accompanied by ulceration and epithelial damage. Mehregan recently stated that elimination accompanied by epidermal necrosis and superficial ulceration constituted one form of transepithelial elimination. Epidermal necrosis and ulceration generally constitute severe damage. However, when Mehregan first proposed the concept of transepithelial elimination, it was defined as a phenomenon with relatively little or no damage to the epithelial structures, differentiating it from other types of elimination. This original definition makes transepithelial elimination a unique and interesting phenomenon, and its most important feature is that there is relatively little or no damage to the epithelial structures. Therefore, the terms "epidermal necrosis" and "ulceration" should not be used in association with transepithelial elimination. Hence, in patients with perforating pilomatricoma, the elimination of tumor components from ulcers with damage to the epithelial structures, as seen in the present case, should not be described as transepithelial elimination.

  14. ParCAT: Parallel Climate Analysis Toolkit

    SciTech Connect

    Smith, Brian E.; Steed, Chad A.; Shipman, Galen M.; Ricciuto, Daniel M.; Thornton, Peter E.; Wehner, Michael; Williams, Dean N.

    2013-01-01

    Climate science is employing increasingly complex models and simulations to analyze the past and predict the future of Earth s climate. This growth in complexity is creating a widening gap between the data being produced and the ability to analyze the datasets. Parallel computing tools are necessary to analyze, compare, and interpret the simulation data. The Parallel Climate Analysis Toolkit (ParCAT) provides basic tools to efficiently use parallel computing techniques to make analysis of these datasets manageable. The toolkit provides the ability to compute spatio-temporal means, differences between runs or differences between averages of runs, and histograms of the values in a data set. ParCAT is implemented as a command-line utility written in C. This allows for easy integration in other tools and allows for use in scripts. This also makes it possible to run ParCAT on many platforms from laptops to supercomputers. ParCAT outputs NetCDF files so it is compatible with existing utilities such as Panoply and UV-CDAT. This paper describes ParCAT and presents results from some example runs on the Titan system at ORNL.

  15. PAR2 regulates regeneration, transdifferentiation, and death

    PubMed Central

    Piran, Ron; Lee, Seung-Hee; Kuss, Pia; Hao, Ergeng; Newlin, Robbin; Millán, José Luis; Levine, Fred

    2016-01-01

    Understanding the mechanisms by which cells sense and respond to injury is central to developing therapies to enhance tissue regeneration. Previously, we showed that pancreatic injury consisting of acinar cell damage+β-cell ablation led to islet cell transdifferentiation. Here, we report that the molecular mechanism for this requires activating protease-activated receptor-2 (PAR2), a G-protein-coupled receptor. PAR2 modulation was sufficient to induce islet cell transdifferentiation in the absence of β-cells. Its expression was modulated in an islet cell type-specific manner in murine and human type 1 diabetes (T1D). In addition to transdifferentiation, PAR2 regulated β-cell apoptosis in pancreatitis. PAR2's role in regeneration is broad, as mice lacking PAR2 had marked phenotypes in response to injury in the liver and in digit regeneration following amputation. These studies provide a pharmacologically relevant target to induce tissue regeneration in a number of diseases, including T1D. PMID:27809303

  16. ATP-regulated interactions between P1 ParA, ParB and non-specific DNA that are stabilized by the plasmid partition site, parS

    PubMed Central

    Havey, James C.; Vecchiarelli, Anthony G.; Funnell, Barbara E.

    2012-01-01

    Localization of the P1 plasmid requires two proteins, ParA and ParB, which act on the plasmid partition site, parS. ParB is a site-specific DNA-binding protein and ParA is a Walker-type ATPase with non-specific DNA-binding activity. In vivo ParA binds the bacterial nucleoid and forms dynamic patterns that are governed by the ParB–parS partition complex on the plasmid. How these interactions drive plasmid movement and localization is not well understood. Here we have identified a large protein–DNA complex in vitro that requires ParA, ParB and ATP, and have characterized its assembly by sucrose gradient sedimentation and light scattering assays. ATP binding and hydrolysis mediated the assembly and disassembly of this complex, while ADP antagonized complex formation. The complex was not dependent on, but was stabilized by, parS. The properties indicate that ParA and ParB are binding and bridging multiple DNA molecules to create a large meshwork of protein–DNA molecules that involves both specific and non-specific DNA. We propose that this complex represents a dynamic adaptor complex between the plasmid and nucleoid, and further, that this interaction drives the redistribution of partition proteins and the plasmid over the nucleoid during partition. PMID:21965538

  17. Clinical inhibition of CYP2D6-catalysed metabolism by the antianginal agent perhexiline

    PubMed Central

    Davies, Benjamin J L; Coller, Janet K; James, Heather M; Gillis, David; Somogyi, Andrew A; Horowitz, John D; Morris, Raymond G; Sallustio, Benedetta C

    2004-01-01

    Aims Perhexiline is an antianginal agent that displays both saturable and polymorphic metabolism via CYP2D6. The aim of this study was to determine whether perhexiline produces clinically significant inhibition of CYP2D6-catalysed metabolism in angina patients. Methods The effects of perhexiline on CYP2D6-catalysed metabolism were investigated by comparing urinary total dextrorphan/dextromethorphan metabolic ratios following a single dose of dextromethorphan (16.4 mg) in eight matched control patients not taking perhexiline and 24 patients taking perhexiline. All of the patients taking perhexiline had blood drawn for CYP2D6 genotyping as well as to measure plasma perhexiline and cis-OH-perhexiline concentrations. Results Median (range) dextrorphan/dextromethorphan metabolic ratios were significantly higher (P < 0.0001) in control patients, 271.1 (40.3–686.1), compared with perhexiline-treated patients, 5.0 (0.3–107.9). In the perhexiline-treated group 10/24 patients had metabolic ratios consistent with poor metabolizer phenotypes; however, none was a genotypic poor metabolizer. Interestingly, 89% of patients who had phenocopied to poor metabolizers had only one functional CYP2D6 gene. There was a significant negative linear correlation between the log of the dextrorphan/dextromethorphan metabolic ratio and plasma perhexiline concentrations (r2 = 0.69, P < 0.0001). Compared with patients with at least two functional CYP2D6 genes, those with one functional gene were on similar perhexiline dosage regimens but had significantly higher plasma perhexiline concentrations, 0.73 (0.21–1.00) vs. 0.36 (0.04–0.69) mg l−1 (P = 0.04), lower cis-OH-perhexiline/perhexiline ratios, 2.85 (0.35–6.10) vs. 6.51 (1.84–11.67) (P = 0.03), and lower dextrorphan/dextromethorphan metabolic ratios, 2.51 (0.33–39.56) vs. 11.80 (2.90–36.93) (P = 0.005). Conclusions Perhexiline significantly inhibits CYP2D6-catalysed metabolism in angina patients. The plasma cis

  18. Antithrombotic effects of PAR1 and PAR4 antagonists evaluated under flow and static conditions.

    PubMed

    Hosokawa, Kazuya; Ohnishi, Tomoko; Miura, Naoki; Sameshima, Hisayo; Koide, Takehiko; Tanaka, Kenichi A; Maruyama, Ikuro

    2014-01-01

    Thrombin-mediated activation of human platelets involves the G-protein-coupled protease-activated receptors PAR1 and PAR4. Inhibition of PAR1 and/or PAR4 is thought to modulate platelet activation and subsequent procoagulant reactions. However, the antithrombotic effects of PAR1 and PAR4 antagonism have not been fully elucidated, particularly under flow conditions. A microchip-based flow chamber system was used to evaluate the influence of SCH79797 (PAR1 antagonist) and YD-3 (PAR4 antagonist) on thrombus formation mediated by collagen and tissue thromboplastin at shear rates simulating those experienced in small- to medium-sized arteries (600s(-1)) and large arteries and small veins (240s(-1)). At a shear rate of 600s(-1), SCH79797 (10μM) efficiently reduced fibrin-rich platelet thrombi and significantly delayed occlusion of the flow chamber capillary (1.44 fold of control; P<0.001). The inhibitory activity of SCH79797 was diminished at 240s(-1). YD-3 (20μM) had no significant effect at either shear rate. The antithrombotic effects of SCH79797 were significantly augmented when combined with aspirin and AR-C66096 (P2Y12 antagonist), but not with YD-3. In contrast, no significant inhibition of tissue factor-induced clot formation under static conditions was observed in blood treated with SCH79797 and YD-3, although thrombin generation in platelet-rich plasma was weakly delayed by these antagonists. Our results suggest that the antithrombotic activities of PAR1 and/or PAR4 antagonism is influenced by shear conditions as well as by combined platelet inhibition with aspirin and a P2Y12-antagonist. © 2013.

  19. Costs and financial feasibility of malaria elimination

    PubMed Central

    Sabot, Oliver; Cohen, Justin M; Hsiang, Michelle S; Kahn, James G; Basu, Suprotik; Tang, Linhua; Zheng, Bin; Gao, Qi; Zou, Linda; Tatarsky, Allison; Aboobakar, Shahina; Usas, Jennifer; Barrett, Scott; Cohen, Jessica L; Jamison, Dean T; Feachem, Richard GA

    2010-01-01

    Summary The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework—potential short-term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed. PMID:21035839

  20. An Investigation into the Effect of Stabiliser Content on the Minimum Characteristic Chamber Length for Homogeneously-Catalysed Hydrogen Peroxide

    DTIC Science & Technology

    2007-11-02

    packs to achieve a heterogeneous catalytic reaction to decompose the propellant into steam and oxygen. The decomposition of highly stabilised ...England, Private Communication. May 2004. [3] Musker, A. J. "Highly Stabilised Hydrogen Peroxide as a Rocket Propellant ", Proceedings of the...Investigation into the Effect of Stabiliser Content on the Minimum Characteristic Chamber Length for Homogeneously-Catalysed Hydrogen Peroxide 5c

  1. DPO and POPOP carboxylate-analog sensors by sequential palladium-catalysed direct arylation of oxazole-4-carboxylates.

    PubMed

    Verrier, Cécile; Fiol-Petit, Catherine; Hoarau, Christophe; Marsais, Francis

    2011-09-21

    Sequential palladium-catalysed direct (het)arylation of oxazole-4-carboxylates is achieved to give rapid access to DPO and POPOP (di)carboxylate-analogs. Three novel DPO- and POPOP-type sensors with unusual Stokes shifts and high quantum yields are discovered.

  2. Lipase-catalysed production of triacylglycerols enriched in pinolenic acid at the sn-2 position from pine nut oil.

    PubMed

    Choi, Jong-Hun; Kim, Byung Hee; Hong, Seung In; Kim, Chong-Tai; Kim, Chul-Jin; Kim, Yangha; Kim, In-Hwan

    2012-03-15

    The purpose of this study was to produce triacylglycerols (TAGs) enriched in pinolenic acid (PLA) at the sn-2 position using the principle of acyl migration, from the pine nut oil containing PLA esterified exclusively at the sn-3 position. Two types of lipase-catalysed reactions, i.e. redistribution and reesterification of fatty acids, were successively performed using seven commercially available lipases as biocatalysts. Of the lipases tested, Novozym 435 and Lipozyme TL IM were effective biocatalysts for positioning PLA at the sn-2 location. These biocatalysts were selected for further evaluation of the effects of reaction parameters, such as temperature and water content on the migration of PLA residues to the sn-2 position and TAG content. For both lipases, a significant decrease in TAG content was observed after the lipase-catalysed redistribution of fatty acids for both lipases. The reduced TAG content could be enhanced up to approx. 92%, through lipase-catalysed re-esterification of the hydrolysed fatty acids under vacuum. TAG enriched in PLA at the sn-2 position was synthesised from pine nut oil via lipase-catalysed redistribution and re-esterification of fatty acid residues using Lipozyme TL IM and Novozym 435 as biocatalysts. Copyright © 2011 Society of Chemical Industry.

  3. Homogeneously catalysed conversion of aqueous formaldehyde to H2 and carbonate

    PubMed Central

    Trincado, M.; Sinha, Vivek; Rodriguez-Lugo, Rafael E.; Pribanic, Bruno; de Bruin, Bas; Grützmacher, Hansjörg

    2017-01-01

    Small organic molecules provide a promising solution for the requirement to store large amounts of hydrogen in a future hydrogen-based energy system. Herein, we report that diolefin–ruthenium complexes containing the chemically and redox non-innocent ligand trop2dad catalyse the production of H2 from formaldehyde and water in the presence of a base. The process involves the catalytic conversion to carbonate salt using aqueous solutions and is the fastest reported for acceptorless formalin dehydrogenation to date. A mechanism supported by density functional theory calculations postulates protonation of a ruthenium hydride to form a low-valent active species, the reversible uptake of dihydrogen by the ligand and active participation of both the ligand and the metal in substrate activation and dihydrogen bond formation. PMID:28452367

  4. Novel chemoenzymatic oxidation of amines into oximes based on hydrolase-catalysed peracid formation.

    PubMed

    Méndez-Sánchez, Daniel; Lavandera, Iván; Gotor, Vicente; Gotor-Fernández, Vicente

    2017-04-11

    The efficient transformation of benzylamines into the corresponding oximes has been described by means of a chemoenzymatic process. This strategy is based on a two-step sequence developed in one-pot at 30 °C and atmospheric pressure. First, the formation of a reactive peracid intermediate occurs by means of a lipase-catalysed perhydrolysis reaction, and then this peracid acts as a chemical oxidising agent of the amines. A total of nine ketoximes were isolated in high purity after a simple extraction protocol (90-98% isolated yield), while for the eleven synthesised aldoximes a further column chromatography purification was required (71-82% isolated yield). In all cases excellent selectivities were attained, offering a practical method for amine oxidation in short reaction times (1 hour). The environmental impact of the process was analysed and compared with a recently published alternative chemical synthesis, finding for this metric a good E-factor value.

  5. Regio- and stereodivergent antibiotic oxidative carbocyclizations catalysed by Rieske oxygenase-like enzymes.

    PubMed

    Sydor, Paulina K; Barry, Sarah M; Odulate, Olanipekun M; Barona-Gomez, Francisco; Haynes, Stuart W; Corre, Christophe; Song, Lijiang; Challis, Gregory L

    2011-05-01

    Oxidative cyclizations, exemplified by the biosynthetic assembly of the penicillin nucleus from a tripeptide precursor, are arguably the most synthetically powerful implementation of C-H activation reactions in nature. Here, we show that Rieske oxygenase-like enzymes mediate regio- and stereodivergent oxidative cyclizations to form 10- and 12-membered carbocyclic rings in the key steps of the biosynthesis of the antibiotics streptorubin B and metacycloprodigiosin, respectively. These reactions represent the first examples of oxidative carbocyclizations catalysed by non-haem iron-dependent oxidases and define a novel type of catalytic activity for Rieske enzymes. A better understanding of how these enzymes achieve such remarkable regio- and stereocontrol in the functionalization of unactivated hydrocarbon chains will greatly facilitate the development of selective man-made C-H activation catalysts.

  6. Homogeneously catalysed conversion of aqueous formaldehyde to H2 and carbonate

    NASA Astrophysics Data System (ADS)

    Trincado, M.; Sinha, Vivek; Rodriguez-Lugo, Rafael E.; Pribanic, Bruno; de Bruin, Bas; Grützmacher, Hansjörg

    2017-04-01

    Small organic molecules provide a promising solution for the requirement to store large amounts of hydrogen in a future hydrogen-based energy system. Herein, we report that diolefin-ruthenium complexes containing the chemically and redox non-innocent ligand trop2dad catalyse the production of H2 from formaldehyde and water in the presence of a base. The process involves the catalytic conversion to carbonate salt using aqueous solutions and is the fastest reported for acceptorless formalin dehydrogenation to date. A mechanism supported by density functional theory calculations postulates protonation of a ruthenium hydride to form a low-valent active species, the reversible uptake of dihydrogen by the ligand and active participation of both the ligand and the metal in substrate activation and dihydrogen bond formation.

  7. A palladium-catalysed multicomponent coupling approach to conjugated poly(1,3-dipoles) and polyheterocycles

    PubMed Central

    Leitch, David C.; Kayser, Laure V.; Han, Zhi-Yong; Siamaki, Ali R.; Keyzer, Evan N.; Gefen, Ashley; Arndtsen, Bruce A.

    2015-01-01

    Conjugated polymers have emerged over the past several decades as key components for a range of applications, including semiconductors, molecular wires, sensors, light switchable transistors and OLEDs. Nevertheless, the construction of many such polymers, especially highly substituted variants, typically involves a multistep synthesis. This can limit the ability to both access and tune polymer structures for desired properties. Here we show an alternative approach to synthesize conjugated materials: a metal-catalysed multicomponent polymerization. This reaction assembles multiple monomer units into a new polymer containing reactive 1,3-dipoles, which can be modified using cycloaddition reactions. In addition to the synthetic ease of this approach, its modularity allows easy adaptation to incorporate a range of desired substituents, all via one-pot reactions. PMID:26077769

  8. Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

    NASA Astrophysics Data System (ADS)

    Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

    2015-08-01

    Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment.

  9. Influence of Fe(2+)-catalysed iron oxide recrystallization on metal cycling.

    PubMed

    Latta, Drew E; Gorski, Christopher A; Scherer, Michelle M

    2012-12-01

    Recent work has indicated that iron (oxyhydr-)oxides are capable of structurally incorporating and releasing metals and nutrients as a result of Fe2+-induced iron oxide recrystallization. In the present paper, we briefly review the current literature examining the mechanisms by which iron oxides recrystallize and summarize how recrystallization affects metal incorporation and release. We also provide new experimental evidence for the Fe2+-induced release of structural manganese from manganese-doped goethite. Currently, the exact mechanism(s) for Fe2+-induced recrystallization remain elusive, although they are likely to be both oxide-and metal-dependent. We conclude by discussing some future research directions for Fe2+-catalysed iron oxide recrystallization.

  10. A palladium-catalysed multicomponent coupling approach to conjugated poly(1,3-dipoles) and polyheterocycles

    NASA Astrophysics Data System (ADS)

    Leitch, David C.; Kayser, Laure V.; Han, Zhi-Yong; Siamaki, Ali R.; Keyzer, Evan N.; Gefen, Ashley; Arndtsen, Bruce A.

    2015-06-01

    Conjugated polymers have emerged over the past several decades as key components for a range of applications, including semiconductors, molecular wires, sensors, light switchable transistors and OLEDs. Nevertheless, the construction of many such polymers, especially highly substituted variants, typically involves a multistep synthesis. This can limit the ability to both access and tune polymer structures for desired properties. Here we show an alternative approach to synthesize conjugated materials: a metal-catalysed multicomponent polymerization. This reaction assembles multiple monomer units into a new polymer containing reactive 1,3-dipoles, which can be modified using cycloaddition reactions. In addition to the synthetic ease of this approach, its modularity allows easy adaptation to incorporate a range of desired substituents, all via one-pot reactions.

  11. Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation

    NASA Astrophysics Data System (ADS)

    Huang, Xin; Wu, Shangze; Wu, Wangteng; Li, Pengbin; Fu, Chunling; Ma, Shengming

    2016-08-01

    Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C-C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility.

  12. Copper catalysed azide-alkyne cycloaddition (CuAAC) in liquid ammonia.

    PubMed

    Ji, Pengju; Atherton, John H; Page, Michael I

    2012-10-21

    Copper(I) catalysed azide-alkyne cycloaddition reactions (CuAAC) occur smoothly in liquid ammonia (LNH(3)) at room temperature to give exclusively 1,4-substituted 1,2,3-triazoles with excellent yields (up to 99%). The CuAAC reactions in liquid ammonia require relatively small amounts of copper(I) catalyst (0.5 mole%) compared with that in conventional solvents. The product can be obtained conveniently by simply evaporation of ammonia, indicating its potential application in industry. The rate of the CuAAC reaction in liquid ammonia shows a second order dependence on the copper(I) concentration and the reaction occurs only with terminal alkynes. Deuterium exchange experiments with phenyl acetylene-d(1) show that the acidity of the alkyne is increased at least 1000-fold with catalytic amounts of copper(I) in liquid ammonia. The mechanism of the CuAAC reaction in liquid ammonia is discussed.

  13. Lipase-catalysed ester synthesis in solvent-free oil system: is it esterification or transesterification?

    PubMed

    Sun, Jingcan; Yu, Bin; Curran, Philip; Liu, Shao-Quan

    2013-12-01

    Ester synthesis was carried out in a solvent-free system of lipase, coconut oil and ethanol or fusel alcohols to ascertain the reaction mechanism. During ester formation, octanoic and decanoic acids increased initially and then decreased gradually, indicating that ester production was a two-step reaction consisting of hydrolysis and esterification, rather than alcoholysis. With ethanol as the alcohol substrate, added butyric acid inhibited ester synthesis. However, when fusel alcohols were used as the alcohol substrate, no significant inhibitory effect by butyric acid was observed. Added octanoic acid did not show any adverse effect on the synthesis of corresponding esters. The results suggest that polarity of the reactants determines lipase activity. This study provides the first evidence on the mechanism of immobilised lipase-catalysed ester synthesis in a solvent-free system involving both hydrolysis and esterification.

  14. Pd-catalysed asymmetric mono- and bis-alkoxycarbonylation of vinylarenes.

    PubMed

    Godard, Cyril; Muñoz, Bianca K; Ruiz, Aurora; Claver, Carmen

    2008-02-21

    The asymmetric alkoxycarbonylation of vinylarenes catalysed by palladium complexes bearing chiral phosphine ligands has attracted much attention over the last decades. The products of both mono- and bis(alkoxycarbonylation) reactions are important intermediates in the syntheses of pharmaceuticals such as 2-arylpropionic acids, the most important class of non-steroidal anti-inflammatory drugs. In this article, a general overview of the topics will be presented and the recent advances in this field will be particularly detailed. Besides the term alkoxycarbonylation, hydroesterification and hydroalkoxycarbonylation are also used in the literature to describe this reaction. Furthermore, more specific terms such as methoxycarbonylation can be found. In this report, the term alkoxycarbonylation will be used as the general term, and specific terms will be used to unambiguously define which reaction is meant.

  15. Efficient and selective N-alkylation of amines with alcohols catalysed by manganese pincer complexes

    PubMed Central

    Elangovan, Saravanakumar; Neumann, Jacob; Sortais, Jean-Baptiste; Junge, Kathrin; Darcel, Christophe; Beller, Matthias

    2016-01-01

    Borrowing hydrogen (or hydrogen autotransfer) reactions represent straightforward and sustainable C–N bond-forming processes. In general, precious metal-based catalysts are employed for this effective transformation. In recent years, the use of earth abundant and cheap non-noble metal catalysts for this process attracted considerable attention in the scientific community. Here we show that the selective N-alkylation of amines with alcohols can be catalysed by defined PNP manganese pincer complexes. A variety of substituted anilines are monoalkylated with different (hetero)aromatic and aliphatic alcohols even in the presence of other sensitive reducible functional groups. As a special highlight, we report the chemoselective monomethylation of primary amines using methanol under mild conditions. PMID:27708259

  16. The ortho-substituent effect on the Ag-catalysed decarboxylation of benzoic acids.

    PubMed

    Grainger, Rachel; Cornella, Josep; Blakemore, David C; Larrosa, Igor; Campanera, Josep M

    2014-12-08

    A combined experimental and computational investigation on the Ag-catalysed decarboxylation of benzoic acids is reported herein. The present study demonstrates that a substituent at the ortho position exerts dual effects in the decarboxylation event. On one hand, ortho-substituted benzoic acids are inherently destabilised starting materials compared to their meta- and para-substituted counterparts. On the other hand, the presence of an ortho-electron-withdrawing group results in an additional stabilisation of the transition state. The combination of both effects results in an overall reduction of the activation energy barrier associated with the decarboxylation event. Furthermore, the Fujita-Nishioka linear free energy relationship model indicates that steric bulk of the substituent can also exert a negative effect by destabilising the transition state of decarboxylation.

  17. Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate.

    PubMed

    Iqbal, Amjid; Sahraoui, El-Habib; Leeper, Finian J

    2014-01-01

    An analogue of thiamine having a furan ring in place of the thiazolium ring has been synthesised by a short and efficient route, involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a very strong inhibitor, with a K i value of 32.5 pM. It was also shown that the furan analogue of thiamine can be functionalised at the C-2 position, which will allow access to mimics of reaction intermediates of various ThDP-dependent enzymes.

  18. Investigation of the stereochemical course of ene reductase-catalysed reactions by deuterium labelling.

    PubMed

    Brenna, Elisabetta; Fronza, Giovanni; Fuganti, Claudio; Parmeggiani, Fabio

    2015-01-01

    The stereoselective reduction of suitably substituted C═C bonds mediated by enzymes, called ene reductases, has received great attention in the last decade. Some successful applications of this biocatalysed procedure to the synthesis of chiral active pharmaceutical ingredients have been reported in the literature. The generation of suitable models to be used for predicting the stereochemical outcome of this kind of reductions is a challenging task. In the last years we have exploited deuterium labelling to investigate the stereochemical course of the enzyme-mediated reductions of a wide collection of substrates belonging to well-defined chemical classes. The results of this research have allowed us to draw conclusions on the relationship between the structural characteristics of the substrate and the binding mode it adopts in the enzyme active site. The collected data can be exploited to create an empirical model to rationalise and predict the stereoselectivity of old yellow enzyme (OYE)-catalysed reductions.

  19. Efficient and selective N-alkylation of amines with alcohols catalysed by manganese pincer complexes

    NASA Astrophysics Data System (ADS)

    Elangovan, Saravanakumar; Neumann, Jacob; Sortais, Jean-Baptiste; Junge, Kathrin; Darcel, Christophe; Beller, Matthias

    2016-10-01

    Borrowing hydrogen (or hydrogen autotransfer) reactions represent straightforward and sustainable C-N bond-forming processes. In general, precious metal-based catalysts are employed for this effective transformation. In recent years, the use of earth abundant and cheap non-noble metal catalysts for this process attracted considerable attention in the scientific community. Here we show that the selective N-alkylation of amines with alcohols can be catalysed by defined PNP manganese pincer complexes. A variety of substituted anilines are monoalkylated with different (hetero)aromatic and aliphatic alcohols even in the presence of other sensitive reducible functional groups. As a special highlight, we report the chemoselective monomethylation of primary amines using methanol under mild conditions.

  20. Chemical synthesis of lactic acid from cellulose catalysed by lead(II) ions in water.

    PubMed

    Wang, Yanliang; Deng, Weiping; Wang, Binju; Zhang, Qinghong; Wan, Xiaoyue; Tang, Zhenchen; Wang, Ye; Zhu, Chun; Cao, Zexing; Wang, Guichang; Wan, Huilin

    2013-01-01

    The direct transformation of cellulose, which is the main component of lignocellulosic biomass, into building-block chemicals is the key to establishing biomass-based sustainable chemical processes. Only limited successes have been achieved for such transformations under mild conditions. Here we report the simple and efficient chemocatalytic conversion of cellulose in water in the presence of dilute lead(II) ions, into lactic acid, which is a high-value chemical used for the production of fine chemicals and biodegradable plastics. The lactic acid yield from microcrystalline cellulose and several lignocellulose-based raw biomasses is >60% at 463 K. Both theoretical and experimental studies suggest that lead(II) in combination with water catalyses a series of cascading steps for lactic acid formation, including the isomerization of glucose formed via the hydrolysis of cellulose into fructose, the selective cleavage of the C3-C4 bond of fructose to trioses and the selective conversion of trioses into lactic acid.

  1. Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water.

    PubMed

    Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F Y; Luan, Tiangang

    2015-08-04

    Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment.

  2. Acidic resin-catalysed conversion of fructose into furan derivatives in low boiling point solvents.

    PubMed

    Zhu, Hong; Cao, Quan; Li, Chunhu; Mu, Xindong

    2011-09-27

    Conversion of fructose into furan derivatives 5-hydroxymethylfurfural (HMF) and 5-methoxymethylfurfural (MMF) is performed in tetrahydrofuran (THF) and methanol-organic solvent systems, catalysed by an acidic resin Amberlyst-15. The melted fructose can be converted into HMF on the surface of the solid resin catalyst in the presence of THF as an extracting phase, which is a good solvent for HMF and other by-products. The solid resin catalyst can be reused eleven times without losing its catalytic ability, with an average HMF yield of approximately 50%. Upon the addition of methanol, the generated HMF can further react with methanol to form MMF, and the total yield of HMF and MMF could be promoted to 65%. GC-MS analysis confirms the formation of a small amount of methyl levulinate in methanolorganic solvent system.

  3. Homogeneously catalysed conversion of aqueous formaldehyde to H2 and carbonate.

    PubMed

    Trincado, M; Sinha, Vivek; Rodriguez-Lugo, Rafael E; Pribanic, Bruno; de Bruin, Bas; Grützmacher, Hansjörg

    2017-04-28

    Small organic molecules provide a promising solution for the requirement to store large amounts of hydrogen in a future hydrogen-based energy system. Herein, we report that diolefin-ruthenium complexes containing the chemically and redox non-innocent ligand trop2dad catalyse the production of H2 from formaldehyde and water in the presence of a base. The process involves the catalytic conversion to carbonate salt using aqueous solutions and is the fastest reported for acceptorless formalin dehydrogenation to date. A mechanism supported by density functional theory calculations postulates protonation of a ruthenium hydride to form a low-valent active species, the reversible uptake of dihydrogen by the ligand and active participation of both the ligand and the metal in substrate activation and dihydrogen bond formation.

  4. Acid-catalysed autoreduction of ferrylmyoblobin in aqueous solution studied by freeze quenching and ESR spectroscopy.

    PubMed

    Kröger-Ohlsen, M V; Andersen, M L; Skibsted, L H

    1999-04-01

    Decay of the hypervalent muscle pigment ferrylmyoglobin, formed by activation of metmyoglobin by hydrogen peroxide, was found, when studied by a combination of ESR and UV/VIS spectroscopy in aqueous solution at physiological pH, to proceed by parallel second- and first-order kinetics. At pH below 6.5 a sharp ESR signal (g = 2.003) with an increasing intensity for decreasing pH were observed in solutions frozen in liquid nitrogen, and a broad signal (g = 2.005) was seen throughout the studied pH range also in frozen solutions. The g = 2.005 signal is suggested to arise from an intermediate formed in an intramolecular rate-determining electron-transfer in ferrylmyoglobin, whereas the g 2.003 signal is caused by a radical formed in a proton-assisted electron-transfer initiating the specific acid-catalysed autoreduction.

  5. Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation

    PubMed Central

    Huang, Xin; Wu, Shangze; Wu, Wangteng; Li, Pengbin; Fu, Chunling; Ma, Shengming

    2016-01-01

    Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C–C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility. PMID:27558203

  6. Regio- and stereodivergent antibiotic oxidative carbocyclizations catalysed by Rieske oxygenase-like enzymes

    NASA Astrophysics Data System (ADS)

    Sydor, Paulina K.; Barry, Sarah M.; Odulate, Olanipekun M.; Barona-Gomez, Francisco; Haynes, Stuart W.; Corre, Christophe; Song, Lijiang; Challis, Gregory L.

    2011-05-01

    Oxidative cyclizations, exemplified by the biosynthetic assembly of the penicillin nucleus from a tripeptide precursor, are arguably the most synthetically powerful implementation of C-H activation reactions in nature. Here, we show that Rieske oxygenase-like enzymes mediate regio- and stereodivergent oxidative cyclizations to form 10- and 12-membered carbocyclic rings in the key steps of the biosynthesis of the antibiotics streptorubin B and metacycloprodigiosin, respectively. These reactions represent the first examples of oxidative carbocyclizations catalysed by non-haem iron-dependent oxidases and define a novel type of catalytic activity for Rieske enzymes. A better understanding of how these enzymes achieve such remarkable regio- and stereocontrol in the functionalization of unactivated hydrocarbon chains will greatly facilitate the development of selective man-made C-H activation catalysts.

  7. Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

    PubMed Central

    Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

    2015-01-01

    Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment. PMID:26239357

  8. Laccase catalysed grafting of phenolic onto xylan to improve its applicability in films

    NASA Astrophysics Data System (ADS)

    Pei, Jicheng; Wang, Bing; Zhang, Fangdong; Li, Zhongyang; Yin, Yunbei; Zhang, Dongxu

    2015-07-01

    Xylan can be tailored for various value-added applications. However, its use in aqueous systems is hampered by its complex structure, and small molecular weight. This research aimed at improving the xylan molecular weight and changing its structure. Laccase-catalysed oxidation of 4-coumaric acid (PCA), ferulic acid (FA), syringaldehyde (SD), and vanillin (VA) onto xylan was grafted to study the changes in its structure, tensile properties, and antibacterial activities. A Fourier transform infrared (FTIR) spectrum analyser was used to observe the changes in functional groups of xylan. The results showed a band at 1635 cm-1 corresponding to the stretching vibration of conjugated carbonyl carboxy hemoglobin and a benzene ring structure were strengthened; the appearance of a new band between 1200 cm-1 and 1270 cm-1 corresponding to alkyl ethers on the aryl C-O stretching vibration was due to the fact that during the grafting process, the number of benzene ring structures increased and covalent connections occurred between phenols and xylan. The reaction mechanism for the laccase-catalysed oxidation of phenol compounds onto xylan was preliminary explored by 13C-NMR. The results showed that PCA-xylan, FA-xylan graft poly onto xylan by Cγ ester bond, SD-xylan graft poly onto xylan by ether bond and an ester bond, and VD-xylan graft poly onto xylan by ether bond. The film strength of xylan derivatives has been significantly increased, especially for the PCA-xylan derivative. The increases in tensile stress at break, tensile strength, tensile yield stress, and Young's modulus were: 24.04%, 31.30%, 55.56%, and 28.21%, respectively. After laccase/phenolics were modified, xylan had a good antibacterial effect to E. coli, Corynebacterium glutamicum, and Bacillus subtilis. The SD-xylan, FA-xylan, and PCA-xylan showed a greater efficacy against E. coli, Corynebacterium glutamicum, and Bacillus subtilis, respectively.

  9. Humanizing the Protease-Activated Receptor (PAR) Expression Profile in Mouse Platelets by Knocking PAR1 into the Par3 Locus Reveals PAR1 Expression Is Not Tolerated in Mouse Platelets

    PubMed Central

    French, Shauna L.; Paramitha, Antonia C.; Moon, Mitchell J.; Dickins, Ross A.; Hamilton, Justin R.

    2016-01-01

    Anti-platelet drugs are the mainstay of pharmacotherapy for heart attack and stroke prevention, yet improvements are continually sought. Thrombin is the most potent activator of platelets and targeting platelet thrombin receptors (protease-activated receptors; PARs) is an emerging anti-thrombotic approach. Humans express two PARs on their platelets–PAR1 and PAR4. The first PAR1 antagonist was recently approved for clinical use and PAR4 antagonists are in early clinical development. However, pre-clinical studies examining platelet PAR function are challenging because the platelets of non-primates do not accurately reflect the PAR expression profile of human platelets. Mice, for example, express Par3 and Par4. To address this limitation, we aimed to develop a genetically modified mouse that would express the same repertoire of platelet PARs as humans. Here, human PAR1 preceded by a lox-stop-lox was knocked into the mouse Par3 locus, and then expressed in a platelet-specific manner (hPAR1-KI mice). Despite correct targeting and the predicted loss of Par3 expression and function in platelets from hPAR1-KI mice, no PAR1 expression or function was detected. Specifically, PAR1 was not detected on the platelet surface nor internally by flow cytometry nor in whole cell lysates by Western blot, while a PAR1-activating peptide failed to induce platelet activation assessed by either aggregation or surface P-selectin expression. Platelets from hPAR1-KI mice did display significantly diminished responsiveness to thrombin stimulation in both assays, consistent with a Par3-/- phenotype. In contrast to the observations in hPAR1-KI mouse platelets, the PAR1 construct used here was successfully expressed in HEK293T cells. Together, these data suggest ectopic PAR1 expression is not tolerated in mouse platelets and indicate a different approach is required to develop a small animal model for the purpose of any future preclinical testing of PAR antagonists as anti-platelet drugs. PMID

  10. Elimination of Onchocerciasis from Mexico

    PubMed Central

    Rodríguez-Pérez, Mario A.; Fernández-Santos, Nadia A.; Orozco-Algarra, María E.; Rodríguez-Atanacio, José A.; Domínguez-Vázquez, Alfredo; Rodríguez-Morales, Kristel B.; Real-Najarro, Olga; Prado-Velasco, Francisco G.; Cupp, Eddie W.; Richards, Frank O.; Hassan, Hassan K.; González-Roldán, Jesús F.; Kuri-Morales, Pablo A.; Unnasch, Thomas R.

    2015-01-01

    Background Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS) surveys were undertaken which employed entomological indicators to check for transmission recrudescence. Methodology/Principal findings In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP) was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population. Conclusions/Significance The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico. PMID:26161558

  11. Elimination of Onchocerciasis from Mexico.

    PubMed

    Rodríguez-Pérez, Mario A; Fernández-Santos, Nadia A; Orozco-Algarra, María E; Rodríguez-Atanacio, José A; Domínguez-Vázquez, Alfredo; Rodríguez-Morales, Kristel B; Real-Najarro, Olga; Prado-Velasco, Francisco G; Cupp, Eddie W; Richards, Frank O; Hassan, Hassan K; González-Roldán, Jesús F; Kuri-Morales, Pablo A; Unnasch, Thomas R

    2015-01-01

    Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS) surveys were undertaken which employed entomological indicators to check for transmission recrudescence. In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP) was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population. The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico.

  12. ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation.

    PubMed

    Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara

    2016-04-01

    In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins.

  13. ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

    PubMed Central

    Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

    2016-01-01

    In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

  14. suPAR and Team Nephrology

    PubMed Central

    2014-01-01

    Primary focal segmental glomerulosclerosis (FSGS) accounts for nearly 10 % of patients who require renal replacement therapy. Elevated circulating levels of soluble urokinase receptor (suPAR) have been identified as a biomarker to discriminate primary FSGS from other glomerulopathies. Subsequent reports have questioned the diagnostic utility of this test. In a study in BMC Medicine, Huang et al. demonstrate that urinary soluble urokinase receptor (suPAR) excretion assists in distinguishing primary FSGS from other glomerular diseases, and that high plasma suPAR concentrations are not directly linked to a decline in glomerular filtration rate (GFR). This observation suggests that further investigation of suPAR is warranted in patients with FSGS. It should be interpreted in light of a recent report that B7-1 is expressed in the podocytes of a subset of patients with FSGS, and that blocking this molecule may represent the first successful targeted intervention for this disease. These advances highlight the rapid pace of scientific progress in the field of nephrology. Nephrologists should work together, share resources, and expedite the design of protocols to evaluate these novel biomarkers in a comprehensive and scientifically valid manner. Please see related article http://www.biomedcentral.com/1741-7015/12/81. PMID:24885021

  15. Mating ecology explains patterns of genome elimination

    PubMed Central

    Gardner, Andy; Ross, Laura

    2014-01-01

    Genome elimination – whereby an individual discards chromosomes inherited from one parent, and transmits only those inherited from the other parent – is found across thousands of animal species. It is more common in association with inbreeding, under male heterogamety, in males, and in the form of paternal genome elimination. However, the reasons for this broad pattern remain unclear. We develop a mathematical model to determine how degree of inbreeding, sex determination, genomic location, pattern of gene expression and parental origin of the eliminated genome interact to determine the fate of genome-elimination alleles. We find that: inbreeding promotes paternal genome elimination in the heterogametic sex; this may incur population extinction under female heterogamety, owing to eradication of males; and extinction is averted under male heterogamety, owing to countervailing sex-ratio selection. Thus, we explain the observed pattern of genome elimination. Our results highlight the interaction between mating system, sex-ratio selection and intragenomic conflict. PMID:25328085

  16. Mating ecology explains patterns of genome elimination.

    PubMed

    Gardner, Andy; Ross, Laura

    2014-12-01

    Genome elimination - whereby an individual discards chromosomes inherited from one parent, and transmits only those inherited from the other parent - is found across thousands of animal species. It is more common in association with inbreeding, under male heterogamety, in males, and in the form of paternal genome elimination. However, the reasons for this broad pattern remain unclear. We develop a mathematical model to determine how degree of inbreeding, sex determination, genomic location, pattern of gene expression and parental origin of the eliminated genome interact to determine the fate of genome-elimination alleles. We find that: inbreeding promotes paternal genome elimination in the heterogametic sex; this may incur population extinction under female heterogamety, owing to eradication of males; and extinction is averted under male heterogamety, owing to countervailing sex-ratio selection. Thus, we explain the observed pattern of genome elimination. Our results highlight the interaction between mating system, sex-ratio selection and intragenomic conflict.

  17. Mapping residual transmission for malaria elimination.

    PubMed

    Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon; Ntshalintshali, Nyasatu; Hsiang, Michelle S; Perkins, T Alex; Greenhouse, Bryan; Tatem, Andrew J; Cohen, Justin M; Smith, David L

    2015-12-29

    Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections . In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show 'malariogenic potential', a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination.

  18. Thrust Vectoring to Eliminate the Vertical Stabilizer

    DTIC Science & Technology

    1979-12-01

    THRUST VECTORING TO ELIMINATE THE VERTICAL STABILIZER THESIS Presented to the Faculty of the School of Engineering of the Air Force Institute of...qualities is shown to be 1 rad/sec. I i~ i 2i, THRUST VECTORING TO ELIMINATE THE VERTICAL STABILIZER I. Introduction There is increasing concern ove" he...the height of the cockpit will not help very much and would reduce the pilot’s visibility. Reduction of the size or elimination of the vertical

  19. Elimination of onchocerciasis from Africa: possible?

    PubMed

    Mackenzie, Charles D; Homeida, Mamoun M; Hopkins, Adrian D; Lawrence, Joni C

    2012-01-01

    Human onchocerciasis, a parasitic disease found in 28 African countries, six Latin American countries and Yemen, causes blindness and severe dermatological problems. In 1987, efforts to control this infection shifted from vector approaches to include the mass distribution of ivermectin - a drug donated by Merck & Co. for disease control in Africa and for disease elimination in the Americas. Currently, almost 25 years later, with the Americas being highly successful and now approaching elimination, new evidence points towards the possibility of successful elimination in Africa. We suggest several major changes in the programmatic approach that through focused goal-directed effort could achieve global elimination of onchocerciasis by 2025.

