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Sample records for acid substitution model

  1. FLU, an amino acid substitution model for influenza proteins

    Gascuel Olivier; Le Quang; Dang Cuong; Le Vinh

    2010-01-01

    Abstract Background The amino acid substitution model is the core component of many protein analysis systems such as sequence similarity search, sequence alignment, and phylogenetic inference. Although several general amino acid substitution models have been estimated from large and diverse protein databases, they remain inappropriate for analyzing specific species, e.g., viruses. Emerging epidemics of influenza viruses raise the need for comprehensive studies of these dangerous viruses. We p...

  2. FLU, an amino acid substitution model for influenza proteins

    Gascuel Olivier

    2010-04-01

    Full Text Available Abstract Background The amino acid substitution model is the core component of many protein analysis systems such as sequence similarity search, sequence alignment, and phylogenetic inference. Although several general amino acid substitution models have been estimated from large and diverse protein databases, they remain inappropriate for analyzing specific species, e.g., viruses. Emerging epidemics of influenza viruses raise the need for comprehensive studies of these dangerous viruses. We propose an influenza-specific amino acid substitution model to enhance the understanding of the evolution of influenza viruses. Results A maximum likelihood approach was applied to estimate an amino acid substitution model (FLU from ~113, 000 influenza protein sequences, consisting of ~20 million residues. FLU outperforms 14 widely used models in constructing maximum likelihood phylogenetic trees for the majority of influenza protein alignments. On average, FLU gains ~42 log likelihood points with an alignment of 300 sites. Moreover, topologies of trees constructed using FLU and other models are frequently different. FLU does indeed have an impact on likelihood improvement as well as tree topologies. It was implemented in PhyML and can be downloaded from ftp://ftp.sanger.ac.uk/pub/1000genomes/lsq/FLU or included in PhyML 3.0 server at http://www.atgc-montpellier.fr/phyml/. Conclusions FLU should be useful for any influenza protein analysis system which requires an accurate description of amino acid substitutions.

  3. Evaluating rare amino acid substitutions (RGC_CAMs in a yeast model clade.

    Kenneth Polzin

    Full Text Available When inferring phylogenetic relationships, not all sites in a sequence alignment are equally informative. One recently proposed approach that takes advantage of this inequality relies on sites that contain amino acids whose replacement requires multiple substitutions. Identifying these so-called RGC_CAM substitutions (after Rare Genomic Changes as Conserved Amino acids-Multiple substitutions requires that, first, at any given site in the amino acid sequence alignment, there must be a minimum of two different amino acids; second, each amino acid must be present in at least two taxa; and third, the amino acids must require a minimum of two nucleotide substitutions to replace each other. Although theory suggests that RGC_CAM substitutions are expected to be rare and less likely to be homoplastic, the informativeness of RGC_CAM substitutions has not been extensively evaluated in biological data sets. We investigated the quality of RGC_CAM substitutions by examining their degree of homoplasy and internode certainty in nearly 2.7 million aligned amino acid sites from 5,261 proteins from five species belonging to the yeast Saccharomyces sensu stricto clade whose phylogeny is well-established. We identified 2,647 sites containing RGC_CAM substitutions, a number that contrasts sharply with the 100,887 sites containing RGC_non-CAM substitutions (i.e., changes between amino acids that require only a single nucleotide substitution. We found that RGC_CAM substitutions had significantly lower homoplasy than RGC_non-CAM ones; specifically RGC_CAM substitutions showed a per-site average homoplasy index of 0.100, whereas RGC_non-CAM substitutions had a homoplasy index of 0.215. Internode certainty values were also higher for sites containing RGC_CAM substitutions than for RGC_non-CAM ones. These results suggest that RGC_CAM substitutions possess a strong phylogenetic signal and are useful markers for phylogenetic inference despite their rarity.