  20. Development and Evaluation of Small Peptidomimetic Ligands to Protease-Activated Receptor-2 (PAR2) through the Use of Lipid Tethering

    PubMed Central

    Boitano, Scott; Hoffman, Justin; Tillu, Dipti V.; Asiedu, Marina N.; Zhang, Zhenyu; Sherwood, Cara L.; Wang, Yan; Dong, Xinzhong; Price, Theodore J.; Vagner, Josef

    2014-01-01

    Protease-activated receptor-2 (PAR2) is a G-Protein Coupled Receptor (GPCR) activated by proteolytic cleavage to expose an attached, tethered ligand (SLIGRL). We evaluated the ability for lipid-tethered-peptidomimetics to activate PAR2 with in vitro physiological and Ca2+ signaling assays to determine minimal components necessary for potent, specific and full PAR2 activation. A known PAR2 activating compound containing a hexadecyl (Hdc) lipid via three polyethylene glycol (PEG) linkers (2at-LIGRL-PEG3-Hdc) provided a potent agonist starting point (physiological EC50 = 1.4 nM; 95% CI: 1.2–2.3 nM). In a set of truncated analogs, 2at-LIGR-PEG3-Hdc retained potency (EC50 = 2.1 nM; 1.3–3.4 nM) with improved selectivity for PAR2 over Mas1 related G-protein coupled receptor type C11, a GPCR that can be activated by the PAR2 peptide agonist, SLIGRL-NH2. 2at-LIG-PEG3-Hdc was the smallest full PAR2 agonist, albeit with a reduced EC50 (46 nM; 20–100 nM). 2at-LI-PEG3-Hdc retained specific activity for PAR2 with reduced EC50 (310 nM; 260–360 nM) but displayed partial PAR2 activation in both physiological and Ca2+ signaling assays. Further truncation (2at-L-PEG3-Hdc and 2at-PEG3-Hdc) eliminated in vitro activity. When used in vivo, full and partial PAR2 in vitro agonists evoked mechanical hypersensitivity at a 15 pmole dose while 2at-L-PEG3-Hdc lacked efficacy. Minimum peptidomimetic PAR2 agonists were developed with known heterocycle substitutes for Ser1 (isoxazole or aminothiazoyl) and cyclohexylalanine (Cha) as a substitute for Leu2. Both heterocycle-tetrapeptide and heterocycle-dipeptides displayed PAR2 specificity, however, only the heterocycle-tetrapeptides displayed full PAR2 agonism. Using the lipid-tethered-peptidomimetic approach we have developed novel structure activity relationships for PAR2 that allows for selective probing of PAR2 function across a broad range of physiological systems. PMID:24927179

  1. PAR Corneal Topography System (PAR CTS): the clinical application of close-range photogrammetry.

    PubMed

    Belin, M W; Cambier, J L; Nabors, J R; Ratliff, C D

    1995-11-01

    The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system which uses close-range photogrammetry (rasterphotogrammetry) to measure and produce a topographic map of the corneal surface. The PAR CTS makes direct point-by-point measurements of surface elevation using a stereo-triangulation technique. The CTS uses a grid pattern composed of horizontal and vertical lines spaced about 0.2 mm (200 microns) apart. Each grid intersection comprises a surface feature which can be located in multiple images and used to generate an (x,y,z) coordinate. Unlike placido disc-based videokeratoscopes, the PAR CTS requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. In addition to surface elevation, the PAR CTS computes axial and tangential curvatures and refractive power. Difference maps are available in all curvatures, refractive power, and in absolute elevation.

  2. View from west to east of PAR site resident engineer's ...

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

    View from west to east of PAR site resident engineer's office building (REOB) - Stanley R. Mickelsen Safeguard Complex, Resident Engineers Office Building, Southeast of intersection of PAR Access Road & Fourth Avenue, Nekoma, Cavalier County, ND

  3. Élaboration de films de molécules organiques par ablation par laser UV

    NASA Astrophysics Data System (ADS)

    Hernandez-Perez, M. A.; Garapon, C.; Champeaux, C.; Coleman, A. W.

    2006-12-01

    Les potentialités des méthodes de dépôt par ablation laser (PLD) pour la préparation de films minces de matériaux organiques sont illustrées par un bref rappel bibliographique et par des résultats expérimentaux concernant des molécules d'intérêt biologique (acides aminés, calix-arènes, protéines). Les films sont préparés par PLD avec un laser KrF sans dégradation de la structure chimique des molécules dans une gamme de fluences de quelques dizaines à quelques centaines de mJ/cm2. Les propriétés structurales et optiques des films sont étudiées en fonction de la fluence du laser et mettent en évidence des arrangements moléculaires particuliers induits par cette méthode de dépôt. Le guidage optique a été obtenu pour des films de toutes ces molécules.

  4. Retrograde signaling for climbing fiber synapse elimination.

    PubMed

    Uesaka, Naofumi; Uchigashima, Motokazu; Mikuni, Takayasu; Hirai, Hirokazu; Watanabe, Masahiko; Kano, Masanobu

    2015-02-01

    Neurons form exuberant synapses with target cells early in development. Then, necessary synapses are selectively strengthened whereas unnecessary connections are weakened and eventually eliminated during postnatal development. This process is known as synapse elimination and is a crucial step for shaping immature neural circuits into functionally mature versions. Accumulating evidence suggests that retrograde signaling from postsynaptic cells regulates synapse elimination, but the underlying mechanisms remain unknown. Here, we show that semaphorin3A (Sema3A) and semaphorin7A (Sema7A) mediate retrograde signals for elimination of redundant climbing fiber (CF) to Purkinje cell (PC) synapses in the developing cerebellum, a representative model of synapse elimination in the central nervous system. We picked up candidate retrograde signaling molecules that are expressed in PCs during the period of CF synapse elimination and the receptors of these candidate molecules that are present in CFs. We then assessed the effects of lentivirus-mediated RNAi-knockdown of these molecules on CF synapse elimination. By this systematic screening, we found that knockdown of Sema3A in PCs or its co-receptor, plexinA4 (PlxnA4), in CFs accelerated CF synapse elimination and decreased CF-mediated synaptic inputs. Conversely, knockdown of Sema7A in PCs or either of the two receptors for Sema7A, plexinC1 (PlxnC1) and integrinB1 (ItgB1), in CFs impaired CF synapse elimination. Importantly, the effect of Sema7A involves signaling by type 1 metabotropic glutamate receptor (mGluR1), a canonical pathway in PCs for the final stage of CF synapse elimination. These results demonstrate that specific semaphorins act as retrograde signaling molecules and regulate distinct processes of CF synapse elimination during postnatal cerebellar development.

  5. A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition Assembly

    SciTech Connect

    B Chaudhuri; S Gupta; V Urban; M Chance; R DMello; L Smith; K Lyons; J Gee

    2011-12-31

    Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

  6. Kallikrein 6 Signals through PAR1 and PAR2 to Promote Neuron Injury and Exacerbate Glutamate Neurotoxicity

    PubMed Central

    Yoon, Hyesook; Radulovic, Maja; Wu, Jianmin; Blaber, Sachiko I.; Blaber, Michael; Fehlings, Michael G.; Scarisbrick, Isobel A.

    2014-01-01

    CNS trauma generates a proteolytic imbalance contributing to secondary injury, including axonopathy and neuron degeneration. Kallikrein 6 (Klk6) is a serine protease implicated in neurodegeneration and here we investigate the role of protease activated receptors 1 (PAR1) and PAR2 in mediating these effects. First we demonstrate Klk6 and the prototypical activator of PAR1, thrombin, as well as PAR1 and PAR2, are each elevated in murine experimental traumatic spinal cord injury (SCI) at acute or subacute time points. Recombinant Klk6 triggered ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line, in a PI3K and MEK-dependent fashion. Importantly, lipopeptide inhibitors of PAR1 or PAR2, and PAR1 genetic deletion, each reduced Klk6-ERK1/2 activation. In addition, Klk6 and thrombin promoted degeneration of cerebellar neurons and exacerbated glutamate neurotoxicity. Moreover, genetic deletion of PAR1 blocked thrombin-mediated cerebellar neurotoxicity and reduced the neurotoxic effects of Klk6. Klk6 also increased glutamate-mediated Bim signaling, PARP cleavage and lactate dehydrogenase (LDH) release in NSC34 motoneurons and these effects were blocked by PAR1 and PAR2 lipopeptide inhibitors. Taken together these data point to a novel Klk6-signaling axis in CNS neurons that is mediated by PAR1 and PAR2 and is positioned to contribute to neurodegeneration. PMID:23647384

  7. A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition

    SciTech Connect

    Chaudhuri, Barnali; Gupta, Sayan; Urban, Volker S; Chance, Mark; D'Mello, Rhijuta; Smith, Lauren; Lyons, Kelly; Gee, Jessica

    2010-01-01

    Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

  8. Host response biomarker in sepsis: suPAR detection.

    PubMed

    Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna

    2015-01-01

    Recent studies of our group have shown that suPAR may complement APACHE II score for risk assessment in sepsis. suPAR may be measured in serum of patients by an enzyme immunosorbent assay developed by Virogates (suPARnostic™). Production of suPAR from circulating neutrophils and monocytes may be assessed after isolation of neutrophils and monocytes and ex vivo culture. This is followed by measurement of suPAR in culture supernatants.

  9. Conversion du methanol en ethanol par carbonylation suivie d'hydrogenolyse

    NASA Astrophysics Data System (ADS)

    Gaucher, Melissa

    Ce projet de maîtrise s'inscrit dans le cadre des nouvelles filières énergétiques renouvelables et s'effectue au sein de la Chaire de recherche industrielle sur l'éthanol cellulosique créée par trois partenaires industriels (Enerkem, CRB et Ethanol Greenfield) et le gouvernement du Québec en collaboration avec l'Université de Sherbrooke. La stratégie d'un des partenaires, Enerkem, est de convertir par gazéification des résidus de biomasse non homogène en Syngas, ce gaz est ensuite converti en méthanol puis en éthanol. L'objectif principal de ce projet est la conversion catalytique de l'acétate en alcool. Un catalyseur commercial, composé de cuivre et de chrome, a permis l'obtention des conversions de plus de 95 % et une sélectivité pour l'éthanol de plus de 50 % avec l'acétate de méthyle, de 99 % avec l'acétate d'éthyle et de 50 % avec l'acétate de butyle. Les conditions optimales trouvées impliquent une température de 215 °C, une pression de 350 psig, une vitesse spatiale de 1800 h -1 H2 STP et un ratio H2 : Acétate de 7. Un catalyseur alternatif, à base de cuivre et de zinc, a aussi été testé. L'objectif secondaire est la carbonylation du méthanol en acétate. Cette étape a été réalisée en phase gazeuse où des rendements très élevés, soit plus de 2000 kg d'acétate de méthyle par kg de métal précieux à l'heure (kg AM/ kg métal précieux/h), ont été obtenus. Les conditions d'opérations testées impliquent une température variant entre 200-240 °C, une pression entre 250-600 psig, des ratios McOH : CO de 1 à 2,5. Mots clés: Carbonylation, Éthanol, Hydrogénolyse, Catalyse hétérogène.

  10. Regiospecific reductive elimination from diaryliodonium salts

    PubMed Central

    Wang, Bijia; Graskemper, Joseph W.; Qin, Linlin; DiMagno, Stephen G.

    2012-01-01

    StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) is provided by the cyclophane substituent on iodine(III). Computational and experimental studies demonstrate that out of plane steric bulk strongly destabilizes the reductive elimination transition state, and leads to regiochemical control. This approach should be general for high valent main group and transition metal ions. PMID:20425876

  11. Enforcement to Address Sewer Overflows | Eliminating ...

    EPA Pesticide Factsheets

    2017-04-10

    EPA's compliance goal is to eliminate sanitary sewer overflows (SSOs) from municipal collection systems and to ensure that wastewater is being conveyed to treatment plants in accordance with the requirements of the Clean Water Act. To eliminate SSOs, EPA uses a mix of compliance and enforcement tools.

  12. Eliminating Tracking-System Clock Errors

    NASA Technical Reports Server (NTRS)

    Wu, Jiun-Tsong; Bertiger, William I.

    1989-01-01

    Problems of redundancy and correlation avoided. ORTHO computer program eliminates effect of clock errors in differential solutions for positions of users of Global Positioning System (GPS). Main application, elimination of clock errors in tracking system based on GPS. Written in FORTRAN 77.

  13. Eliminating Tracking-System Clock Errors

    NASA Technical Reports Server (NTRS)

    Wu, Jiun-Tsong; Bertiger, William I.

    1989-01-01

    Problems of redundancy and correlation avoided. ORTHO computer program eliminates effect of clock errors in differential solutions for positions of users of Global Positioning System (GPS). Main application, elimination of clock errors in tracking system based on GPS. Written in FORTRAN 77.

  14. Metal-catalysed azidation of tertiary C-H bonds suitable for late-stage functionalization.

    PubMed

    Sharma, Ankit; Hartwig, John F

    2015-01-29

    Many enzymes oxidize unactivated aliphatic C-H bonds selectively to form alcohols; however, biological systems do not possess enzymes that catalyse the analogous aminations of C-H bonds. The absence of such enzymes limits the discovery of potential medicinal candidates because nitrogen-containing groups are crucial to the biological activity of therapeutic agents and clinically useful natural products. In one prominent example illustrating the importance of incorporating nitrogen-based functionality, the conversion of the ketone of erythromycin to the -N(Me)CH2- group in azithromycin leads to a compound that can be dosed once daily with a shorter treatment time. For such reasons, synthetic chemists have sought catalysts that directly convert C-H bonds to C-N bonds. Most currently used catalysts for C-H bond amination are ill suited to the intermolecular functionalization of complex molecules because they require excess substrate or directing groups, harsh reaction conditions, weak or acidic C-H bonds, or reagents containing specialized groups on the nitrogen atom. Among C-H bond amination reactions, those forming a C-N bond at a tertiary alkyl group would be particularly valuable, because this linkage is difficult to form from ketones or alcohols that might be created in a biosynthetic pathway by oxidation. Here we report a mild, selective, iron-catalysed azidation of tertiary C-H bonds that occurs without excess of the valuable substrate. The reaction tolerates aqueous environments and is suitable for the functionalization of complex structures in the late stages of a multistep synthesis. Moreover, this azidation makes it possible to install a range of nitrogen-based functional groups, including those from Huisgen 'click' cycloadditions and the Staudinger ligation. We anticipate that these reactions will create opportunities to modify natural products, their precursors and their derivatives to produce analogues that contain different polarity and charge as a

  15. Hydrolysis of p-nitrophenyl phenylphosphonate catalysed by bovine pancreatic deoxyribonuclease.

    PubMed

    Liao, T H; Hsieh, J C

    1988-11-01

    The ability of bovine pancreatic DNAase to hydrolyse the synthetic substrate p-nitrophenyl phenylphosphonate (NPPP) is intrinsic and is not due to the contamination of the DNAase preparation by nonspecific phosphodiesterases because the activities of DNA and NPPP hydrolysis are co-eluted from a DEAE-cellulose column with use of the Ca2+-affinity elution method and because the two activities are decreased simultaneously when the purified enzyme is treated with Cu2+/iodoacetate, an active-site-labelling agent for DNAase. NPPP hydrolysis is facilitated by the metal ion-DNAase. At relatively high Na+ concentrations, where the metal ion-DNA interaction is weak, DNA hydrolysis is also facilitated by the metal ion-DNAase. With NPPP as substrate the Michaelis constants are Km 3.7 mM for Mn2+ and Km 49 mM for Mg2+ in 0.2 M-Tris/HCl buffer, pH 7.2. Ca2+ competes with Mn2+, with Ki 64 mM. Free Cu2+ ions non-competitively inhibit DNAase-catalysed DNA or NPPP hydrolysis in the presence of Mn2+ or Mg2+ and the inhibition is not relieved by Ca2+. The affinity of Cu2+ for free DNAase is higher than that for Mn2+-DNAase. Mn2+ is not bound to DNAase via a simple ionic interaction, as Mn2+ remains bound in the presence of relatively high Na+ concentrations and induces a near-u.v. difference absorption spectrum. The kinetics of NPPP hydrolysis catalysed by Mn2+-DNAase are sigmoidal. From the Hill equation, h = 2.0 is obtained, suggesting that more than two NPPP molecules are bound per molecule of DNAase with a certain amount of co-operativity. Because DNAase in solution is a monomer with a single catalytic site, the multiple NPPP molecules on a single protein molecule are probably in one location, resulting in a co-operative interaction that may resemble that in the stacked base-pairs of double-helical DNA.

  16. Metal-catalysed azidation of tertiary C-H bonds suitable for late-stage functionalization

    NASA Astrophysics Data System (ADS)

    Sharma, Ankit; Hartwig, John F.

    2015-01-01

    Many enzymes oxidize unactivated aliphatic C-H bonds selectively to form alcohols; however, biological systems do not possess enzymes that catalyse the analogous aminations of C-H bonds. The absence of such enzymes limits the discovery of potential medicinal candidates because nitrogen-containing groups are crucial to the biological activity of therapeutic agents and clinically useful natural products. In one prominent example illustrating the importance of incorporating nitrogen-based functionality, the conversion of the ketone of erythromycin to the -N(Me)CH2- group in azithromycin leads to a compound that can be dosed once daily with a shorter treatment time. For such reasons, synthetic chemists have sought catalysts that directly convert C-H bonds to C-N bonds. Most currently used catalysts for C-H bond amination are ill suited to the intermolecular functionalization of complex molecules because they require excess substrate or directing groups, harsh reaction conditions, weak or acidic C-H bonds, or reagents containing specialized groups on the nitrogen atom. Among C-H bond amination reactions, those forming a C-N bond at a tertiary alkyl group would be particularly valuable, because this linkage is difficult to form from ketones or alcohols that might be created in a biosynthetic pathway by oxidation. Here we report a mild, selective, iron-catalysed azidation of tertiary C-H bonds that occurs without excess of the valuable substrate. The reaction tolerates aqueous environments and is suitable for the functionalization of complex structures in the late stages of a multistep synthesis. Moreover, this azidation makes it possible to install a range of nitrogen-based functional groups, including those from Huisgen `click' cycloadditions and the Staudinger ligation. We anticipate that these reactions will create opportunities to modify natural products, their precursors and their derivatives to produce analogues that contain different polarity and charge as a

  17. Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation.

    PubMed

    Benton, Richard; Palacios, Isabel M; St Johnston, Daniel

    2002-11-01

    PAR-1 kinases are required to determine the anterior-posterior (A-P) axis in C. elegans and Drosophila, but little is known about their molecular function. We identified 14-3-3 proteins as Drosophila PAR-1 interactors and show that PAR-1 binds a domain of 14-3-3 distinct from the phosphoserine binding pocket. PAR-1 kinases phosphorylate proteins to generate 14-3-3 binding sites and may therefore directly deliver 14-3-3 to these targets. 14-3-3 mutants display identical phenotypes to par-1 mutants in oocyte determination and the polarization of the A-P axis. Together, these results indicate that PAR-1's function is mediated by the binding of 14-3-3 to its substrates. The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries.

  18. Cola beverage and delayed elimination of methotrexate

    PubMed Central

    Santucci, Raoul; Levêque, Dominique; Herbrecht, Raoul

    2010-01-01

    AIMS To report a case of severe delayed methotrexate elimination attributable to consumption of a cola beverage. METHODS To investigate unexplained low urinary pH in a lymphoma patient treated with high-dose methotrexate. RESULTS Unexpected urinary acidity, despite administration of large amounts of sodium bicarbonate, could be attributed to repeated consumption of a cola beverage. It resulted in a delayed elimination of methotrexate and acute renal failure. Discontinuation of cola drinks, increase in calcium folinate rescue and in sodium bicarbonate allowed satisfactory elimination of methotrexate on day 12 after infusion and recovery from renal impairment without other severe toxicity. No other cause of delay in methotrexate elimination could be identified. CONCLUSIONS Cola beverages have a low pH due to their phosphoric acid content that is excreted by renal route. We recommend patients receiving high dose methotrexate abstain from any cola drink within 24 h before and during methotrexate administration and until complete elimination of the drug. PMID:21545633

  19. Clause Elimination Procedures for CNF Formulas

    NASA Astrophysics Data System (ADS)

    Heule, Marijn; Järvisalo, Matti; Biere, Armin

    We develop and analyze clause elimination procedures, a specific family of simplification techniques for conjunctive normal form (CNF) formulas. Extending known procedures such as tautology, subsumption, and blocked clause elimination, we introduce novel elimination procedures based on hidden and asymmetric variants of these techniques. We analyze the resulting nine (including five new) clause elimination procedures from various perspectives: size reduction, BCP-preservance, confluence, and logical equivalence. For the variants not preserving logical equivalence, we show how to reconstruct solutions to original CNFs from satisfying assignments to simplified CNFs. We also identify a clause elimination procedure that does a transitive reduction of the binary implication graph underlying any CNF formula purely on the CNF level.

  20. Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis

    PubMed Central

    Sales, Katiuchia Uzzun; Friis, Stine; Konkel, Joanne E.; Godiksen, Sine; Hatakeyama, Marcia; Hansen, Karina K.; Rogatto, Silvia Regina; Szabo, Roman; Vogel, Lotte K.; Chen, Wanjun; Gutkind, J. Silvio; Bugge, Thomas H.

    2014-01-01

    The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of NFκB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia, and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis. PMID:24469043

  1. QM/MM Molecular Dynamics Study of the Galactopyranose → Galactofuranose Reaction Catalysed by Trypanosoma cruzi UDP-Galactopyranose Mutase

    PubMed Central

    Pierdominici-Sottile, Gustavo; Cossio Pérez, Rodrigo; Galindo, Johan F.; Palma, Juliana

    2014-01-01

    The enzyme UDP-Galactopyranose Mutase (UGM) catalyses the conversion of galactopyranose into galactofuranose. It is known to be critical for the survival and proliferation of several pathogenic agents, both prokaryotic and eukaryotic. Among them is Trypanosoma cruzi, the parasite responsible for Chagas' disease. Since the enzyme is not present in mammals, it appears as a promising target for the design of drugs to treat this illness. A precise knowledge of the mechanism of the catalysed reaction would be crucial to assist in such design. In this article we present a detailed study of all the putative steps of the mechanism. The study is based on QM/MM free energy calculations along properly selected reaction coordinates, and on the analysis of the main structural changes and interactions taking place at every step. The results are discussed in connection with the experimental evidence and previous theoretical studies. PMID:25299056

  2. Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

    PubMed Central

    Brahim, Mariem

    2016-01-01

    Summary The use of a bromo-substituent as blocking group at the C2-position of 3-substituted thiophenes allows the regioselective introduction of aryl substituents at C5-position via Pd-catalysed direct arylation. With 1 mol % of a phosphine-free Pd catalyst, KOAc as the base and DMA as the solvent and various electron-deficient aryl bromides as aryl sources, C5-(hetero)arylated thiophenes were synthesized in moderate to high yields, without cleavage of the thienyl C–Br bond. Moreover, sequential direct thienyl C5-arylation followed by Pd-catalysed direct arylation or Suzuki coupling at the C2-position allows to prepare 2,5-di(hetero)arylated thiophenes bearing two different (hetero)aryl units in only two steps. This method provides a “green” access to arylated thiophene derivatives as it reduces the number of steps to prepare these compounds and also the formation of wastes. PMID:27829927

  3. Flavan-3-ols isolated from some medicinal plants inhibiting COX-1 and COX-2 catalysed prostaglandin biosynthesis.

    PubMed

    Noreen, Y; Serrano, G; Perera, P; Bohlin, L

    1998-08-01

    Extracts from the four plant species Atuna racemosa Raf. ssp. racemosa, Syzygium corynocarpum (A. Gray) C. Muell., Syzygium malaccense (L.) Merr. & Perry and Vantanea peruviana Macbr., traditionally used for inflammatory conditions, were fractionated using a cyclooxygenase-1 catalysed prostaglandin biosynthesis in vitro assay. The flavan-3-ol derivatives (+)-catechin, (+)-gallocatechin, 4'-O-Me-ent-gallocatechin, ouratea-catechin and ouratea-proanthocynidin A were isolated as active principles. The IC50 values ranged from 3.3 microM to 138 microM whilst indomethacin under the same test conditions had an IC50 value of 1.1 microM. The flavonol rhamnosides mearnsitrin, myricitrin and quercitrin were also isolated. When further tested for inhibitory effect on cyclooxygenase-2 catalysed prostaglandin biosynthesis, the five flavan-3-ol derivatives exhibited from equal to weaker inhibitory potencies, as compared to their cyclooxygenase-1 inhibitory effects. The flavonol rhamnosides were inactive towards both enzymes.

  4. Silver-catalysed azide-alkyne cycloaddition (AgAAC): assessing the mechanism by density functional theory calculations

    NASA Astrophysics Data System (ADS)

    Banerji, Biswadip; Chandrasekhar, K.; Killi, Sunil Kumar; Pramanik, Sumit Kumar; Uttam, Pal; Sen, Sudeshna; Maiti, Nakul Chandra

    2016-09-01

    `Click reactions' are the copper catalysed dipolar cycloaddition reaction of azides and alkynes to incorporate nitrogens into a cyclic hydrocarbon scaffold forming a triazole ring. Owing to its efficiency and versatility, this reaction and the products, triazole-containing heterocycles, have immense importance in medicinal chemistry. Copper is the only known catalyst to carry out this reaction, the mechanism of which remains unclear. We report here that the `click reactions' can also be catalysed by silver halides in non-aqueous medium. It constitutes an alternative to the well-known CuAAC click reaction. The yield of the reaction varies on the type of counter ion present in the silver salt. This reaction exhibits significant features, such as high regioselectivity, mild reaction conditions, easy availability of substrates and reasonably good yields. In this communication, the findings of a new catalyst along with the effect of solvent and counter ions will help to decipher the still obscure mechanism of this important reaction.

  5. Experimental and kinetic modelling studies on the acid-catalysed hydrolysis of the water hyacinth plant to levulinic acid.

    PubMed

    Girisuta, B; Danon, B; Manurung, R; Janssen, L P B M; Heeres, H J

    2008-11-01

    A comprehensive experimental and modelling study on the acid-catalysed hydrolysis of the water hyacinth plant (Eichhornia crassipes) to optimise the yield of levulinic acid (LA) is reported (T=150-175 degrees CH2SO4 = 0.1-1M, water hyacinth intake=1-5wt%). At high acid concentrations (>0.5M), LA was the major organic acid whereas at low acid concentrations (<0.1M) and high initial intakes of water hyacinth, the formation of propionic acid instead of LA was favoured. The highest yield of LA was 53mol% (35wt%) based on the amount of C6-sugars in the water hyacinth (T=175 degrees CH2SO4 =1M , water hyacinth intake=1wt%). The LA yield as a function of the process conditions was modelled using a kinetic model originally developed for the acid-catalysed hydrolysis of cellulose and good agreement between the experimental and modelled data was obtained.

  6. Isotopic effects in mechanistic studies of biotransformations of fluorine derivatives of L-alanine catalysed by L-alanine dehydrogenase.

    PubMed

    Szymańska-Majchrzak, Jolanta; Pałka, Katarzyna; Kańska, Marianna

    2017-05-01

    Synthesis of 3-fluoro-[2-(2)H]-L-alanine (3-F-[(2)H]-L-Ala) in reductive amination of 3-fluoropyruvic acid catalysed by L-alanine dehydrogenase (AlaDH) was described. Fluorine derivative was used to study oxidative deamination catalysed by AlaDH applied kinetic (for 3-F-L-Ala in H2O - KIE's on Vmax: 1.1; on Vmax/KM: 1.2; for 3-F-L-Ala in (2)H2O - on Vmax: 1.4; on Vmax/KM: 2.1) and solvent isotope effect methods (for 3-F-L-Ala - SIE's on Vmax: 1.0; on Vmax/KM: 0.87; for 3-F-[2-(2)H]-L-Ala - on Vmax: 1.4; on Vmax/KM: 1.5). Studies explain some details of reaction mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Silver-catalysed azide-alkyne cycloaddition (AgAAC): assessing the mechanism by density functional theory calculations.

    PubMed

    Banerji, Biswadip; Chandrasekhar, K; Killi, Sunil Kumar; Pramanik, Sumit Kumar; Uttam, Pal; Sen, Sudeshna; Maiti, Nakul Chandra

    2016-09-01

    'Click reactions' are the copper catalysed dipolar cycloaddition reaction of azides and alkynes to incorporate nitrogens into a cyclic hydrocarbon scaffold forming a triazole ring. Owing to its efficiency and versatility, this reaction and the products, triazole-containing heterocycles, have immense importance in medicinal chemistry. Copper is the only known catalyst to carry out this reaction, the mechanism of which remains unclear. We report here that the 'click reactions' can also be catalysed by silver halides in non-aqueous medium. It constitutes an alternative to the well-known CuAAC click reaction. The yield of the reaction varies on the type of counter ion present in the silver salt. This reaction exhibits significant features, such as high regioselectivity, mild reaction conditions, easy availability of substrates and reasonably good yields. In this communication, the findings of a new catalyst along with the effect of solvent and counter ions will help to decipher the still obscure mechanism of this important reaction.

  8. [Ambroise Paré in French literature].

    PubMed

    Dumaitre, P

    1995-01-01

    The 16th century by its passionate side has been the favourite one of authors of historical novels in which among the heroes of "cloak and dagger stories" appears sometime Ambroise Paré. Alexandre Dumas (the father) has shown him at the court of Charles IX in La Reine Margot (1845) where he does not however play a great role. On the contrary, Balzac in Le Martyr calviniste (1842) has given him a capital part close to the dying François II, whom he intended to trepanize but had to give up this idea as a consequence of the opposition of the queen-mother Catherine de Médicis. In the present century, Robert Merle in Paris ma bonne ville (Fortune de France, 3, 1980) shows Paré at the time of the Saint Barthélemy.

  9. [Ambroise Paré and Latin].

    PubMed

    Drouin, Emmanuel

    2010-06-01

    We report a study of a medical book written by Antoine Mizaud (Memorabilium utilium, in ac iucundorum aphorismos Arcanorum omnis generis locupletes, perpulchre digestae), which was written in Latin, but has been extensively annotated in French.The book is from the personal collection of one of the physicians of Napoleon III. There is an oral tradition within his family that one of the works in the book had been annotated by Ambroise Paré. We know very little, apart from a few receipts and his signature, about the writing of the master of French surgery. Did he understand the language of Galen? There are many annotated passages in the works of Pare which are in the book. We examine whether these annotations were actually made by Ambroise Paré or whether they were done for him.

  10. Les Brulures Chimiques Par Le Laurier Rose

    PubMed Central

    Bakkali, H.; Ababou, M.; Nassim Sabah, T.; Moussaoui, A.; Ennouhi, A.; Fouadi, F.Z.; Siah, S.; Ihrai, H.

    2010-01-01

    Summary Le laurier rose ou Nerium oleander est un arbuste qui pousse naturellement dans les régions méditerranéennes. Au Maroc on le trouve dans les lieux humides. Il est réputé par ses risques de toxicité systémique en cas d'empoisonnement à cause de la présence de deux alcaloïdes, surtout l'oléandrine. La littérature illustre des cas d'utilisation locale des feuilles de cette plante contre la gale, les hémorroïdes et les furoncles. Nous rapportons deux cas de brûlures chimiques par le laurier rose de gravité différente. Cela doit aboutir à une information élargie de la population, ainsi qu'une réglementation stricte de sa commercialisation. PMID:21991211

  11. Combined DSEK and Transconjunctival Pars Plana Vitrectomy

    PubMed Central

    Sane, Mona; Shaikh, Naazli

    2016-01-01

    We report here three patients who underwent combined Descemet's stripping with endothelial keratoplasty and transconjunctival pars plana vitrectomy for bullous keratopathy and posterior segment pathology. A surgical technique and case histories are described. Anatomic and visual outcomes of combined Descemet's stripping with endothelial keratoplasty and vitrectomy were excellent. Our experience provides technical guidelines and limitations. The combined minimally invasive techniques allow for rapid anatomical recovery and return of function and visual acuity in a single sitting. PMID:27413563

  12. Par Pond refill water quality sampling

    SciTech Connect

    Koch, J.W. II; Martin, F.D.; Westbury, H.M.

    1996-08-01

    This study was designed to document anoxia and its cause in the event that the anoxia caused a fish kill. However, no fish kill was observed during this study, and dissolved oxygen and nutrient concentrations generally remained within the range expected for southeastern reservoirs. Par Pond water quality monitoring will continue during the second summer after refill as the aquatic macrophytes become reestablished and nutrients in the sediments are released to the water column.

  13. Laccase‐catalysed oxidations of naturally occurring phenols: from in vivo biosynthetic pathways to green synthetic applications

    PubMed Central

    Jeon, Jong‐Rok; Baldrian, Petr; Murugesan, Kumarasamy; Chang, Yoon‐Seok

    2012-01-01

    Summary Laccases are oxidases that contain several copper atoms, and catalyse single‐electron oxidations of phenolic compounds with concomitant reduction of oxygen to water. The enzymes are particularly widespread in ligninolytic basidiomycetes, but also occur in certain prokaryotes, insects and plants. Depending on the species, laccases are involved in various biosynthetic processes contributing to carbon recycling in land ecosystems and the morphogenesis of biomatrices, wherein low‐molecular‐weight naturally occurring phenols serve as key enzyme substrates. Studies of these in vivo synthetic pathways have afforded new insights into fungal laccase applicability in green synthetic chemistry. Thus, we here review fungal laccase‐catalysed oxidations of naturally occurring phenols that are particularly relevant to the synthesis of fine organic chemicals, and we discuss how the discovered synthetic strategies mimic laccase‐involved in vivo pathways, thus enhancing the green nature of such reactions. Laccase‐catalysed in vivo processes yield several types of biopolymers, including those of cuticles, lignin, polyflavonoids, humus and the melanin pigments, using natural mono‐ or poly‐phenols as building blocks. The in vivo synthetic pathways involve either phenoxyl radical‐mediated coupling or cross‐linking reactions, and can be adapted to the design of in vitro oxidative processes involving fungal laccases in organic synthesis; the laccase substrates and the synthetic mechanisms reflect in vivo processes. Notably, such in vitro synthetic pathways can also reproduce physicochemical properties (e.g. those of chromophores, and radical‐scavenging, hydration and antimicrobial activities) found in natural biomaterials. Careful study of laccase‐associated in vivo metabolic pathways has been rewarded by the discovery of novel green applications for fungal laccases. This review comprehensively summarizes the available data on laccase‐catalysed

  14. Selective route to 2-propenyl aryls directly from wood by a tandem organosolv and palladium-catalysed transfer hydrogenolysis.

    PubMed

    Galkin, Maxim V; Samec, Joseph S M

    2014-08-01

    A tandem organosolv pulping and Pd-catalysed transfer hydrogenolysis depolymerisation and deoxygenation has been developed. The tandem process generated 2-methoxy-4-(prop-1-enyl)phenol in 23% yield (92% theoretical monomer yield) starting from pine wood and 2,6-dimethoxy-4-(prop-1-enyl)phenol in 49% yield (92% theoretical monomer yield) starting from birch wood. Only endogenous hydrogen from wood was consumed, and the reaction was performed using green solvents.

  15. Chirality Transfer in Gold(I)‐Catalysed Hydroalkoxylation of 1,3‐Disubstituted Allenes

    PubMed Central

    Webster, Stacey; Sutherland, Daniel R.

    2016-01-01

    Abstract Gold(I)‐catalysed intermolecular hydroalkoxylation of enantioenriched 1,3‐disubstituted allenes was previously reported to occur with poor chirality transfer due to rapid allene racemisation. The first intermolecular hydroalkoxylation of allenes with efficient chirality transfer is reported here, exploiting conditions that suppress allene racemisation. A full substrate scope study reveals that excellent regio‐ and stereoselectivities are achieved when a σ‐withdrawing substituent is present. PMID:27862422

  16. Anion effect controlling the selectivity in the zinc-catalysed copolymerisation of CO2 and cyclohexene oxide

    PubMed Central

    Elmas, Sait; Subhani, Muhammad Afzal; Leitner, Walter

    2015-01-01

    Summary The choice of the anion has a surprisingly strong effect on the incorporation of CO2 into the polymer obtained during the zinc-catalysed copolymerisation of CO2 and cyclohexene oxide. The product span ranges from polyethercarbonates, where short polyether sequences alternate with carbonate linkages, to polycarbonates with a strictly alternating sequence of the repeating units. Herein, we report on the influence of the coordination ability of the anion on the selectivity and kinetics of the copolymerisation reaction. PMID:25670991

  17. Effect of dextran and ammonium sulphate on the reaction catalysed by a glucosyltransferase complex from Streptococcus mutans.

    PubMed

    Newman, B M; White, P; Mohan, S B; Cole, J A

    1980-06-01

    The highly aggregated proteins precipitated by (NH4)2SO4 from the culture fluid of three strains of Streptococcus mutans gradually released less aggregated glucosyltransferase activities - dextransucrase and mutansucrase - which catalysed the synthesis of water-soluble and insoluble glucans from sucrose. Mutansucrase was eluted from a column of Sepharose 6B before dextransucrase. This activity was lost during subsequent dialysis and gel filtration, but there was a corresponding increase in dextransucrase activity which catalysed the formation of soluble glucan when incubated with sucrose alone, and insoluble glucan when incubated with sucrose and 1.55 M-(NH4)2SO4. Relative rates of synthesis of soluble and insoluble glucan in the presence of 1.55 M-(MH4)2SO4 were dependent upon the enzyme concentration: high concentrations favoured insoluble glucan synthesis. Insoluble glucans synthesized by mutansucrase or by dextransucrase in the presence of 1.55 M-(NH4)2SO4 were more sensitive to hydrolysis by mutanase than by dextranse, but soluble glucans were more extensively hydrolysed by dextranase than by mutanase. Partially purified dextransucrase sedimented through glycerol density gradients as a single symmetrical peak with an apparent molecular weight in the range 100000 to 110000. In the presence of 1.55 M-(NH4)2SO4, part of the activity sedimented rapidly as a high molecular weight aggregate. The results strongly suggest that soluble and insoluble glucans are synthesized by interconvertible forms of the same glucosyltransferase. The aggregated form, mutansucrase, preferentially catalyses (1 leads to 3)-alpha bond formation but dissociates during gel filtration to the dextransucrase form which catalyses (1 leads to 6)-alpha bond formation.

  18. Chemoenzymatic one-pot synthesis in an aqueous medium: combination of metal-catalysed allylic alcohol isomerisation-asymmetric bioamination.

    PubMed

    Ríos-Lombardía, Nicolás; Vidal, Cristian; Cocina, María; Morís, Francisco; García-Álvarez, Joaquín; González-Sabín, Javier

    2015-07-11

    The ruthenium-catalysed isomerisation of allylic alcohols was coupled, for the first time, with asymmetric bioamination in a one-pot process in an aqueous medium. In the cases involving prochiral ketones, the ω-TA exhibited excellent enantioselectivity, identical to that observed in the single step. As a result, amines were obtained from allylic alcohols with high overall yields and excellent enantiomeric excesses.

  19. Elimination behavior patterns of domestic cats (Felis catus) with and without elimination behavior problems.

    PubMed

    Sung, Wailani; Crowell-Davis, Sharon L

    2006-09-01

    To investigate the relationship of litter box location as it relates to cats' use of space in the house, elimination problems, and certain behaviors associated with elimination. 40 cats in single-cat house-holds with or without elimination behavior problems (20 cats/group). Camcorders were used to record the cats' behaviors at the litter box and other areas in which they eliminated during a 72-hour period. Use of space in the house was recorded by direct observation during 400 minutes of the 72-hour period. Elimination behaviors and other cat- and litter box-associated variables were compared between groups; litter box location with respect to inappropriate elimination was assessed. Litter box location did not differ between cats with and without elimination behavior problems. An inverse correlation was found between time spent sniffing and the distance of the litter box from the central core area. Cats with elimination problems spent significantly less time digging at the litter box than cats without elimination problems. There was no significant difference in the time spent pawing in litter box, sniffing, or covering excreta after elimination between the 2 groups of cats. Times spent digging in litter boxes by cats with and without elimination problems have been determined, and data suggest that actual digging times could be used as a means to test for litter preference and litter aversion. This information may also be used to identify cats with litter aversion prior to the development of an elimination problem.

  20. Iridium-catalysed regioselective borylation of carboranes via direct B-H activation

    NASA Astrophysics Data System (ADS)

    Cheng, Ruofei; Qiu, Zaozao; Xie, Zuowei

    2017-03-01

    Carboranes are carbon-boron molecular clusters, which can be viewed as three-dimensional analogues to benzene. They are finding many applications in medicine, materials and organometallic chemistry. On the other hand, their exceptional thermal and chemical stabilities, as well as 3D structures, make them very difficult to be functionalized, in particular the regioselective functionalization of BH vertex among ten similar B-H bonds. Here we report a very efficient iridium-catalysed borylation of cage B(3,6)-H bonds of o-carboranes with excellent yields and regioselectivity using bis(pinacolato)diboron (B2pin2) as a reagent. Selective cage B(4)-H borylation has also been achieved by introducing a bulky TBDMS (tert-butyldimethylsilyl) group to one cage carbon vertex. The resultant 3,6-(Bpin)2-o-carboranes are useful synthons for the synthesis of a wide variety of B(3,6)-difunctionalized o-carboranes bearing cage B-X (X=O, N, C, I and Br) bonds.

  1. Characterization of uronate dehydrogenases catalysing the initial step in an oxidative pathway

    PubMed Central

    Pick, André; Schmid, Jochen; Sieber, Volker

    2015-01-01

    Uronate dehydrogenases catalyse the oxidation of uronic acids to aldaric acids, which represent ‘top value-added chemicals’ that have the potential to substitute petroleum-derived chemicals. The identification and annotation of three uronate dehydrogenases derived from Fulvimarina pelagi HTCC2506, Streptomyces viridochromogenes DSM 40736 and Oceanicola granulosus DSM 15982 via sequence analysis is described. Characterization and comparison with two known uronate dehydrogenases in regard to substrate spectrum, catalytic activity and pH as well as temperature dependence was performed. The catalytic efficiency was investigated in two different buffer systems; potassium phosphate and Tris-HCl. In addition to the typical and well available substrates glucuronate and galacturonate also mannuronate as part of many structural polysaccharides were tested. The uronate dehydrogenase of Agrobacterium tumefaciens and Pseudomonas syringae showed catalytic dependency on the buffer system resulting in an increased Km especially for glucuronate in potassium phosphate compared with Tris-HCl buffer. Enzyme stability at 37°C of the different Udhs was in the order: P. syringae < S. viridochromogens < A. tumefaciens < F. pelagi < O. granulosus. All enzymes showed activity within a broad pH range from 7.0 to 9.5, only O. granulosus had a very narrow range around 7.0. PMID:25884328

  2. Palladium-catalysed transannular C-H functionalization of alicyclic amines.

    PubMed

    Topczewski, Joseph J; Cabrera, Pablo J; Saper, Noam I; Sanford, Melanie S

    2016-03-10

    Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline.

  3. Sequence-defined bioactive macrocycles via an acid-catalysed cascade reaction

    NASA Astrophysics Data System (ADS)

    Porel, Mintu; Thornlow, Dana N.; Phan, Ngoc N.; Alabi, Christopher A.

    2016-06-01

    Synthetic macrocycles derived from sequence-defined oligomers are a unique structural class whose ring size, sequence and structure can be tuned via precise organization of the primary sequence. Similar to peptides and other peptidomimetics, these well-defined synthetic macromolecules become pharmacologically relevant when bioactive side chains are incorporated into their primary sequence. In this article, we report the synthesis of oligothioetheramide (oligoTEA) macrocycles via a one-pot acid-catalysed cascade reaction. The versatility of the cyclization chemistry and modularity of the assembly process was demonstrated via the synthesis of >20 diverse oligoTEA macrocycles. Structural characterization via NMR spectroscopy revealed the presence of conformational isomers, which enabled the determination of local chain dynamics within the macromolecular structure. Finally, we demonstrate the biological activity of oligoTEA macrocycles designed to mimic facially amphiphilic antimicrobial peptides. The preliminary results indicate that macrocyclic oligoTEAs with just two-to-three cationic charge centres can elicit potent antibacterial activity against Gram-positive and Gram-negative bacteria.

  4. Epoxidation of cottonseed oil by aqueous hydrogen peroxide catalysed by liquid inorganic acids.

    PubMed

    Dinda, Srikanta; Patwardhan, Anand V; Goud, Vaibhav V; Pradhan, Narayan C

    2008-06-01

    The kinetics of epoxidation of cottonseed oil by peroxyacetic acid generated in situ from hydrogen peroxide and glacial acetic acid in the presence of liquid inorganic acid catalysts were studied. It was possible to obtain up to 78% relative conversion to oxirane with very less oxirane cleavage by in situ technique. The rate constants for sulphuric acid catalysed epoxidation of cottonseed oil were in the range 0.39-5.4 x 10(-6)L mol(-1)s(-1) and the activation energy was found to be 11.7 kcal mol(-1). Some thermodynamic parameters such as enthalpy, entropy, and free energy of activation were determined to be of 11.0 kcal mol(-1), -51.4 cal mol(-1)K(-1) and 28.1 kcal mol(-1), respectively. The order of effectiveness of catalysts was found to be sulphuric acid>phosphoric acid>nitric acid>hydrochloric acid. Acetic acid was found to be superior to formic acid for the in situ cottonseed oil epoxidation.

  5. Acid-catalysed xylose dehydration into furfural in the presence of kraft lignin.

    PubMed

    Lamminpää, Kaisa; Ahola, Juha; Tanskanen, Juha

    2015-02-01

    In this study, the effects of kraft lignin (Indulin AT) on acid-catalysed xylose dehydration into furfural were studied in formic and sulphuric acids. The study was done using D-optimal design. Three variables in both acids were included in the design: time (20-80 min), temperature (160-180°C) and initial lignin concentration (0-20 g/l). The dependent variables were xylose conversion, furfural yield, furfural selectivity and pH change. The results showed that the xylose conversion and furfural yield decreased in sulphuric acid, while in formic acid the changes were minor. Additionally, it was showed that lignin has an acid-neutralising capacity, and the added lignin increased the pH of reactant solutions in both acids. The pH rise was considerably lower in formic acid than in sulphuric acid. However, the higher pH did not explain all the changes in conversion and yield, and thus lignin evidently inhibits the formation of furfural.

  6. Glycolysis of carbon fiber-epoxy unidirectional mat catalysed by sodium hydroxide

    SciTech Connect

    Zaini, Mariana Binti Mohd; Badri, Khairiah Haji

    2014-09-03

    This study was conducted to recycle carbon fibre-epoxy (CFRP) composite in woven sheet/ mat form. The CFRP was recycled through glycolysis with polyethlyene glycol (PEG 200) as the solvent. The CFRP was loaded into the solvent at a ratio of 4:1 (w/w). PEG200 was diluted with water to a ratio of 80:20 (v/v). This reaction was catalysed by sodium hydroxide (NaOH) solution with varying concentrations at 1.5, 1.7 and 1.9% (w/v). The glycolysis was conducted at 180-190 °C. The recovered CF (rCF) was analysed using Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray (EDX) while the degraded solution was analysed using FTIR and the epoxy content was determined. The FTIR spectrum of the rCF exhibited the disappearance of the COC peak belonged to epoxy and supported by the SEM micrographs that showed clear rCF. On the other hand, the analysed filtrate detected the disappearance of oxygen peak element in the EDX spectrum for all rCF samples. This gave an indication that the epoxy resin has been removed from the surface of the carbon fiber.

  7. Glycolysis of carbon fiber-epoxy unidirectional mat catalysed by sodium hydroxide

    NASA Astrophysics Data System (ADS)

    Zaini, Mariana Binti Mohd; Badri, Khairiah Haji

    2014-09-01

    This study was conducted to recycle carbon fibre-epoxy (CFRP) composite in woven sheet/ mat form. The CFRP was recycled through glycolysis with polyethlyene glycol (PEG 200) as the solvent. The CFRP was loaded into the solvent at a ratio of 4:1 (w/w). PEG200 was diluted with water to a ratio of 80:20 (v/v). This reaction was catalysed by sodium hydroxide (NaOH) solution with varying concentrations at 1.5, 1.7 and 1.9% (w/v). The glycolysis was conducted at 180-190 °C. The recovered CF (rCF) was analysed using Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray (EDX) while the degraded solution was analysed using FTIR and the epoxy content was determined. The FTIR spectrum of the rCF exhibited the disappearance of the COC peak belonged to epoxy and supported by the SEM micrographs that showed clear rCF. On the other hand, the analysed filtrate detected the disappearance of oxygen peak element in the EDX spectrum for all rCF samples. This gave an indication that the epoxy resin has been removed from the surface of the carbon fiber.

  8. Meiotic Recombination in Arabidopsis Is Catalysed by DMC1, with RAD51 Playing a Supporting Role

    PubMed Central

    Da Ines, Olivier; Degroote, Fabienne; Goubely, Chantal; Amiard, Simon; Gallego, Maria E.; White, Charles I.

    2013-01-01

    Recombination establishes the chiasmata that physically link pairs of homologous chromosomes in meiosis, ensuring their balanced segregation at the first meiotic division and generating genetic variation. The visible manifestation of genetic crossing-overs, chiasmata are the result of an intricate and tightly regulated process involving induction of DNA double-strand breaks and their repair through invasion of a homologous template DNA duplex, catalysed by RAD51 and DMC1 in most eukaryotes. We describe here a RAD51-GFP fusion protein that retains the ability to assemble at DNA breaks but has lost its DNA break repair capacity. This protein fully complements the meiotic chromosomal fragmentation and sterility of Arabidopsis rad51, but not rad51 dmc1 mutants. Even though DMC1 is the only active meiotic strand transfer protein in the absence of RAD51 catalytic activity, no effect on genetic map distance was observed in complemented rad51 plants. The presence of inactive RAD51 nucleofilaments is thus able to fully support meiotic DSB repair and normal levels of crossing-over by DMC1. Our data demonstrate that RAD51 plays a supporting role for DMC1 in meiotic recombination in the flowering plant, Arabidopsis. PMID:24086145

  9. Vanillin formation from ferulic acid in Vanilla planifolia is catalysed by a single enzyme.

    PubMed

    Gallage, Nethaji J; Hansen, Esben H; Kannangara, Rubini; Olsen, Carl Erik; Motawia, Mohammed Saddik; Jørgensen, Kirsten; Holme, Inger; Hebelstrup, Kim; Grisoni, Michel; Møller, Birger Lindberg

    2014-06-19

    Vanillin is a popular and valuable flavour compound. It is the key constituent of the natural vanilla flavour obtained from cured vanilla pods. Here we show that a single hydratase/lyase type enzyme designated vanillin synthase (VpVAN) catalyses direct conversion of ferulic acid and its glucoside into vanillin and its glucoside, respectively. The enzyme shows high sequence similarity to cysteine proteinases and is specific to the substitution pattern at the aromatic ring and does not metabolize caffeic acid and p-coumaric acid as demonstrated by coupled transcription/translation assays. VpVAN localizes to the inner part of the vanilla pod and high transcript levels are found in single cells located a few cell layers from the inner epidermis. Transient expression of VpVAN in tobacco and stable expression in barley in combination with the action of endogenous alcohol dehydrogenases and UDP-glucosyltransferases result in vanillyl alcohol glucoside formation from endogenous ferulic acid. A gene encoding an enzyme showing 71% sequence identity to VpVAN was identified in another vanillin-producing plant species Glechoma hederacea and was also shown to be a vanillin synthase as demonstrated by transient expression in tobacco.

  10. Effect of metal ions on the kinetics of tyrosine oxidation catalysed by tyrosinase.

    PubMed

    Palumbo, A; Misuraca, G; D'Ischia, M; Prota, G

    1985-06-15

    The conversion of tyrosine into dopa [3-(3,4-dihydroxyphenyl)alanine] is the rate limiting step in the biosynthesis of melanins catalysed by tyrosinase. This hydroxylation reaction is characterized by a lag period, the extent of which depends on various parameters, notably the presence of a suitable hydrogen donor such as dopa or tetrahydropterin. We have now found that catalytic amounts of Fe2+ ions have the same effect as dopa in stimulating the tyrosine hydroxylase activity of the enzyme. Kinetic experiments showed that the shortening of the induction time depends on the concentration of the added metal and the nature of the buffer system used and is not suppressed by superoxide dismutase, catalase, formate or mannitol. Notably, Fe3+ ions showed only a small delaying effect on tyrosinase activity. Among the other metals which were tested, Zn2+, Co2+, Cd2+ and Ni2+ had no detectable influence, whereas Cu2+ and Mn2+ exhibited a marked inhibitory effect on the kinetics of tyrosine oxidation. These findings are discussed in the light of the commonly accepted mechanism of action of tyrosinase.

  11. Topological analysis of the MraY protein catalysing the first membrane step of peptidoglycan synthesis.

    PubMed

    Bouhss, A; Mengin-Lecreulx, D; Le Beller, D; Van Heijenoort, J

    1999-11-01

    The two-dimensional membrane topology of the Escherichia coli and Staphylococcus aureus MraY transferases, which catalyse the formation of the first lipid intermediate of peptidoglycan synthesis, was established using the beta-lactamase fusion system. All 28 constructed mraY-blaM fusions produced hybrid proteins. Analysis of the ampicillin resistance of the strains with hybrids led to a common topological model possessing 10 transmembrane segments, five cytoplasmic domains and six periplasmic domains including the N- and C-terminal ends. The agreement between the topologies of E. coli and S. aureus, their agreement to a fair extent with predicted models and a number of features arising from the comparative analysis of 25 orthologue sequences strongly suggested the validity of the model for all eubacterial MraYs. The primary structure of the 10 transmembrane segments diverged among orthologues, but they retained their hydrophobicity, number and size. The similarity of the sequences and distribution of the five cytoplasmic domains in both models, as well as their conservation among the MraY orthologues, clearly suggested their possible involvement in substrate recognition and in the catalytic process. Complementation tests showed that only fusions with untruncated mraY restored growth. It was noteworthy that S. aureus MraY was functional in E. coli. An increased MraY transferase activity was observed only with the untruncated hybrids from both organisms.

  12. Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases

    PubMed Central

    Walport, Louise J.; Hopkinson, Richard J.; Chowdhury, Rasheduzzaman; Schiller, Rachel; Ge, Wei; Kawamura, Akane; Schofield, Christopher J.

    2016-01-01

    While the oxygen-dependent reversal of lysine Nɛ-methylation is well established, the existence of bona fide Nω-methylarginine demethylases (RDMs) is controversial. Lysine demethylation, as catalysed by two families of lysine demethylases (the flavin-dependent KDM1 enzymes and the 2-oxoglutarate- and oxygen-dependent JmjC KDMs, respectively), proceeds via oxidation of the N-methyl group, resulting in the release of formaldehyde. Here we report detailed biochemical studies clearly demonstrating that, in purified form, a subset of JmjC KDMs can also act as RDMs, both on histone and non-histone fragments, resulting in formaldehyde release. RDM catalysis is studied using peptides of wild-type sequences known to be arginine-methylated and sequences in which the KDM's methylated target lysine is substituted for a methylated arginine. Notably, the preferred sequence requirements for KDM and RDM activity vary even with the same JmjC enzymes. The demonstration of RDM activity by isolated JmjC enzymes will stimulate efforts to detect biologically relevant RDM activity. PMID:27337104

  13. Mechanistic investigation of the iridium-catalysed alkylation of amines with alcohols.

    PubMed

    Fristrup, Peter; Tursky, Matyas; Madsen, Robert

    2012-04-07

    The [Cp*IrCl(2)](2)-catalysed alkylation of amines with alcohols was investigated using a combination of experimental and theoretical methods. A Hammett study involving a series of para-substituted benzyl alcohols resulted in a line with a negative slope. This clearly documents that a positive charge is built up in the transition state, which in combination with the measurement of a significant kinetic isotope effect determines hydride abstraction as being the selectivity-determining step under these conditions. A complementary Hammett study using para-substituted anilines was also carried out. Again, a line with a negative slope was obtained suggesting that nucleophilic attack on the aldehyde is selectivity-determining. A computational investigation of the entire catalytic cycle with full-sized ligands and substrates was performed using density functional theory. The results suggest a catalytic cycle where the intermediate aldehyde stays coordinated to the iridium catalyst and reacts with the amine to give a hemiaminal which is also bound to the catalyst. Dehydration to the imine and reduction to the product amine also takes place without breaking the coordination to the catalyst. The fact that the entire catalytic cycle takes place with all the intermediates bound to the catalyst is important for the further development of this synthetic transformation.

  14. Iridium-catalysed regioselective borylation of carboranes via direct B–H activation

    PubMed Central

    Cheng, Ruofei; Qiu, Zaozao; Xie, Zuowei

    2017-01-01

    Carboranes are carbon–boron molecular clusters, which can be viewed as three-dimensional analogues to benzene. They are finding many applications in medicine, materials and organometallic chemistry. On the other hand, their exceptional thermal and chemical stabilities, as well as 3D structures, make them very difficult to be functionalized, in particular the regioselective functionalization of BH vertex among ten similar B–H bonds. Here we report a very efficient iridium-catalysed borylation of cage B(3,6)–H bonds of o-carboranes with excellent yields and regioselectivity using bis(pinacolato)diboron (B2pin2) as a reagent. Selective cage B(4)–H borylation has also been achieved by introducing a bulky TBDMS (tert-butyldimethylsilyl) group to one cage carbon vertex. The resultant 3,6-(Bpin)2-o-carboranes are useful synthons for the synthesis of a wide variety of B(3,6)-difunctionalized o-carboranes bearing cage B–X (X=O, N, C, I and Br) bonds. PMID:28300061

  15. Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

    PubMed Central

    Omedes-Pujol, Marta

    2010-01-01

    Summary Propylene carbonate can be used as a green solvent for the asymmetric synthesis of cyanohydrin trimethylsilyl ethers from aldehydes and trimethylsilyl cyanide catalysed by VO(salen)NCS, though reactions are slower in this solvent than the corresponding reactions carried out in dichloromethane. A mechanistic study has been undertaken, comparing the catalytic activity of VO(salen)NCS in propylene carbonate and dichloromethane. Reactions in both solvents obey overall second-order kinetics, the rate of reaction being dependent on the concentration of both the aldehyde and trimethylsilyl cyanide. The order with respect to VO(salen)NCS was determined and found to decrease from 1.2 in dichloromethane to 1.0 in propylene carbonate, indicating that in propylene carbonate, VO(salen)NCS is present only as a mononuclear species, whereas in dichloromethane dinuclear species are present which have previously been shown to be responsible for most of the catalytic activity. Evidence from 51V NMR spectroscopy suggested that propylene carbonate coordinates to VO(salen)NCS, blocking the free coordination site, thus inhibiting its Lewis acidity and accounting for the reduction in catalytic activity. This explanation was further supported by a Hammett analysis study, which indicated that Lewis base catalysis made a much greater contribution to the overall catalytic activity of VO(salen)NCS in propylene carbonate than in dichloromethane. PMID:21085513

  16. Extraction of copper from an oxidized (lateritic) ore using bacterially catalysed reductive dissolution.

    PubMed

    Nancucheo, Ivan; Grail, Barry M; Hilario, Felipe; du Plessis, Chris; Johnson, D Barrie

    2014-01-01

    An oxidized lateritic ore which contained 0.8 % (by weight) copper was bioleached in pH- and temperature-controlled stirred reactors under acidic reducing conditions using pure and mixed cultures of the acidophilic chemolithotrophic bacterium Acidithiobacillus ferrooxidans. Sulfur was provided as the electron donor for the bacteria, and ferric iron present in goethite (the major ferric iron mineral present in the ore) acted as electron acceptor. Significantly more copper was leached by bacterially catalysed reductive dissolution of the laterite than in aerobic cultures or in sterile anoxic reactors, with up to 78 % of the copper present in the ore being extracted. This included copper that was leached from acid-labile minerals (chiefly copper silicates) and that which was associated with ferric iron minerals in the lateritic ore. In the anaerobic bioreactors, soluble iron in the leach liquors was present as iron (II) and copper as copper (I), but both metals were rapidly oxidized (to iron (III) and copper (II)) when the reactors were aerated. The number of bacteria added to the reactors had a critical role in dictating the rate and yield of copper solubilised from the ore. This work has provided further evidence that reductive bioprocessing, a recently described approach for extracting base metals from oxidized deposits, has the potential to greatly extend the range of metal ores that can be biomined.

  17. ‘Impact hunters’ catalyse cooperative hunting in two wild chimpanzee communities

    PubMed Central

    Gilby, Ian C.; Machanda, Zarin P.; Mjungu, Deus C.; Rosen, Jeremiah; Muller, Martin N.; Pusey, Anne E.; Wrangham, Richard W.

    2015-01-01

    Even when hunting in groups is mutually beneficial, it is unclear how communal hunts are initiated. If it is costly to be the only hunter, individuals should be reluctant to hunt unless others already are. We used 70 years of data from three communities to examine how male chimpanzees ‘solve’ this apparent collective action problem. The ‘impact hunter’ hypothesis proposes that group hunts are sometimes catalysed by certain individuals that hunt more readily than others. In two communities (Kasekela and Kanyawara), we identified a total of five males that exhibited high hunt participation rates for their age, and whose presence at an encounter with red colobus monkeys increased group hunting probability. Critically, these impact hunters were observed to hunt first more often than expected by chance. We argue that by hunting first, these males dilute prey defences and create opportunities for previously reluctant participants. This by-product mutualism can explain variation in group hunting rates within and between social groups. Hunting rates declined after the death of impact hunter FG in Kasekela and after impact hunter MS stopped hunting frequently in Kanyawara. There were no impact hunters in the third, smaller community (Mitumba), where, unlike the others, hunting probability increased with the number of females present at an encounter with prey. PMID:26503679

  18. Lewis acid-catalysed formation of two-dimensional phthalocyanine covalent organic frameworks.

    PubMed

    Spitler, Eric L; Dichtel, William R

    2010-08-01

    Covalent organic frameworks (COFs) offer a new strategy for assembling organic semiconductors into robust networks with atomic precision and long-range order. General methods for COF synthesis will allow complex building blocks to be incorporated into these emerging materials. Here we report a new Lewis acid-catalysed protocol to form boronate esters directly from protected catechols and arylboronic acids. This transformation also provides crystalline boronate ester-linked COFs from protected polyfunctional catechols and bis(boronic acids). Using this method, we prepared a new COF that features a square lattice composed of phthalocyanine macrocycles joined by phenylene bis(boronic acid) linkers. The phthalocyanines stack in an eclipsed fashion within the COF to form 2.3 nm pores that run parallel to the stacked chromophores. The material's broad absorbance over the solar spectrum, potential for efficient charge transport through the stacked phthalocyanines, good thermal stability and the modular nature of COF synthesis, show strong promise for applications in organic photovoltaic devices.

  19. Graphitic platform for self-catalysed InAs nanowires growth by molecular beam epitaxy

    PubMed Central

    2014-01-01

    We report the self-catalysed growth of InAs nanowires (NWs) on graphite thin films using molecular beam epitaxy via a droplet-assisted technique. Through optimising metal droplets, we obtained vertically aligned InAs NWs with highly uniform diameter along their entire length. In comparison with conventional InAs NWs grown on Si (111), the graphite surface led to significant effects on the NWs geometry grown on it, i.e. larger diameter, shorter length with lower number density, which were ascribed to the absence of dangling bonds on the graphite surface. The axial growth rate of the NWs has a strong dependence on growth time, which increases quickly in the beginning then slows down after the NWs reach a length of approximately 0.8 μm. This is attributed to the combined axial growth contributions from the surface impingement and sidewall impingement together with the desorption of adatoms during the diffusion. The growth of InAs NWs on graphite was proposed following a vapour-solid mechanism. High-resolution transmission electron microscopy reveals that the NW has a mixture of pure zinc-blende and wurtzite insertions. PMID:25024683

  20. Graphitic platform for self-catalysed InAs nanowires growth by molecular beam epitaxy.

    PubMed

    Zhuang, Qian D; Anyebe, Ezekiel A; Sanchez, Ana M; Rajpalke, Mohana K; Veal, Tim D; Zhukov, Alexander; Robinson, Benjamin J; Anderson, Frazer; Kolosov, Oleg; Fal'ko, Vladimir

    2014-01-01

    We report the self-catalysed growth of InAs nanowires (NWs) on graphite thin films using molecular beam epitaxy via a droplet-assisted technique. Through optimising metal droplets, we obtained vertically aligned InAs NWs with highly uniform diameter along their entire length. In comparison with conventional InAs NWs grown on Si (111), the graphite surface led to significant effects on the NWs geometry grown on it, i.e. larger diameter, shorter length with lower number density, which were ascribed to the absence of dangling bonds on the graphite surface. The axial growth rate of the NWs has a strong dependence on growth time, which increases quickly in the beginning then slows down after the NWs reach a length of approximately 0.8 μm. This is attributed to the combined axial growth contributions from the surface impingement and sidewall impingement together with the desorption of adatoms during the diffusion. The growth of InAs NWs on graphite was proposed following a vapour-solid mechanism. High-resolution transmission electron microscopy reveals that the NW has a mixture of pure zinc-blende and wurtzite insertions.

  1. Discrimination against diacylglycerol ethers in lipase-catalysed ethanolysis of shark liver oil.

    PubMed

    Fernández, Óscar; Vázquez, Luis; Reglero, Guillermo; Torres, Carlos F

    2013-01-15

    Lipase-catalysed ethanolysis of squalene-free shark liver oil was investigated. The mentioned shark liver oil was comprised mainly of diacylglycerol ether and triacylglycerols. In order to test discrimination against diacylglycerol ether, up to 10 different lipases were compared. The ratio of oil to ethanol and lipase stability were also evaluated. Surprisingly, lipase from Pseudomonas stutzeri was the fastest biocatalyst among all assayed, although poor discrimination against diacylglycerol ether was observed. The best results in terms of selectivity and stability were obtained with immobilised lipase from Candida antarctica (Novozym 435). Ethanolysis reaction after 24h in the presence of Novozym 435 produced total disappearance of triacylglycerol and a final reaction mixture comprised mainly of diacylglycerol ethers (10.6%), monoacylglycerol ethers (32.9%) and fatty acid ethyl esters (46.0%). In addition, when an excess of ethanol was used, diacylglycerol ethers completely disappeared after 15 h, giving a final product mainly composed of monoacylglycerol ethers (36.6%) and fatty acid ethyl esters (46.4%).

  2. Synthesis of deuterium-labelled halogen derivatives of L-tryptophan catalysed by tryptophanase.

    PubMed

    Winnicka, Elżbieta; Szymańska, Jolanta; Kańska, Marianna

    2016-06-01

    The isotopomers of halogen derivatives of l-tryptophan (l-Trp) (4'-F-, 7'-F-, 5'-Cl- and 7'-Br-l-Trp), specifically labelled with deuterium in α-position of the side chain, were obtained by enzymatic coupling of the corresponding halogenated derivatives of indole with S-methyl-l-cysteine in (2)H2O, catalysed by enzyme tryptophanase (EC 4.1.99.1). The positional deuterium enrichment of the resulting tryptophan derivatives was controlled using (1)H NMR. In accordance with the mechanism of the lyase reaction, a 100% deuterium labelling was observed in the α-position; the chemical yields were between 23 and 51%. Furthermore, β-F-l-alanine, synthesized from β-F-pyruvic acid by the l-alanine dehydrogenase reaction, has been tested as a coupling agent to obtain the halogenated deuterium-labelled derivatives of l-Trp. The chemical yield (∼30%) corresponded to that as observed with S-methyl-l-cysteine but the deuterium label was only 63%, probably due to the use of a not completely deuterated incubation medium.

  3. Meiotic recombination in Arabidopsis is catalysed by DMC1, with RAD51 playing a supporting role.

    PubMed

    Da Ines, Olivier; Degroote, Fabienne; Goubely, Chantal; Amiard, Simon; Gallego, Maria E; White, Charles I

    2013-01-01

    Recombination establishes the chiasmata that physically link pairs of homologous chromosomes in meiosis, ensuring their balanced segregation at the first meiotic division and generating genetic variation. The visible manifestation of genetic crossing-overs, chiasmata are the result of an intricate and tightly regulated process involving induction of DNA double-strand breaks and their repair through invasion of a homologous template DNA duplex, catalysed by RAD51 and DMC1 in most eukaryotes. We describe here a RAD51-GFP fusion protein that retains the ability to assemble at DNA breaks but has lost its DNA break repair capacity. This protein fully complements the meiotic chromosomal fragmentation and sterility of Arabidopsis rad51, but not rad51 dmc1 mutants. Even though DMC1 is the only active meiotic strand transfer protein in the absence of RAD51 catalytic activity, no effect on genetic map distance was observed in complemented rad51 plants. The presence of inactive RAD51 nucleofilaments is thus able to fully support meiotic DSB repair and normal levels of crossing-over by DMC1. Our data demonstrate that RAD51 plays a supporting role for DMC1 in meiotic recombination in the flowering plant, Arabidopsis.

  4. Hydrogen tunnelling in enzyme-catalysed H-transfer reactions: flavoprotein and quinoprotein systems

    PubMed Central

    Sutcliffe, Michael J; Masgrau, Laura; Roujeinikova, Anna; Johannissen, Linus O; Hothi, Parvinder; Basran, Jaswir; Ranaghan, Kara E; Mulholland, Adrian J; Leys, David; Scrutton, Nigel S

    2006-01-01

    It is now widely accepted that enzyme-catalysed C–H bond breakage occurs by quantum mechanical tunnelling. This paradigm shift in the conceptual framework for these reactions away from semi-classical transition state theory (TST, i.e. including zero-point energy, but with no tunnelling correction) has been driven over the recent years by experimental studies of the temperature dependence of kinetic isotope effects (KIEs) for these reactions in a range of enzymes, including the tryptophan tryptophylquinone-dependent enzymes such as methylamine dehydrogenase and aromatic amine dehydrogenase, and the flavoenzymes such as morphinone reductase and pentaerythritol tetranitrate reductase, which produced observations that are also inconsistent with the simple Bell-correction model of tunnelling. However, these data—especially, the strong temperature dependence of reaction rates and the variable temperature dependence of KIEs—are consistent with other tunnelling models (termed full tunnelling models), in which protein and/or substrate fluctuations generate a configuration compatible with tunnelling. These models accommodate substrate/protein (environment) fluctuations required to attain a configuration with degenerate nuclear quantum states and, when necessary, motion required to increase the probability of tunnelling in these states. Furthermore, tunnelling mechanisms in enzymes are supported by atomistic computational studies performed within the framework of modern TST, which incorporates quantum nuclear effects. PMID:16873125

  5. Rhodium-catalysed syn-carboamination of alkenes via a transient directing group.

    PubMed

    Piou, Tiffany; Rovis, Tomislav

    2015-11-05

    Alkenes are the most ubiquitous prochiral functional groups--those that can be converted from achiral to chiral in a single step--that are accessible to synthetic chemists. For this reason, difunctionalization reactions of alkenes (whereby two functional groups are added to the same double bond) are particularly important, as they can be used to produce highly complex molecular architectures. Stereoselective oxidation reactions, including dihydroxylation, aminohydroxylation and halogenation, are well established methods for functionalizing alkenes. However, the intermolecular incorporation of both carbon- and nitrogen-based functionalities stereoselectively across an alkene has not been reported. Here we describe the rhodium-catalysed carboamination of alkenes at the same (syn) face of a double bond, initiated by a carbon-hydrogen activation event that uses enoxyphthalimides as the source of both the carbon and the nitrogen functionalities. The reaction methodology allows for the intermolecular, stereospecific formation of one carbon-carbon and one carbon-nitrogen bond across an alkene, which is, to our knowledge, unprecedented. The reaction design involves the in situ generation of a bidentate directing group and the use of a new cyclopentadienyl ligand to control the reactivity of rhodium. The results provide a new way of synthesizing functionalized alkenes, and should lead to the convergent and stereoselective assembly of amine-containing acyclic molecules.

  6. Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids

    NASA Astrophysics Data System (ADS)

    Sidera, Mireia; Fletcher, Stephen P.

    2015-11-01

    Csp2-Csp2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals. Csp2-Csp3 cross-coupling reactions have been developed, but enantioselective variations are rare and simply retaining the stereochemistry is a problem. Here we report a highly enantioselective Csp2-Csp3 bond-forming method that couples arylboronic acids to racemic allyl chlorides. Both enantiomers of a cyclic chloride are converted into a single enantiomer of product via a dynamic kinetic asymmetric transformation. This Rh-catalysed method uses readily available and inexpensive building blocks and is mild and broadly applicable. For electron-deficient, electron-rich or ortho-substituted boronic acids better results are obtained with racemic allyl bromides. Oxygen substitution in the allyl halide is tolerated and the products can be functionalized to provide diverse building blocks. The approach fills a significant gap in the methods for catalytic asymmetric synthesis.

  7. Lactococcus lactis catalyses electricity generation at microbial fuel cell anodes via excretion of a soluble quinone.

    PubMed

    Freguia, Stefano; Masuda, Masaki; Tsujimura, Seiya; Kano, Kenji

    2009-09-01

    Lactococcus lactis is a gram-positive, normally homolactic fermenter that is known to produce several kinds of membrane associated quinones, which are able to mediate electron transfer to extracellular electron acceptors such as Fe(3+), Cu(2+) and hexacyanoferrate. Here we show that this bacterium is also capable of performing extracellular electron transfer to anodes by utilizing at least two soluble redox mediators, as suggested by the two-step catalytic current developed. One of these two mediators was herein suggested to be 2-amino-3-dicarboxy-1,4-naphthoquinone (ACNQ), via evaluation of standard redox potential, ability of the bacterium to exploit the quinone when exogenously provided, as well as by high performance liquid chromatography coupled with UV spectrum analysis. During electricity generation, L. lactis slightly deviated from its normal homolactic metabolism by excreting acetate and pyruvate in stoichiometric amounts with respect to the electrical current. In this metabolism, the anode takes on the role of electron sink for acetogenic fermentation. The finding that L. lactis self-catalyses anodic electron transfer by excretion of redox mediators is remarkable as the mechanisms of extracellular electron transfer by pure cultures of gram-positive bacteria had previously never been elucidated.

  8. Vanillin formation from ferulic acid in Vanilla planifolia is catalysed by a single enzyme

    PubMed Central

    Gallage, Nethaji J.; Hansen, Esben H.; Kannangara, Rubini; Olsen, Carl Erik; Motawia, Mohammed Saddik; Jørgensen, Kirsten; Holme, Inger; Hebelstrup, Kim; Grisoni, Michel; Møller, Birger Lindberg

    2014-01-01

    Vanillin is a popular and valuable flavour compound. It is the key constituent of the natural vanilla flavour obtained from cured vanilla pods. Here we show that a single hydratase/lyase type enzyme designated vanillin synthase (VpVAN) catalyses direct conversion of ferulic acid and its glucoside into vanillin and its glucoside, respectively. The enzyme shows high sequence similarity to cysteine proteinases and is specific to the substitution pattern at the aromatic ring and does not metabolize caffeic acid and p-coumaric acid as demonstrated by coupled transcription/translation assays. VpVAN localizes to the inner part of the vanilla pod and high transcript levels are found in single cells located a few cell layers from the inner epidermis. Transient expression of VpVAN in tobacco and stable expression in barley in combination with the action of endogenous alcohol dehydrogenases and UDP-glucosyltransferases result in vanillyl alcohol glucoside formation from endogenous ferulic acid. A gene encoding an enzyme showing 71% sequence identity to VpVAN was identified in another vanillin-producing plant species Glechoma hederacea and was also shown to be a vanillin synthase as demonstrated by transient expression in tobacco. PMID:24941968

  9. Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

    NASA Astrophysics Data System (ADS)

    Schäfer, Philipp; Palacin, Thomas; Sidera, Mireia; Fletcher, Stephen P.

    2017-06-01

    Using asymmetric catalysis to simultaneously form carbon-carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib--an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery.

  10. Spirochaete flagella hook proteins self-catalyse a lysinoalanine covalent crosslink for motility.

    PubMed

    Miller, Michael R; Miller, Kelly A; Bian, Jiang; James, Milinda E; Zhang, Sheng; Lynch, Michael J; Callery, Patrick S; Hettick, Justin M; Cockburn, Andrew; Liu, Jun; Li, Chunhao; Crane, Brian R; Charon, Nyles W

    2016-08-08

    Spirochaetes are bacteria responsible for several serious diseases, including Lyme disease (Borrelia burgdorferi), syphilis (Treponema pallidum) and leptospirosis (Leptospira interrogans), and contribute to periodontal diseases (Treponema denticola)(1). These spirochaetes employ an unusual form of flagella-based motility necessary for pathogenicity; indeed, spirochaete flagella (periplasmic flagella) reside and rotate within the periplasmic space(2-11). The universal joint or hook that links the rotary motor to the filament is composed of ∼120-130 FlgE proteins, which in spirochaetes form an unusually stable, high-molecular-weight complex(9,12-17). In other bacteria, the hook can be readily dissociated by treatments such as heat(18). In contrast, spirochaete hooks are resistant to these treatments, and several lines of evidence indicate that the high-molecular-weight complex is the consequence of covalent crosslinking(12,13,17). Here, we show that T. denticola FlgE self-catalyses an interpeptide crosslinking reaction between conserved lysine and cysteine, resulting in the formation of an unusual lysinoalanine adduct that polymerizes the hook subunits. Lysinoalanine crosslinks are not needed for flagellar assembly, but they are required for cell motility and hence infection. The self-catalytic nature of FlgE crosslinking has important implications for protein engineering, and its sensitivity to chemical inhibitors provides a new avenue for the development of antimicrobials targeting spirochaetes.

  11. The key nickel enzyme of methanogenesis catalyses the anaerobic oxidation of methane.

    PubMed

    Scheller, Silvan; Goenrich, Meike; Boecher, Reinhard; Thauer, Rudolf K; Jaun, Bernhard

    2010-06-03

    Large amounts (estimates range from 70 Tg per year to 300 Tg per year) of the potent greenhouse gas methane are oxidized to carbon dioxide in marine sediments by communities of methanotrophic archaea and sulphate-reducing bacteria, and thus are prevented from escaping into the atmosphere. Indirect evidence indicates that the anaerobic oxidation of methane might proceed as the reverse of archaeal methanogenesis from carbon dioxide with the nickel-containing methyl-coenzyme M reductase (MCR) as the methane-activating enzyme. However, experiments showing that MCR can catalyse the endergonic back reaction have been lacking. Here we report that purified MCR from Methanothermobacter marburgensis converts methane into methyl-coenzyme M under equilibrium conditions with apparent V(max) (maximum rate) and K(m) (Michaelis constant) values consistent with the observed in vivo kinetics of the anaerobic oxidation of methane with sulphate. This result supports the hypothesis of 'reverse methanogenesis' and is paramount to understanding the still-unknown mechanism of the last step of methanogenesis. The ability of MCR to cleave the particularly strong C-H bond of methane without the involvement of highly reactive oxygen-derived intermediates is directly relevant to catalytic C-H activation, currently an area of great interest in chemistry.

  12. Activating lattice oxygen redox reactions in metal oxides to catalyse oxygen evolution

    NASA Astrophysics Data System (ADS)

    Grimaud, Alexis; Diaz-Morales, Oscar; Han, Binghong; Hong, Wesley T.; Lee, Yueh-Lin; Giordano, Livia; Stoerzinger, Kelsey A.; Koper, Marc T. M.; Shao-Horn, Yang

    2017-05-01

    Understanding how materials that catalyse the oxygen evolution reaction (OER) function is essential for the development of efficient energy-storage technologies. The traditional understanding of the OER mechanism on metal oxides involves four concerted proton-electron transfer steps on metal-ion centres at their surface and product oxygen molecules derived from water. Here, using in situ 18O isotope labelling mass spectrometry, we provide direct experimental evidence that the O2 generated during the OER on some highly active oxides can come from lattice oxygen. The oxides capable of lattice-oxygen oxidation also exhibit pH-dependent OER activity on the reversible hydrogen electrode scale, indicating non-concerted proton-electron transfers in the OER mechanism. Based on our experimental data and density functional theory calculations, we discuss mechanisms that are fundamentally different from the conventional scheme and show that increasing the covalency of metal-oxygen bonds is critical to trigger lattice-oxygen oxidation and enable non-concerted proton-electron transfers during OER.

  13. Inhibition by ethanol, acetaldehyde and trifluoroethanol of reactions catalysed by yeast and horse liver alcohol dehydrogenases.

    PubMed Central

    Dickenson, C J; Dickinson, F M

    1978-01-01

    1. Produced inhibition by ethanol of the acetaldehyde-NADH reaction, catalysed by the alcohol dehydrogenases from yeast and horse liver, was studied at 25 degrees C and pH 6-9. 2. The results with yeast alcohol dehydrogenase are generally consistent with the preferred-pathway mechanism proposed previously [Dickenson & Dickinson (1975) Biochem. J. 147, 303-311]. The observed hyperbolic inhibition by ethanol of the maximum rate of acetaldehyde reduction confirms the existence of the alternative pathway involving an enzyme-ethanol complex. 3. The maximum rate of acetaldehyde reduction with horse liver alcohol dehydrogenase is also subject to hyperbolic inhibition by ethanol. 4. The measured inhibition constants for ethanol provide some of the information required in the determination of the dissociation constant for ethanol from the active ternary complex. 5. Product inhibition by acetaldehyde of the ethanol-NAD+ reaction with yeast alcohol dehydrogenase was examined briefly. The results are consistent with the proposed mechanism. However, the nature of the inhibition of the maximum rate cannot be determined within the accessible range of experimental conditions. 6. Inhibition of yeast alcohol dehydrogenase by trifluoroethanol was studied at 25 degrees C and pH 6-10. The inhibition was competitive with respect to ethanol in the ethanol-NAD+ reaction. Estimates were made of the dissociation constant for trifluoroethanol from the enzyme-NAD+-trifluoroethanol complex in the range pH6-10. PMID:208509

  14. Transglycosylation specificity of glycosyl donors in transglycosylation of stevioside catalysed by cyclodextrin glucanotransferase.

    PubMed

    Lu, Tong; Xia, Yong-mei

    2014-09-15

    Specificity of glycosyl donors is a critical issue in transglycosylation of stevioside, the main methodology to improve edulcorant quality of stevioside. The most popular glucanotransferase applied in this reaction is cyclodextrin glucanotransferase (CGTase) that catalyses cyclisation, coupling, hydrolysis and disproportionation simultaneously; which results a crosstalk in the glycosyl donors that comes from initial reactants, reaction intermediates as well as side products in parallel reactions. In this work, the specificity of glycosyl donors was studied to understand the transglucosylation pathways with the designed experiments and material balance analysis on the products using a commercial CGTase. It has been found that cyclodextrins and starches provided the best transglucosylation yield, while the assayed mono- and disaccharides were not effective glycosyl donors to stevioside with the CGTase. It is proposed that α- and β-cyclodextrins performed transglycosylation via coupling to produce intermediates of reducing sugar and followed by disproportionation with stevioside; while starches may perform the transglycosylation combined the cyclodextrins pathway and hydrolysis pathway of starches. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Palladium-catalysed transannular C-H functionalization of alicyclic amines

    NASA Astrophysics Data System (ADS)

    Topczewski, Joseph J.; Cabrera, Pablo J.; Saper, Noam I.; Sanford, Melanie S.