  4. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl amino substituted triazine amino... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  5. Trends in Substitution Models of Molecular Evolution

    Miguel eArenas

    2015-10-01

    Full Text Available Substitution models of evolution describe the process of genetic variation through fixed mutations and constitute the basis of the evolutionary analysis at the molecular level. Almost forty years after the development of first substitution models, highly sophisticated and data-specific substitution models continue emerging with the aim of better mimicking real evolutionary processes. Here I describe current trends in substitution models of DNA, codon and amino acid sequence evolution, including advantages and pitfalls of the most popular models. The perspective concludes that despite the large number of currently available substitution models, further research is required for more realistic modeling, especially for DNA coding and amino acid data. Additionally, the development of more accurate complex models should be coupled with new implementations and improvements of methods and frameworks for substitution model selection and downstream evolutionary analysis.

  6. Radiation chemistry of salicylic and methyl substituted salicylic acids: Models for the radiation chemistry of pharmaceutical compounds

    Ayatollahi, Shakiba; Kalnina, Daina; Song, Weihua; Turks, Maris; Cooper, William J.

    2013-11-01

    Salicylic acid and its derivatives are components of many medications and moieties found in numerous pharmaceutical compounds. They have been used as models for various pharmaceutical compounds in pharmacological studies, for the treatment of pharmaceuticals and personal care products (PPCPs), and, reactions with natural organic matter (NOM). In this study, the radiation chemistry of benzoic acid, salicylic acid and four methyl substituted salicylic acids (MSA) is reported. The absolute bimolecular reaction rate constants for hydroxyl radical reaction with benzoic and salicylic acids as well as 3-methyl-, 4-methyl-, 5-methyl-, and 6-methyl-salicylic acid were determined (5.86±0.54)×109, (1.07±0.07)×1010, (7.48±0.17)×109, (7.31±0.29)×109, (5.47±0.25)×109, (6.94±0.10)×109 (M-1 s-1), respectively. The hydrated electron reaction rate constants were measured (3.02±0.10)×109, (8.98±0.27)×109, (5.39±0.21)×109, (4.33±0.17)×109, (4.72±0.15)×109, (1.42±0.02)×109 (M-1 s-1), respectively. The transient absorption spectra for the six model compounds were examined and their role as model compounds for the radiation chemistry of pharmaceuticals investigated.

  7. Radiation chemistry of salicylic and methyl substituted salicylic acids: Models for the radiation chemistry of pharmaceutical compounds

    Salicylic acid and its derivatives are components of many medications and moieties found in numerous pharmaceutical compounds. They have been used as models for various pharmaceutical compounds in pharmacological studies, for the treatment of pharmaceuticals and personal care products (PPCPs), and, reactions with natural organic matter (NOM). In this study, the radiation chemistry of benzoic acid, salicylic acid and four methyl substituted salicylic acids (MSA) is reported. The absolute bimolecular reaction rate constants for hydroxyl radical reaction with benzoic and salicylic acids as well as 3-methyl-, 4-methyl-, 5-methyl-, and 6-methyl-salicylic acid were determined (5.86±0.54)×109, (1.07±0.07)×1010, (7.48±0.17)×109, (7.31±0.29)×109, (5.47±0.25)×109, (6.94±0.10)×109 (M−1 s−1), respectively. The hydrated electron reaction rate constants were measured (3.02±0.10)×109, (8.98±0.27)×109, (5.39±0.21)×109, (4.33±0.17)×109, (4.72±0.15)×109, (1.42±0.02)×109 (M−1 s−1), respectively. The transient absorption spectra for the six model compounds were examined and their role as model compounds for the radiation chemistry of pharmaceuticals investigated. - Highlights: • Free radical chemistry of salicylic and 4 methyl salicylic acids is investigated. • The transient absorptions spectra for model compounds are measured. • Absolute bimolecular reaction rate constants for hydroxyl radical are determined. • Solvated electron reaction rate constants are calculated. • The use of salicylic acids as models for pharmaceuticals is explored

  8. Substituted Indoleacetic Acids Tested in Tissue Cultures

    Engvild, Kjeld Christensen

    1978-01-01

    Monochloro substituted IAA inhibited shoot induction in tobacco tissue cultures about as much as IAA. Dichloro substituted IAA inhibited shoot formation less. Other substituted IAA except 5-fluoro- and 5-bromoindole-3-acetic acid were less active than IAA. Callus growth was quite variable and not...... and not correlated with auxin strength measured in the Avena coleoptile test....

  9. Capillary Electrophoresis of Substituted Benzoic Acids

    Mills, Nancy S.; Spence, John D.; Bushey, Michelle M.