    2016-03-01

    Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline.

  16. Pd-catalysed ligand-enabled carboxylate-directed highly regioselective arylation of aliphatic acids

    PubMed Central

    Zhu, Yan; Chen, Xiaolan; Yuan, Chunchen; Li, Guobao; Zhang, Jingyu; Zhao, Yingsheng

    2017-01-01

    α-amino acids bearing aromatic side chains are important synthetic units in the synthesis of peptides and natural products. Although various β-C-H arylation methodologies for amino acid derivatives involving the assistance of directing groups have been extensively developed, syntheses that directly employ N-protected amino acids as starting materials remain rare. Herein, we report an N-acetylglycine-enabled Pd-catalysed carboxylate-directed β-C(sp3)-H arylation of aliphatic acids. In this way, various non-natural amino acids can be directly prepared from phthaloylalanine in one step in good to excellent yields. Furthermore, a series of aliphatic acids have been shown to be amenable to this transformation, affording β-arylated propionic acid derivatives in moderate to good yields. More importantly, this ligand-enabled direct β-C(sp3)-H arylation could be easily scaled-up to 10 g under reflux conditions, highlighting the potential utility of this synthetic method. PMID:28383026

  17. Unravelling RNA-substrate interactions in a ribozyme-catalysed reaction using fluorescent turn-on probes.

    PubMed

    Gaffarogullari, Ece Cazibe; Greulich, Peter; Kobitski, Andrei Yu; Nierth, Alexander; Nienhaus, G Ulrich; Jäschke, Andres

    2015-04-07

    The Diels-Alder reaction is one of the most important C-C bond-forming reactions in organic chemistry, and much effort has been devoted to controlling its enantio- and diastereoselectivity. The Diels-Alderase ribozyme (DAse) catalyses the reaction between anthracene dienes and maleimide dienophiles with multiple-turnover, stereoselectivity, and up to 1100-fold rate acceleration. Here, a new generation of anthracene-BODIPY-based fluorescent probes was developed to monitor catalysis by the DAse. The brightness of these probes increases up to 93-fold upon reaction with N-pentylmaleimide (NPM), making these useful tools for investigating the stereochemistry of the ribozyme-catalysed reaction. With these probes, we observed that the DAse catalyses the reaction with >91% de and >99% ee. The stereochemistry of the major product was determined unambiguously by rotating-frame nuclear Overhauser NMR spectroscopy (ROESY-NMR) and is in agreement with crystallographic structure information. The pronounced fluorescence change of the probes furthermore allowed a complete kinetic analysis, which revealed an ordered bi uni type reaction mechanism, with the dienophile binding first.

  18. An ecotoxicological study on tin- and bismuth-catalysed PDMS based coatings containing a surface-active polymer.

    PubMed

    Pretti, Carlo; Oliva, Matteo; Mennillo, Elvira; Barbaglia, Martina; Funel, Marco; Reddy Yasani, Bhaskar; Martinelli, Elisa; Galli, Giancarlo

    2013-12-01

    Novel films were prepared by condensation curing reaction of a poly(dimethyl siloxane) (PDMS) matrix with bismuth neodecanoate and dibutyltin diacetate catalysts. An ecotoxicological study was performed on the leachates of the coatings using the bacterium Vibrio fischeri, the unicellular alga Dunaliella tertiolecta, the crustacean Artemia salina and the fish Sparus aurata (larvae) as testing organisms. A copper-based self-polishing commercial paint was also tested as reference. The results showed that the tin-catalysed coatings and the copper paint were highly toxic against at least two of the four test organisms, whereas bismuth-catalysed coatings did not show any toxic effect. Moreover, the same biological assessment was also carried out on PDMS coatings containing a surface-active fluorinated polymer. The toxicity of the entire polymeric system resulted only from the tin catalyst used for the condensation curing reaction, as the bismuth catalysed coatings incorporating the surface-active polymer remained atoxic toward all the tested organisms. © 2013 Elsevier Inc. All rights reserved.

  19. Fluorescent labelling of in situ hybridisation probes through the copper-catalysed azide-alkyne cycloaddition reaction.

    PubMed

    Hesse, Susann; Manetto, Antonio; Cassinelli, Valentina; Fuchs, Jörg; Ma, Lu; Raddaoui, Nada; Houben, Andreas

    2016-09-01

    In situ hybridisation is a powerful tool to investigate the genome and chromosome architecture. Nick translation (NT) is widely used to label DNA probes for fluorescence in situ hybridisation (FISH). However, NT is limited to the use of long double-stranded DNA and does not allow the labelling of single-stranded and short DNA, e.g. oligonucleotides. An alternative technique is the copper(I)-catalysed azide-alkyne cycloaddition (CuAAC), at which azide and alkyne functional groups react in a multistep process catalysed by copper(I) ions to give 1,4-distributed 1,2,3-triazoles at a high yield (also called 'click reaction'). We successfully applied this technique to label short single-stranded DNA probes as well as long PCR-derived double-stranded probes and tested them by FISH on plant chromosomes and nuclei. The hybridisation efficiency of differently labelled probes was compared to those obtained by conventional labelling techniques. We show that copper(I)-catalysed azide-alkyne cycloaddition-labelled probes are reliable tools to detect different types of repetitive sequences on chromosomes opening new promising routes for the detection of single copy gene. Moreover, a combination of FISH using such probes with other techniques, e.g. immunohistochemistry (IHC) and cell proliferation assays using 5-ethynyl-deoxyuridine, is herein shown to be easily feasible.

  20. Uncatalysed and catalysed soot combustion under NO{sub x} + O{sub 2}: Real diesel versus model soots

    SciTech Connect

    Atribak, I.; Bueno-Lopez, A.; Garcia-Garcia, A.

    2010-11-15

    In this work, the uncatalysed and catalysed combustion of two commercial carbon blacks and three diesel soot samples were analysed and related to the physico-chemical properties of these carbon materials. Model soot samples are less reactive than real soot samples, which can be attributed, mainly, to a lower proportion in heteroatoms and a higher graphitic order for the case of one of the carbon blacks. Among the diesel soot samples tested, the most relevant differences are the volatile matter/fixed carbon contents, which are directly related to the engine operating conditions (idle or loaded) and to the use of an oxidation catalyst or not in the exhaust. The soot collected after an oxidation catalyst (A-soot) is more reactive than the counterpart virgin soot obtained under the same engine operating modes but before the oxidation catalyst. The reactivity of the different soot samples follows the same trend under uncatalysed and catalysed combustion, the combustion profiles being always shifted towards lower temperatures for the catalysed reactions. The differences between the soot samples become less relevant in the presence of a catalyst. The ceria-zirconia catalysts tested are very effective not only to oxidise soot but also to combust the soluble organic fraction emitted at low temperatures. The most reactive soot (A-soot) exhibits a T{sub 50%} parameter of 450 C when using the most active catalyst. (author)

  1. Modelling malaria elimination on the internet.

    PubMed

    Maude, Richard J; Saralamba, Sompob; Lewis, Adrian; Sherwood, Dean; White, Nicholas J; Day, Nicholas P J; Dondorp, Arjen M; White, Lisa J

    2011-07-14

    Unprecedented efforts are underway to eliminate malaria. Mathematical modelling can help to determine the optimal strategies for malaria elimination in different epidemiological settings. This is necessary as there is limited scope for expensive and time-consuming field studies and failure of planned elimination strategies is likely to discourage ongoing investment by funders. However, there has been very little modelling of malaria elimination and little direct involvement of policymakers in its development. There is thus an urgent need for user-friendly and accessible models purpose-designed in collaboration with policymakers to answer pertinent questions arising from the field. An internet site is presented with a simple mathematical modelling platform for population level models of malaria elimination. It is freely accessible to all and designed to be flexible so both the platform and models can be developed through interaction with users. The site is an accessible introduction to modelling for a non-mathematical audience, and lessons learned from the project will help inform future development of mathematical models and improve communication of modelling results. Currently it hosts a simple model of strategies for malaria elimination and this will be developed, and more models added, over time. The iterative process of feedback and development will result in an educational and planning tool for non-modellers to assist with malaria elimination efforts worldwide. By collaboration with end users, iterative development of mathematical models of malaria elimination through this internet platform will maximize its potential as an educational and public health policy planning tool. It will also assist with preliminary optimisation of local malaria elimination strategies before commitment of valuable resources.

  2. Kinetics of the hydrolysis of N-benzoyl-l-serine methyl ester catalysed by bromelain and by papain. Analysis of modifier mechanisms by lattice nomography, computational methods of parameter evaluation for substrate-activated catalyses and consequences of postulated non-productive binding in bromelain- and papain-catalysed hydrolyses

    PubMed Central

    Wharton, Christopher W.; Cornish-Bowden, Athel; Brocklehurst, Keith; Crook, Eric M.

    1974-01-01

    1. N-Benzoyl-l-serine methyl ester was synthesized and evaluated as a substrate for bromelain (EC 3.4.22.4) and for papain (EC 3.4.22.2). 2. For the bromelain-catalysed hydrolysis at pH7.0, plots of [S0]/vi (initial substrate concn./initial velocity) versus [S0] are markedly curved, concave downwards. 3. Analysis by lattice nomography of a modifier kinetic mechanism in which the modifier is substrate reveals that concave-down [S0]/vi versus [S0] plots can arise when the ratio of the rate constants that characterize the breakdown of the binary (ES) and ternary (SES) complexes is either less than or greater than 1. In the latter case, there are severe restrictions on the values that may be taken by the ratio of the dissociation constants of the productive and non-productive binary complexes. 4. Concave-down [S0]/vi versus [S0] plots cannot arise from compulsory substrate activation. 5. Computational methods, based on function minimization, for determination of the apparent parameters that characterize a non-compulsory substrate-activated catalysis are described. 6. In an attempt to interpret the catalysis by bromelain of the hydrolysis of N-benzoyl-l-serine methyl ester in terms of substrate activation, the general substrate-activation model was simplified to one in which only one binary ES complex (that which gives rise directly to products) can form. 7. In terms of this model, the bromelain-catalysed hydrolysis of N-benzoyl-l-serine methyl ester at pH7.0, I=0.1 and 25°C is characterized by Km1 (the dissociation constant of ES)=1.22±0.73mm, k (the rate constant for the breakdown of ES to E+products, P)=1.57×10−2±0.32×10−2s−1, Ka2 (the dissociation constant that characterizes the breakdown of SES to ES and S)=0.38±0.06m, and k′ (the rate constant for the breakdown of SES to E+P+S)=0.45±0.04s−1. 8. These parameters are compared with those in the literature that characterize the bromelain-catalysed hydrolysis of α-N-benzoyl-l-arginine ethyl ester and

  3. Critical Role for PAR1 in Kallikrein 6-Mediated Oligodendrogliopathy

    PubMed Central

    Burda, Joshua E.; Radulovic, Maja; Yoon, Hyesook; Scarisbrick, Isobel A.

    2014-01-01

    Kallikrein 6 (Klk6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of Klk6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke and glioblastoma. Taken with recent evidence establishing Klk6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that Klk6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR+/+ but not PAR−/− mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1+ oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that PAR1 or PAR1-agonists may represent new targets to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease. PMID:23832758

  4. Advocating for malaria elimination - learning from the successes of other infectious disease elimination programmes

    PubMed Central

    2014-01-01

    Malaria elimination is back on the agenda, but it remains challenging for countries to make the transition from effective control to elimination. Many other infectious diseases have been targeted by globally-coordinated elimination advocacy campaigns, and advocacy has been considered an essential component of the success of other disease elimination programmes. What can the malaria community learn from these successes? A review of infectious disease elimination programmes to identify successful elements of advocacy for disease elimination was undertaken. Key elements are: (i) a global elimination plan, supported by international health bodies; (ii) thorough costings and tools to support the business case; (iii) an approach that is positioned within a development framework; (iv) core elimination advocacy messages; (v) provision of advocacy tools for partners (vi) extensive and effective community engagement; and (vii) strong partnerships. These features provide insights into ‘what works’ in global elimination advocacy. Advocacy is a powerful tool to support the long-term political and financial commitment necessary for malaria elimination. The global malaria community needs to work together, to ensure that the early steps towards the end goal of malaria elimination are taken. PMID:24902848

  5. Advocating for malaria elimination - learning from the successes of other infectious disease elimination programmes.

    PubMed

    Whittaker, Maxine A; Dean, Angela J; Chancellor, Arna

    2014-06-05

    Malaria elimination is back on the agenda, but it remains challenging for countries to make the transition from effective control to elimination. Many other infectious diseases have been targeted by globally-coordinated elimination advocacy campaigns, and advocacy has been considered an essential component of the success of other disease elimination programmes. What can the malaria community learn from these successes? A review of infectious disease elimination programmes to identify successful elements of advocacy for disease elimination was undertaken. Key elements are: (i) a global elimination plan, supported by international health bodies; (ii) thorough costings and tools to support the business case; (iii) an approach that is positioned within a development framework; (iv) core elimination advocacy messages; (v) provision of advocacy tools for partners (vi) extensive and effective community engagement; and (vii) strong partnerships. These features provide insights into 'what works' in global elimination advocacy. Advocacy is a powerful tool to support the long-term political and financial commitment necessary for malaria elimination. The global malaria community needs to work together, to ensure that the early steps towards the end goal of malaria elimination are taken.

  6. The New York State Office of Mental Health Positive Alternatives to Restraint and Seclusion (PARS) Project.

    PubMed

    Wisdom, Jennifer P; Wenger, David; Robertson, David; Van Bramer, Jayne; Sederer, Lloyd I

    2015-08-01

    The Positive Alternatives to Restraint and Seclusion (PARS) project of the New York State Office of Mental Health (OMH) was designed to build capacity to use alternatives to restraint and seclusion within state-operated and licensed inpatient and residential treatment programs serving children with severe emotional disturbances. Its long-term goal was to eliminate the use of these restrictive interventions throughout the state's mental health system of care by creating coercion- and violence-free treatment environments governed by a philosophy of recovery, resiliency, and wellness. The central feature of the PARS project was training in, implementation of, and engagement with the Six Core Strategies to Reduce the Use of Seclusion and Restraint, a comprehensive approach developed by the National Association of State Mental Health Program Directors. This report provides an overview of the project, results from January 2007 through December 2011, and lessons learned by OMH. The three participating mental health treatment facilities demonstrated significant decreases in restraint and seclusion episodes per 1,000 client-days. Each identified specific activities that contributed to success, including ways to facilitate open, respectful two-way communication between management and staff and between staff and youths and greater involvement of youths in program decision making. All three facilities continued to implement key components of the PARS initiative after termination of grant-funded activities, and OMH initiated multiple activities to disseminate lessons learned during the project to all inpatient and residential treatment programs throughout the state mental health system.

  7. Unique slider bed eliminates problematic idler rollers

    SciTech Connect

    Not Available

    1988-01-01

    Solidur Plastic's impact slide bed is an innovative solution to problems with idler rollers. The unit provides increased conveyor efficiency and prolonged belt life. It also reduces costly downtime and maintenance needs by eliminating typical idler and conveyor belting problems.

  8. Plan to eliminate villages, April 1988.

    PubMed

    1988-01-01

    In April 1988, the Government of Romania announced a plan to consolidate rural communities by eliminating half of Romania's 13,000 rural villages. Some are to be replaced with modern cities containing light industry.

  9. Diagnostic Tools for Onchocerciasis Elimination Programs.

    PubMed

    Vlaminck, Johnny; Fischer, Peter U; Weil, Gary J

    2015-11-01

    Onchocerciasis (river blindness) is a major public health problem in sub-Saharan Africa. Major disease-control programs have greatly reduced both disease and infection prevalence by mass distribution of donated ivermectin. Recent studies have shown that local elimination was achieved in some areas following many years of ivermectin. The global health community has recently decided to build on these successes with a new program that aims to eliminate onchocerciasis. Diagnostic tests that were useful for identifying priority areas for disease prevention may not be adequate tools for elimination programs. This paper reviews available and emerging diagnostic tests for onchocerciasis and considers how they might be best employed during different stages of onchocerciasis elimination programs.

  10. Mapping residual transmission for malaria elimination

    PubMed Central

    Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon; Ntshalintshali, Nyasatu; Hsiang, Michelle S; Perkins, T Alex; Greenhouse, Bryan; Tatem, Andrew J; Cohen, Justin M; Smith, David L

    2015-01-01

    Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections. In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show ‘malariogenic potential’, a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination. DOI: http://dx.doi.org/10.7554/eLife.09520.001 PMID:26714110

  11. The novel PAR2 ligand C391 blocks multiple PAR2 signalling pathways in vitro and in vivo

    PubMed Central

    Boitano, Scott; Hoffman, Justin; Flynn, Andrea N; Asiedu, Marina N; Tillu, Dipti V; Zhang, Zhenyu; Sherwood, Cara L; Rivas, Candy M; DeFea, Kathryn A; Vagner, Josef; Price, Theodore J

    2015-01-01

    Background and Purpose Proteinase-activated receptor-2 (PAR2) is a GPCR linked to diverse pathologies, including acute and chronic pain. PAR2 is one of the four PARs that are activated by proteolytic cleavage of the extracellular amino terminus, resulting in an exposed, tethered peptide agonist. Several peptide and peptidomimetic agonists, with high potency and efficacy, have been developed to probe the functions of PAR2, in vitro and in vivo. However, few similarly potent and effective antagonists have been described. Experimental Approach We modified the peptidomimetic PAR2 agonist, 2-furoyl-LIGRLO-NH2, to create a novel PAR2 peptidomimetic ligand, C391. C391 was evaluated for PAR2 agonist/antagonist activity to PAR2 across Gq signalling pathways using the naturally expressing PAR2 cell line 16HBE14o-. For antagonist studies, a highly potent and specific peptidomimetic agonist (2-aminothiazo-4-yl-LIGRL-NH2) and proteinase agonist (trypsin) were used to activate PAR2. C391 was also evaluated in vivo for reduction of thermal hyperalgesia, mediated by mast cell degranulation, in mice. Key Results C391 is a potent and specific peptidomimetic antagonist, blocking multiple signalling pathways (Gq-dependent Ca2+, MAPK) induced following peptidomimetic or proteinase activation of human PAR2. In a PAR2-dependent behavioural assay in mice, C391 dose-dependently (75 μg maximum effect) blocked the thermal hyperalgesia, mediated by mast cell degranulation. Conclusions and Implications C391 is the first low MW antagonist to block both PAR2 Ca2+ and MAPK signalling pathways activated by peptidomimetics and/or proteinase activation. C391 represents a new molecular structure for PAR2 antagonism and can serve as a basis for further development for this important therapeutic target. PMID:26140338

  12. Review of PAR parameterizations in ocean ecosystem models

    NASA Astrophysics Data System (ADS)

    Byun, Do-Seong; Wang, Xiao Hua; Hart, Deirdre E.; Zavatarelli, Marco

    2014-12-01

    Commonly-used empirical equations for calculating downward 'photosynthetically available radiation' or PAR were reviewed in order to identify a more theoretically-sound parameterization for application to ocean biogeochemical models. Three different forms of broadband PAR parameterization are currently employed in biogeochemical models, each of them originating from the downward irradiance formulations normally applied to ocean circulation models, which produce poor attenuation estimates for PAR. Two of the PAR formulations, a single-exponential function and a double-exponential function, are parameterized by multiplying surface irradiance by a coefficient determining the portion of underwater PAR. The third formulation uses the second term of the double-exponential function. After elucidating the theoretical problems of modeling PAR using these parameterizations, we suggest an improved, R-modified double-exponential PAR formulation, including Paulson and Simpson's (1977) parameter values. We also newly estimate PAR penetration via least-squares fitting of values digitized from Jerlov's (1976) observations in different oceanic water types, and compare this PAR-observation derived parameterization with our new, theoretical, R-modified parameterization. Finally, we discuss a universal limitation inherent in current theoretical approaches to PAR parameterization.

  13. Modelisation par elements finis du muscle strie

    NASA Astrophysics Data System (ADS)

    Leonard, Mathieu

    Ce present projet de recherche a permis. de creer un modele par elements finis du muscle strie humain dans le but d'etudier les mecanismes engendrant les lesions musculaires traumatiques. Ce modele constitue une plate-forme numerique capable de discerner l'influence des proprietes mecaniques des fascias et de la cellule musculaire sur le comportement dynamique du muscle lors d'une contraction excentrique, notamment le module de Young et le module de cisaillement de la couche de tissu conjonctif, l'orientation des fibres de collagene de cette membrane et le coefficient de poisson du muscle. La caracterisation experimentale in vitro de ces parametres pour des vitesses de deformation elevees a partir de muscles stries humains actifs est essentielle pour l'etude de lesions musculaires traumatiques. Le modele numerique developpe est capable de modeliser la contraction musculaire comme une transition de phase de la cellule musculaire par un changement de raideur et de volume a l'aide des lois de comportement de materiau predefinies dans le logiciel LS-DYNA (v971, Livermore Software Technology Corporation, Livermore, CA, USA). Le present projet de recherche introduit donc un phenomene physiologique qui pourrait expliquer des blessures musculaires courantes (crampes, courbatures, claquages, etc.), mais aussi des maladies ou desordres touchant le tissu conjonctif comme les collagenoses et la dystrophie musculaire. La predominance de blessures musculaires lors de contractions excentriques est egalement exposee. Le modele developpe dans ce projet de recherche met ainsi a l'avant-scene le concept de transition de phase ouvrant la porte au developpement de nouvelles technologies pour l'activation musculaire chez les personnes atteintes de paraplegie ou de muscles artificiels compacts pour l'elaboration de protheses ou d'exosquelettes. Mots-cles Muscle strie, lesion musculaire, fascia, contraction excentrique, modele par elements finis, transition de phase

  14. Kinetics of acyl transfer reactions in organic media catalysed by Candida antarctica lipase B.

    PubMed

    Martinelle, M; Hult, K

    1995-09-06

    The acyl transfer reactions catalysed by Candida antartica lipase B in organic media followed a bi-bi ping-pong mechanism, with competitive substrate inhibition by the alcohols used as acyl acceptors. The effect of organic solvents on Vm and Km was investigated. The Vm values in acetonitrile was 40-50% of those in heptane. High Km values in acetonitrile compared to those in heptane could partly be explained by an increased solvation of the substrates in acetonitrile. Substrate solvation caused a 10-fold change in substrate specificity, defined as (Vm/Km)ethyl octanoate/(Vm/Km)octanoic acid, going from heptane to acetonitrile. Deacylation was the rate determining step for the acyl transfer in heptane with vinyl- and ethyl octanoate as acyl donors and (R)-2-octanol as acyl acceptor. With 1-octanol, a rate determining deacylation step in heptane was indicated using the same acyl donors. Using 1-octanol as acceptor in heptane, S-ethyl thiooctanoate had a 25- to 30-fold lower Vm/Km value and vinyl octanoate a 4-fold higher Vm/Km value than that for ethyl octanoate. The difference showed to be a Km effect for vinyl octanoate and mainly a Km effect for S-ethyl thiooctanoate. The Vm values of the esterification of octanoic acid with different alcohols was 10-30-times lower than those for the corresponding transesterification of ethyl octanoate. The low activity could be explained by a low pH around the enzyme caused by the acid or a withdrawing of active enzyme by nonproductive binding by the acid.

  15. Kinetic and inhibition studies on substrate channelling in the bifunctional enzyme catalysing C-terminal amidation.

    PubMed Central

    Moore, A B; May, S W

    1999-01-01

    A series of experiments has been conducted to investigate the possibility that substrate channelling might occur in the bifunctional forms of enzymes carrying out C-terminal amidation, a post-translational modification essential to the biological activity of many neuropeptides. C-terminal amidation entails sequential action by peptidylglycine mono-oxygenase (PAM, EC 1.14.17.3) and peptidylamidoglycolate lyase (PGL, EC 4.3.2.5), with the mono-oxygenase catalysing conversion of a glycine-extended pro-peptide into the corresponding alpha-hydroxyglycine derivative, which is then converted by the lyase into amidated peptide plus glyoxylate. Since the mono-oxygenase and lyase reactions exhibit tandem reaction stereospecificities, channelling of the alpha-hydroxy intermediate might occur, as is the case for some other multifunctional enzymes. Selective inhibition of the mono-oxygenase domain by competitive ester inhibitors, as well as mechanism-based mono-oxygenase inactivation by the novel olefinic inhibitor 5-acetamido-4-oxo-6-phenylhex-2-enoate (N-acetylphenylalanyl acrylate), has little to no effect on the kinetic parameters of the lyase domain of the AE from Xenopus laevis. Similarly, inhibition of the lyase domain by the potent dioxo inhibitor 2,4-dioxo-5-acetamido-6-phenylhexanoate has little effect on the activity of the monooxygenase domain in the bifunctional enzyme. A series of experiments on intermediate accumulation and conversion were also carried out, along with kinetic investigations of the reactivities of the monofunctional and bifunctional forms of PAM and PGL towards substrates and inhibitors. Taken together, the results demonstrate the kinetic independence of the mono-oxygenase and lyase domains, and provide no evidence for substrate channelling between these domains in the bifunctional amidating enzyme. PMID:10377242

  16. Low-temperature oxidation of CO catalysed by Co(3)O(4) nanorods.

    PubMed

    Xie, Xiaowei; Li, Yong; Liu, Zhi-Quan; Haruta, Masatake; Shen, Wenjie

    2009-04-09

    Low-temperature oxidation of CO, perhaps the most extensively studied reaction in the history of heterogeneous catalysis, is becoming increasingly important in the context of cleaning air and lowering automotive emissions. Hopcalite catalysts (mixtures of manganese and copper oxides) were originally developed for purifying air in submarines, but they are not especially active at ambient temperatures and are also deactivated by the presence of moisture. Noble metal catalysts, on the other hand, are water tolerant but usually require temperatures above 100 degrees C for efficient operation. Gold exhibits high activity at low temperatures and superior stability under moisture, but only when deposited in nanoparticulate form on base transition-metal oxides. The development of active and stable catalysts without noble metals for low-temperature CO oxidation under an ambient atmosphere remains a significant challenge. Here we report that tricobalt tetraoxide nanorods not only catalyse CO oxidation at temperatures as low as -77 degrees C but also remain stable in a moist stream of normal feed gas. High-resolution transmission electron microscopy demonstrates that the Co(3)O(4) nanorods predominantly expose their {110} planes, favouring the presence of active Co(3+) species at the surface. Kinetic analyses reveal that the turnover frequency associated with individual Co(3+) sites on the nanorods is similar to that of the conventional nanoparticles of this material, indicating that the significantly higher reaction rate that we have obtained with a nanorod morphology is probably due to the surface richness of active Co(3+) sites. These results show the importance of morphology control in the preparation of base transition-metal oxides as highly efficient oxidation catalysts.

  17. Creating a climate that catalyses healthcare innovation in the United Kingdom - learning lessons from international innovators.

    PubMed

    Cresswell, Kathrin; Cunningham-Burley, Sarah; Sheikh, Aziz

    2017-01-25

    The United Kingdom (UK) lags behind other high-income countries in relation to technological innovation in healthcare. In order to inform UK strategy on how to catalyse innovation, we sought to understand what national strategies can help to promote a climate for innovation in healthcare settings by extracting lessons for the UK from international innovators. We undertook a series of qualitative semi-structured interviews with senior international innovators from a range of health related policy, care/service delivery, commercial and academic backgrounds. Thematic analysis helped to explore how different stakeholder groups could facilitate/inhibit innovation at individual, organisational, and wider societal levels. We conducted 14 interviews and found that a conducive climate for healthcare innovation comprised of national/regional strategies stimulating commercial competition, promoting public/private relationships, and providing central direction (e.g. incentives for adoption and regulation through standards) without being restrictive. Organisational attitudes with a willingness to experiment and to take risks were also seen as important, but a bottom-up approach to innovation, based on the identification of clinical need, was seen as a crucial first step to construct relevant national policies.  There is now a need to create mechanisms through which frontline National Health Service staff in relation can raise ideas/concerns and suggest opportunities for improvement, and then build national innovation environments that seek to address these needs. This should be accompanied by creating competitive health technology markets to stimulate a commercial environment that attracts high-quality health information technology experts and innovators working in partnership with staff and patients.

  18. Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen heterocycles

    NASA Astrophysics Data System (ADS)

    McNally, Andrew; Haffemayer, Benjamin; Collins, Beatrice S. L.; Gaunt, Matthew J.

    2014-06-01

    The development of new chemical transformations based on catalytic functionalization of unactivated C-H bonds has the potential to simplify the synthesis of complex molecules dramatically. Transition metal catalysis has emerged as a powerful tool with which to convert these unreactive bonds into carbon-carbon and carbon-heteroatom bonds, but the selective transformation of aliphatic C-H bonds is still a challenge. The most successful approaches involve a `directing group', which positions the metal catalyst near a particular C-H bond, so that the C-H functionalization step occurs via cyclometallation. Most directed aliphatic C-H activation processes proceed through a five-membered-ring cyclometallated intermediate. Considering the number of new reactions that have arisen from such intermediates, it seems likely that identification of distinct cyclometallation pathways would lead to the development of other useful chemical transformations. Here we report a palladium-catalysed C-H bond activation mode that proceeds through a four-membered-ring cyclopalladation pathway. The chemistry described here leads to the selective transformation of a methyl group that is adjacent to an unprotected secondary amine into a synthetically versatile nitrogen heterocycle. The scope of this previously unknown bond disconnection is highlighted through the development of C-H amination and carbonylation processes, leading to the synthesis of aziridines and β-lactams (respectively), and is suggestive of a generic C-H functionalization platform that could simplify the synthesis of aliphatic secondary amines, a class of small molecules that are particularly important features of many pharmaceutical agents.

  19. TagR promotes PpkA-catalysed type VI secretion activation in Pseudomonas aeruginosa.

    PubMed

    Hsu, FoSheng; Schwarz, Sandra; Mougous, Joseph D

    2009-06-01

    Type VI secretion systems (T6SSs) contribute to interactions of bacterial pathogens and symbionts with their hosts. Previously, we showed that Pseudomonas aeruginosa T6S is posttranslationally activated upon phosphorylation of Fha1, an FHA domain protein, by PpkA, a membrane-spanning threonine kinase. Herein, additional structural, enzymatic and genetic requirements for PpkA-catalysed T6SS activation are identified. We found that PpkA plays an essential structural role in the T6SS, and that this role is intimately linked to its ability to promote secretion and phosphorylate Fha1. Protein localization and protein-protein interaction studies show that a complex containing Fha1 and the T6S ATPase, ClpV1 is recruited to the T6S apparatus in a phosphorylation-dependent manner. The mechanism of PpkA activation was also investigated. We identified critical PpkA autophosphorylation sites and showed that small molecule-induced dimerization of the extracellular domains of PpkA is sufficient to activate the T6SS. Finally, we discovered TagR, a component of the T6S posttranslational regulatory pathway that functions upstream of PpkA to promote kinase activity. We present a model whereby an unknown cue causes dimerization of the extracellular domains of PpkA, leading to its autophosphorylation, recruitment of the Fha1-ClpV1 complex, phosphorylation of Fha1, and T6SS activation. Our findings should facilitate approaches for identifying physiological activators of T6S.

  20. Defective Cytochrome P450-Catalysed Drug Metabolism in Niemann-Pick Type C Disease.

    PubMed

    Nicoli, Elena-Raluca; Al Eisa, Nada; Cluzeau, Celine V M; Wassif, Christopher A; Gray, James; Burkert, Kathryn R; Smith, David A; Morris, Lauren; Cologna, Stephanie M; Peer, Cody J; Sissung, Tristan M; Uscatu, Constantin-Daniel; Figg, William D; Pavan, William J; Vite, Charles H; Porter, Forbes D; Platt, Frances M

    2016-01-01

    Niemann-Pick type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 gene. NPC is characterised by storage of multiple lipids in the late endosomal/lysosomal compartment, resulting in cellular and organ system dysfunction. The underlying molecular mechanisms that lead to the range of clinical presentations in NPC are not fully understood. While evaluating potential small molecule therapies in Npc1-/- mice, we observed a consistent pattern of toxicity associated with drugs metabolised by the cytochrome P450 system, suggesting a potential drug metabolism defect in NPC1 disease. Investigation of the P450 system in the context of NPC1 dysfunction revealed significant changes in the gene expression of many P450 associated genes across the full lifespan of Npc1-/- mice, decreased activity of cytochrome P450 reductase, and a global decrease of multiple cytochrome P450 catalysed dealkylation reactions. In vivo drug metabolism studies using a prototypic P450 metabolised drug, midazolam, confirmed dysfunction in drug clearance in the Npc1-/- mouse. Expression of the Phase II enzyme uridinediphosphate-glucuronosyltransferase (UGT) was also significantly reduced in Npc1-/- mice. Interestingly, reduced activity within the P450 system was also observed in heterozygous Npc1+/- mice. The reduced activity of P450 enzymes may be the result of bile acid deficiency/imbalance in Npc1-/- mice, as bile acid treatment significantly rescued P450 enzyme activity in Npc1-/- mice and has the potential to be an adjunctive therapy for NPC disease patients. The dysfunction in the cytochrome P450 system were recapitulated in the NPC1 feline model. Additionally, we present the first evidence that there are alterations in the P450 system in NPC1 patients.

  1. Visual determination of Cu2+ through copper-catalysed in situ formation of Ag nanoparticles.

    PubMed

    Yuan, Xun; Chen, Yi

    2012-10-07

    A new strategy was explored for the visual determination of Cu(2+) using copper-catalysed in situ formation of Ag nanoparticles. In this method, only common reagents were used and the pre-synthesis and modification of nanoparticles are avoided. Ag(+) can form a milk-white suspension (AgBr) with Br(-) in an aqueous solution composed of AgNO(3), cetyltrimethylammonium bromide, ascorbic acid, bovine serum albumin, and NaNO(3). The reaction will be stopped by addition of Cu(2+), accompanied by a colour change from milk-white to orange or brilliant yellow. Cu(+) (the reduction product of Cu(2+)) consumes the dissolved O(2) and prevents the O(2) from oxidizing the newly reduced Ag atoms (by ascorbic acid) back to Ag(+), facilitating the further aggregation of Ag atoms to become Ag nanoparticles. The visible colour change was shown to be specific towards Cu(2+) over most other metal ions. The limit of detection was 0.75 μM Cu(2+) by the naked eye and 0.25 μM by spectrometer. Quantitation of Cu(2+) was achieved in a linear range from 0.25 to 2.0 μM. This method was validated by measuring real water and serum samples, giving results agreeing well with the data reported and measured by inductively coupled plasma mass spectrometry. The recovery was 95.6-106% for untreated tap water and 96.0-100% for resin-pre-treated water and serum samples.

  2. Properties of dental resins submitted to pH catalysed hydrolysis.

    PubMed

    Cilli, Renato; Pereira, Jose Carlos; Prakki, Anuradha

    2012-12-01

    This study evaluated the surface microhardness (SM) and roughness (SR) alterations of dental resins submitted to pH catalysed degradation regimens. Thirty discs of each TPH Spectrum (Dentsply), Z100 (3M-ESPE), or an unfilled experimental bis-GMA/TEGDMA resin were fabricated, totaling 90 specimens. Each specimen was polymerized for 40 s, finished, polished, and individually stored in deionized water at 37 °C for 7 days. Specimens were randomly assigned to the following pH solutions: 1.0, 6.9 or 13, and for SM or SR evaluations (n = 5). Baseline Knoop-hardness of each specimen was obtained by the arithmetic mean of five random micro-indentations. For SR, mean baseline values were obtained by five random surface tracings (R(a)). Specimens were then soaked in one of the following storage media at 37 °C: (1) 0.1 M, pH 1.0 HCl, (2) 0.1 N, pH 13.0 NaOCl, and (3) deionized water (pH 6.9). Solutions were replaced daily. Repeated SM and SR measurements were performed at the 3-, 7- and 14-day storage time intervals. For each test and resin, data were analysed by two-way ANOVA followed by Tukey's test (α = 0.05). There was significant decrease in SM and increase in SR values of composites after storage in alkaline medium. TPH and Z100 presented similar behaviour for SM and SR after immersion in the different media, whereas unfilled resin values showed no significant change. Hydrolytic degradation of resin composites seems to begin with the silanized inorganic particles and therefore depend on their composition. To accelerate composite hydrolysis and produce quick in vitro microstructural damage, alkaline medium appears to be more suitable than acidic medium. Contemporary resin composite properties seem to withstand neutral and acidic oral environments tolerably well. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Eukaryotic formylglycine-generating enzyme catalyses a monooxygenase type of reaction.

    PubMed

    Peng, Jianhe; Alam, Sarfaraz; Radhakrishnan, Karthikeyan; Mariappan, Malaiyalam; Rudolph, Markus Georg; May, Caroline; Dierks, Thomas; von Figura, Kurt; Schmidt, Bernhard

    2015-09-01

    C α-formylglycine (FGly) is the catalytic residue of sulfatases in eukaryotes. It is generated by a unique post-translational modification catalysed by the FGly-generating enzyme (FGE) in the endoplasmic reticulum. FGE oxidizes a cysteine residue within the conserved CxPxR sequence motif of nascent sulfatase polypeptides to FGly. Here we show that this oxidation is strictly dependent on molecular oxygen (O2) and consumes 1 mol O2 per mol FGly formed. For maximal activity FGE requires an O2 concentration of 9% (105 μM). Sustained FGE activity further requires the presence of a thiol-based reductant such as DTT. FGly is also formed in the absence of DTT, but its formation ceases rapidly. Thus inactivated FGE accumulates in which the cysteine pair Cys336/Cys341 in the catalytic site is oxidized to form disulfide bridges between either Cys336 and Cys341 or Cys341 and the CxPxR cysteine of the sulfatase. These results strongly suggest that the Cys336/Cys341 pair is directly involved in the O2 -dependent conversion of the CxPxR cysteine to FGly. The available data characterize eukaryotic FGE as a monooxygenase, in which Cys336/Cys341 disulfide bridge formation donates the electrons required to reduce one oxygen atom of O2 to water while the other oxygen atom oxidizes the CxPxR cysteine to FGly. Regeneration of a reduced Cys336/Cys341 pair is accomplished in vivo by a yet unknown reductant of the endoplasmic reticulum or in vitro by DTT. Remarkably, this monooxygenase reaction utilizes O2 without involvement of any activating cofactor.

  4. The mechanism of the reaction catalysed by adenosine triphosphate–creatine phosphotransferase

    PubMed Central

    Morrison, J. F.; James, Elizabeth

    1965-01-01

    1. The forward and reverse reactions catalysed by ATP–creatine phosphotransferase have been studied kinetically at pH8·0 in the presence and absence of products, under conditions in which the free Mg2+ concentration was maintained constant at 1mm. Thus at fixed pH the reaction may be considered as being bireactant and expressed as:MgATP2−+creatine0⇌MgADP−+phosphocreatine2−2. The initial-velocity pattern in the absence of products and the product-inhibition pattern have been determined. These are consistent with a random mechanism in which all steps are in rapid equilibrium except that concerned with the interconversion of the central ternary complexes, and in which two dead-end complexes (enzyme–MgADP–creatine and enzyme–MgATP–phosphocreatine) are formed. The results are in accord with previous suggestions that the enzyme possesses distinct sites for the combination of the nucleotide and guanidino substrates. 3. Values have been determined for the Michaelis and dissociation constants involved in the combination of each substrate with various enzyme forms. Although these values cannot be regarded as absolute, they appear to indicate that the presence of one substrate on the enzyme enhances the combination of the second substrate. In addition, it would seem that in the formation of the enzyme–MgADP–creatine complex the concentration of one reactant does not affect the combination of the other. This contrasts with the formation of the enzyme–MgATP–phosphocreatine complex, where each reactant hinders the combination of the other. PMID:16749122

  5. Insights into networks of functional microbes catalysing methanization of cellulose under mesophilic conditions.

    PubMed

    Li, Tianlun; Mazéas, Laurent; Sghir, Abdelghani; Leblon, Gérard; Bouchez, Théodore

    2009-04-01

    combination of DNA-SIP and FISH applied with a series of functionally connected substrates can shed light on the networks of uncultured microbes catalysing the methanization of the most abundant chemical renewable energy source on Earth.

  6. Defective Cytochrome P450-Catalysed Drug Metabolism in Niemann-Pick Type C Disease

    PubMed Central

    Wassif, Christopher A.; Gray, James; Burkert, Kathryn R.; Smith, David A.; Morris, Lauren; Cologna, Stephanie M.; Peer, Cody J.; Sissung, Tristan M.; Uscatu, Constantin-Daniel; Figg, William D.; Pavan, William J.; Vite, Charles H.; Porter, Forbes D.; Platt, Frances M.

    2016-01-01

    Niemann-Pick type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 gene. NPC is characterised by storage of multiple lipids in the late endosomal/lysosomal compartment, resulting in cellular and organ system dysfunction. The underlying molecular mechanisms that lead to the range of clinical presentations in NPC are not fully understood. While evaluating potential small molecule therapies in Npc1-/- mice, we observed a consistent pattern of toxicity associated with drugs metabolised by the cytochrome P450 system, suggesting a potential drug metabolism defect in NPC1 disease. Investigation of the P450 system in the context of NPC1 dysfunction revealed significant changes in the gene expression of many P450 associated genes across the full lifespan of Npc1-/- mice, decreased activity of cytochrome P450 reductase, and a global decrease of multiple cytochrome P450 catalysed dealkylation reactions. In vivo drug metabolism studies using a prototypic P450 metabolised drug, midazolam, confirmed dysfunction in drug clearance in the Npc1-/- mouse. Expression of the Phase II enzyme uridinediphosphate-glucuronosyltransferase (UGT) was also significantly reduced in Npc1-/- mice. Interestingly, reduced activity within the P450 system was also observed in heterozygous Npc1+/- mice. The reduced activity of P450 enzymes may be the result of bile acid deficiency/imbalance in Npc1-/- mice, as bile acid treatment significantly rescued P450 enzyme activity in Npc1-/- mice and has the potential to be an adjunctive therapy for NPC disease patients. The dysfunction in the cytochrome P450 system were recapitulated in the NPC1 feline model. Additionally, we present the first evidence that there are alterations in the P450 system in NPC1 patients. PMID:27019000

  7. Leprosy New Case Detection Trends and the Future Effect of Preventive Interventions in Pará State, Brazil: A Modelling Study.

    PubMed

    de Matos, Haroldo José; Blok, David J; de Vlas, Sake J; Richardus, Jan Hendrik

    2016-03-01

    Leprosy remains a public health problem in Brazil. Although the overall number of new cases is declining, there are still areas with a high disease burden, such as Pará State in the north of the country. We aim to predict future trends in new case detection rate (NCDR) and explore the potential impact of contact tracing and chemoprophylaxis on NCDR in Pará State. We used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae, in a population structured by households. The model was quantified to simulate the population and observed NCDR of leprosy in Pará State for the period 1990 to 2014. The baseline scenario was the current control program, consisting of multidrug therapy, passive case detection, and active case detection from 2003 onwards. Future projections of the NCDR were made until 2050 given the continuation of the current control program (i.e. baseline). We further investigated the potential impact of two scenarios for future control of leprosy: 1) discontinuation of contact tracing; and 2) continuation of current control in combination with chemoprophylaxis. Both scenarios started in 2015 and were projected until 2050. The modelled NCDR in Pará State after 2014 shows a continuous downward trend, reaching the official elimination target of 10 cases per 100,000 population by 2030. The cessation of systematic contact tracing would not result in a higher NCDR in the long run. Systematic contact tracing in combination with chemoprophylaxis for contacts would reduce the NCDR by 40% and bring attainment of the elimination target two years forward to 2028. The NCDR of leprosy continues to decrease in Pará State. Elimination of leprosy as a public health problem could possibly be achieved around 2030, if the current control program is maintained. Providing chemoprophylaxis would decrease the NCDR further and would bring elimination forward by two years.

  8. Structure-activity relationships for chemical and glutathione S-transferase-catalysed glutathione conjugation reactions of a series of 2-substituted 1-chloro-4-nitrobenzenes.

    PubMed Central

    Van der Aar, E M; Bouwman, T; Commandeur, J N; Vermeulen, N P

    1996-01-01

    Glutathione S-transferases (GSTs) constitute an important class of phase II (de)toxifying enzymes, catalysing the conjugation of glutathione (GSH) with electrophilic compounds. In the present study, Km, kcat and kcat/Km values for the rat GST 1-1-, 3-3-, 4-4- and 7-7-catalysed conjugation reactions between GSH and a series of 10 different 2-substituted 1-chloro-4-nitrobenzenes, and the second-order rate constants (ks) of the corresponding base-catalysed reactions, were correlated with nine classical physicochemical parameters (electronic, steric and lipophilic) of the substituents and with 16 computer-calculated molecular parameters of the substrates and of the corresponding Meisenheimer complexes with MeS- as a model nucleophile for GS- (charge distributions and several energy values), giving structure-activity relationships. On the basis of an identical dependence of the base-catalysed as well as the GST 1-1- and GST 7-7-catalysed reactions on electronic parameters (among others, Hammett substituent constant sigma p and charge on p-nitro substituents), and the finding that the corresponding reactions catalysed by GSTs 3-3 and 4-4 depend to a significantly lesser extent on these parameters, it was concluded that the Mu-class GST isoenzymes have a rate-determining transition state in the conjugation reaction between 2-substituted 1-chloro-4-nitrobenzenes and GSH which is different from that of the other two GSTs. Several alternative rate-limiting transition states for GST 3-3 and 4-4 are discussed. Furthermore, based on the obtained structure-activity relationships, it was possible to predict the kcat/Km values of the four GST isoenzymes and the ks of the base-catalysed GSH conjugation of 1-chloro-4-nitrobenzene. PMID:8973562

  9. A Conserved Mode of Protein Recognition and Binding in a ParD−ParE Toxin−Antitoxin Complex

    SciTech Connect

    Dalton, Kevin M.; Crosson, Sean

    2010-05-06

    Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 {angstrom} resolution. This TA system forms an {alpha}{sub 2}{beta}{sub 2} heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and binding groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding subdomain that is conserved between distantly related members of the RelE/ParE toxin superfamily despite a low level of overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.

  10. Martian Atmospheric Pressure Static Charge Elimination Tool

    NASA Technical Reports Server (NTRS)

    Johansen, Michael R.

    2014-01-01

    A Martian pressure static charge elimination tool is currently in development in the Electrostatics and Surface Physics Laboratory (ESPL) at NASA's Kennedy Space Center. In standard Earth atmosphere conditions, static charge can be neutralized from an insulating surface using air ionizers. These air ionizers generate ions through corona breakdown. The Martian atmosphere is 7 Torr of mostly carbon dioxide, which makes it inherently difficult to use similar methods as those used for standard atmosphere static elimination tools. An initial prototype has been developed to show feasibility of static charge elimination at low pressure, using corona discharge. A needle point and thin wire loop are used as the corona generating electrodes. A photo of the test apparatus is shown below. Positive and negative high voltage pulses are sent to the needle point. This creates positive and negative ions that can be used for static charge neutralization. In a preliminary test, a floating metal plate was charged to approximately 600 volts under Martian atmospheric conditions. The static elimination tool was enabled and the voltage on the metal plate dropped rapidly to -100 volts. This test data is displayed below. Optimization is necessary to improve the electrostatic balance of the static elimination tool.

  11. Body elimination attitude family resemblance in Kuwait.

    PubMed

    Al-Fayez, Ghenaim; Awadalla, Abdelwahid; Arikawa, Hiroko; Templer, Donald I; Hutton, Shane

    2009-12-01

    The purpose of the present study was to determine the family resemblance of attitude toward body elimination in Kuwaiti participants. This study was conceptualized in the context of the theories of moral development, importance of cleanliness in the Muslim religion, cross-cultural differences in personal hygiene practices, previous research reporting an association between family attitudes and body elimination attitude, and health implications. The 24-item Likert-type format Body Elimination Attitude Scale-Revised was administered to 277 Kuwaiti high school students and 437 of their parents. Females scored higher, indicating greater disgust, than the males. Moreover, sons' body elimination attitude correlated more strongly with fathers' attitude (r = .85) than with that of the mothers (r = .64). Daughters' attitude was similarly associated with the fathers' (r = .89) and the mothers' attitude (r = .86). The high correlations were discussed within the context of Kuwait having a collectivistic culture with authoritarian parenting style. The higher adolescent correlations, and in particular the boys' correlation with fathers than with mothers, was explained in terms of the more dominant role of the Muslim father in the family. Public health and future research implications were suggested. A theoretical formulation was advanced in which "ideal" body elimination attitude is relative rather than absolute, and is a function of one's life circumstances, one's occupation, one's culture and subculture, and the society that one lives in.

  12. Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins.

    PubMed

    Barrera, G J; Tortolero, G Sanchez

    2016-01-01

    Trefoil factors are effector molecules in gastrointestinal tract physiology. Each one improves healing of the gastrointestinal tract. Trefoil factors may be grouped into three classes: the gastric peptides (TFF1), spasmolytic peptide (TFF2) and intestinal trefoil factor (TFF3). Significant amounts of TFF3 are present in human breast milk. Previously, we have reported that trefoil factor 3 isolated from human breast milk produces down regulation of cytokines and promotes human beta defensins expression in intestinal epithelial cells. This study aimed to determine the molecular mechanism involved. Here we showed that the presence of TFF3 strongly correlated with protease activated receptors 2 (PAR-2) activation in human intestinal cells. Intracellular calcium ((Ca2+)i)mobilization was induced by the treatment with: 1) TFF3, 2) synthetic PAR-2 agonist peptide. The co-treatment with a synthetic PAR-2 antagonist peptide and TFF3 eliminates the latter's effect. Additionally, we demonstrated the existence of interactions among TFF3 and PAR-2 receptors through far Western blot and co-precipitation. Finally, down regulation of PAR-2 by siRNA resulted in a decrease of TFF3 induced intracellular (Ca2+)i mobilization, cytokine regulation and defensins expression. These findings suggest that TFF3 activates intestinal cells through PAR-2 (Fig. 4, Ref. 19).

  13. A new model for estimating boreal forest fPAR

    NASA Astrophysics Data System (ADS)

    Majasalmi, Titta; Rautiainen, Miina; Stenberg, Pauline

    2014-05-01

    Life on Earth is continuously sustained by the extraterrestrial flux of photosynthetically active radiation (PAR, 400-700 nm) from the sun. This flux is converted to biomass by chloroplasts in green vegetation. Thus, the fraction of absorbed PAR (fPAR) is a key parameter used in carbon balance studies, and is listed as one of the Essential Climate Variables (ECV). Temporal courses of fPAR for boreal forests are difficult to measure, because of the complex 3D structures. Thus, they are most often estimated based on models which quantify the dependency of absorbed radiation on canopy structure. In this study, we adapted a physically-based canopy radiation model into a fPAR model, and compared modeled and measured fPAR in structurally different boreal forest stands. The model is based on the spectral invariants theory, and uses leaf area index (LAI), canopy gap fractions and spectra of foliage and understory as input data. The model differs from previously developed more detailed fPAR models in that the complex 3D structure of coniferous forests is described using an aggregated canopy parameter - photon recollision probability p. The strength of the model is that all model inputs are measurable or available through other simple models. First, the model was validated with measurements of instantaneous fPAR obtained with the TRAC instrument in nine Scots pine, Norway spruce and Silver birch stands in a boreal forest in southern Finland. Good agreement was found between modeled and measured fPAR. Next, we applied the model to predict temporal courses of fPAR using data on incoming radiation from a nearby flux tower and sky irradiance models. Application of the model to simulate diurnal and seasonal values of fPAR indicated that the ratio of direct-to-total incident radiation and leaf area index are the key factors behind the magnitude and variation of stand-level fPAR values.

  14. Reactions of the ionized enol tautomer of acetanilide: elimination of HNCO via a novel rearrangement.

    PubMed

    Heydorn, Lisa N; Carter, Lynn M; Bowen, Richard D; Terlouw, Johan K

    2003-01-01

    The reactions of ionised acetanilide, C(6)H(5)NH(=O)CH(3)(.+), and its enol, C(6)H(5)NH(OH)=CH(2)(.+), have been studied by a combination of tandem mass spectrometric and computational methods. These two isomeric radical cations have distinct chemistries at low internal energies. The keto tautomer eliminates exclusively CH(2)=C=O to give ionised aniline. In contrast, the enol tautomer loses H-N=C=O, via an unusual skeletal rearrangement, to form predominantly ionised methylene cyclohexadiene. Hydrogen atom loss also occurs from the enol tautomer, with the formation of protonated oxindole. The mechanisms for H-N=C=O and hydrogen atom loss both involve cyclisation; the former proceeds via a spiro transition state formed by attachment of the methylene group to the ipso position, whereas the latter entails the formation of a five-membered ring by attachment to the ortho position. The behaviour of labelled analogues reveals that these two processes have different site selectivities. Hydrogen atom loss involves a reverse critical energy and is subject to an isotope effect. Surprisingly, attempts to promote the enolisation of ionised acetanilide by proton-transport catalysis were unsuccessful. In a reversal of the usual situation for ionised carbonyl compounds, ionised acetanilide is actually more stable than its enol tautomer. The enol tautomer was resistant to proton-transport catalysed ketonisation to ionised acetanilide, possibly because the favoured geometry of the encounter complex with the base molecule is inappropriate for facilitating tautomerisation.

  15. Can Lymphatic Filariasis Be Eliminated by 2020?

    PubMed

    Rebollo, Maria P; Bockarie, Moses J

    2017-02-01

    Interventions against neglected tropical diseases (NTD), including lymphatic filariasis (LF), scaled up dramatically after the signing of the London Declaration (LD) in 2012. LF is targeted for elimination by 2020, but some countries are considered not on track to meet the 2020 target using the recommended preventive chemotherapy and morbidity management strategies. In this Opinion article we review the prospects for achieving LF elimination by 2020 in the light of the renewed global action against NTDs and the global efforts to achieve the sustainable development goals (SDGs) by 2030. We conclude that LF can be eliminated by 2020 using cross-sectoral and integrated approaches because of the compound effect of the other SDG activities related to poverty reduction and water and sanitation.

  16. 2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) ...

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

    2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) BARRACKS WITH RADAR ATTACHED. - Nike Hercules Missile Battery Summit Site, Battery Control Administration & Barracks Building, Anchorage, Anchorage, AK

  17. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori.

    PubMed

    Ziebarth, D; Spiegelhalder, B; Bartsch, H

    1997-02-01

    Micro-organisms commonly present in human saliva and three DSM strains (Helicobacter pylori, Campylobacter jejuni and Neisseria cinerea), which can be isolated from the human gastro-intestinal tract, were assayed in vitro for their capacity to catalyse N-nitrosation of a series of medicinal drugs and other compounds. Following incubation at pH 7.2 in the presence of nitrate (or nitrite) for up to 24 (48) h, the yield of N-nitroso compounds (NOC) was quantified by HPLC equipped with a post-column derivatization device, allowing the sensitive detection of acid-labile and acid-stable NOC. Eleven out of the 23 test compounds underwent bacteria-catalysed nitrosation by salivary bacteria, the yield of the respective nitrosation products varying 800-fold. 4-(Methylamino)antipyrine exhibited the highest rate of nitrosation, followed by dichlofenac > metamizole > piperazine > five other drugs, whilst L-proline and L-thioproline had the lowest nitrosation rate. Ten drugs including aminophenazone, cimetidine and nicotine, did not inhibit bacterial growth, allowing transitory nitrite to be formed, but no N-nitroso derivatives were detected. Three drugs inhibited the proliferation of bacteria and neither nitrite nor any NOC were formed. Using metamizole as an easily nitrosatable precursor, two strains, Campylobacter jejuni and Helicobacter pylori, were shown to catalyse nitrosation in the presence of nitrite at pH 7.2. As compared to Neisseria cinerea used as a nitrosation-proficient control strain, H. pylori was 30-100 times less effective, whilst C. jejuni had intermediary activity. The results of our sensitive nitrosation assay further confirm that bacteria isolated from human sources, possessing nitrate reductase and/or nitrosating enzymes such as cytochrome cd1-nitrite reductase (Calmels et al., Carcinogenesis, 17, 533-536, 1996), can contribute to intragastric nitrosamine formation in the anacidic stomach when nitrosatable precursors from exogenous and endogenous sources

  18. Has Wild Poliovirus Been Eliminated from Nigeria?

    PubMed

    Famulare, Michael

    2015-01-01

    Wild poliovirus type 3 (WPV3) has not been seen anywhere since the last case of WPV3-associated paralysis in Nigeria in November 2012. At the time of writing, the most recent case of wild poliovirus type 1 (WPV1) in Nigeria occurred in July 2014, and WPV1 has not been seen in Africa since a case in Somalia in August 2014. No cases associated with circulating vaccine-derived type 2 poliovirus (cVDPV2) have been detected in Nigeria since November 2014. Has WPV1 been eliminated from Africa? Has WPV3 been eradicated globally? Has Nigeria interrupted cVDPV2 transmission? These questions are difficult because polio surveillance is based on paralysis and paralysis only occurs in a small fraction of infections. This report provides estimates for the probabilities of poliovirus elimination in Nigeria given available data as of March 31, 2015. It is based on a model of disease transmission that is built from historical polio incidence rates and is designed to represent the uncertainties in transmission dynamics and poliovirus detection that are fundamental to interpreting long time periods without cases. The model estimates that, as of March 31, 2015, the probability of WPV1 elimination in Nigeria is 84%, and that if WPV1 has not been eliminated, a new case will be detected with 99% probability by the end of 2015. The probability of WPV3 elimination (and thus global eradication) is > 99%. However, it is unlikely that the ongoing transmission of cVDPV2 has been interrupted; the probability of cVDPV2 elimination rises to 83% if no new cases are detected by April 2016.

  19. Noise elimination algorithm for modal analysis

    SciTech Connect

    Bao, X. X.; Li, C. L.; Xiong, C. B.

    2015-07-27

    Modal analysis is an ongoing interdisciplinary physical issue. Modal parameters estimation is applied to determine the dynamic characteristics of structures under vibration excitation. Modal analysis is more challenging for the measured vibration response signals are contaminated with noise. This study develops a mathematical algorithm of structured low rank approximation combined with the complex exponential method to estimate the modal parameters. Physical experiments using a steel cantilever beam with ten accelerometers mounted, excited by an impulse load, demonstrate that this method can significantly eliminate noise from measured signals and accurately identify the modal frequencies and damping ratios. This study provides a fundamental mechanism of noise elimination using structured low rank approximation in physical fields.

  20. Recognizing, Confronting, and Eliminating Workplace Bullying.

    PubMed

    Berry, Peggy Ann; Gillespie, Gordon L; Fisher, Bonnie S; Gormley, Denise K

    2016-07-01

    Workplace bullying (WPB) behaviors negatively affect nurse productivity, satisfaction, and retention, and hinder safe patient care. The purpose of this article is to define WPB, differentiate between incivility and WPB, and recommend actions to prevent WPB behaviors. Informed occupational and environmental health nurses and nurse leaders must recognize, confront, and eliminate WPB in their facilities and organizations. Recognizing, confronting, and eliminating WPB behaviors in health care is a crucial first step toward sustained improvements in patient care quality and the health and safety of health care employees. © 2016 The Author(s).

  1. Dynamics of Hydrogen Elimination from Unsaturated Hydrocarbons

    NASA Astrophysics Data System (ADS)

    Cromwell, Evan Francis

    State-of-the-art laser and molecular beam techniques are used to study the dynamics of H_2 elimination from 1,4-cyclohexadiene and ethylene. Information on the transition state configurations and the dynamics of the dissociation processes for these reactions is reported. A brief introduction to these studies is presented in Chapter I. An ultrahigh-brightness laser system, developed to study the spectroscopy and dynamics of molecules and clusters from the vacuum ultraviolet (VUV) and extreme ultraviolet (XUV) to the near infra-red spectral regions is described in Chapter II. The laser utilizes pulse amplification of a single-mode ring dye laser, frequency doubling, and four-wave mixing in a pulsed jet. Pulse energies of > 120mJ in the visible, >35mJ in the uv, >15mJ in the infra-red and > 10^{11} photons/pulse in the VUV-XUV have been obtained. The bandwidth of the laser has been measured to be 91MHz in the visible and 210MHz in the XUV. In Chapter III a comprehensive study of the dynamics of H_2 elimination from 1,4- and 1,3-cyclohexadiene is reported. Rotational and vibrational quantum state distributions as well as translation energy distributions for the H_2 product are measured. State specific detection of H_2 is accomplished with a transform limited vuv-xuv laser system via (1 + 1) REMPI. Rate constants for the H_2 elimination and 1,4 to 1,3 isomerization reactions are derived. A (v, J) correlation for H _2 with {bf v}| {bf J} primarily is observed from anisotropy in the Doppler profiles. A clear picture of the transition state configuration of 1,4-cyclohexadiene is provided from the information obtained. A study of the dynamics of H_2 elimination from ethylene is presented in the last Chapter. A complete H_2 product energy distribution is obtained. The distribution of energy in H_2 product from the dissociation of 1,1-d_2 ethylene is also presented. Two separate H_2 elimination channels are observed, a 1,1 elimination and a 1,2 elimination, in the

  2. Eliminating the Rayleigh anomalies in metal grating

    NASA Astrophysics Data System (ADS)

    Gao, Hongtao; Yan, Wei; Hu, Song; Zhang, Yudong

    2017-12-01

    We demonstrate that Rayleigh anomalies of some diffraction order of metal reflection gratings and transmission grating can be eliminated. The studied grating consists of a one-dimensional (1-D) periodic rectangular slit array. A systemic rule has been reported that can be used to counteract the infinity of the Green function resulted from working at the Rayleigh cutoff wavelength, by choosing a suitable value of the ratio of the slit width to the period of the grating. Eliminating the Rayleigh anomalies is of intrinsic physical interest as well as of vital concern in the design of the optical element.

  3. Pd-catalysed direct arylation polymerisation for synthesis of low-bandgap conjugated polymers and photovoltaic performance.

    PubMed

    Chang, Shu-Wei; Waters, Huw; Kettle, Jeff; Kuo, Zi-Rui; Li, Chun-Han; Yu, Chin-Yang; Horie, Masaki

    2012-11-23

    Low-bandgap conjugated copolymers based on a donor-acceptor structure have been synthesised via palladium-complex catalysed direct arylation polymerisation. Initially, we report the optimisation of the synthesis of poly(cyclopentadithiophene-alt-benzothiadiazole) (PCPDTBT) formed between cyclopentadithiophene and dibromobenzothiadiazole units. The polymerisation condition has been optimised, which affords high-molecular-weight polymers of up to M(n) = 70 k using N-methylpyrrolidone as a solvent. The polymers are used to fabricate organic photovoltaic devices and the best performing PCPDTBT device exhibits a moderate improvement over devices fabricated using the related polymer via Suzuki coupling. Similar polymerisation conditions have also been applied for other monomer units.

  4. Nickel-catalysed retro-hydroamidocarbonylation of aliphatic amides to olefins

    NASA Astrophysics Data System (ADS)

    Hu, Jiefeng; Wang, Minyan; Pu, Xinghui; Shi, Zhuangzhi

    2017-05-01

    Amide and olefins are important synthetic intermediates with complementary reactivity which play a key role in the construction of natural products, pharmaceuticals and manmade materials. Converting the normally highly stable aliphatic amides into olefins directly is a challenging task. Here we show that a Ni/NHC-catalytic system has been established for decarbonylative elimination of aliphatic amides to generate various olefins via C-N and C-C bond cleavage. This study not only overcomes the acyl C-N bond activation in aliphatic amides, but also encompasses distinct chemical advances on a new type of elimination reaction called retro-hydroamidocarbonylation. This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for late-stage olefination of amide groups in complex compounds.

  5. Eliminating War By Eliminating Warriors: A Case Study in Costa Rica

    DTIC Science & Technology

    2016-03-01

    eliminating individual national forces. The key to promoting peace through abolishing the military lies in four elements: culture, economic evolution ...of culture, economic evolution , domestic development, and external threats appear in virtually every source, so this work analyzes each element in...eliminating individual national forces. The key to promoting peace through abolishing the military lies in four elements: culture, economic evolution

  6. Formation of Olefins by Eliminative Dimerization and Eliminative Cross-Coupling of Carbenoids: A Stereochemical Exercise.

    PubMed

    Blakemore, Paul R; Hoffmann, Reinhard W

    2017-08-22

    Two carbenoids combine to generate an olefin by a mechanism involving ate-complex formation, 1,2-metallate rearrangement, and beta-elimination. Because each stage of this eliminative coupling is stereospecific, the overall stereochemical outcome can be understood, and in principle fully controlled, providing that the absolute stereochemical configurations of the reacting carbenoid species are defined. By contrast to traditional alkene syntheses, the eliminative cross-coupling of carbenoids offers a connective approach to olefins capable of precisely targeting a given isomer regardless of the nature of the features distinguishing isomers. The formation of olefins by eliminative dimerization and eliminative cross-coupling of carbenoids is reviewed for a range of illustrative examples, including the reactions of lithiated -haloalkanes, -epoxides, and -carbamates. An emphasis is placed on stereochemical analysis and methods to generate sp3-hybridized carbenoids in stereodefined form are surveyed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Taare Zameen Par and dyslexic savants

    PubMed Central

    Chakravarty, Ambar

    2009-01-01

    The film Taare Zameen Par (Stars upon the Ground) portrays the tormented life at school and at home of a child with dyslexia and his eventual success after his artistic talents are discovered by his art teacher at the boarding school. The film hints at a curious neurocognitive phenomenon of creativity in the midst of language disability, as exemplified in the lives of people like Leonardo da Vinci and Albert Einstein, both of whom demonstrated extraordinary creativity even though they were probably affected with developmental learning disorders. It has been hypothesized that a developmental delay in the dominant hemisphere most likely ‘disinhibits’ the nondominant parietal lobe, unmasking talents—artistic or otherwise—in some such individuals. It has been suggested that, in remedial training, children with learning disorders be encouraged to develop such hidden talents to full capacity, rather than be subjected to the usual overemphasis on the correction of the disturbed coded symbol operations. PMID:20142854

  8. A multimodal approach to elimination of stuttering.

    PubMed

    Beaty, D T

    1980-02-01

    Various approaches have been used in the treatment of stuttering. However, none of these approaches have been systematically incorporated via a multifaceted treatment program for the elimination of this disorder. The following case of a 15-yr.-old stutterer is presented to illustrate Lazarus' Multimodal Behavior Therapy Model, which is proposed to integrate various procedures whose singular effectiveness has been demonstrated.

  9. Guidelines for Eliminating and Preventing Sex Discrimination.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing.

    The major part of this booklet presents the guidelines delineated by Michigan State Task Force to Study Sexism in the Schools for eliminating and preventing sex discrimination in educational settings. The guidelines are divided into five areas: (1) all levels of educational agencies and their governing boards, (2) all levels of teachers and…

  10. Eliminate Gross Disparities under Your Control.

    ERIC Educational Resources Information Center

    Haycock, Kati

    1997-01-01

    Discusses how the absence of equal resources for schools or adequate support for families must not prevent educators from eliminating the gross inequalities brought about by assigning our least-qualified teachers to the neediest students, tolerating shoddy practice, steering students to inferior curricular choices, and generally miseducating the…

  11. Rabies in South Asia: fighting for elimination.

    PubMed

    Chowdhury, Fazle-Rabbi; Basher, Ariful; Amin, Mohammad R; Hassan, Nazia; Patwary, Mohammad I

    2015-01-01

    South Asia is regarded as the hot spot for the tourist and travelers. Unfortunately, three big countries (India, Pakistan and Bangladesh) of this region belong to top five rabies endemic countries of the world. Around 55,000 people die of rabies every year globally and 45% of them belong to South and South East Asia. Countries are now working on the elimination of rabies by the year 2020. Elimination of animal rabies is the pivotal of controlling human rabies. Dog (primary source) registration, population control and mass vaccination are the different ways of eliminating animal rabies. Pre (for risk groups including travelers) and post-exposure vaccine is the core for controlling human rabies. Post-exposure vaccine consists of nerve tissue vaccine and tissue culture vaccine. Due to low antigenicity and post-vaccine neurological complications all countries of South Asia except Pakistan have phased out the production and use of nerve tissue vaccine. To reduce the cost intramuscular regimen is now largely replaced by intradermal regimen and equine rabies immunoglobulin will probably replace human immunoglobulin in future for category III animal bite. 'SAARC' took initiatives for rabies elimination through 'SAARC development fund' which would hopefully play a vital role in regional collaboration to make the region rabies free.

  12. Thinking outside the box: feline elimination.

    PubMed

    Neilson, Jacqui

    2004-02-01

    Feline elimination problems are the leading behavioral complaint of cat owners. When presented with a feline elimination problem there are three main diagnostic categories: medical problems, marking or toileting problems. It is important to first perform diagnostic tests to rule out and/or address underlying medical issues and all feline house soiling patients should receive a comprehensive physical examination. When the elimination problem persists after a medical problem has either been ruled out or remedied, a behavioral diagnosis should be obtained. The primary distinction that must be made in a behavioral diagnosis is whether the cat is engaging in marking behavior or selecting a spot other than the litterbox for elimination (a toileting problem). The motivation for urine marking may be territorial behavior or anxiety/stress whereas toileting problems are often triggered by medical causes, aversions, preferences or anxiety. Marking animals should be neutered and additional treatment measures may include reducing conflict and stress in the environment. Drug therapy has been long used to help control urine marking and recent studies have furthered our knowledge about the most appropriate treatments. Treatment for toileting problems should focus on providing an attractive litterbox while reducing the attractiveness or accessibility of inappropriate target spots.

  13. Eliminating Barriers for All E-Learners.

    ERIC Educational Resources Information Center

    Holstrom, Lisa

    2003-01-01

    Discusses ways to eliminate barriers to electronic learning based on experiences at the University of Cincinnati. Topics include meeting demands from a population that lacks access and skills; weak English proficiency; low income adults; acquiring computer skills; media use; computer hardware capabilities; and the need for continuing feedback.…

  14. Teaching Projectile Motion to Eliminate Misconceptions

    ERIC Educational Resources Information Center

    Prescott, Anne; Mitchelmore, Michael

    2005-01-01

    Student misconceptions of projectile motion are well documented, but their effect on the teaching and learning of the mathematics of motion under gravity has not been investigated. An experimental unit was designed that was intended to confront and eliminate misconceptions in senior secondary school students. The approach was found to be…

  15. Promoting Relationships and Eliminating Violence in Canada

    ERIC Educational Resources Information Center

    Pepler, Debra; Craig, Wendy

    2011-01-01

    The Promoting Relationships and Eliminating Violence Network (PREVNet) involves Canadian researchers and national organizations working to promote healthy relationships and prevent bullying. In this paper, we provide the rationale for establishing PREVNet, a description of the work of the network, and an assessment of the success of PREVNet.…

  16. Influence of mexiletine on caffeine elimination.

    PubMed

    Joeres, R; Klinker, H; Heusler, H; Epping, J; Richter, E

    1987-01-01

    In an acute experiment in healthy volunteers and in patients under long-term treatment for cardiac arrhythmias, mexiletine inhibits caffeine elimination by about 50%. The clearance of mexiletine is not influenced by caffeine. Some side effects of mexiletine may possibly at least partially be attributable to a retention of caffeine.

  17. Telescoping of instrumentation tubing eliminates swaging

    NASA Technical Reports Server (NTRS)

    Mc Clellan, E. L.

    1966-01-01

    Short sections of stainless steel tubing of slide-fit sizes fitted together and silver-soldered at the junctions form small-diameter tubing assemblies with accurately stepped-down dimensions. This method of fabrication eliminates the costly swaging operations formerly used.

  18. Digital telemetry system eliminates data redundancy

    NASA Technical Reports Server (NTRS)

    Hymer, R. L.

    1971-01-01

    Floating aperature, zero-order predictor /ZOP/ circuit eliminates telemetered data redundancy by examining data from each sensor before it is multiplexed and transmitted. Digital devices to implement design are off-the-shelf items such as gates, registers and flip-flops, which are readily amenable to large-scale integration techniques.

  19. Challenges for malaria elimination in Brazil.

    PubMed

    Ferreira, Marcelo U; Castro, Marcia C

    2016-05-20

    Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years. In 2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country's malaria burden. This paper reviews major lessons learned from past and current malaria control policies in Brazil. A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015. Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission. Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas.

  20. Eliminating Barriers to Dual Enrollment in Oklahoma

    ERIC Educational Resources Information Center

    Roach, Rick; Gamez Vargas, Juanita; David, Kevin M.

    2015-01-01

    Policy, financial, and transportation barriers have limited participation in dual enrollment for marginalized (low-socioeconomic, first-generation, and ethnic minority) students in Oklahoma. This chapter presents a collaborative effort by education and community leaders that has successfully eliminated these barriers and increased the number of…

  1. Gram-Schmidt Orthogonalization by Gauss Elimination.

    ERIC Educational Resources Information Center

    Pursell, Lyle; Trimble, S. Y.

    1991-01-01

    Described is the hand-calculation method for the orthogonalization of a given set of vectors through the integration of Gaussian elimination with existing algorithms. Although not numerically preferable, this method adds increased precision as well as organization to the solution process. (JJK)

  2. Dispensing system eliminates torsion in deployed hoses

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Dispensing system uses a rotating drum, transfer arm, and stationary drum to deploy, reel in, and store an attached hose. This system which eliminates torsion and minimizes strain and wear of flexible hoses, is used for handling flexible cables that have one end permanently attached to an outlet or connector.

  3. Tackling Imported Malaria: An Elimination Endgame

    PubMed Central

    Sturrock, Hugh J. W.; Roberts, Kathryn W.; Wegbreit, Jennifer; Ohrt, Colin; Gosling, Roly D.

    2015-01-01

    As countries move toward malaria elimination, imported infections become increasingly significant as they often represent the majority of cases, can sustain transmission, cause resurgences, and lead to mortality. Here we review and critique current methods to prevent malaria importation in countries pursuing elimination and explore methods applied in other transmission settings and to other diseases that could be transferred to support malaria elimination. To improve intervention targeting we need a better understanding of the characteristics of populations importing infections and their patterns of migration, improved methods to reliably classify infections as imported or acquired locally, and ensure early and accurate diagnosis. The potential for onward transmission in the most receptive and vulnerable locations can be predicted through high-resolution risk mapping that can help malaria elimination or prevention of reintroduction programs target resources. Cross border and regional initiatives can be highly effective when based on an understanding of human and parasite movement. Ultimately, determining the optimal combinations of approaches to address malaria importation will require an evaluation of their impact, cost effectiveness, and operational feasibility. PMID:26013369

  4. Gram-Schmidt Orthogonalization by Gauss Elimination.

    ERIC Educational Resources Information Center

    Pursell, Lyle; Trimble, S. Y.

    1991-01-01

    Described is the hand-calculation method for the orthogonalization of a given set of vectors through the integration of Gaussian elimination with existing algorithms. Although not numerically preferable, this method adds increased precision as well as organization to the solution process. (JJK)

  5. Eliminating Barriers to Dual Enrollment in Oklahoma

    ERIC Educational Resources Information Center

    Roach, Rick; Gamez Vargas, Juanita; David, Kevin M.

    2015-01-01

    Policy, financial, and transportation barriers have limited participation in dual enrollment for marginalized (low-socioeconomic, first-generation, and ethnic minority) students in Oklahoma. This chapter presents a collaborative effort by education and community leaders that has successfully eliminated these barriers and increased the number of…

  6. Endemicity response timelines for Plasmodium falciparum elimination.

    PubMed

    Smith, David L; Hay, Simon I

    2009-04-30

    The scaling up of malaria control and renewed calls for malaria eradication have raised interest in defining timelines for changes in malaria endemicity. The epidemiological theory for the decline in the Plasmodium falciparum parasite rate (PfPR, the prevalence of infection) following intervention was critically reviewed and where necessary extended to consider superinfection, heterogeneous biting, and aging infections. Timelines for malaria control and elimination under different levels of intervention were then established using a wide range of candidate mathematical models. Analysis focused on the timelines from baseline to 1% and from 1% through the final stages of elimination. The Ross-Macdonald model, which ignores superinfection, was used for planning during the Global Malaria Eradication Programme (GMEP). In models that consider superinfection, PfPR takes two to three years longer to reach 1% starting from a hyperendemic baseline, consistent with one of the few large-scale malaria control trials conducted in an African population with hyperendemic malaria. The time to elimination depends fundamentally upon the extent to which malaria transmission is interrupted and the size of the human population modelled. When the PfPR drops below 1%, almost all models predict similar and proportional declines in PfPR in consecutive years from 1% through to elimination and that the waiting time to reduce PfPR from 10% to 1% and from 1% to 0.1% are approximately equal, but the decay rate can increase over time if infections senesce. The theory described herein provides simple "rules of thumb" and likely time horizons for the impact of interventions for control and elimination. Starting from a hyperendemic baseline, the GMEP planning timelines, which were based on the Ross-Macdonald model with completely interrupted transmission, were inappropriate for setting endemicity timelines and they represent the most optimistic scenario for places with lower endemicity. Basic

  7. Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa

    PubMed Central

    2013-01-01

    Background The ParS/ParR two component regulatory system plays critical roles for multidrug resistance in Pseudomonas aeruginosa. It was demonstrated that in the presence of antimicrobials, ParR enhances bacterial survival by distinct mechanisms including activation of the mexXY efflux genes, enhancement of lipopolysaccharide modification through the arn operon, and reduction of the expression of oprD porin. Results In this study, we report on transcriptomic analyses of P. aeruginosa PAO1 wild type and parS and parR mutants growing in a defined minimal medium. Our transcriptomic analysis provides the first estimates of transcript abundance for the 5570 coding genes in P. aeruginosa PAO1. Comparative transcriptomics of P. aeruginosa PAO1 and par mutants identified a total of 464 genes regulated by ParS and ParR. Results also showed that mutations in the parS/parR system abolished expression of the mexEF-oprN operon by down-regulating the regulatory gene mexS. In addition to the known effects on drug resistance genes, transcript abundances of the quorum sensing genes (rhlIR and pqsABCDE-phnAB) were higher in both parS and parR mutants. In accordance with these results, a significant portion of the ParS/ParR regulated genes belonged to the MexEF-OprN and quorum sensing regulons. Deletion of the par genes also led to increased phenazine production and swarming motility, consistent with the up-regulation of the phenazine and rhamnolipid biosynthetic genes, respectively. Conclusion Our results link the ParS/ParR two component signal transduction system to MexEF-OprN and quorum sensing systems in P. aeruginosa. These results expand our understanding of the roles of the ParS/ParR system in the regulation of gene expression in P. aeruginosa, especially in the absence of antimicrobials. PMID:24034668

  8. Ethanol elimination rates in an ED population.

    PubMed

    Brennan, D F; Betzelos, S; Reed, R; Falk, J L

    1995-05-01

    Knowledge of the rate of ethanol elimination is essential in the assessment of the intoxicated patient. Surprisingly little literature is available regarding ethanol elimination rates in emergency department (ED) patients; prior studies almost exclusively examined populations of alcoholics or normal controls. Consequently, this prospective observational study was undertaken to assess the rate of ethanol elimination in an ED population. Twenty-four consecutive adult ED patients clinically suspected of intoxication who had serum ethanol determinations drawn were enrolled. Patients underwent serial ethanol determinations via breathalyzer (Intoxilyzer 1400, CMI Inc., Owensboro, KY). Linear regression analysis of the plot of decrease in ethanol level over time was performed to determine the rate of ethanol elimination. Initial ethanol levels in the 24 patients ranged from 58 to 447 mg/dL (mean, 249 +/- 109 [SD] mg/dL). Patients were observed for a minimum of 2 and a maximum of 9 observations (mean, 3.9 +/- 1.7), over a period of 0.5 to 12.1 hours (mean, 4.4 +/-3.5 h). Clinical features of intoxication were poorly correlated with ethanol level (r < .5). The rate of ethanol elimination in the ED population was 19.6 mg/dL/h (r = .83; 95% confidence interval [CI], 16.9 to 22.3 mg/dL/h). Subgroup analysis found differences that were statistically significant but small. Multiple regression analysis showed that time was the major variable useful in predicting changes in ethanol level (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

  9. TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

    PubMed Central

    Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

    2011-01-01

    This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions. PMID:21864891

  10. Tumour-suppression activity of the proapoptotic regulator Par4.

    PubMed

    García-Cao, Isabel; Duran, Angeles; Collado, Manuel; Carrascosa, Maria J; Martín-Caballero, Juan; Flores, Juana M; Diaz-Meco, Maria T; Moscat, Jorge; Serrano, Manuel

    2005-06-01

    The proapoptotic protein encoded by Par4 (prostate apoptosis response 4) has been implicated in tumour suppression, particularly in the prostate. We report here that Par4-null mice are prone to develop tumours, both spontaneously and on carcinogenic treatment. The endometrium and prostate of Par4-null mice were particularly sensitive to the development of proliferative lesions. Most (80%) Par4-null females presented endometrial hyperplasia by 9 months of age, and a significant proportion (36%) developed endometrial adenocarcinomas after 1 year of age. Similarly, Par4-null males showed a high incidence of prostate hyperplasia and prostatic intraepithelial neoplasias, and were extraordinarily sensitive to testosterone-induced prostate hyperplasia. Finally, the uterus and prostate of young Par4-null mice have increased levels of the apoptosis inhibitor XIAP (X-chromosome-linked inhibitor of apoptosis), supporting the previously proposed function of Par4 as an inhibitor of the (zeta)PKC (atypical protein kinase)-NF-(kappa)B (nuclear factor-(kappa)B)-XIAP pathway. These data show that Par4 has an important role in tumour suppression, with a particular relevance in the endometrium and prostate.

  11. Tumour-suppression activity of the proapoptotic regulator Par4

    PubMed Central

    García-Cao, Isabel; Duran, Angeles; Collado, Manuel; Carrascosa, Maria J.; Martín-Caballero, Juan; Flores, Juana M.; Diaz-Meco, Maria T.; Moscat, Jorge; Serrano, Manuel

    2005-01-01

    The proapoptotic protein encoded by Par4 (prostate apoptosis response 4) has been implicated in tumour suppression, particularly in the prostate. We report here that Par4-null mice are prone to develop tumours, both spontaneously and on carcinogenic treatment. The endometrium and prostate of Par4-null mice were particularly sensitive to the development of proliferative lesions. Most (80%) Par4-null females presented endometrial hyperplasia by 9 months of age, and a significant proportion (36%) developed endometrial adenocarcinomas after 1 year of age. Similarly, Par4-null males showed a high incidence of prostate hyperplasia and prostatic intraepithelial neoplasias, and were extraordinarily sensitive to testosterone-induced prostate hyperplasia. Finally, the uterus and prostate of young Par4-null mice have increased levels of the apoptosis inhibitor XIAP (X-chromosome-linked inhibitor of apoptosis), supporting the previously proposed function of Par4 as an inhibitor of the ζPKC (atypical protein kinase)–NF-κB (nuclear factor-κB)–XIAP pathway. These data show that Par4 has an important role in tumour suppression, with a particular relevance in the endometrium and prostate. PMID:15877079

  12. Analysis of stereochemical convergence in asymmetric pd-catalysed allylic alkylation reactions complicated by halide and memory effects.