    2005-01-01

    A series of substituted benzoic acids (SBAs) are prepared by students. The pKa shift, a result of the electron-withdrawing or electron-donating characteristics of the subsistent is examined in reference to the electrophoretic migration behavior of benzoic acid.

  10. Biological activities of substituted trichostatic acid derivatives

    Cédric Charrier; Joëlle Roche; Jean-Pierre Gesson; Philippe Bertrand

    2009-07-01

    New substituted trichostatic acid derivatives have been synthesized and evaluated for their biological activities towards the H661 non-small lung cancer cell line. These syntheses were achieved by alkylation of propiophenones to introduce the side chain with a terminal precursor of hydroxamic acid and aminobenzamide derivatives. The first fluorinated derivatives of trichostatic acid are described, such as 6-fluoro trichostatin A, with antiproliferative activities in the micromolar range and with histone deacetylase inhibitory activity.

  11. Nonlinear optical properties of p-substituted benzalbarbituric acids

    Kondo, K.; Ochiai, S.; Takemoto, K.; Irie, M.

    1990-02-01

    A number of p-substituted benzalbarbituric acid derivatives were synthesized by the reaction of p-substituted benzaldehyde with barbituric acid, and their nonlinear optical properties were investigated by using the Kurtz powder test. p-acetamidobenzalbarbituric acid derivatives were found to exhibit the relatively high second-harmonic intensity and have the higher thermal stability.

  12. Quantitative Structure-Property Relationship (QSPR) Models for a Local Quantum Descriptor: Investigation of the 4- and 3-Substituted-Cinnamic Acid Esterification.

    Rodrigues-Santos, Cláudio E; Echevarria, Aurea; Sant'Anna, Carlos M R; Bitencourt, Thiago B; Nascimento, Maria G; Bauerfeldt, Glauco F

    2015-01-01

    In this work, the theoretical description of the 4- and 3-substituted-cinnamic acid esterification with different electron donating and electron withdrawing groups was performed at the B3LYP and M06-2X levels, as a two-step process: the O-protonation and the nucleophile attack by ethanol. In parallel, an experimental work devoted to the synthesis and characterization of the substituted-cinnamate esters has also been performed. In order to quantify the substituents effects, quantitative structure-property relationship (QSPR) models based on the atomic charges, Fukui functions and the Frontier Effective-for-Reaction Molecular Orbitals (FERMO) energies were investigated. In fact, the Fukui functions, ƒ⁺C and ƒ(-)O, indicated poor correlations for each individual step, and in contrast with the general literature, the O-protonation step is affected both by the FERMO energies and the O-charges of the carbonyl group. Since the process was shown to not be totally described by either charge- or frontier-orbitals, it is proposed to be frontier-charge-miscere controlled. Moreover, the observed trend for the experimental reaction yields suggests that the electron withdrawing groups favor the reaction and the same was observed for Step 2, which can thus be pointed out as the determining step. PMID:26402661

  13. Quantitative Structure–Property Relationship (QSPR Models for a Local Quantum Descriptor: Investigation of the 4- and 3-Substituted-Cinnamic Acid Esterification

    Cláudio E. Rodrigues-Santos

    2015-09-01

    Full Text Available In this work, the theoretical description of the 4- and 3-substituted-cinnamic acid esterification with different electron donating and electron withdrawing groups was performed at the B3LYP and M06-2X levels, as a two-step process: the O-protonation and the nucleophile attack by ethanol. In parallel, an experimental work devoted to the synthesis and characterization of the substituted-cinnamate esters has also been performed. In order to quantify the substituents effects, quantitative structure–property relationship (QSPR models based on the atomic charges, Fukui functions and the Frontier Effective-for-Reaction Molecular Orbitals (FERMO energies were investigated. In fact, the Fukui functions, ƒ+C and ƒ−O, indicated poor correlations for each individual step, and in contrast with the general literature, the O-protonation step is affected both by the FERMO energies and the O-charges of the carbonyl group. Since the process was shown to not be totally described by either charge- or frontier-orbitals, it is proposed to be frontier-charge-miscere controlled. Moreover, the observed trend for the experimental reaction yields suggests that the electron withdrawing groups favor the reaction and the same was observed for Step 2, which can thus be pointed out as the determining step.