    PubMed

    Fairlamb, Ian J S; Lloyd-Jones, Guy C; Vyskocil, Stepán; Kocovský, Pavel

    2002-10-04

    A quantitative two-term description of memory effects arising in Pd-catalysed allylic alkylation reactions formally proceeding through 'meso'-type pi-allylpalladium intermediates is presented. The utility of this description (stereochemical convergence (sc) and global enantiomeric excess (ee(g))) is demonstrated by application to a series of Pd-catalysed allylic alkylation reactions involving racemic cyclopentenyl esters. Analysis of such reactions, by employing a range of enantiomerically pure monophosphine ligands, reinforces the conclusion that selectivities (enantiomeric excess (ee) values) obtained under standard 'benchmark' type conditions may be very misleading when powerful memory effects are operative. However, by comparison of sc and ee for a given ligand/solvent combination under a range of related conditions, one may predict the limiting ('latent') selectivity that will be obtained when the memory effect is negated. This technique is exemplified with one particular ligand (4 b, 'MAP') for which a number of strategies were employed to find conditions that negate the memory effect and reveal the limiting selectivity of the ligand. These conditions give a higher limiting global selectivity than that obtainable by using standard diastereoisomer equilibration methods such as added halide. Thus, the analysis of sc versus ee(g) also allows subtle changes in selectivity to be discerned. The difference in limiting selectivity (chloride versus non-chloride conditions) is proposed to arise through the nucleophilic attack of neutral monodentate versus cationic bidentate MAP (4 b) or MOP (4 a) complexes.

  13. Reversed reactivity of anilines with alkynes in the rhodium-catalysed C–H activation/carbonylation tandem

    PubMed Central

    Midya, Siba P.; Sahoo, Manoj K.; Landge, Vinod G.; Rajamohanan, P. R.; Balaraman, Ekambaram

    2015-01-01

    Development of multicatalytic approach consisting of two or more mechanistically distinct catalytic steps using a single-site catalyst for rapid and straightforward access of structurally complex molecules under eco-benign conditions has significance in contemporary science. We have developed herein a rhodium-catalysed C–H activation strategy which uses an unprotected anilines and an electron-deficient alkynes to C–C bonded products as a potential intermediate in contrast to the archetypical C–N bonded products with high levels of regioselectivity. This is followed by carbonylation of C–H bond activated intermediate and subsequent annulation into quinolines has been described. This rhodium-catalysed auto-tandem reaction operates under mild, environmentally benign conditions using water as the solvent and CO surrogates as the carbonyl source with the concomitant generation of hydrogen gas. The strategy may facilitate the development of new synthetic protocols for the efficient and sustainable production of chemicals in an atom-economic way from simple, abundant starting materials. PMID:26486182

  14. The stereospecificity and catalytic efficiency of the tryptophan synthase-catalysed exchange of the α-protons of amino acids

    PubMed Central

    2004-01-01

    13C-NMR has been used to follow the tryptophan synthase (EC 4.2.1.20) catalysed hydrogen–deuterium exchange of the pro-2R and pro-2S protons of [2-13C]glycine at pH 7.8. 1H-NMR has also been used to follow the tryptophan-synthase-catalysed hydrogen–deuterium exchange of the α-protons of a range of L- and D-amino acids at pH 7.8. The pKa values of the α-protons of these amino acids have been estimated and we have determined whether or not their exchange rates can be predicted from their pKa values. With the exception of tryptophan and norleucine, the stereospecificities of the first-order α-proton exchange rates are independent of the size and electronegativity of the amino acid R-group. Similar results are obtained with the second-order α-proton exchange rates, except that both L-tryptophan and L-serine have much higher stereospecificities than all the other amino acids studied. PMID:15107013

  15. The fascinating construction of pyridine ring systems by transition metal-catalysed [2 + 2 + 2] cycloaddition reactions.

    PubMed

    Heller, Barbara; Hapke, Marko

    2007-07-01

    Cycloaddition reactions compose one of the most important classes of reactions when it comes to the simultaneous formation of several bonds in one reaction step. The de novo construction of carbocyclic aromatic systems from acetylenes was also found as an excellent possibility for the assembly of heteroaromatic systems. The transition metal-catalysed [2 + 2 + 2] cycloaddition reaction constitutes a fascinating tool for the synthesis of pyridines from nitriles and the most recent developments demonstrate the ability to control the substitution pattern as well as the possibility of introducing chirality by the use of achiral substrates and a chiral catalyst under mild conditions. In this tutorial review we are focusing on the de novo construction of pyridine ring systems by the transition metal-catalysed [2 + 2 + 2] cycloaddition reaction. After surveying the mechanistic features and intermediates of the reaction depending on the different metal complexes used, we depict the preparation of achiral pyridine derivatives. The last section describes the advances in the synthesis of chiral pyridines and biaryls using the cyclotrimerization method. The various possibilities of introducing chirality by catalytic means are presented and illustrated by instructive examples. This review will be of interest for people active in: Organic Chemistry, Organometallic Chemistry, Transition Metal Chemistry, Stereoselective Synthesis, Heterocyclic Chemistry.

  16. Evaluation of fluoropyruvate as nucleophile in reactions catalysed by N-acetyl neuraminic acid lyase variants: scope, limitations and stereoselectivity.

    PubMed

    Stockwell, Jennifer; Daniels, Adam D; Windle, Claire L; Harman, Thomas A; Woodhall, Thomas; Lebl, Tomas; Trinh, Chi H; Mulholland, Keith; Pearson, Arwen R; Berry, Alan; Nelson, Adam

    2016-01-07

    The catalysis of reactions involving fluoropyruvate as donor by N-acetyl neuraminic acid lyase (NAL) variants was investigated. Under kinetic control, the wild-type enzyme catalysed the reaction between fluoropyruvate and N-acetyl mannosamine to give a 90 : 10 ratio of the (3R,4R)- and (3S,4R)-configured products; after extended reaction times, equilibration occurred to give a 30 : 70 mixture of these products. The efficiency and stereoselectivity of reactions of a range of substrates catalysed by the E192N, E192N/T167V/S208V and E192N/T167G NAL variants were also studied. Using fluoropyruvate and (2R,3S)- or (2S,3R)-2,3-dihydroxy-4-oxo-N,N-dipropylbutanamide as substrates, it was possible to obtain three of the four possible diastereomeric products; for each product, the ratio of anomeric and pyranose/furanose forms was determined. The crystal structure of S. aureus NAL in complex with fluoropyruvate was determined, assisting rationalisation of the stereochemical outcome of C-C bond formation.

  17. A novel Dps-type protein from insect gut bacteria catalyses hydrolysis and synthesis of N-acyl amino acids.

    PubMed

    Ping, Liyan; Büchler, Rita; Mithöfer, Axel; Svatos, Ales; Spiteller, Dieter; Dettner, Konrad; Gmeiner, Sophie; Piel, Jörn; Schlott, Bernhard; Boland, Wilhelm

    2007-06-01

    A novel type of a microbial N-acyl amino acid hydrolase (AAH) from insect gut bacteria was purified, cloned and functionally characterized. The enzyme was obtained from Microbacterium arborescens SE14 isolated from the foregut of larvae of the generalist herbivore Spodoptera exigua. The substrates of AAH are N-acyl-glutamines previously reported to elicit plant defence reactions after introduction into the leaf during feeding. The isolated AAH catalyses the hydrolysis of the amide bond (K(m) = 36 micromol l(-1)) and, less efficient, the formation (K(m) = 3 mmol l(-1)) of the elicitor active N-acyl amino acids. The AAH from M. arborescens SE14 shows no homology to known fatty acyl amidases (EC 3.5.1.4) but belongs to the family of Dps proteins (DNA-binding protein from starved cell). In line with other DPS proteins AAH is a homododecamer (monomer 17 181 Da) and contains iron atoms (c. 1-16 iron atoms per subunit). Unlike genuine DPS proteins the enzyme does not significantly bind DNA. Amino acid hydrolase is the first member of the DPS family that catalyses the cleavage or formation of amide bonds. The participation of a microbial enzyme in the homeostasis of N-acyl-glutamines in the insect gut adds further complexity to the interaction between plants and their herbivores.

  18. Chiral induction effects in ruthenium(II) amino alcohol catalysed asymmetric transfer hydrogenation of ketones: an experimental and theoretical approach

    PubMed

    Petra; Reek; Handgraaf; Meijer; Dierkes; Kamer; Brussee; Schoemaker; van Leeuwen PW

    2000-08-04

    The enantioselective outcome of transfer hydrogenation reactions that are catalysed by ruthenium(II) amino alcohol complexes was studied by means of a systematically varied series of ligands. It was found that both the substituent at the 1-position in the 2-amino-1-alcohol ligand and the substituent at the amine functionality influence the enantioselectivity of the reaction to a large extent: enantioselectivities (ee values) of up to 95% were obtained for the reduction of acetophenone. The catalytic cycle of ruthenium(II) amino alcohol catalysed transfer hydrogenation was examined at the density functional theory level. The formation of a hydrogen bond between the carbonyl functionality of the substrate and the amine proton of the ligand, as well as the formation of an intramolecular H...H bond and a planar H-Ru-N-H moiety are crucially important for the reaction mechanism. The enantioselective outcome of the reaction can be illustrated with the aid of molecular modelling by the visualisation of the steric interactions between the ketone and the ligand backbone in the ruthenium(II) catalysts.

  19. Bifunctional CYP81AA proteins catalyse identical hydroxylations but alternative regioselective phenol couplings in plant xanthone biosynthesis

    PubMed Central

    El-Awaad, Islam; Bocola, Marco; Beuerle, Till; Liu, Benye; Beerhues, Ludger

    2016-01-01

    Xanthones are natural products present in plants and microorganisms. In plants, their biosynthesis starts with regioselective cyclization of 2,3′,4,6-tetrahydroxybenzophenone to either 1,3,5- or 1,3,7-trihydroxyxanthones, catalysed by cytochrome P450 (CYP) enzymes. Here we isolate and express CYP81AA-coding sequences from Hypericum calycinum and H. perforatum in yeast. Microsomes catalyse two consecutive reactions, that is, 3′-hydroxylation of 2,4,6-trihydroxybenzophenone and C–O phenol coupling of the resulting 2,3′,4,6-tetrahydroxybenzophenone. Relative to the inserted 3′-hydroxyl, the orthologues Hc/HpCYP81AA1 cyclize via the para position to form 1,3,7-trihydroxyxanthone, whereas the paralogue HpCYP81AA2 directs cyclization to the ortho position, yielding the isomeric 1,3,5-trihydroxyxanthone. Homology modelling and reciprocal mutagenesis reveal the impact of S375, L378 and A483 on controlling the regioselectivity of HpCYP81AA2, which is converted into HpCYP81AA1 by sextuple mutation. However, the reciprocal mutations in HpCYP81AA1 barely affect its regiospecificity. Product docking rationalizes the alternative C–O phenol coupling reactions. Our results help understand the machinery of bifunctional CYPs. PMID:27145837

  20. The activity of the dinuclear cobalt-β-lactamase from Bacillus cereus in catalysing the hydrolysis of β-lactams

    PubMed Central

    Badarau, Adriana; Damblon, Christian; Page, Michael I.

    2006-01-01

    Metallo-β-lactamases are native zinc enzymes that catalyse the hydrolysis of β-lactam antibiotics, but are also able to function with cobalt(II) and require one or two metal-ions for catalytic activity. The hydrolysis of cefoxitin, cephaloridine and benzylpenicillin catalysed by CoBcII (cobalt-substituted β-lactamase from Bacillus cereus) has been studied at different pHs and metal-ion concentrations. An enzyme group of pKa 6.52±0.1 is found to be required in its deprotonated form for metal-ion binding and catalysis. The species that results from the loss of one cobalt ion from the enzyme has no significant catalytic activity and is thought to be the mononuclear CoBcII. It appears that dinuclear CoBcII is the active form of the enzyme necessary for turnover, while the mononuclear CoBcII is only involved in substrate binding. The cobalt-substituted enzyme is a more efficient catalyst than the native enzyme for the hydrolysis of some β-lactam antibiotics suggesting that the role of the metal-ion is predominantly to provide the nucleophilic hydroxide, rather than to act as a Lewis acid to polarize the carbonyl group and stabilize the oxyanion tetrahedral intermediate. PMID:16961465

  1. The formation of high-purity isocyanurate through proazaphosphatrane-catalysed isocyanate cyclo-trimerisation: computational insights.

    PubMed

    Gibb, Jack N; Goodman, Jonathan M

    2013-01-07

    Polyurethane foams are widely used materials and control of their physical properties is a significant challenge. Management of cyclo-trimerisation during the polymerisation process is vital when tailoring the mechanical properties of the foam. Proazaphosphatranes are known to efficiently catalyse the cyclo-trimerisation of organic isocyanates, giving high purity isocyanurate with little uretdione by-product. The mechanism of this catalysis was previously unknown, although some zwitterionic intermediates have been identified spectroscopically. We have investigated a nucleophilic-catalysis reaction pathway involving sequential addition of methyl isocyanate to activated zwitterionic intermediates using density functional theory calculations. Evidence for significant transannulation by the proazaphosphatrane nitrogen was found for all intermediates, offering stabilisation of the phosphonium cation. Steric crowding at the proazaphosphatrane nucleophilic phosphorus gives rise to a preference for direct isocyanurate formation rather than via the uretdione, in sharp contrast to the uncatalysed system which has been found to preferentially proceed via the kinetic uretdione product. The investigations suggest the mechanism of proazaphosphatrane catalysed cyclo-oligomerisation does not proceed via the uretdione product, and hence why little of this impurity is observed experimentally.

  2. Silver-catalysed azide–alkyne cycloaddition (AgAAC): assessing the mechanism by density functional theory calculations

    PubMed Central

    Chandrasekhar, K.; Killi, Sunil Kumar; Pramanik, Sumit Kumar; Uttam, Pal; Sen, Sudeshna; Maiti, Nakul Chandra

    2016-01-01

    ‘Click reactions’ are the copper catalysed dipolar cycloaddition reaction of azides and alkynes to incorporate nitrogens into a cyclic hydrocarbon scaffold forming a triazole ring. Owing to its efficiency and versatility, this reaction and the products, triazole-containing heterocycles, have immense importance in medicinal chemistry. Copper is the only known catalyst to carry out this reaction, the mechanism of which remains unclear. We report here that the ‘click reactions’ can also be catalysed by silver halides in non-aqueous medium. It constitutes an alternative to the well-known CuAAC click reaction. The yield of the reaction varies on the type of counter ion present in the silver salt. This reaction exhibits significant features, such as high regioselectivity, mild reaction conditions, easy availability of substrates and reasonably good yields. In this communication, the findings of a new catalyst along with the effect of solvent and counter ions will help to decipher the still obscure mechanism of this important reaction. PMID:27703683

  3. Redox process catalysed by growing crystal-strengite, FePO4,2H2O, crystallizing from solution with iron(II) and hydroxylamine

    NASA Astrophysics Data System (ADS)

    Lundager Madsen, Hans Erik

    2014-09-01

    In an attempt to grow pure crystals of the iron(II) phosphate vivianite, Fe3(PO4)2,8H2O, from a solution of Mohr's salt, Fe(NH4)2(SO4)2,6H2O, added to a solution of ammonium phosphate, hydroxylammonium chloride, NH3OHCl, was added to the iron(II) stock solution to eliminate oxidation of iron(II) by oxygen from the air. However, the effect turned out to be the opposite of the expected: whereas hydroxylamine reduces iron(III) in bulk solution, it acted as a strong oxidant in the presence of growing iron phosphate crystals, causing the crystallization of the iron(III) phosphate strengite, FePO4,2H2O, as the only solid phase. Evidently the crystal surface catalyses oxidation of iron(II) by hydroxylamine. The usual composite kinetics of spiral growth and surface nucleation was found. The surface-nucleation part yielded edge free energy λ in the range 12-45 pJ/m, virtually independent of temperature and in the range typical for phosphates of divalent metals. The scatter of values for λ presumably arises from contributions from different crystal forms to the overall growth rate. The low mean value points to strong adsorption of iron(II), which is subsequently oxidized at the crystal surface, forming strengite. The state of the system did not tend to thermodynamic equilibrium, but to a metastable state, presumably controlled by the iron(II) rich surface layer of the crystal. In addition to crystal growth, it was possible to measure nucleation kinetics by light scattering (turbidimetry). A point of transition from heterogeneous to homogeneous nucleation was found, and from the results for the homogeneous domain a rather precise value of crystal surface free energy γ=55 mJ/m2 was found. This is a relatively low value as well, indicating that the redox process plays a role already at the nucleation stage.

  4. [Around Ambroise Paré: his pupils and friends].

    PubMed

    Dumaître, P

    1996-01-01

    The most important pupil of Paré was Jacques Guillemeau (1550-1613), a famous surgeon from Montpellier. He lived at Paré's during eight years and wrote there his first work "Traité des maladies des yeux" (1585) and was really his "spiritual son". The barber-surgeon Martin Boursier, husband of the famous midwife Louise Bourgeois stayed twenty years with Paré and she learned her practice in his works. Attracted by Paré's fame, Melchior Sebiz (1539-1625) who shall become a famous professor of medicine in Strasbourg attended Paré's lessons and "was with him in great friendship". Among his friends, Thierry de Héry (ca. 1505-ca. 1560), companion of his youth as a barber-surgeon and author of the first French book on syphilis seems to have been the dearest and the nearest to his heart.

  5. Reactivity of alkynylindole-2-carboxamides in [Pd]-catalysed C-H activation and phase transfer catalysis: formation of pyrrolo-diindolones vs. β-carbolinones.

    PubMed

    Tulichala, R N Prasad; Swamy, K C Kumara

    2016-05-11

    The divergent behaviour of 3-alkynylindole-2-carboxamides, under palladium catalysed conditions and phase-transfer catalytic conditions, is described. Thus, palladium catalysed intramolecular C-N and C-C bond formation in a single step by C-H activation involving 3-alkynylindole-2-carboxamides and leading to pyrrolodiindolones in high yields is developed. In contrast, using the same precursors, a high yielding regio- and chemo-selective route for 3-substituted β-carbolinones by phase-transfer catalysis is established via intramolecular C-N bond formation. The structures of key products are confirmed by X-ray crystallography.

  6. Structures of partition protein ParA with nonspecific DNA and ParB effector reveal molecular insights into principles governing Walker-box DNA segregation.

    PubMed

    Zhang, Hengshan; Schumacher, Maria A

    2017-03-01

    Walker-box partition systems are ubiquitous in nature and mediate the segregation of bacterial and archaeal DNA. Well-studied plasmid Walker-box partition modules require ParA, centromere-DNA, and a centromere-binding protein, ParB. In these systems, ParA-ATP binds nucleoid DNA and uses it as a substratum to deliver ParB-attached cargo DNA, and ParB drives ParA dynamics, allowing ParA progression along the nucleoid. How ParA-ATP binds nonspecific DNA and is regulated by ParB is unclear. Also under debate is whether ParA polymerizes on DNA to mediate segregation. Here we describe structures of key ParA segregation complexes. The ParA-β,γ-imidoadenosine 5'-triphosphate (AMPPNP)-DNA structure revealed no polymers. Instead, ParA-AMPPNP dimerization creates a multifaceted DNA-binding surface, allowing it to preferentially bind high-density DNA regions (HDRs). DNA-bound ParA-AMPPNP adopts a dimer conformation distinct from the ATP sandwich dimer, optimized for DNA association. Our ParA-AMPPNP-ParB structure reveals that ParB binds at the ParA dimer interface, stabilizing the ATPase-competent ATP sandwich dimer, ultimately driving ParA DNA dissociation. Thus, the data indicate how harnessing a conformationally adaptive dimer can drive large-scale cargo movement without the requirement for polymers and suggest a segregation mechanism by which ParA-ATP dimers equilibrate to HDRs shown to be localized near cell poles of dividing chromosomes, thus mediating equipartition of attached ParB-DNA substrates. © 2017 Zhang and Schumacher; Published by Cold Spring Harbor Laboratory Press.

  7. Recombination in the Human Pseudoautosomal Region PAR1

    PubMed Central

    Hinch, Anjali G.; Altemose, Nicolas; Noor, Nudrat; Donnelly, Peter; Myers, Simon R.

    2014-01-01

    The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome. PMID:25033397

  8. Recombination in the human Pseudoautosomal region PAR1.

    PubMed

    Hinch, Anjali G; Altemose, Nicolas; Noor, Nudrat; Donnelly, Peter; Myers, Simon R

    2014-07-01

    The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

  9. Hydrogen generation from alcohols (α-hydroxy carboxylic acids) and alcohol-ammonia coupling in aqueous media catalysed by water-soluble bipyridine-Cp*Ir (Rh or Os) catalyst: a computational mechanism insight

    NASA Astrophysics Data System (ADS)

    Zhang, Dan-Dan; Chen, Xian-Kai; Liu, Hui-Ling; Huang, Xu-Ri

    2015-06-01

    Density functional theory (DFT) calculations were performed to elucidate the mechanism of the dehydrogenative oxidation of various primary alcohols (or α-hydroxy carboxylic acids) and the dehydrogenative coupling of alcohols with ammonia catalysed by the same water-soluble Cp*Ir complex bearing a 2-pyridonate-based ligand (A-Ir). Another two new catalysts A-Rh and A-Os are computationally designed for the dehydrogenative oxidation of alcohols. The plausible pathway for alcohol dehydrogenation includes three steps: alcohol oxidation to aldehyde (step I); the generation of dihydrogen in the metal coordination sphere (step II); and the liberation of dihydrogen accompanied with the regeneration of active catalyst A (step III). Among them, the step I follows bifunctional concerted double hydrogen transfer mechanism rather than the β-H elimination. For step II, the energy barriers involving the addition of one or two water molecules are higher than in absence of water. Our results also confirm that A-Ir can be applied in the dehydrogenation of various α-hydroxy carboxylic acids by the similar mechanism. Remarkably, A-Ir is also found to be efficient for the coupling reactions of various primary benzyl alcohols with ammonia to afford amides.

  10. Megestrol acetate NCD oral suspension -- Par Pharmaceutical: megestrol acetate nanocrystal dispersion oral suspension, PAR 100.2, PAR-100.2.

    PubMed

    2007-01-01

    Par Pharmaceutical has developed megestrol acetate (Megace ES) oral suspension for the treatment of anorexia, cachexia and a significant weight loss associated with AIDS. Par Pharmaceutical used Elan Corporation's NanoCrystal Dispersion (NCD) technology to develop an advanced, concentrated formulation of megestrol acetate with improved bioavailability, more rapid onset of action, more convenient dosing and a lower dosing regimen compared with the original marketed formulation of megestrol acetate oral suspension. Patients are administered a teaspoon (5mL) of the new NCD formulation once daily, compared with a daily 20mL dosage cup of the original formulation. The new megestrol acetate NCD formulation represents a line-extension of Par's megestrol acetate oral suspension (800mg/20mL, Megace O/S) that has been marketed for anorexia, cachexia and AIDS-related weight loss since July 2001. Par's megestrol acetate is the generic version of Bristol-Myers Squibb's Megace Oral Suspension. NanoCrystal Dispersion (NCD) is a trademark of Elan Corporation. Par Pharmaceutical will market megestol acetate NCD oral suspension under the Megace brand name. The company licensed the Megace name from Bristol-Myers Squib in August 2003. The US FDA approved megestrol acetate oral suspension (625 mg/mL) in July 2005 for the treatment of anorexia, cachexia or a significant, unexplained weight loss in patients with AIDS. The NDA for the product was accepted for review by the agency in September 2004, following its submission in June of that year.Par Pharmaceutical commenced the first of two phase III clinical trials of megestrol acetate oral suspension (PAR 100.2) in cancer-induced anorexia in the first quarter of 2006. However, this trial was discontinued in September 2006 because of slow patient enrolment. The company intends to discuss future development options in this indication with the FDA.New formulations or dosage forms of megestrol acetate concentrated suspension are also in

  11. Megestrol acetate NCD oral suspension--Par Pharmaceutical: megestrol acetate nanocrystal dispersion oral suspension, PAR 100.2, PAR-100.2.

    PubMed

    2007-01-01

    Par Pharmaceutical has developed megestrol acetate (Megace ES) oral suspension for the treatment of anorexia, cachexia and a significant weight loss associated with AIDS. Par Pharmaceutical used Elan Corporation's NanoCrystal Dispersion (NCD) technology to develop an advanced, concentrated formulation of megestrol acetate with improved bioavailability, more rapid onset of action, more convenient dosing and a lower dosing regimen compared with the original marketed formulation of megestrol acetate oral suspension. Patients are administered a teaspoon (5mL) of the new NCD formulation once daily, compared with a daily 20mL dosage cup of the original formulation. The new megestrol acetate NCD formulation represents a line-extension of Par's megestrol acetate oral suspension (800mg/20mL, Megace O/S) that has been marketed for anorexia, cachexia and AIDS-related weight loss since July 2001. Par's megestrol acetate is the generic version of Bristol-Myers Squibb's Megace Oral Suspension. NanoCrystal Dispersion (NCD) is a trademark of Elan Corporation. Par Pharmaceutical will market megestol acetate NCD oral suspension under the Megace brand name. The company licensed the Megace name from Bristol-Myers Squib in August 2003. The US FDA approved megestrol acetate oral suspension (625 mg/mL) in July 2005 for the treatment of anorexia, cachexia or a significant, unexplained weight loss in patients with AIDS. The NDA for the product was accepted for review by the agency in September 2004, following its submission in June of that year.Par Pharmaceutical commenced the first of two phase III clinical trials of megestrol acetate oral suspension (PAR 100.2) in cancer-induced anorexia in the first quarter of 2006. However, this trial was discontinued in September 2006 because of slow patient enrolment. The company intends to discuss future development options in this indication with the FDA.New formulations or dosage forms of megestrol acetate concentrated suspension are also in

  12. Energy disposal in unimolecular elimination reactions

    NASA Astrophysics Data System (ADS)

    Zamir, F.; Levine, R. D.

    1980-11-01

    The distribution of vibrational energy is diatomic molecules following unimolecular elimination is shown to be well represented as a distribution of maximal entropy subject to a constraint on the mean vibrational excitation. The nature of the constraint does not appear to depend on the activation process. The value of the constraint depends primarily on the height of the barrier in the elimination channel and, more weakly, on the excess energy above the barrier. A quantitative expression of these trends, in the form of a "sum rule", provides a route for the estimation of the energy distribution in the products at different total energies. The more limited results on the energy released into the relative translation or into the organic fragment can be largely accounted for using the same constraint. Different partitionings of a given total energy among the diatomic molecule and the organic olefin (or acetylene) are shown to lead to only a moderate change in the rate of addition reactions.

  13. Condensation and localization of the partitioning protein ParB on the bacterial chromosome.

    PubMed

    Broedersz, Chase P; Wang, Xindan; Meir, Yigal; Loparo, Joseph J; Rudner, David Z; Wingreen, Ned S

    2014-06-17

    The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB-DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein-DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB-DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB-DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB-DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes.

  14. Condensation and localization of the partitioning protein ParB on the bacterial chromosome

    PubMed Central

    Broedersz, Chase P.; Wang, Xindan; Meir, Yigal; Loparo, Joseph J.; Rudner, David Z.; Wingreen, Ned S.

    2014-01-01

    The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB–DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein–DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB–DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB–DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB–DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes. PMID:24927534

  15. Eliminating Deadbands In Resistive Angle Sensors

    NASA Technical Reports Server (NTRS)

    Salomon, Phil M.; Allen, Russell O.; Marchetto, Carl A.

    1992-01-01

    Proposed shaft-angle-measuring circuit provides continuous indication of angle of rotation from 0 degree to 360 degrees. Sensing elements are two continuous-rotation potentiometers, and associated circuitry eliminates deadband that occurs when wiper contact of potentiometer crosses end contacts near 0 degree position of circular resistive element. Used in valve-position indicator or similar device in which long operating life and high angular precision not required.

  16. Eliminating swine dysentery from selected herds.

    PubMed

    Glock, R D

    1984-08-01

    In attempts to eliminate swine dysentery from a herd, the total cost of nitroimidazole medication in the water can be estimated at 16/gal over 3-4 weeks and for carbadox in the feed at 70/100 lb over 6-8 weeks. Use of dimetridazole or ipronidazole in the water for 3-4 weeks or carbadox in the feed for 6-8 weeks eliminates Treponema hyodysenteriae from the porcine gut. A 30-day (10 weeks with carbadox) preslaughter withdrawal time should be provided. Impervious surfaces should be thoroughly sanitized, while permeable surfaces and lots should be cleaned, dried and aired well for 2-3 weeks in warm, dry weather and for at least 60 days in cool, damp weather. Animal vectors and fomites must be controlled. Isolation of new breeding stock for 3-4 weeks helps prevent recontamination. While elimination of swine dysentery is not practical in many herds because of poor facilities or lack of producer commitment, a properly designed program can result in economic benefits.

  17. Malaria elimination in India and regional implications.

    PubMed

    Wangdi, Kinley; Gatton, Michelle L; Kelly, Gerard C; Banwell, Cathy; Dev, Vas; Clements, Archie C A

    2016-10-01

    The malaria situation in India is complex as a result of diverse socio-environmental conditions. India contributes a substantial burden of malaria outside sub-Saharan Africa, with the third highest Plasmodium vivax prevalence in the world. Successful malaria control in India is likely to enhance malaria elimination efforts in the region. Despite modest gains, there are many challenges for malaria elimination in India, including: varied patterns of malaria transmission in different parts of the country demanding area-specific control measures; intense malaria transmission fuelled by favourable climatic and environment factors; varying degrees of insecticide resistance of vectors; antimalarial drug resistance; a weak surveillance system; and poor national coordination of state programmes. Prevention and protection against malaria are low as a result of a weak health-care system, as well as financial and socioeconomic constraints. Additionally, the open borders of India provide a potential route of entry for artesunate-resistant parasites from southeast Asia. This situation calls for urgent dialogue around tackling malaria across borders-between India's states and neighbouring countries-through sharing of information and coordinated control and preventive measures, if we are to achieve the aim of malaria elimination in the region. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Elimination of Rhodnius prolixus in Central America

    PubMed Central

    2012-01-01

    Rhodnius prolixus is one of the main vectors of Trypanosoma cruzi, causative agent of Chagas disease. In Central America, it was first discovered in 1915 in El Salvador, from where it spread northwest to Guatemala and Mexico, and southeast to Nicaragua and Costa Rica, arriving also in Honduras in the late 1950s. Indoor residual spraying (IRS) by the antimalaria services of Costa Rica prevented its spread southwards, and similar IRS programmes appear to have eliminated it from El Salvador by the late 1970s. In 1997, by resolution of the Ministers of Health of the seven Central American countries, a multinational initiative against Chagas disease (IPCA) was launched with one of the specific objectives being the elimination of R. prolixus from the region. As a result, more and more infested areas were encountered, and progressively sprayed using an IRS strategy already deployed against Triatoma infestans in the southern cone countries of South America. In 2008, Guatemala became the first of these countries to be formally certified as free of Chagas disease transmission due to R. prolixus. The other infested countries have since been similarly certified, and none of these has reported the presence of R. prolixus since June 2010. Further surveillance is required, but current evidence suggests that R. prolixus may now been eliminated from throughout the mesoamerican region, with a corresponding decline in the incidence of T. cruzi infections. PMID:22357219

  19. Comparing materials used in mist eliminators

    SciTech Connect

    Looney, B.; Baleno, B.; Boles, G.L.; Telow, J.

    2007-11-15

    Wet flue gas desulfurization (FGD) systems, or wet scrubbers, are notoriously capital - and maintenance-intensive. Mist eliminators are an integral part of most wet FGD systems. These are available in a variety of materials - polypropylene, fiberglass reinforced polymer (FRP), polysulfone and stainless steel. The article discusses the material properties, performance attributes and relative cost differences associated with each of these four materials. It describes the common problems with mist eliminators - fouling and corrosion. These can be minimised by routine cleaning and use of chemical additives to prevent deposition. An analysis was carried out to compare the four materials at APS Cholla power plant. As a result the facility is retrofitting its remaining wet scrubber towers in Unit 2 with mist eliminators constructed from polysulfone as each of the current ones of the existing polypropylene needs replacing. Polysulfone is cheaper to clean and components require replacing less frequently than polypropylene. Switching from stainless steel to polypropylene has proved advantageous on 22 wet scrubbers operated by PPL Montana. 5 figs. 2 tabs.

  20. Role of genomics in eliminating health disparities

    PubMed Central

    Kashyap, Meghana V; Nolan, Michael; Sprouse, Marc; Chakraborty, Ranajit; Cross, Deanna; Roby, Rhonda; Vishwanatha, Jamboor K

    2015-01-01

    The Texas Center for Health Disparities, a National Institute on Minority Health and Health Disparities Center of Excellence, presents an annual conference to discuss prevention, awareness education, and ongoing research about health disparities both in Texas and among the national population. The 2014 Annual Texas Conference on Health Disparities brought together experts in research, patient care, and community outreach on the “Role of Genomics in Eliminating Health Disparities.” Rapid advances in genomics and pharmacogenomics are leading the field of medicine to use genetics and genetic risk to build personalized or individualized medicine strategies. We are at a critical juncture of ensuring such rapid advances benefit diverse populations. Relatively few forums have been organized around the theme of the role of genomics in eliminating health disparities. The conference consisted of three sessions addressing “Gene-Environment Interactions and Health Disparities,” “Personalized Medicine and Elimination of Health Disparities,” and “Ethics and Public Policy in the Genomic Era.” This article summarizes the basic science, clinical correlates, and public health data presented by the speakers. PMID:26435701

  1. Control of cleavage spindle orientation in Caenorhabditis elegans: The role of the genes par-2 and par-3

    SciTech Connect

    Cheng, N.N.; Kirby, C.M.; Kemphues, K.J.

    1995-02-01

    Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity of these divisions. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2 (it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage. 44 refs., 5 figs., 5 tabs.

  2. Scleral Buckling for Rhegmatogenous Retinal Detachment Associated with Pars Planitis

    PubMed Central

    Ahn, Jae Kyoun

    2016-01-01

    Purpose. To evaluate the surgical outcome of scleral buckling (SB) in rhegmatogenous retinal detachment (RRD) patients associated with pars planitis. Methods. Retrospective review of RRD patients (32 eyes of pars planitis RRD and 180 eyes of primary RRD) who underwent SB. We compared primary and final anatomical success rates and visual outcomes between two groups. Results. Primary and final anatomical success were achieved in 25 (78.1%) and 31 (96.8%) eyes in the pars planitis RRD group and in 167 eyes (92.7%) and 176 eyes (97.7%) in primary RRD group, respectively. Both groups showed significant visual improvement (p < 0.001) and there were no significant differences in final visual acuity. Pars planitis RRD group was associated with higher rate of postoperative proliferative vitreoretinopathy (PVR) development (12.5% versus 2.8%, p = 0.031). Pars planitis and high myopia were significant preoperative risk factors and pseudophakia was borderline risk for primary anatomical failure after adjusting for various clinical factors. Conclusions. Pars planitis associated RRD showed inferior primary anatomical outcome after SB due to postoperative PVR development. However, final anatomical and visual outcomes were favorable. RRD cases associated with pars planitis, high myopia, and pseudophakia might benefit from different surgical approaches, such as combined vitrectomy and SB. PMID:27688907

  3. The Pars Triangularis in Dyslexia and ADHD

    PubMed Central

    Kibby, Michelle Y.; Kroese, Judith M.; Krebbs, Hillery; Hill, Crystal E.; Hynd, George W.

    2009-01-01

    Limited research has been conducted on the structure of the pars triangularis (PT) in dyslexia despite functional neuroimaging research finding it may play a role in phonological processing. Furthermore, research to date has not examined PT size in ADHD even though the right inferior frontal region has been implicated in the disorder. Hence, one of the purposes of this study was to examine the structure of the PT in dyslexia and ADHD. The other purposes included examining the PT in relation to overall expressive language ability and in relation to several specific linguistic functions given language functioning often is affected in both dyslexia and ADHD. Participants included 50 children: 10 with dyslexia, 15 with comorbid dyslexia/ADHD, 15 with ADHD, and 10 controls. Using a 2 (dyslexia or not) X 2 (ADHD or not) MANCOVA, findings revealed PT length and shape were comparable between those with and without dyslexia. However, children with ADHD had smaller right PT lengths than those without ADHD, and right anterior ascending ramus length was related to attention problems in the total sample. In terms of linguistic functioning, presence of an extra sulcus in the left PT was related to poor expressive language ability. In those with adequate expressive language functioning, left PT length was related to phonological awareness, phonological short-term memory and rapid automatic naming (RAN). Right PT length was related to RAN and semantic processing. Further work on PT morphology in relation to ADHD and linguistic functioning is warranted. PMID:19356794

  4. Multi-scale photoacoustic remote sensing (PARS) (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Haji Reza, Parsin; Bell, Kevan; Shi, W.; Zemp, Roger J.

    2016-03-01

    We introduce a novel multi-scale photoacoustic remote sensing (PARS) imaging system. Our system can provide optical resolution details for superficial structures as well as acoustic resolution for deep-tissue imaging down to 5 cm, in a non-contact setting. PARS system does not require any contact with the sample or ultrasound coupling medium. The optical resolution PARS (OR-OARS) system uses optically focused pulsed excitation with optical detection of photoacoustic signatures using a long-coherence interrogation beam co-focused and co-scanned with the excitation spot. In the OR-PARS initial pressures are sampled right at their subsurface origin where acoustic pressures are largest. The Acoustic resolution PARS (AR-PARS) picks up the surface oscillation of the tissue caused by generated photoacoustic signal using a modified version of Michelson interferometry. By taking advantage of 4-meters polarization maintaining single-mode fiber and a green fiber laser we have generated a multi-wavelength source using stimulated Raman scattering. Remote functional imaging using this multi-wavelength excitation source and PARS detection mechanism has been demonstrated. The oxygen saturation estimations are shown for both phantom and in vivo studies. Images of blood vessel structures for an In vivo chicken embryo model is demonstrated. The Phantom studies indicates ~3µm and ~300µm lateral resolution for OR-PARS and AR-PARS respectively. To the best of our knowledge this is the first dual modality non-contact optical and acoustic resolution system used for in vivo imaging.

  5. Pd(II)-catalysed and Hg(II)-co-catalysed oxidation of D-glucose and D-fructose by N-bromoacetamide in the presence of perchloric acid: a kinetic and mechanistic study.

    PubMed

    Singh, Ashok Kumar; Srivastava, Jaya; Rahmani, Shahla; Singh, Vineeta

    2006-02-27

    The kinetics of Pd(II)-catalysed and Hg(II)-co-catalysed oxidation of D-glucose (Glc) and D-fructose (Fru) by N-bromoacetamide (NBA) in the presence of perchloric acid using mercury(II) acetate as a scavenger for Br- ions have been studied. The results show first-order kinetics with respect to NBA at low concentrations, tending to zero order at high concentrations. First-order kinetics with respect to Pd(II) and inverse fractional order in Cl- ions throughout their variation have also been noted. The observed direct proportionality between the first-order rate constant (k1) and the reducing sugar concentration shows departure from the straight line only at very higher concentration of sugar. Addition of acetamide (NHA) decreases the first-order rate constant while the oxidation rate is not influenced by the change in the ionic strength (mu) of the medium. Variation of [Hg(OAc)2] shows a positive effect on the rate of reaction. The observed negative effect in H+ at lower concentrations tends to an insignificant effect at its higher concentrations. The first-order rate constant decreases with an increase in the dielectric constant of the medium. The various activation parameters have also been evaluated. The products of the reactions were identified as arabinonic acid and formic acid for both the hexoses. A plausible mechanism involving HOBr as the reactive oxidising species, Hg(II) as co-catalyst, and [PdCl3.S]-1 as the reactive Pd(II)-sugar complex in the rate-controlling step is proposed.

  6. Predicted PAR1 inhibitors from multiple computational methods

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Liu, Jinfeng; Zhu, Tong; Zhang, Lujia; He, Xiao; Zhang, John Z. H.

    2016-08-01

    Multiple computational approaches are employed in order to find potentially strong binders of PAR1 from the two molecular databases: the Specs database containing more than 200,000 commercially available molecules and the traditional Chinese medicine (TCM) database. By combining the use of popular docking scoring functions together with detailed molecular dynamics simulation and protein-ligand free energy calculations, a total of fourteen molecules are found to be potentially strong binders of PAR1. The atomic details in protein-ligand interactions of these molecules with PAR1 are analyzed to help understand the binding mechanism which should be very useful in design of new drugs.

  7. Limnological database for Par Pond: 1959 to 1980

    SciTech Connect

    Tilly, L.J.

    1981-03-01

    A limnological database for Par Pond, a cooling reservoir for hot reactor effluent water at the Savannah River Plant, is described. The data are derived from a combination of research and monitoring efforts on Par Pond since 1959. The approximately 24,000-byte database provides water quality, primary productivity, and flow data from a number of different stations, depths, and times during the 22-year history of the Par Pond impoundment. The data have been organized to permit an interpretation of the effects of twenty years of cooling system operations on the structure and function of an aquatic ecosystem.

  8. Observation of a ferric hydroperoxide complex during the non-heme iron catalysed oxidation of alkenes and alkanes by O2.

    PubMed

    He, Yu; Goldsmith, Christian R

    2012-11-04

    A non-heme iron complex catalyses the oxidation of allylic, benzylic, and aliphatic C-H bonds by O(2). During this reactivity, a ferric hydroperoxide species is observed. The kinetic analysis of this complex's formation may suggest a ferric superoxo species as the initial metal-based oxidant.

  9. Enantioselective conjugate addition of phenylboronic acid to enones catalysed by a chiral tropos/atropos rhodium complex at the coalescence temperature.

    PubMed

    Monti, Chiara; Gennari, Cesare; Piarulli, Umberto

    2005-11-14

    A highly enantioselective rhodium-catalysed conjugate addition of phenylboronic acid to cyclic enones has been achieved using a dynamic library of chiral phosphorus ligands; the tropos/atropos nature of the ligands in the rhodium complex has been characterised via 31P-NMR.

  10. Synthesis of cinnolines via Rh(iii)-catalysed dehydrogenative C-H/N-H functionalization: aggregation induced emission and cell imaging.

    PubMed

    Mayakrishnan, Sivakalai; Arun, Yuvaraj; Balachandran, Chandrasekar; Emi, Nobuhiko; Muralidharan, Doraiswamy; Perumal, Paramasivan Thirumalai

    2016-02-14

    Rhodium catalysed dehydrogenative C-H/N-H functionalization was developed to construct phthalazino[2,3-a]-/indazolo[1,2-a]cinnolines by reacting N-phenyl phthalazine/indazole with alkynes. The synthesized compounds exhibit prominent fluorescence properties in solid and aggregation states. Their application in cell imaging was investigated using various cancer cell lines.