  14. Colorimetric Sugar Sensing Using Boronic Acid-Substituted Azobenzenes

    Yuya Egawa

    2014-02-01

    Full Text Available In association with increasing diabetes prevalence, it is desirable to develop new glucose sensing systems with low cost, ease of use, high stability and good portability. Boronic acid is one of the potential candidates for a future alternative to enzyme-based glucose sensors. Boronic acid derivatives have been widely used for the sugar recognition motif, because boronic acids bind adjacent diols to form cyclic boronate esters. In order to develop colorimetric sugar sensors, boronic acid-conjugated azobenzenes have been synthesized. There are several types of boronic acid azobenzenes, and their characteristics tend to rely on the substitute position of the boronic acid moiety. For example, o-substitution of boronic acid to the azo group gives the advantage of a significant color change upon sugar addition. Nitrogen-15 Nuclear Magnetic Resonance (NMR studies clearly show a signaling mechanism based on the formation and cleavage of the B–N dative bond between boronic acid and azo moieties in the dye. Some boronic acid-substituted azobenzenes were attached to a polymer or utilized for supramolecular chemistry to produce glucose-selective binding, in which two boronic acid moieties cooperatively bind one glucose molecule. In addition, boronic acid-substituted azobenzenes have been applied not only for glucose monitoring, but also for the sensing of glycated hemoglobin and dopamine.

  15. Amine substitution into sulfuric acid – ammonia clusters

    O. Kupiainen

    2011-11-01

    Full Text Available The substitution of ammonia by dimethylamine in sulfuric acid – ammonia – dimethylamine clusters was studied using a collision and evaporation dynamics model. Quantum chemical formation free energies were computed using B3LYP/CBSB7 for geometries and frequencies and RI-CC2/aug-cc-pV(T+dZ for electronic energies. We first demonstrate the good performance of our method by a comparison with an experimental study investigating base substitution in positively charged clusters, and then continue by simulating base exchange in neutral clusters, which cannot be measured directly. Collisions of a dimethylamine molecule with an ammonia containing positively charged cluster result in the instantaneous evaporation of an ammonia molecule, while the dimethylamine molecule remains in the cluster. According to our simulations, a similar base exchange can take place in neutral clusters, although the overall process is more complicated. Neutral sulfuric acid – ammonia clusters are significantly less stable than their positively charged counterparts, resulting in a competition between cluster evaporation and base exchange.

  16. Amine substitution into sulfuric acid – ammonia clusters

    H. Vehkamäki

    2012-04-01

    Full Text Available The substitution of ammonia by dimethylamine in sulfuric acid – ammonia – dimethylamine clusters was studied using a collision and evaporation dynamics model. Quantum chemical formation free energies were computed using B3LYP/CBSB7 for geometries and frequencies and RI-CC2/aug-cc-pV(T+dZ for electronic energies. We first demonstrate the good performance of our method by a comparison with an experimental study investigating base substitution in positively charged clusters, and then continue by simulating base exchange in neutral clusters, which cannot be measured directly. Collisions of a dimethylamine molecule with an ammonia containing positively charged cluster result in the instantaneous evaporation of an ammonia molecule, while the dimethylamine molecule remains in the cluster. According to our simulations, a similar base exchange can take place in neutral clusters, although the overall process is more complicated. Neutral sulfuric acid – ammonia clusters are significantly less stable than their positively charged counterparts, resulting in a competition between cluster evaporation and base exchange.

  17. Amino acid derived 1,4-dialkyl substituted imidazolones

    Diness, Frederik; Meldal, Morten Peter

    2010-01-01

    A general method for synthesis of 1,4-substituted imidazolones from amino acids on solid support or in solution has been developed. Amino acid derived 3-Boc-(1,3)-oxazinane (Box) protected amino aldehyde building blocks were coupled through urea bonds to the amino terminal of dipeptides or amino...

  18. Modeling competitive substitution in a polyelectrolyte complex

    Peng, B.; Muthukumar, M.