  11. Mn-salen catalysed benzylic C-H activation for the synthesis of aryl [(18)F]CF3-containing PET probes.

    PubMed

    Carroll, L; Evans, H L; Spivey, A C; Aboagye, E O

    2015-05-18

    The development of a Mn-salen complex catalysed oxidative benzylic fluorination of non-activated C-H bonds using [(18)F]fluoride is described for installation of [(18)F]CHRF, [(18)F]CR2F and particularly [(18)F]CF3 containing groups in the presence of other functional groups.

  12. Dendron-anchored organocatalysts: the asymmetric reduction of imines with trichlorosilane, catalysed by an amino acid-derived formamide appended to a dendron.

    PubMed

    Figlus, Marek; Caldwell, Stuart T; Walas, Dawid; Yesilbag, Gulen; Cooke, Graeme; Kocovský, Pavel; Malkov, Andrei V; Sanyal, Amitav

    2010-01-07

    Asymmetric reduction of ketimines with trichlorosilane can be catalysed by the Lewis-basic N-methylvaline-derived formamide anchored to a soluble dendron () with good enantioselectivity (

  13. Recent applications of the Cu(I)-catalysed Huisgen azide-alkyne 1,3-dipolar cycloaddition reaction in carbohydrate chemistry.

    PubMed

    Dedola, Simone; Nepogodiev, Sergey A; Field, Robert A

    2007-04-07

    This article surveys recent applications of Cu(I)-catalysed 1,3-dipolar cycloaddition of azides and alkynes in carbohydrate chemistry, highlighting developments in the preparation of simple glycoside and oligosaccharide mimetics, glyco-macrocycles, glycopeptides, glyco-clusters and carbohydrate arrays.

  14. Synthesis of a Double-Network Supramolecular Hydrogel by Having One Network Catalyse the Formation of the Second.

    PubMed

    Singh, Nishant; Maity, Chandan; Zhang, Kai; Angulo-Pachón, César A; van Esch, Jan H; Eelkema, Rienk; Escuder, Beatriu

    2017-02-10

    Self-assembly of biomolecules catalytically controls the formation of natural supramolecular structures, giving highly ordered complex materials. Such desirable hybrid systems are very difficult to design and construct synthetically. A hybrid double-network hydrogel with a maximum storage modulus (G'max ) of up to 55 kPa can be synthesized by using a self-assembled hydrogel that catalyses the formation of another kinetically arrested hydrogel network. Tuning of the catalytic efficiency of the first network allowed spatiotemporal control over the evolution of the second network and the resulting mechanical properties. The distribution of active catalytic sites was optimal for catalytic fibres prepared at the minimum gelation concentration (MGC) to give the double-network hydrogel with highest storage modulus. This approach could be very useful in preparing complex hierarchical structures with tailor-made properties.

  15. A unique Pd-catalysed Heck arylation as a remote trigger for cyclopropane selective ring-opening.

    PubMed

    Singh, Sukhdev; Bruffaerts, Jeffrey; Vasseur, Alexandre; Marek, Ilan

    2017-02-07

    Combining functionalization at a distant position from a reactive site with the creation of several consecutive stereogenic centres, including the formation of a quaternary carbon stereocentre, in acyclic system represents a pinnacle in organic synthesis. Here we report the regioselective Heck arylation of terminal olefins as a distant trigger for the ring-opening of cyclopropanes. This Pd-catalysed unfolding of the strained cycle, driving force of the chain-walking process, remarkably proved its efficiency and versatility, as the reaction proceeded regardless of the molecular distance between the initiation (double bond) and termination (alcohol) sites. Moreover, employing stereodefined polysubstituted cyclopropane vaults allowed to access sophisticated stereoenriched acyclic scaffolds in good yields. Conceptually, we demonstrated that merging catalytically a chain walking process with a selective C-C bond cleavage represents a powerful approach to construct linear skeleton possessing two stereogenic centres.

  16. A unique Pd-catalysed Heck arylation as a remote trigger for cyclopropane selective ring-opening

    NASA Astrophysics Data System (ADS)

    Singh, Sukhdev; Bruffaerts, Jeffrey; Vasseur, Alexandre; Marek, Ilan

    2017-02-01

    Combining functionalization at a distant position from a reactive site with the creation of several consecutive stereogenic centres, including the formation of a quaternary carbon stereocentre, in acyclic system represents a pinnacle in organic synthesis. Here we report the regioselective Heck arylation of terminal olefins as a distant trigger for the ring-opening of cyclopropanes. This Pd-catalysed unfolding of the strained cycle, driving force of the chain-walking process, remarkably proved its efficiency and versatility, as the reaction proceeded regardless of the molecular distance between the initiation (double bond) and termination (alcohol) sites. Moreover, employing stereodefined polysubstituted cyclopropane vaults allowed to access sophisticated stereoenriched acyclic scaffolds in good yields. Conceptually, we demonstrated that merging catalytically a chain walking process with a selective C-C bond cleavage represents a powerful approach to construct linear skeleton possessing two stereogenic centres.

  17. A unique Pd-catalysed Heck arylation as a remote trigger for cyclopropane selective ring-opening

    PubMed Central

    Singh, Sukhdev; Bruffaerts, Jeffrey; Vasseur, Alexandre; Marek, Ilan

    2017-01-01

    Combining functionalization at a distant position from a reactive site with the creation of several consecutive stereogenic centres, including the formation of a quaternary carbon stereocentre, in acyclic system represents a pinnacle in organic synthesis. Here we report the regioselective Heck arylation of terminal olefins as a distant trigger for the ring-opening of cyclopropanes. This Pd-catalysed unfolding of the strained cycle, driving force of the chain-walking process, remarkably proved its efficiency and versatility, as the reaction proceeded regardless of the molecular distance between the initiation (double bond) and termination (alcohol) sites. Moreover, employing stereodefined polysubstituted cyclopropane vaults allowed to access sophisticated stereoenriched acyclic scaffolds in good yields. Conceptually, we demonstrated that merging catalytically a chain walking process with a selective C–C bond cleavage represents a powerful approach to construct linear skeleton possessing two stereogenic centres. PMID:28169276

  18. Diversity-Oriented Peptide Stapling: A Third Generation Copper-Catalysed Azide-Alkyne Cycloaddition Stapling and Functionalisation Strategy.

    PubMed

    Tran, Phuong Thu; Larsen, Christian Ørnbøl; Røndbjerg, Tobias; De Foresta, Martina; Kunze, Micha B A; Marek, Ales; Løper, Jacob Hartvig; Boyhus, Lotte-Emilie; Knuhtsen, Astrid; Lindorff-Larsen, Kresten; Pedersen, Daniel Sejer

    2017-01-20

    The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides incorporating two azide-modified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and (i, i+9)-stapled peptides with a single free alkyne positioned on the staple, which can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access to radiolabelled stapled peptides by catalytic tritiation of the alkyne positioned on the staple.

  19. Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life

    PubMed Central

    Ferris, James P

    2006-01-01

    Large deposits of montmorillonite are present on the Earth today and it is believed to have been present at the time of the origin of life and has recently been detected on Mars. It is formed by aqueous weathering of volcanic ash. It catalyses the formation of oligomers of RNA that contain monomer units from 2 to 30–50. Oligomers of this length are formed because this catalyst controls the structure of the oligomers formed and does not generate all possible isomers. Evidence of sequence-, regio- and homochiral selectivity in these oligomers has been obtained. Postulates on the role of selective versus specific catalysts on the origins of life are discussed. An introduction to the origin of life is given with an emphasis on reaction conditions based on the recent data obtained from zircons 4.0–4.5 Ga. PMID:17008218

  20. A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination

    NASA Astrophysics Data System (ADS)

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L.

    2016-02-01

    Amines with remote stereocentres (stereocentres that are three or more bonds away from the C-N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original carbon-carbon double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process.

  1. Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study

    PubMed Central

    Barker, Graeme; Johnson, David G; Young, Paul C; Macgregor, Stuart A; Lee, Ai-Lan

    2015-01-01

    Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au–allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive. PMID:26248980

  2. Experimental and theoretical studies on the bismuth-triflate-catalysed cycloisomerisation of 1,6,10-trienes and aryl polyenes.

    PubMed

    Godeau, Julien; Fontaine-Vive, Fabien; Antoniotti, Sylvain; Duñach, Elisabet

    2012-12-21

    Cycloisomerisation of polyenes such as diethyl geranylprenylmalonate [(E)-1 a], diethyl geranylphenylmalonate [(E)-2 a] and diethyl cinnamylgeranylmalonate [(E,E)-3 a] catalysed by bismuth triflate was studied from experimental and theoretical viewpoints. Several intermediates were isolated and characterised, and calculated transition-state structures are proposed for the three reactions. The diastereoselectivity observed during the reaction of (E)- or (Z)-2 a in favour of the formation of trans-fused bicyclic products is discussed in detail. The nature of the active catalytic species derived from bismuth triflate was also investigated, and the formation of a hybrid Lewis acid/Brønsted acid catalyst with water molecules is proposed, supported by experimental and theoretical data.

  3. Ruthenium(II)-catalysed remote C-H alkylations as a versatile platform to meta-decorated arenes

    NASA Astrophysics Data System (ADS)

    Li, Jie; Korvorapun, Korkit; de Sarkar, Suman; Rogge, Torben; Burns, David J.; Warratz, Svenja; Ackermann, Lutz

    2017-06-01

    The full control of positional selectivity is of prime importance in C-H activation technology. Chelation assistance served as the stimulus for the development of a plethora of ortho-selective arene functionalizations. In sharp contrast, meta-selective C-H functionalizations continue to be scarce, with all ruthenium-catalysed transformations currently requiring difficult to remove or modify nitrogen-containing heterocycles. Herein, we describe a unifying concept to access a wealth of meta-decorated arenes by a unique arene ligand effect in proximity-induced ruthenium(II) C-H activation catalysis. The transformative nature of our strategy is mirrored by providing a step-economical entry to a range of meta-substituted arenes, including ketones, acids, amines and phenols--key structural motifs in crop protection, material sciences, medicinal chemistry and pharmaceutical industries.

  4. Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life.

    PubMed

    Ferris, James P

    2006-10-29

    Large deposits of montmorillonite are present on the Earth today and it is believed to have been present at the time of the origin of life and has recently been detected on Mars. It is formed by aqueous weathering of volcanic ash. It catalyses the formation of oligomers of RNA that contain monomer units from 2 to 30-50. Oligomers of this length are formed because this catalyst controls the structure of the oligomers formed and does not generate all possible isomers. Evidence of sequence-, regio- and homochiral selectivity in these oligomers has been obtained. Postulates on the role of selective versus specific catalysts on the origins of life are discussed. An introduction to the origin of life is given with an emphasis on reaction conditions based on the recent data obtained from zircons 4.0-4.5Ga.

  5. Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study.

    PubMed

    Barker, Graeme; Johnson, David G; Young, Paul C; Macgregor, Stuart A; Lee, Ai-Lan

    2015-09-21

    Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au-allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive.

  6. Copper-catalysed cyanoalkylative cycloetherification of alkenes to 1,3-dihydroisobenzofurans: development and application to the synthesis of citalopram.

    PubMed

    Ha, Tu M; Wang, Qian; Zhu, Jieping

    2016-09-25

    A copper-catalysed cyanoalkylative cycloetherification of alkenes was developed. Heating a solution of substituted (2-vinylphenyl)methanol in MeCN/MeOH (v/v 7/3) in the presence of a catalytic amount of copper(ii) tetrafluoroborate hydrate [Cu(BF4)2·6H2O], bathophenanthroline, K3PO4, BnOH and (tBuO)2 afforded 1,3-dihydroisobenzofurans (phthalanes) via formation of one C(sp(3))-C(sp(3)) and one C(sp(3))-O bonds. A concise synthesis of citalopram, a marketed anti-depressant drug, was accomplished by applying this novel synthetic transformation.

  7. Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process

    PubMed Central

    Li, Bao-Sheng; Wang, Yuhuang; Proctor, Rupert S. J.; Zhang, Yuexia; Webster, Richard D.; Yang, Song; Song, Baoan; Chi, Yonggui Robin

    2016-01-01

    Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions. PMID:27671606

  8. A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination.

    PubMed

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L

    2016-02-01

    Amines with remote stereocentres (stereocentres that are three or more bonds away from the C-N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original carbon-carbon double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process.

  9. A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination

    PubMed Central

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L.

    2015-01-01

    Amines with remote stereocenters (stereocenters that are three or more bonds away from the C–N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here we report a copper hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters, and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original C–C double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process. PMID:26791897

  10. Toluene Dioxygenase-Catalysed Oxidation of Benzyl Azide to Benzonitrile: Mechanistic Insights for an Unprecedented Enzymatic Transformation.

    PubMed

    Vila, María Agustina; Pazos, Mariana; Iglesias, César; Veiga, Nicolás; Seoane, Gustavo; Carrera, Ignacio

    2016-02-15

    Enzymatic dioxygenation of benzyl azide by toluene dioxygenase (TDO) produces significant amounts of the cis-cyclohexadienediol derived from benzonitrile, along with the expected azido diols. We demonstrate that TDO catalyses the oxidation of benzyl azide to benzonitrile, which is further dioxygenated to produce the observed cis-diol. A proposed mechanism for this transformation involves initial benzylic monooxygenation followed by a nitrene-mediated rearrangement to form an oxime, which is further dehydrated to afford the nitrile. To the best of our knowledge, this is the first report of enzymatic oxidation of an alkyl azide to a nitrile. In addition, the described oxime-dehydration activity has not been reported for Rieske dioxygenases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process

    NASA Astrophysics Data System (ADS)

    Li, Bao-Sheng; Wang, Yuhuang; Proctor, Rupert S. J.; Zhang, Yuexia; Webster, Richard D.; Yang, Song; Song, Baoan; Chi, Yonggui Robin

    2016-09-01

    Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions.

  12. Waveguide arrangements based on adiabatic elimination

    SciTech Connect

    Suchowski, Haim; Mrejen, Michael; Wu, Chihhui; Zhang, Xiang

    2016-09-13

    This disclosure provides systems, methods, and apparatus related to nanophotonics. In one aspect, an arrangement of waveguides includes a substrate and three waveguides. Each of the three waveguides may be a linear waveguide. A second waveguide is positioned between a first waveguide and a third waveguide. The dimensions and positions of the first, the second, and the third waveguides are specified to substantially eliminate coupling between the first waveguide and the third waveguide over a distance of about 1 millimeter to 2 millimeters along lengths of the first waveguide, the second waveguide, and the third waveguide.

  13. Approaches to Eliminating Sociocultural Disparities in Health

    PubMed Central

    Horowitz, Carol R.; Davis, Margaret H.; Palermo, Ann-Gel S.; Vladeck, Bruce C.

    2000-01-01

    The recent flurry of studies documenting the presence of racial, ethnic, and socioeconomic disparities in health care and health have outpaced articles that describe effective strategies to eliminate disparities. Through literature review and informal interviews with research, policy, and program experts, we developed a framework of programs that address disparities through targeting clinicians, patients and communities, and health systems. We found that the lack of technical expertise, resources, and sensitive tools are all common barriers to evaluating programs. To stimulate more effective programs and rigorous evaluations, we describe specialized implementation and evaluation techniques programs can use, and make recommendations for future efforts. PMID:11481745

  14. Stable parallel elimination for boundary valve ODEs

    SciTech Connect

    Wright, S.J.

    1991-04-01

    A parallelizable and vectorizable algorithm for solving linear algebraic systems arising from two-point boundary value ODEs is described. The method is equivalent to Gaussian elimination, with row partial pivoting, applied to a certain row- and column-reordered version of the usual almost block-diagonal coefficient matrix. Analytical and numerical evidence is presented to show that the algorithm is stable. Results from implementation on a shared-memory multiprocessor and a vector processor are given. The approach can be extended to handle problems with multipoint and integral conditions or algebraic parameters.

  15. Self-catalysed InAs{sub 1-x}Sb{sub x} nanowires grown directly on bare Si substrates

    SciTech Connect

    Anyebe, E.A. Zhuang, Q.

    2014-12-15

    Highlights: • Self-catalysed InAs{sub 1-x}Sb{sub x} nanowires grown directly on bare Si substrates. • InAs{sub 1-x}Sb{sub x} nanowires directly grown on bare Si substrates without employing the commonly used nucleation nanowire stems which could be problematic in device applications. • Pre-deposited Indium droplets were employed to facilitate InAs{sub 1-x}Sb{sub x} nanowire nucleation and growth. • Unravels a promising route for the direct integration of InAs{sub 1-x}Sb{sub x} nanowires with the well-established Silicon platform. - Abstract: We report the self-catalysed growth of InAs{sub 1-x}Sb{sub x} nanowires directly on bare Si substrates. Vertically aligned and non-tapered InAs{sub 1-x}Sb{sub x} nanowires were realized via indium-assisted nucleation without using nanowire stems. The compositions of the InAs{sub 1-x}Sb{sub x} nanowires were determined by high resolution X-ray diffraction (HRXRD). It is observed that the geometry of the nanowires is modified by the Sb flux resulting in an almost doubling of the lateral dimension and a corresponding suppression in the axial growth of the InAs{sub 1-x}Sb{sub x} nanowires. This observation unravels a method to modify the geometry of InAs nanowire and open up a promising route for the direct integration of InAs{sub 1-x}Sb{sub x} nanowires with the well-established Si platform.

  16. Positron Accumulator Ring (PAR) power supply

    SciTech Connect

    Fathizadeh, M.

    1995-08-01

    The Positron Accumulator Ring (PAR) consists of 8 dipole magnets connected in series. These magnets are energized via one 12-pulse dc power supply. The power supply consists of four phase controlled half-wave wye group converters. Each of the two half-wave converters are connected through an interphase transformer to obtain a full-wave converter with 120{degrees} conduction. The input voltage for these two half-wave converters are 180{degrees} apart. The two full-wave converters are connected in parallel through a third interphase transformer. This type of connection of the converters not only provides the required output current, it also improves the input power factor of the power supply. The output of the wye group converters is filtered through a passive L-R-C filter to reduce the ripple content of the output current. At low current values of the power supply the current ripple is high, thus a large filter is needed, which adds to the cost of the power supply, however at high output current levels, the current ripple is less severe. The large size of the filter can be reduced by adding an anti-parallel rectifier diode(D1) to the output of the power supply. A freewheeling diode(D2) is connected before the choke to circulate the current once the power supply is turned off. In order to measure the current in the magnet a high precision, low drift, zero flux current transductor is used. This transductor senses the magnet current which provides a feedback signal to control the gating of the converter`s thyristors. A true 14 bit Digital to Analog Converter (DAC) is programmed by the control computer for the required current value, providing a reference for the current regulator. Fast correction of the line transients is provided by a relatively fast voltage loop controlled by a high gain slow response current loop.

  17. PARS: Programs for Analysis and Resizing of Structures, user manual

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.; Prasad, B.; Tsach, U.

    1979-01-01

    PARS processors and their use, flutter analysis, sensitivity analysis for stresses, and resizing are presented. Design variable definition and interface with finite element model, static constraints and their derivatives, flutter derivatives, and optimization are discussed.

  18. View from southwest to northeast of PAR site fresh water ...

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

    View from southwest to northeast of PAR site fresh water pump house - Stanley R. Mickelsen Safeguard Complex, Fresh Water Pump House, In Limited Access Area, on Patrol Road next to Open Storage Reservoir No. 736, Nekoma, Cavalier County, ND

  19. The use of statistical techniques in par-level management.

    PubMed

    Klee, W B

    1994-02-01

    The total quality management movement has allowed the reintroduction of statistics in the materials management workplace. Statistical methods can be applied to the par level management process with significant results.

  20. View from northeast to southwest of PAR site sentry station; ...

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

    View from northeast to southwest of PAR site sentry station; formerly the bachelor's enlisted men's quarter (BEQ) - Stanley R. Mickelsen Safeguard Complex, Sentry Station, North of Second Avenue & West of Electrical Switch Station No. 2, Nekoma, Cavalier County, ND

  1. Malaria elimination without stigmatization: a note of caution about the use of terminology in elimination settings.

    PubMed

    Smith, Catherine; Whittaker, Maxine

    2014-09-22

    This commentary offers a note of caution about the negative social impact that may be inadvertently generated through malaria elimination activities. In particular, the commentary is concerned with the practice of describing people who remain at risk of malaria in low transmission settings as 'hotpops' or 'reservoirs of infection'. The authors argue that since those at risk of malaria in elimination settings are often already socially marginalized - such as migrants, indigenous groups, ethnic minorities and poor rural communities - that care should be taken to avoid implementing programmes in ways that may inadvertently add to the social stigmatization of those most at risk of malaria in a low transmission setting. Programmes should avoid using language that identifies particular groups as a source of infection, and instead begin a broader shift in orientation toward engaging constructively with communities within elimination strategies. Programmes should promote monitoring and evaluation to ensure that unintended negative consequences such as stigma do not occur; advocate for appropriate resourcing (human, financial, other) to minimize the risk of short cuts being used to achieve an end game that may discriminate against specific groups; and strengthen community engagement activities in elimination setting to avoid targeting stigmatized groups and to empower communities to prevent outbreaks and re-introduction of malaria. In this way malaria elimination can be achieved without stigmatization.

  2. Croissance epitaxiale de GaAs sur substrats de Ge par epitaxie par faisceaux chimiques

    NASA Astrophysics Data System (ADS)

    Belanger, Simon

    La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis

  3. Molecular Mechanisms of Par-4-Induced Apoptosis in Prostate Cancer

    DTIC Science & Technology

    2007-05-01

    Sambrook J, Fritsch EF, Maniatis T. (1989). Molecular Cloning : A Laboratory Manual (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory...AD_________________ Award Number: W81XWH-05-1-0622 TITLE: Molecular Mechanisms of Par-4-Induced...SUBTITLE 5a. CONTRACT NUMBER Molecular Mechanisms of Par-4-Induced Apoptosis in Prostate Cancer 5b. GRANT NUMBER W81XWH-05-1-0622 5c. PROGRAM

  4. StePar: an automatic code for stellar parameter determination

    NASA Astrophysics Data System (ADS)

    Tabernero, H. M.; González Hernández, J. I.; Montes, D.

    2013-05-01

    We introduce a new automatic code (StePar) for determinig stellar atmospheric parameters (T_{eff}, log{g}, ξ and [Fe/H]) in an automated way. StePar employs the 2002 version of the MOOG code (Sneden 1973) and a grid of Kurucz ATLAS9 plane-paralell model atmospheres (Kurucz 1993). The atmospheric parameters are obtained from the EWs of 263 Fe I and 36 Fe II lines (obtained from Sousa et al. 2008, A&A, 487, 373) iterating until the excitation and ionization equilibrium are fullfilled. StePar uses a Downhill Simplex method that minimizes a quadratic form composed by the excitation and ionization equilibrium conditions. Atmospheric parameters determined by StePar are independent of the stellar parameters initial-guess for the problem star, therefore we employ the canonical solar values as initial input. StePar can only deal with FGK stars from F6 to K4, also it can not work with fast rotators, veiled spectra, very metal poor stars or Signal to noise ratio below 30. Optionally StePar can operate with MARCS models (Gustafson et al. 2008, A&A, 486, 951) instead of Kurucz ATLAS9 models, additionally Turbospectrum (Alvarez & Plez 1998, A&A, 330, 1109) can replace the MOOG code and play its role during the parameter determination. StePar has been used to determine stellar parameters for some studies (Tabernero et al. 2012, A&A, 547, A13; Wisniewski et al. 2012, AJ, 143, 107). In addition StePar is being used to obtain parameters for FGK stars from the GAIA-ESO Survey.

  5. Genetic elimination of dengue vector mosquitoes.

    PubMed

    Wise de Valdez, Megan R; Nimmo, Derric; Betz, John; Gong, Hong-Fei; James, Anthony A; Alphey, Luke; Black, William C

    2011-03-22

    An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti, was engineered to have a repressible female-specific flightless phenotype. This strain circumvents the need for radiation-induced sterilization, allows genetic sexing resulting in male-only releases, and permits the release of eggs instead of adult mosquitoes. OX3604C males introduced weekly into large laboratory cages containing stable target mosquito populations at initial ratios of 8.5-101 OX3604Ctarget eliminated the populations within 10-20 weeks. These data support the further testing of this strain in contained or confined field trials to evaluate mating competitiveness and environmental and other effects. Successful completion of the field trials should facilitate incorporation of this approach into area-wide dengue control or elimination efforts as a component of an integrated vector management strategy.

  6. Manual sorting to eliminate aflatoxin from peanuts.

    PubMed

    Galvez, F C F; Francisco, M L D L; Villarino, B J; Lustre, A O; Resurreccion, A V A

    2003-10-01

    A manual sorting procedure was developed to eliminate aflatoxin contamination from peanuts. The efficiency of the sorting process in eliminating aflatoxin-contaminated kernels from lots of raw peanuts was verified. The blanching of 20 kg of peanuts at 140 degrees C for 25 min in preheated roasters facilitated the manual sorting of aflatoxin-contaminated kernels after deskinning. The manual sorting of raw materials with initially high aflatoxin contents (300 ppb) resulted in aflatoxin-free peanuts (i.e., peanuts in which no aflatoxin was detected). Verification procedures showed that the sorted sound peanuts contained no aflatoxin or contained low levels (<15 ppb) of aflatoxin. The results obtained confirmed that the sorting process was effective in separating contaminated peanuts whether or nor contamination was extensive. At the commercial level, when roasters were not preheated, the dry blanching of 50 kg of peanuts for 45 to 55 min facilitated the proper deskinning and subsequent manual sorting of aflatoxin-contaminated peanut kernels from sound kernels.

  7. Elimination of Plasmodium vivax Malaria in Azerbaijan

    PubMed Central

    Mammadov, Suleyman; Gasimov, Elkhan; Kurdova-Mintcheva, Rossitza; Wongsrichanalai, Chansuda

    2016-01-01

    Azerbaijan in the south caucasus region of far southeastern Europe has a long history of malaria endemicity but just successfully eliminated local transmission. After a period of relatively stable malaria situation (1960–1970), the country witnessed an epidemic followed by a series of outbreaks of various magnitudes in the following two decades, all caused by Plasmodium vivax. Compared with 1993, the number of malaria cases in the country jumped 29 times in 1994, 123 times in 1995, and 571 times in 1996 at the peak of the epidemic, when 13,135 cases were officially registered. Incidence rate increased dramatically from 0.2/100,000 population in 1991 to over 17/100,000 population in 1996. Scaled-up malaria control led to the containment of the epidemic and to a dramatic decrease of malaria burden nationwide. Azerbaijan has applied contemporary, complex control and surveillance strategies and approaches and is currently in the prevention of reintroduction phase. This article describes Azerbaijan's public health experience in conducting malaria control and elimination interventions over several decades until 2013 when the country reached an important milestone—no indigenous malaria cases were recorded. PMID:27708184

  8. Auditing reduces accidents by eliminating unsafe practices

    SciTech Connect

    Collinge, J.A. )

    1992-08-24

    This paper reports that auditing for unsafe acts can remove the basic causes of accidents through the adoption of a proactive approach to safety. The process of auditing for unsafe acts is aimed at eliminating unsafe situations and practices by a method of constructive dialogue between managers and workers. One of the major objectives of the process is to change the cultural attitude toward safety so that it is viewed as a personal responsibility of each member of management, supervision, and the workforce. In large organizations it is common to see policy statements concerning the health and safety of employees and people associated with the business, such as contractors. In recent years, such organizations have also placed emphasis on statements related to protecting the environment. Policy guidelines for Shell companies are unambiguous: Health. The companies conduct business in such a way as to avoid harm to the health of employees and others, and to promote, as appropriate, the health of employees. Safety. Companies work on the principle that all injuries should be prevented and actively promote the high standards of safety consciousness and discipline that this principle demands. Environment. Companies pursue progressive reductions of emissions, effluents, and discharges of waste materials known to have a negative impact on the environment, with the ultimate aim of eliminating those discharges.

  9. Herbivory eliminates fitness costs of mutualism exploiters.

    PubMed

    Simonsen, Anna K; Stinchcombe, John R

    2014-04-01

    A common empirical observation in mutualistic interactions is the persistence of variation in partner quality and, in particular, the persistence of exploitative phenotypes. For mutualisms between hosts and symbionts, most mutualism theory assumes that exploiters always impose fitness costs on their host. We exposed legume hosts to mutualistic (nitrogen-fixing) and exploitative (non-nitrogen-fixing) symbiotic rhizobia in field conditions, and manipulated the presence or absence of insect herbivory to determine if the costly fitness effects of exploitative rhizobia are context-dependent. Exploitative rhizobia predictably reduced host fitness when herbivores were excluded. However, insects caused greater damage on hosts associating with mutualistic rhizobia, as a consequence of feeding preferences related to leaf nitrogen content, resulting in the elimination of fitness costs imposed on hosts by exploitative rhizobia. Our experiment shows that herbivory is potentially an important factor in influencing the evolutionary dynamic between legumes and rhizobia. Partner choice and host sanctioning are theoretically predicted to stabilize mutualisms by reducing the frequency of exploitative symbionts. We argue that herbivore pressure may actually weaken selection on choice and sanction mechanisms, thus providing one explanation of why host-based discrimination mechanisms may not be completely effective in eliminating nonbeneficial partners.

  10. Elimination of frequency noise from groundwater measurements

    SciTech Connect

    Chien, Y.M.; Bryce, R.W.; Strait, S.R.; Yeatman, R.A.

    1986-04-01

    Groundwater response to atmospheric fluctuation can be effectively removed from downhole-pressure records using the systematic approach. The technique is not as successful for removal of earth tides, due to a probable discrepancy between the actual earth tide and the theoretical earth tide. The advantage of the systematic technique is that a causative relationship is established for each component of the pressure response removed. This concept of data reduction is easily understood and well accepted. The disadvantage is that a record of the stress causing the pressure fluctuation must be obtained. This may be done by monitoring or synthesizing the stress. Frequency analysis offers a simpler way to eliminate the undesirable hydrologic fluctuations from the downhole pressure. Frequency analysis may prove to be impractical if the fluctuations being removed have broadband characteristics. A combination of the two techniques, such as eliminating the atmospheric effect with the systematic method and the earth-tide fluctuations with the frequency method, is the most effective and efficient approach.

  11. Positive moods can eliminate intentional forgetting.

    PubMed

    Bäuml, Karl-Heinz; Kuhbandner, Christof

    2009-02-01

    People can intentionally forget previously studied information if, after study, a forget cue and new material to be encoded are provided. We examined how the affective state people experience during encoding of the new material modulates such directed forgetting. Positive, negative, and neutral moods were induced immediately before the new material was studied. The study materials themselves were neutral. The results showed sustained forgetting of the previously studied materials in negative moods but an elimination of the forgetting in positive moods. These findings agree with the effects of mood found for other cognitive tasks. They suggest that in positive moods, associative networks are activated, which leads to reactivation of List-1 items, and thus to elimination of the directed forgetting effects. These results contrast with recent reports on the role of emotional content in directed forgetting, which have described equivalent effects for neutral and emotional materials. Together, our findings suggest that directed forgetting is mainly affected by mood, and hardly at all by emotional content.

  12. Eliminating ultrasonic interference from respiratory muscle EMG.

    PubMed

    Platt, R S; Kieser, T M; Easton, P A

    1998-05-01

    Fine wire recordings of the respiratory muscle electromyogram are often employed to represent muscle activity, and recently ultrasound-sonomicrometry has become a common method of measuring length of respiratory muscles in both acute and chronic preparations. Although recording both EMG and sonomicrometry simultaneously has become standard practice, there has not been any consideration of the potential confounding influence of ultrasound noise upon the recorded EMG spectrum. Activation of the sonomicrometry-ultrasound tranducer introduces a high frequency, high amplitude voltage pulse plus harmonics, which can contaminate the EMG spectrum directly, as well as through aliasing when EMG is sampled directly digitally. We describe the use of a new, combined, wing stabilized sonomicrometry- and EMG measurement transducer to characterize exactly the influence of ultrasound upon the crural diaphragm EMG spectrum, and the development of digital filtering techniques which effectively eliminate the ultrasound interference. Two alternative methods of avoiding ultrasound-EMG interference are also considered. The isolation and elimination of ultrasound-sonomicrometry signal interference may be important in studies where EMG and length are measured together.

  13. Getting to Zero: Tuberculosis Elimination in California.

    PubMed

    Barry, Pennan M; Kay, Alexander W; Flood, Jennifer M; Watt, James

    This review of tuberculosis epidemiology is intended to provide a historical perspective on the public health approach to tuberculosis (TB) control in California. This historical context offers a lens through which to view current epidemiologic trends and insight into how new therapeutic tools can be applied. Since 1993, the year detailed case reporting was instituted, California has had a decrease in recent TB transmission as evidenced by a reduction in pediatric cases and an increased percentage of cases attributable to progression of latent infection to TB disease in the foreign-born population. Overall, there has been a dramatic decline in the annual TB case count, but the speed of the decline has slowed over the last several years. At the current pace and case count of 2137 in 2015, California will not achieve TB elimination (<1 TB case per one million population) for at least 100 years. There are an estimated 2.1 million persons in California with latent TB infection. Modeling suggests that LTBI detection and treatment are important in reaching TB elimination. For this reason, a coalition of stakeholders in California is exploring novel approaches to accelerate the case decline in order to prevent unnecessary disease and death.

  14. Advanced nitrogen elimination by encapsulated nitrifiers.

    PubMed

    Sievers, M; Vorlop, K D; Hahne, J; Schlieker, M; Schäfer, S

    2003-01-01

    By introducing a mixed population of nitrifiers encapsulated in gel lens beads a more selective nitrification process was found in treatment of settled sewage in lab scale at a hydraulic retention time (HRT) of about 30 to 60 minutes. The reaction rates for oxidation of soluble chemical oxygen demand (SCOD) were found to vary between 25 to 150 mg/L x h while nitrification takes place around 50 mg nitrogen per hour and litre reaction volume. However, based on this SCOD removal in the nitrification step, a consequent post-denitrification process without nitrate recycle and dosage of external carbon sources has been proven to reach substantial nitrate elimination of up to 20 mg nitrogen per litre at COD/N-ratios of approx. 6 in settled sewage. At such COD/N-ratios, suitable nitrogen elimination seems to be possible, because the bioflocs of settled sewage, produced so far by SCOD oxidation and entrapment of particulate COD, are passing through the nitrification process having a substantial contribution to the denitrification rate additionally to the remaining SCOD.

  15. Air elimination capability in rapid infusion systems.

    PubMed

    Zoremba, N; Gruenewald, C; Zoremba, M; Rossaint, R; Schaelte, G

    2011-11-01

    Pressure infusion devices are used in clinical practice to apply large volumes of fluid over a short period of time. Although air infusion is a major complication, they have limited capability to detect and remove air during pressure infusion. In this investigation, we tested the air elimination capabilities of the Fluido(®) (The Surgical Company), Level 1(®) (Level 1 Technologies Inc.) and Ranger(®) (Augustine Medical GmbH) pressure infusion devices. Measurements were undertaken with a crystalloid solution during an infusion flow of 100, 200, 400 and 800 ml.min(-1). Four different volumes of air (25, 50, 100 and 200 ml) were injected as boluses in one experimental setting, or infused continuously over the time needed to perfuse 2 l saline in the other setting. The perfusion fluid was collected in an airtight infusion bag and the amount of air obtained in the bag was measured. The delivered air volume was negligible and would not cause any significant air embolism in all experiments. In our experimental setting, we found, during high flow, an increased amount of uneliminated air in all used devices compared with lower perfusion flows. All tested devices had a good air elimination capability. The use of ultrasonic air detection coupled with an automatic shutoff is a significant safety improvement and can reliably prevent accidental air embolism at rapid flows. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  16. Dispositifs opto-électropiques à commande par coordonnées

    NASA Astrophysics Data System (ADS)

    Smovge, A. K.

    1994-06-01

    The approach has been explained theoretically and experimentally considering analog coordinate-controlled optoelectronic devices as an alternative to custom potentiometers and variable resistors, whose potentially unreliable element, a wiping electromechanical contact, is eliminated through the use of an optoelectronic conversion principle. The new designs have been proposed and requirements for discrete-continuous photoresistor structure have been determined by using both simple numeric and analytical models for a realization of the coordinate dependence of the output voltage and internal resistance with predetermined accuracy. The new type of optoelectronic coordinate-controlled delay line of millisecond-range pulsed signals have been proposed as well as the design of two-dimensional sensor of displacements. The new method for upgradding the noise immunity, based on the use of the photoconductivity response time dependence from the illuminance have been proposed. Une direction de recherches a été justifiée théoriquement et expérimentalement. Cette étude considère les dipositifs opto-électroniques à commande par coordonnées comme une alternative aux potentiomètres classiques dont l'élément défaillant éventuel, à savoir le contact électrique mobile de frottement, est supprimé par l'emploi d'une méthode de conversion optoélectronique. La nouvelle construction a été proposée et les exigences concernant la structure photorésistance discret-continu ont été déterminées par l'emploi des deux méthodes de calcul numérique et analytique. De nouvelles structures du dispositif de retard des signaux impulsionnels dans la gamme des millisecondes avec une durée de retard réglable à commande par coordonnées aussi bien que du vidéocapteur positionnel bidimensionnel sont proposées. Une nouvelle méthode de l'augmentation de sensibilité de ce vidéocapteur aux obstacles optiques, basée sur la dépendance du temps de la photoréponse du niveau d

  17. The signaling adaptor GAB1 regulates cell polarity by acting as a PAR protein scaffold.

    PubMed

    Yang, Ziqiang; Xue, Bin; Umitsu, Masataka; Ikura, Mitsuhiko; Muthuswamy, Senthil K; Neel, Benjamin G

    2012-08-10

    Cell polarity plays a key role in development and is disrupted in tumors, yet the molecules and mechanisms that regulate polarity remain poorly defined. We found that the scaffolding adaptor GAB1 interacts with two polarity proteins, PAR1 and PAR3. GAB1 binds PAR1 and enhances its kinase activity. GAB1 brings PAR1 and PAR3 into a transient complex, stimulating PAR3 phosphorylation by PAR1. GAB1 and PAR6 bind the PAR3 PDZ1 domain and thereby compete for PAR3 binding. Consequently, GAB1 depletion causes PAR3 hypophosphorylation and increases PAR3/PAR6 complex formation, resulting in accelerated and enhanced tight junction formation, increased transepithelial resistance, and lateral domain shortening. Conversely, GAB1 overexpression, in a PAR1/PAR3-dependent manner, disrupts epithelial apical-basal polarity, promotes multilumen cyst formation, and enhances growth factor-induced epithelial cell scattering. Our results identify GAB1 as a negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Detergent water use eliminates VOC concerns

    SciTech Connect

    Chang, M.

    1996-01-01

    The article describes an electronics manufacturer`s use of detergent water and mechanical equipment (heated pressure washers and floor scrubbers) to replace volatile organic compounds. The cleaning formula development and detergent recovery system are emphasized. Detailed chemical analyses of the waste detergent water and spent filters are provided. The rationale for using detergent water; a process flow diagram for cleaning, recovery and storage; and cost considerations are summarized. At a cost of $300,000, the system removed a significant source of air emissions and enabled the plant to eliminate 30 tons of liquid hazardous waste, improve cleaning effectiveness, and save $99,000 per year in cleaning-related costs. 2 figs., 2 tabs.

  19. Adiabatic elimination in nonlinear dynamical systems

    NASA Astrophysics Data System (ADS)

    Lugiato, L. A.; Mandel, P.; Narducci, L. M.

    1984-03-01

    The problem of the adiabatic elimination of selected dynamical variables in the description of nonlinear systems is reconsidered, with emphasis on the identification of suitable criteria for the global validity of this procedure. The problem is analyzed in detail using as a guideline the one-mode homogeneously broadened laser model, with an injected signal and an arbitrary population difference for added flexibility. Five conditions for the global validity of the adiabatic limit are proposed, after consideration not only of the relative size of the time scales involved, but also of the magnitude of all parameters, of the physical variables, and of their fluctuations. From the analysis, it is considered evident that the main conclusions are model independent and not at all restricted to the specific features of the dynamical system selected as a test case.

  20. Cell competition: how to eliminate your neighbours

    PubMed Central

    Amoyel, Marc; Bach, Erika A.

    2014-01-01

    A conventional view of development is that cells cooperate to build an organism. However, based on studies of Drosophila, it has been known for years that viable cells can be eliminated by their neighbours through a process termed cell competition. New studies in mammals have revealed that this process is universal and that many factors and mechanisms are conserved. During cell competition, cells with lower translation rates or those with lower levels of proteins involved in signal transduction, polarity and cellular growth can survive in a homogenous environment but are killed when surrounded by cells of higher fitness. Here, we discuss recent advances in the field as well as the mechanistic steps involved in this phenomenon, which have shed light on how and why cell competition exists in developing and adult organisms. PMID:24550108

  1. Elimination of the hazards from hazardous wastes.

    PubMed Central

    Gloyna, E F; Taylor, R D

    1978-01-01

    The "hazard" associated with a waste essentially controls the overall engineering approach to finding suitable alternatives for solving potential disposal problems. It should be recognized that all factors affecting environmental equilibrium must be considered, including product sales, process design, financing, pre- and end-of-pipe treatment, residuals management, and ultimate bioaccumulation of residuals. To meet this challenge, a systems approach to waste treatment and residuals disposal provides a logical approach, but this management concept requires a thorough understanding of the important physical and chemical aspects of the problem, as well as many social implications of the resulting decisions. Thus waste management within a plant necessarily involves process control, pretreatment and end-of-pipe treatment. Further, it follows that residuals management from a disposal point-of-view must ultimately embrace what is called the "multi-barrier concept." In essence, hazard elimination occurs in varying degrees during each phase of a properly engineered system. PMID:738249

  2. Targeting Human Transmission Biology for Malaria Elimination

    PubMed Central

    Buckee, Caroline; Marti, Matthias

    2015-01-01

    Malaria remains one of the leading causes of death worldwide, despite decades of public health efforts. The recent commitment by many endemic countries to eliminate malaria marks a shift away from programs aimed at controlling disease burden towards one that emphasizes reducing transmission of the most virulent human malaria parasite, Plasmodium falciparum. Gametocytes, the only developmental stage of malaria parasites able to infect mosquitoes, have remained understudied, as they occur in low numbers, do not cause disease, and are difficult to detect in vivo by conventional methods. Here, we review the transmission biology of P. falciparum gametocytes, featuring important recent discoveries of genes affecting parasite commitment to gametocyte formation, microvesicles enabling parasites to communicate with each other, and the anatomical site where immature gametocytes develop. We propose potential parasite targets for future intervention and highlight remaining knowledge gaps. PMID:26086192

  3. Lean for Government: Eliminating the Seven Wastes

    NASA Technical Reports Server (NTRS)

    Shepherd, Christena C.

    2012-01-01

    With shrinking budgets and a slow economy, it is becoming increasingly important for all government agencies to become more efficient. Citizens expect and deserve efficient and effective services from federal, state and local government agencies. One of the best methods to improve efficiency and eliminate waste is to institute the business process improvement methodologies known collectively as Lean; however, with reduced budgets, it may not be possible to train everyone in Lean or to engage the services of a trained consultant. It is possible, however, to raise awareness of the "Seven Wastes" of Lean in each employee, and encourage them to identify areas for improvement. Management commitment is vital to the success of these initiatives, and it is also important to develop the right metrics that will track the success of these changes.

  4. Error-eliminating rapid ultrasonic firing

    DOEpatents

    Borenstein, J.; Koren, Y.

    1993-08-24

    A system for producing reliable navigation data for a mobile vehicle, such as a robot, combines multiple range samples to increase the confidence'' of the algorithm in the existence of an obstacle. At higher vehicle speed, it is crucial to sample each sensor quickly and repeatedly to gather multiple samples in time to avoid a collision. Erroneous data is rejected by delaying the issuance of an ultrasonic energy pulse by a predetermined wait-period, which may be different during alternate ultrasonic firing cycles. Consecutive readings are compared, and the corresponding data is rejected if the readings differ by more than a predetermined amount. The rejection rate for the data is monitored and the operating speed of the navigation system is reduced if the data rejection rate is increased. This is useful to distinguish and eliminate noise from the data which truly represents the existence of an article in the field of operation of the vehicle.

  5. Error-eliminating rapid ultrasonic firing

    DOEpatents

    Borenstein, Johann; Koren, Yoram

    1993-08-24

    A system for producing reliable navigation data for a mobile vehicle, such as a robot, combines multiple range samples to increase the "confidence" of the algorithm in the existence of an obstacle. At higher vehicle speed, it is crucial to sample each sensor quickly and repeatedly to gather multiple samples in time to avoid a collision. Erroneous data is rejected by delaying the issuance of an ultrasonic energy pulse by a predetermined wait-period, which may be different during alternate ultrasonic firing cycles. Consecutive readings are compared, and the corresponding data is rejected if the readings differ by more than a predetermined amount. The rejection rate for the data is monitored and the operating speed of the navigation system is reduced if the data rejection rate is increased. This is useful to distinguish and eliminate noise from the data which truly represents the existence of an article in the field of operation of the vehicle.

  6. Astrocytes Control Synapse Formation, Function, and Elimination

    PubMed Central

    Chung, Won-Suk; Allen, Nicola J.; Eroglu, Cagla

    2015-01-01

    Astrocytes, through their close associations with synapses, can monitor and alter synaptic function, thus actively controlling synaptic transmission in the adult brain. Besides their important role at adult synapses, in the last three decades a number of critical findings have highlighted the importance of astrocytes in the establishment of synaptic connectivity in the developing brain. In this article, we will review the key findings on astrocytic control of synapse formation, function, and elimination. First, we will summarize our current structural and functional understanding of astrocytes at the synapse. Then, we will discuss the cellular and molecular mechanisms through which developing and mature astrocytes instruct the formation, maturation, and refinement of synapses. Our aim is to provide an overview of astrocytes as important players in the establishment of a functional nervous system. PMID:25663667

  7. Eliminating the Decision Review Board. Final rules.

    PubMed

    2011-05-03

    We are eliminating the Decision Review Board (DRB) portions of part 405 of our rules, which we currently use as the final step in our administrative review process for adjudicating initial disability claims in our Boston region. As of the effective date of this regulation, we will replace the DRB step with review by the Appeals Council. The Appeals Council will follow most of the rules in parts 404 and 416 that we use in the rest of the country to adjudicate disability claims at the Appeals Council level, with some differences needed to accommodate the rules that govern administrative law judge (ALJ) hearings in the Boston region. We will also authorize attorney advisors in the Boston region to conduct certain prehearing proceedings and make fully favorable decisions as they do in the rest of the country. We are making these changes to improve service to claimants and to increase consistency in our program rules.

  8. Evaluation of static eliminators containing polonium-210

    SciTech Connect

    Czajkowski, C.J.

    1999-01-01

    Six static eliminators containing radioactive polonium-210 microspheres were examined subsequent to a contamination incident at a commercial facility. It was found that cracked and broken microspheres were being produced and incorporated into new devices and even as received devices were potential sources of contamination. It is shown that rough handling of the devices may initiate polonium-210 leakage during or prior to service. The epoxy binder used in the devices appears to suffer significant environmental and material damage even under ambient conditions. The effects of solvents, heat, moisture, or vibration during service may accelerate this damage. The breakdown of the epoxy binder appears to be a significant contributor to the contamination by loose microspheres or microsphere fragments.

  9. Adaptive elimination of synchronization in coupled oscillator

    NASA Astrophysics Data System (ADS)

    Zhou, Shijie; Ji, Peng; Zhou, Qing; Feng, Jianfeng; Kurths, Jürgen; Lin, Wei

    2017-08-01

    We present here an adaptive control scheme with a feedback delay to achieve elimination of synchronization in a large population of coupled and synchronized oscillators. We validate the feasibility of this scheme not only in the coupled Kuramoto’s oscillators with a unimodal or bimodal distribution of natural frequency, but also in two representative models of neuronal networks, namely, the FitzHugh-Nagumo spiking oscillators and the Hindmarsh-Rose bursting oscillators. More significantly, we analytically illustrate the feasibility of the proposed scheme with a feedback delay and reveal how the exact topological form of the bimodal natural frequency distribution influences the scheme performance. We anticipate that our developed scheme will deepen the understanding and refinement of those controllers, e.g. techniques of deep brain stimulation, which have been implemented in remedying some synchronization-induced mental disorders including Parkinson disease and epilepsy.

  10. Malaria Elimination in Iran, Importance and Challenges

    PubMed Central

    Hemami, Mohsen Rezaei; Sari, Ali Akbari; Raeisi, Ahmad; Vatandoost, Hassan; Majdzadeh, Reza

    2013-01-01

    Background: The aim of study is to assess the importance and challenges of Malaria elimination (ME) in Iran's health system. Material: Opinion of experts from Ministry of Health and Medical Education and the chancellors of medical universities affected by malaria were gathered using Focus Group Discussions and in-depth interviews. We asked them about the importance and main challenges of ME in Iran. Results: Main factors on importance of ME were: it's a struggle to reach to equity in the poorest regions of county, prevention of emerging disease in susceptible regions, lowering the cost of control and its effects on the region's socioeconomic condition. Main challenges were Iran's long border with malaria-endemic countries Pakistan and Afghanistan and illegal immigrants, underdevelopment in rural areas, system's insensitivity and diagnosis problem due to reduction of cases. Conclusion: Quantitative and holistic researches are needed for assessing the consequences of ME. PMID:23413116

  11. Priorities for the elimination of sleeping sickness.

    PubMed

    Welburn, Susan C; Maudlin, Ian

    2012-01-01

    Sleeping sickness describes two diseases, both fatal if left untreated: (i) Gambian sleeping sickness caused by Trypanosoma brucei gambiense, a chronic disease with average infection lasting around 3 years, and (ii) Rhodesian sleeping sickness caused by T. b. rhodesiense, an acute disease with death occurring within weeks of infection. Control of Gambian sleeping sickness is based on case detection and treatment involving serological screening, followed by diagnostic confirmation and staging. In stage I, patients can remain asymptomatic as trypanosomes multiply in tissues and body fluids; in stage II, trypanosomes cross the blood-brain barrier, enter the central nervous system and, if left untreated, death follows. Staging is crucial as it defines the treatment that is prescribed; for both forms of disease, stage II involves the use of the highly toxic drug melarsoprol or, in the case of Gambian sleeping sickness, the use of complex and very expensive drug regimes. Case detection of T. b. gambiense sleeping sickness is known to be inefficient but could be improved by the identification of parasites using molecular tools that are, as yet, rarely used in the field. Diagnostics are not such a problem in relation to T. b. rhodesiense sleeping sickness, but the high level of under-reporting of this disease suggests that current strategies, reliant on self-reporting, are inefficient. Sleeping sickness is one of the 'neglected tropical diseases' that attracts little attention from donors or policymakers. Proper quantification of the burden of sleeping sickness matters, as the primary reason for its 'neglect' is that the true impact of the disease is unknown, largely as a result of under-reporting. Certainly, elimination will not be achieved without vast improvements in field diagnostics for both forms of sleeping sickness especially if there is a hidden reservoir of 'chronic carriers'. Mass screening would be a desirable aim for Gambian sleeping sickness and could be

  12. Toward the Elimination of Paper Orders

    PubMed Central

    Ramirez, Ricardo; Webster, S. Luke

    2016-01-01

    Summary With the adoption of Computerized Patient Order Entry (CPOE), many physicians – particularly consultants and those who are affiliated with multiple hospital systems – are faced with the challenge of learning to navigate and commit to memory the details of multiple EHRs and CPOE software modules. These physicians may resist CPOE adoption, and their refusal to use CPOE presents a risk to patient safety when paper and electronic orders co-exist, as paper orders generated in an electronic ordering environment can be missed or acted upon after delay, are frequently illegible, and bypass the Clinical Decision Support (CDS) that is part of the evidence-based value of CPOE. We defined a category of CPOE Low Frequency Users (LFUs) – physicians issuing a total of less than 10 orders per month – and found that 50.4% of all physicians issuing orders in 3 urban/suburban hospitals were LFUs and actively issuing orders across all shifts and days of the week. Data are presented for 2013 on the number of LFUs by month, day of week, shift and facility, over 2.3 million orders issued. A menu of 6 options to assist LFUs in the use of CPOE, from which hospital leaders could select, was instituted so that paper orders could be increasingly eliminated. The options, along with their cost implications, are described, as is the initial option selected by hospital leaders. In practice, however, a mixed pattern involving several LFU support options emerged. We review data on how the option mix selected may have impacted CPOE adoption and physician use rates at the facilities. The challenge of engaging LFU physicians in CPOE adoption may be common in moderately sized hospitals, and these options can be deployed by other systems in advancing CPOE pervasiveness of use and the eventual elimination of paper orders. PMID:27081405

  13. Par Pond vegetation status Summer 1995 -- June survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-06-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the shoreline aquatic plant communities in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level, indicated that much of the original plant communities and the intermediate shoreline communities present on the exposed sediments have been lost. The extensive old-field and emergent marsh communities that were present on the exposed shoreline during the drawdown have been flooded and much of the pre-drawdown Par Pond aquatic plant communities have not had sufficient time for re-establishment. The shoreline does, however, have extensive beds of maidencane which extend from the shoreline margin to areas as deep as 2 and perhaps 3 meters. Scattered individual plants of lotus and watershield are common and may indicate likely directions of future wetland development in Par Pond. In addition, within isolated coves, which apparently received ground water seepage and/or stream surface flows during the period of the Par Pond draw down, extensive beds of waterlilies and spike rush are common. Invasion of willow and red maple occurred along the lake shoreline as well. Although not absent from this survey, evidence of the extensive redevelopment of the large cattail and eel grass beds was not observed in this first survey of Par Pond. Future surveys during the growing seasons of 1995, 1996, and 1997 along with the evaluation of satellite date to map the areal extent of the macrophyte beds of Par Pond are planned.

  14. Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual Prognosis

    PubMed Central

    Ozdal, Pinar Cakar; Berker, Nilufer; Tugal-Tutkun, Ilknur

    2015-01-01

    Pars planitis is an idiopathic chronic intermediate uveitis which predominantly affects children and adolescents, and accounts for 5-26.7% of pediatric uveitis. Although an autoimmune process with a genetic predisposition has been suggested, its etiology still remains unknown. The most common presenting symptoms are floaters and blurred vision. Diffuse vitreous cells, haze, snowballs and snowbanks are typical findings of pars planitis. Peripheral retinal vasculitis, optic disc edema and anterior segment inflammation are other well-known findings. Although pars planitis is known to be a benign form of uveitis in most cases, it may become a potentially blinding disease due to complications including cataract, cystoid macular edema, vitreous opacities and optic disc edema. Cystoid macular edema is the most common cause of visual morbidity. Band keratopathy, epiretinal membrane formation, vitreous condensation, neovascularizations, vitreous hemorrhage, retinal detachment, cyclitic membranes, glaucoma and amblyopia may develop as a consequence of the chronic course of the disease. Exclusion of infectious and non-infectious causes which may present with intermediate uveitis is of utmost importance before starting treatment. Treatment of pars planitis has been a controversial issue. There is no consensus specifically for treatment of cases with minimal inflammation and relatively good visual acuity. However, current experience shows that pars planitis may cause severe inflammation and needs an aggressive treatment. A stepladder approach including corticosteroids, immunosupressive agents, anti-tumor necrosis factor-alpha and pars plana vitrectomy and/or laser photocoagulation is the most commonly used method for treatment of pars planitis. Adequate control of inflammation and prompt detection of associated complications are crucial in order to improve the overall prognosis of the disease. PMID:27051493

  15. Parallel Gaussian Elimination with Linear Work and Fill,

    DTIC Science & Technology

    1997-05-01

    This paper presents an algorithm for finding parallel elimination orderings for Gaussian elimination . Viewing a system of equations as a graphs, the...height at most O(log(3) n) times optimal, fill at most O(m), and work at most O(W*(G)), where W*(G) is the minimum possible work over all elimination

  16. Enhanced noscapine delivery using uPAR-targeted optical-MR imaging trackable nanoparticles for prostate cancer therapy.

    PubMed

    Abdalla, Mohamed O; Karna, Prasanthi; Sajja, Hari Krishna; Mao, Hui; Yates, Clayton; Turner, Timothy; Aneja, Ritu

    2011-02-10

    The tubulin-binding anticancer activity of noscapine, an orally available plant-derived anti-tussive alkaloid, has been recently identified. Noscapine inhibits tumor growth in nude mice bearing human xenografts of hematopoietic, breast, lung, ovarian, brain and prostate origin. Despite its nontoxic attributes, significant elimination of the disease has not been achieved, perhaps since the bioavailability of noscapine to tumors saturates at an oral dose of 300 mg/kg body weight. To enable the selective and specific delivery of noscapine to prostate cancer cells, we have engineered a multifunctional nanoscale delivery vehicle that takes advantage of urokinase plasminogen activator receptor (uPAR) overexpression in prostate cancer compared to normal prostate epithelia and can be tracked by magnetic resonance imaging (MRI) and near-infrared (NIR) imaging. Specifically, we employed the human-type 135 amino-acid amino-terminal fragment (hATF) of urokinase plasminogen activator (uPA), a high-affinity natural ligand for uPAR. Noscapine (Nos) was efficiently adsorbed onto the amphiphilic polymer coating of uPAR-targeted nanoparticles (NPs). Nos-loaded NPs were uniformly compact-sized, stable at physiological pH and efficiently released the drug at pH 4 to 5 within a span of 4h. Our results demonstrate that these uPAR-targeted NPs were capable of binding to the receptor and were internalized by PC-3 cells. uPAR-targeted Nos-loaded NPs enhanced intracellular noscapine accumulation as evident by the ~6-fold stronger inhibitory effect on PC-3 growth compared to free noscapine. In addition, Nos-loaded iron oxide NPs maintained their T2 MRI contrast effect upon internalization into tumor cells owing to their significant susceptibility effect in cells. Thus, our data provide compelling evidence that these optically and magnetic resonance imaging (MRI)-trackable uPAR-targeted NPs may offer a great potential for image-directed targeted delivery of noscapine for the management of

  17. Biodegradable Lipids Enabling Rapidly Eliminated Lipid Nanoparticles for Systemic Delivery of RNAi Therapeutics

    PubMed Central

    Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

    2013-01-01

    In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available. PMID:23799535

  18. Par Pond vegetation status Summer 1995 -- October survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-11-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this late October survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maiden cane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  19. Par Pond vegetation status Summer 1995 -- September survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-09-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this mid-September survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maidencane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys during the late growing seasons of 1995, and throughout 1996 and 1997, along with the evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  20. Bimetallic Reductive Elimination from Dinuclear Pd(III) Complexes

    PubMed Central

    Powers, David C.; Benitez, Diego; Tkatchouk, Ekaterina; Goddard, William A.

    2010-01-01

    In 2009, we reported C–halogen reductive elimination reactions from dinuclear Pd(III) complexes and implicated dinuclear intermediates in Pd(OAc)2-catalyzed C–H oxidation chemistry. Herein, we report results of a thorough experimental and theoretical investigation of the mechanism of reductive elimination from such dinuclear Pd(III) complexes, which establish the role of each metal during reductive elimination. Our results implicate reductive elimination from a complex in which the dinuclear core is intact and suggest that redox synergy between both metals is responsible for the facile reductive elimination reactions observed. PMID:20858006

  1. ORTHO- ELIMINATION OF TRACKING SYSTEM CLOCK ERRORS

    NASA Technical Reports Server (NTRS)

    Wu, J. T.

    1994-01-01

    ORTHO is part of the Global Positioning System (GPS) being developed by the U.S. Air Force, a navigational system that will use 18 NAVSTAR satellites to broadcast navigation messages and achieve worldwide coverage. The normal positioning technique uses one receiver which receives signals from at least four GPS satellites. For higher accuracy work it is often necessary to use a differential technique in which more than one receiver is used. The geodetic measurement has all receivers on the ground and allows the determination of the relative locations of the ground sites. The main application of the ORTHO program is in the elimination of clock errors in a GPS based tracking system. The measured distance (pseudo-range) from a GPS receiver contains errors due to differences in the receiver and satellite clocks. The conventional way of eliminating clock errors is to difference pseudo-ranges between different GPS satellites and receivers. The Householder transformation used in this program performs a function similar to the conventional single differencing or double differencing. This method avoids the problem of redundancy and correlation encountered in a differencing scheme. It is able to keep all information contained in the measurements within the scope of a least square estimation. For multiple transmitter and receiver GPS tracking network, this method is in general more accurate than the differencing technique. This program assumes that the non-clock measurement partial derivatives for the particular application are computed earlier by another program. With the partial derivatives and information to identify the transmitters and receivers as the input, the program performs the Householder transformation on the partial derivatives. The transformed partials are output by the program and may be used as an input to the filter program in the subsequent estimation process. Clock partial derivatives are generated internally and are not part of the input to the program

  2. Polio elimination in Nigeria: A review

    PubMed Central

    Nasir, Usman Nakakana; Bandyopadhyay, Ananda Sankar; Montagnani, Francesca; Akite, Jacqueline Elaine; Mungu, Etaluka Blanche; Uche, Ifeanyi Valentine; Ismaila, Ahmed Mohammed

    2016-01-01

    abstract Nigeria has made tremendous strides towards eliminating polio and has been free of wild polio virus (WPV) for more than a year as of August 2015. However, sustained focus towards getting rid of all types of poliovirus by improving population immunity and enhancing disease surveillance will be needed to ensure it sustains the polio-free status. We reviewed the pertinent literature including published and unpublished, official reports and working documents of the Global Polio Eradication Initiative (GPEI) partners as well as other concerned organizations. The literature were selected based on the following criteria: published in English Language, published after year 2000, relevant content and conformance to the theme of the review and these were sorted accordingly. The challenges facing the Polio Eradication Initiative (PEI) in Nigeria were found to fall into 3 broad categories viz failure to vaccinate, failure of the Oral Polio Vaccine (OPV) and epidemiology of the virus. Failure to vaccinate resulted from insecurity, heterogeneous political support, programmatic limitation in implementation of vaccination campaigns, poor performance of vaccination teams in persistently poor performing Local Government areas and sporadic vaccine refusals in Northern Nigeria. Sub optimal effectiveness of OPV in some settings as well as the rare occurrence of VDPVs associated with OPV type 2 in areas of low immunization coverage were also found to be key issues. Some of the innovations which helped to manage the threats to the PEI include a strong government accountability frame work, change from type 2 containing OPV to bi valent OPVs for supplementary immunization activities (SIA), enhancing environmental surveillance in key states (Sokoto, Kano and Borno) along with an overall improvement in SIA quality. There has been an improvement in coverage of routine immunization and vaccination campaigns, which has resulted in Nigeria being removed from the list of endemic

  3. ORTHO- ELIMINATION OF TRACKING SYSTEM CLOCK ERRORS

    NASA Technical Reports Server (NTRS)

    Wu, J. T.

    1994-01-01

    ORTHO is part of the Global Positioning System (GPS) being developed by the U.S. Air Force, a navigational system that will use 18 NAVSTAR satellites to broadcast navigation messages and achieve worldwide coverage. The normal positioning technique uses one receiver which receives signals from at least four GPS satellites. For higher accuracy work it is often necessary to use a differential technique in which more than one receiver is used. The geodetic measurement has all receivers on the ground and allows the determination of the relative locations of the ground sites. The main application of the ORTHO program is in the elimination of clock errors in a GPS based tracking system. The measured distance (pseudo-range) from a GPS receiver contains errors due to differences in the receiver and satellite clocks. The conventional way of eliminating clock errors is to difference pseudo-ranges between different GPS satellites and receivers. The Householder transformation used in this program performs a function similar to the conventional single differencing or double differencing. This method avoids the problem of redundancy and correlation encountered in a differencing scheme. It is able to keep all information contained in the measurements within the scope of a least square estimation. For multiple transmitter and receiver GPS tracking network, this method is in general more accurate than the differencing technique. This program assumes that the non-clock measurement partial derivatives for the particular application are computed earlier by another program. With the partial derivatives and information to identify the transmitters and receivers as the input, the program performs the Householder transformation on the partial derivatives. The transformed partials are output by the program and may be used as an input to the filter program in the subsequent estimation process. Clock partial derivatives are generated internally and are not part of the input to the program

  4. FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus.

    PubMed

    Steffan, Nicola; Grundmann, Alexander; Afiyatullov, Shamil; Ruan, Hanli; Li, Shu-Ming

    2009-10-07

    Verruculogen is a tremorgenic mycotoxin and contains an endoperoxide bond. In this study, we describe the cloning, overexpression and purification of a non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase FtmOx1 from Aspergillus fumigatus, which catalyses the conversion of fumitremorgin B to verruculogen by inserting an endoperoxide bond between two prenyl moieties. Incubation with (18)O(2)-enriched atmosphere demonstrated that both oxygen atoms of the endoperoxide bond are derived from one molecule of O(2). FtmOx1 is the first endoperoxide-forming non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase reported so far. A mechanism of FtmOx1-catalysed verruculogen formation is postulated and discussed.

  5. The case for eliminating battlefield nuclear weapons

    SciTech Connect

    Sigal, L.V.

    1989-09-01

    The primary reasons for the elimination of NATO's BNW are two. First, BNW are superfluous for deterrence. Other weapons are better suited for that purpose. Second, and more important, any deployment of nuclear weapons in Western Europe necessarily involves three critical trade-offs: a trade-off between deterrence and reassurance in peacetime, a trade-off between deterrence and crisis stability in times of high political tension, and a trade-off between deterrence and controlled use in war. Whatever purpose BNW purportedly serve as deterrents come at a disproportionate cost to peacetime reassurance, crisis stability, and wartime control. The continued presence of BNW in Western Europe is hard to explain in rational terms; it is more readily explicable by organizational and political inertia. To see why continued inertia is dangerous, the author first examine briefly the military purposes that nuclear weapons allegedly serve for NATO - that is, what they are said to deter and how. Then, he examines the paradoxes in the logic of deterrence of conventional attack in Europe and, flowing from those paradoxes, the critical policy dilemmas posed by BNW. Next, and fundamental to the discussion, he raises the critical organizational and political predicaments that any coherent strategy for continued deployment of these weapons must overcome. Finally, he discusses the political ramifications of keeping these weapons in place.

  6. Eliminating poverty will help women most.

    PubMed

    Short, C

    1997-01-01

    It is both possible and affordable to eliminate poverty. It is also necessary to promote peaceful existence in the next century and to reduce population pressure. A key to poverty reduction is to increase equality between men and women. Women must be given access to reproductive health services and care so that they can bear their children safely and protect themselves from infection. The maternal mortality risk in Africa far exceeds that in developed countries, and many more women suffer permanent disability from child birth. At least 120 million have an unmet need for contraception, and more than 90% of AIDS cases occur among the impoverished and marginalized population of developing countries. In addition to meeting the reproductive health needs of men and women, the needs of youth must be met through coherent and coordinated efforts that support the work of all partners in development according to an agreed upon agenda crafted by developing countries. The priorities must be to 1) increase access to reproductive health information, services, and commodities and 2) to minimize the need for abortion while recognizing that women should be able to make their own moral choices and to obtain a safe abortion. The goals of the international development community for 2015 are to halve the proportion of people living in extreme poverty, to ensure reproductive health for all, and to achieve a 75% reduction in maternal mortality.

  7. Eliminating Tuberculosis One Neighborhood at a Time

    PubMed Central

    Griffith, David E.; McGaha, Paul K.; Wolfgang, Melanie; Robinson, Celia B.; Clark, Patricia A.; Hassell, Willis L.; Robison, Valerie A.; Walker, Kerfoot P.; Wallace, Charles

    2014-01-01

    Objectives. We evaluated a strategy for preventing tuberculosis (TB) in communities most affected by it. Methods. In 1996, we mapped reported TB cases (1985–1995) and positive tuberculin skin test (TST) reactors (1993–1995) in Smith County, Texas. We delineated the 2 largest, densest clusters, identifying 2 highest-incidence neighborhoods (180 square blocks, 3153 residents). After extensive community preparation, trained health care workers went door-to-door offering TST to all residents unless contraindicated. TST-positive individuals were escorted to a mobile clinic for radiography, clinical evaluation, and isoniazid preventive treatment (IPT) as indicated. To assess long-term impact, we mapped all TB cases in Smith County during the equivalent time period after the project. Results. Of 2258 eligible individuals, 1291 (57.1%) were tested, 229 (17.7%) were TST positive, and 147 were treated. From 1996 to 2006, there were no TB cases in either project neighborhood, in contrast with the preintervention decade and the continued occurrence of TB in the rest of Smith County. Conclusions. Targeting high-incidence neighborhoods for active, community-based screening and IPT may hasten TB elimination in the United States. PMID:24899457

  8. Eliminating Xenoantigen Expression on Swine RBC.

    PubMed

    Wang, Zheng-Yu; Martens, Gregory R; Blankenship, Ross L; Sidner, Richard A; Li, Ping; Estrada, Jose L; Tector, Matthew; Tector, A Joseph

    2017-03-01

    The rapidly improving tools of genetic engineering may make it possible to overcome the humoral immune barrier that prevents xenotransplantation. We hypothesize that levels of human antibody binding to donor tissues from swine must approximate the antibody binding occurring in allotransplantation. It is uncertain if this is an attainable goal. Here we perform an initial analysis of this issue by comparing human antibody binding to red blood cells (RBC) isolated from knockout swine and to allogeneic or autologous human RBC. Human sera were incubated with RBC isolated from various genetically engineered swine or from humans. The level of IgG and IgM binding to these cells were compared using either flow cytometry or a novel mass spectrometric assay. Mass spectroscopic quantitation of human antibody binding demonstrated that as few as 3 gene inactivations can reduce the levels human antibody binding to swine RBC that is as low as autologous human RBC. Flow cytometry showed that RBC from 2-gene knockout swine exhibited less human antibody binding than human blood group O allogeneic RBC in 22% of tested sera. Deletion of a third gene from pigs resulted in 30% of human samples having less IgG and IgM RBC xenoreactivity than alloreactivity. Xenoantigenicity of swine RBC can be eliminated via gene disruption. These results suggest that the gene knockout approach may be able reduce antigenicity in other pig tissues to levels that enable the xenotransplantation humoral barrier to be overcome.

  9. Elimination kinetic of recombinant somatotropin in bovine.

    PubMed

    Le Breton, Marie-Hélène; Rochereau-Roulet, Sandrine; Pinel, Gaud; Cesbron, Nora; Le Bizec, Bruno

    2009-04-01

    Bovine somatotropin (bST), also called growth hormone is a protein hormone produced by the pituitary gland and responsible directly or indirectly for various effects on growth, development and reproductive functions. Its recombinant bovine somatotropin form (rbST) is used in dairy cattle to enhance milk production. Even if the effects of treatment with rbST have been largely studied, until now analytical methods able to detect rbST were limited to immunoassays, which suffer from the impossibility to distinguish between the endogenous and the recombinant form. In this study, a sample preparation procedure based on different precipitation steps, extraction on solid phase and enzymatic digestion was used to purify rbST from serum. The detection was performed by liquid chromatography coupled to tandem mass spectrometry in positive electrospray ionization mode (LC-ESI(+)-MS/MS) allowing the unambiguous identification and quantification of rbST in serum. Samples collected from a cow treated with recombinant bovine somatotropin were analysed and for the first time, the elimination kinetic specific to recombinant somatotropin has been characterized in serum. Detection of rbST was possible from 4h 30min to 4 days after administration and concentration was found up to 10ngmL(-1) during the kinetic.

  10. Seasonal blood shortages can be eliminated.

    PubMed

    Gilcher, Ronald O; McCombs, Suzanne

    2005-11-01

    This review is designed to help readers understand seasonal blood shortages and provide solutions through the use of technology that can increase the number of red blood cell units collected and the use of recruitment and marketing initiatives that appeal to the increasingly diverse donor base. Seasonal shortages are, in reality, mostly shortages of group O red blood cells and occur most commonly during midsummer and early winter. The shortages occur primarily from increased use of group O red blood cells at times of decreased donor availability. While reducing the disproportionate use of red cells will help, blood centers can more quickly reduce the seasonal deficits by using automated red cell technology to collect double red blood cell units; targeted marketing programs to provide effective messages; seasonal advertising campaigns; and recognition, benefits, and incentives to enhance the donor motivation donation threshold. A multi-level approach to increasing blood donations at difficult times of the year can ensure that donations are increased at a time when regular donor availability is decreased. Seasonal blood shortages can be eliminated by understanding the nature of the shortages, why and when they occur, and using more sophisticated recruitment and marketing strategies as well as automated collection technologies to enhance the blood supply.

  11. Minimizing or eliminating refueling of nuclear reactor

    DOEpatents

    Doncals, Richard A.; Paik, Nam-Chin; Andre, Sandra V.; Porter, Charles A.; Rathbun, Roy W.; Schwallie, Ambrose L.; Petras, Diane S.

    1989-01-01

    Demand for refueling of a liquid metal fast nuclear reactor having a life of 30 years is eliminated or reduced to intervals of at least 10 years by operating the reactor at a low linear-power density, typically 2.5 kw/ft of fuel rod, rather than 7.5 or 15 kw/ft, which is the prior art practice. So that power of the same magnitude as for prior art reactors is produced, the volume of the core is increased. In addition, the height of the core and it diameter are dimensioned so that the ratio of the height to the diameter approximates 1 to the extent practicable considering the requirement of control and that the pressure drop in the coolant shall not be excessive. The surface area of a cylinder of given volume is a minimum if the ratio of the height to the diameter is 1. By minimizing the surface area, the leakage of neutrons is reduced. By reducing the linear-power density, increasing core volume, reducing fissile enrichment and optimizing core geometry, internal-core breeding of fissionable fuel is substantially enhanced. As a result, core operational life, limited by control worth requirements and fuel burnup capability, is extended up to 30 years of continuous power operation.

  12. Eliminating tuberculosis one neighborhood at a time.

    PubMed

    Cegielski, J Peter; Griffith, David E; McGaha, Paul K; Wolfgang, Melanie; Robinson, Celia B; Clark, Patricia A; Hassell, Willis L; Robison, Valerie A; Walker, Kerfoot P; Wallace, Charles

    2014-04-01

    We evaluated a strategy for preventing tuberculosis (TB) in communities most affected by it. In 1996, we mapped reported TB cases (1985-1995) and positive tuberculin skin test (TST) reactors (1993-1995) in Smith County, Texas. We delineated the 2 largest, densest clusters, identifying 2 highest-incidence neighborhoods (180 square blocks, 3153 residents). After extensive community preparation, trained health care workers went door-to-door offering TST to all residents unless contraindicated. TST-positive individuals were escorted to a mobile clinic for radiography, clinical evaluation, and isoniazid preventive treatment (IPT) as indicated. To assess long-term impact, we mapped all TB cases in Smith County during the equivalent time period after the project. Of 2258 eligible individuals, 1291 (57.1%) were tested, 229 (17.7%) were TST positive, and 147 were treated. From 1996 to 2006, there were no TB cases in either project neighborhood, in contrast with the preintervention decade and the continued occurrence of TB in the rest of Smith County. Targeting high-incidence neighborhoods for active, community-based screening and IPT may hasten TB elimination in the United States.

  13. Grating lobe elimination in steerable parametric loudspeaker.

    PubMed

    Shi, Chuang; Gan, Woon-Seng

    2011-02-01

    In the past two decades, the majority of research on the parametric loudspeaker has concentrated on the nonlinear modeling of acoustic propagation and pre-processing techniques to reduce nonlinear distortion in sound reproduction. There are, however, very few studies on directivity control of the parametric loudspeaker. In this paper, we propose an equivalent circular Gaussian source array that approximates the directivity characteristics of the linear ultrasonic transducer array. By using this approximation, the directivity of the sound beam from the parametric loudspeaker can be predicted by the product directivity principle. New theoretical results, which are verified through measurements, are presented to show the effectiveness of the delay-and-sum beamsteering structure for the parametric loudspeaker. Unlike the conventional loudspeaker array, where the spacing between array elements must be less than half the wavelength to avoid spatial aliasing, the parametric loudspeaker can take advantage of grating lobe elimination to extend the spacing of ultrasonic transducer array to more than 1.5 wavelengths in a typical application.

  14. Customized optimal filter for eliminating operator's tremor

    NASA Astrophysics Data System (ADS)

    Gonzalez, Juan G.; Heredia, Edwin A.; Rahman, Tariq; Barner, Kenneth E.; Arce, Gonzalo R.

    1995-12-01

    Remote manually operated tasks such as those found in teleoperation, virtual reality, or joystick-based computer access, require the generation of an intermediate signal which is transmitted to the controlled subsystem (robot arm, virtual environment or cursor). When man-machine movements are distorted by tremor, performance can be improved by digitally filtering the intermediate signal before it reaches the controlled device. This paper introduces a novel filtering framework in which digital equalizers are optimally designed after pursuit tracking task experiments. Due to inherent properties of the man-machine system, the design of tremor suppression equalizers presents two serious problems: (1) performance criteria leading to optimizations that minimize mean-squared error are not efficient for tremor elimination, and (2) movement signals show highly ill-conditioned autocorrelation matrices, which often result in useless or unstable solutions. A new performance indicator is introduced, namely the F-MSEd, and the optimal equalizer according to this new criterion is developed. Ill-condition of the autocorrelation matrix is overcome using a novel method which we call pulled-optimization. Experiments performed with both a person with tremor disability, and a vibration inducing device, show significant results.

  15. Ringing effects eliminated spin echo in solids

    NASA Astrophysics Data System (ADS)

    Ma, Chao; Li, Peng; Chen, Qun; Zhang, Shanmin

    2013-08-01

    Two types of ringing effects eliminated spin echo sequences have been introduced. To achieve the task, two additional 90° pulses with proper phase cycles are placed at the beginning of the pulse sequences. The spin echo time is calculated with the perturbation method to the first order, i.e. taking into account only the dipolar secular term. The non-secular term causes an imaginary part of the FID, leading to an unsymmetrical NMR spectrum. This effect, according to a symmetry of NMR sequences under phase inversion, can be compensated by inverting all the x and -x or y and -y phases. The properties of the symmetry are derived based on the theory of density matrix. In addition, the non-secular term also results in a small drop (several per cent) of the echo amplitude, but it nearly does not affect the echo time. With these pulse sequences we are able to get a spectrum with an echo delay only 1.1 μs without distortion using a Bruker AVANCE III NMR instrument.

  16. Ringing effects eliminated spin echo in solids.

    PubMed

    Ma, Chao; Li, Peng; Chen, Qun; Zhang, Shanmin

    2013-08-01

    Two types of ringing effects eliminated spin echo sequences have been introduced. To achieve the task, two additional 90° pulses with proper phase cycles are placed at the beginning of the pulse sequences. The spin echo time is calculated with the perturbation method to the first order, i.e. taking into account only the dipolar secular term. The non-secular term causes an imaginary part of the FID, leading to an unsymmetrical NMR spectrum. This effect, according to a symmetry of NMR sequences under phase inversion, can be compensated by inverting all the x and -x or y and -y phases. The properties of the symmetry are derived based on the theory of density matrix. In addition, the non-secular term also results in a small drop (several per cent) of the echo amplitude, but it nearly does not affect the echo time. With these pulse sequences we are able to get a spectrum with an echo delay only 1.1μs without distortion using a Bruker AVANCE III NMR instrument. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Tardive dyskinesia: eliminated, forgotten, or overshadowed?

    PubMed

    Remington, Gary

    2007-03-01

    The present review focuses on atypical antipsychotics and tardive dyskinesia. We have known for many years that clozapine has a diminished risk of tardive dyskinesia compared with typical antipsychotics. The last decade has seen the introduction of a number of other atypical antipsychotics, allowing us to begin evaluating whether they too share this attribute. In addition, the opportunity to use these drugs as first-line treatment permits a more precise means of establishing risk. While longer-term data are required, the limited evidence available clearly indicates that the atypical antipsychotics have a decreased liability of tardive dyskinesia, approximately 1% compared with 5% for typical agents annually. Like clozapine, the other atypical antipsychotics also demonstrate antidyskinetic properties in individuals with preexisting tardive dyskinesia. The underlying mechanisms remain unclear, and without such information it is not possible to say what clinical conditions, if any, might diminish or even eliminate these advantages. An update is provided regarding the atypical antipsychotics and tardive dyskinesia. This information is critical in our decision-making regarding choice of antipsychotic and optimal use in the clinical setting.

  18. [Elimination of all trans fatty acids].

    PubMed

    Katan, M B

    2008-02-09

    At the start of the 20th century, the production of trans fatty acids was originally largely driven by the increasing demand for margarine. The two Dutch margarine firms Van den Bergh and Jurgens played an important role in this early development. In the early 1990s it was shown that trans fatty acids increase the risk of heart disease. Unilever, the successor to Van den Bergh and Jurgens, then took the lead in eliminating trans fatty acids from retail foods worldwide. As a result, intake in The Netherlands fell from 15 g per day in 1980 to 3 g per day in 2003. Dairy products and meat are now the major source of trans fatty acids. The effects on health of these ruminant trans fatty acids are unclear. There are three lessons to be learned from the rise and fall of trans fatty acids. First, a history of safe use does not guarantee safety of food components, because routine surveillance will fail to detect adverse effects on common illnesses with long incubation periods. Second, it shows that it is more effective and easier to change the composition of foods than to change consumer behaviour. And third, governments can have a major impact on consumers' health by mandating the use of healthier food ingredients.

  19. Method for eliminating artifacts in CCD imagers

    DOEpatents

    Turko, B.T.; Yates, G.J.

    1992-06-09

    An electronic method for eliminating artifacts in a video camera employing a charge coupled device (CCD) as an image sensor is disclosed. The method comprises the step of initializing the camera prior to normal read out and includes a first dump cycle period for transferring radiation generated charge into the horizontal register while the decaying image on the phosphor being imaged is being integrated in the photosites, and a second dump cycle period, occurring after the phosphor image has decayed, for rapidly dumping unwanted smear charge which has been generated in the vertical registers. Image charge is then transferred from the photosites and to the vertical registers and read out in conventional fashion. The inventive method allows the video camera to be used in environments having high ionizing radiation content, and to capture images of events of very short duration and occurring either within or outside the normal visual wavelength spectrum. Resultant images are free from ghost, smear and smear phenomena caused by insufficient opacity of the registers and, and are also free from random damage caused by ionization charges which exceed the charge limit capacity of the photosites. 3 figs.

  20. Elimination of formate production in Clostridium thermocellum

    DOE PAGES

    Rydzak, Thomas; Lynd, Lee R.; Guss, Adam M.

    2015-07-11

    We study the ability of Clostridium thermocellum to rapidly degrade cellulose and ferment resulting hydrolysis products into ethanol makes it a promising platform organism for cellulosic biofuel production via consolidated bioprocessing. Currently, however, ethanol yield are far below theoretical maximum due to branched product pathways that divert carbon and electrons towards formate, H2, lactate, acetate, and secreted amino acids. To redirect carbon and electron flux away from formate, pyruvate:formate lyase (pfl) and respective PFL-activating enzyme were deleted. Formate production in the resulting Δpfl strain was eliminated and acetate production decreased by 50% on both complex and defined medium. Growth ratemore » of Δpfl decreased by 2.9-fold on defined medium and diauxic growth was observed on complex medium. Supplementation of defined medium with 2 mM formate restored Δpfl growth rate to 80% of the parent strain. Finally, we discuss the role of pfl in metabolic engineering strategies and C1 metabolism.« less