    2015-12-01

    We have simulated the invasion of a polyelectrolyte complex made of a polycation chain and a polyanion chain, by another longer polyanion chain, using the coarse-grained united atom model for the chains and the Langevin dynamics methodology. Our simulations reveal many intricate details of the substitution reaction in terms of conformational changes of the chains and competition between the invading chain and the chain being displaced for the common complementary chain. We show that the invading chain is required to be sufficiently longer than the chain being displaced for effecting the substitution. Yet, having the invading chain to be longer than a certain threshold value does not reduce the substitution time much further. While most of the simulations were carried out in salt-free conditions, we show that presence of salt facilitates the substitution reaction and reduces the substitution time. Analysis of our data shows that the dominant driving force for the substitution process involving polyelectrolytes lies in the release of counterions during the substitution.

  19. Modeling competitive substitution in a polyelectrolyte complex

    Peng, B.; Muthukumar, M., E-mail: muthu@polysci.umass.edu [Department of Polymer Science and Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003 (United States)

    2015-12-28

    We have simulated the invasion of a polyelectrolyte complex made of a polycation chain and a polyanion chain, by another longer polyanion chain, using the coarse-grained united atom model for the chains and the Langevin dynamics methodology. Our simulations reveal many intricate details of the substitution reaction in terms of conformational changes of the chains and competition between the invading chain and the chain being displaced for the common complementary chain. We show that the invading chain is required to be sufficiently longer than the chain being displaced for effecting the substitution. Yet, having the invading chain to be longer than a certain threshold value does not reduce the substitution time much further. While most of the simulations were carried out in salt-free conditions, we show that presence of salt facilitates the substitution reaction and reduces the substitution time. Analysis of our data shows that the dominant driving force for the substitution process involving polyelectrolytes lies in the release of counterions during the substitution.

  20. Amino acid "little Big Bang": Representing amino acid substitution matrices as dot products of Euclidian vectors

    Zimmermann Karel

    2010-01-01

    Full Text Available Abstract Background Sequence comparisons make use of a one-letter representation for amino acids, the necessary quantitative information being supplied by the substitution matrices. This paper deals with the problem of finding a representation that provides a comprehensive description of amino acid intrinsic properties consistent with the substitution matrices. Results We present a Euclidian vector representation of the amino acids, obtained by the singular value decomposition of the substitution matrices. The substitution matrix entries correspond to the dot product of amino acid vectors. We apply this vector encoding to the study of the relative importance of various amino acid physicochemical properties upon the substitution matrices. We also characterize and compare the PAM and BLOSUM series substitution matrices. Conclusions This vector encoding introduces a Euclidian metric in the amino acid space, consistent with substitution matrices. Such a numerical description of the amino acid is useful when intrinsic properties of amino acids are necessary, for instance, building sequence profiles or finding consensus sequences, using machine learning algorithms such as Support Vector Machine and Neural Networks algorithms.

  1. Biologically inactive growth hormone caused by an amino acid substitution.

    Takahashi, Y.; Shirono, H; Arisaka, O; K. Takahashi; Yagi, T; Koga, J; Kaji, H; Okimura, Y; ABE, H.; Tanaka, T; Chihara, K.

    1997-01-01

    Short stature caused by biologically inactive growth hormone (GH) is characterized by lack of GH action despite high immunoassayable GH levels in serum and marked catch-up growth to exogenous GH administration. We found a heterozygous single-base substitution (A-->G) in exon 4 of the GH-1 gene of a girl with short stature, clinically suspected to indicate the presence of bioinactive GH and resulting in the substitution of glycine for aspartic acid at codon 112. We confirmed the presence of mu...

  2. Application of Substitutional Model in Oxide Systems

    2003-01-01

    The application of substitutional model in oxide systems, in comparison with that of sublattice model, is discussed.The results show that in the case of crystalline phases and liquid phases without molecular-like associates or theshortage of element in sublattice, these two models get consistent in the description of the formalism of Gibbs freeenergies of phases and obtain the same result of phase diagram calculation when the valence of the cations keep thesame.

  3. Correlated Mutations: A Hallmark of Phenotypic Amino Acid Substitutions

    Kowarsch, Andreas; Fuchs, Angelika; Frishman, Dmitrij; Pagel, Philipp

    2010-01-01

    Point mutations resulting in the substitution of a single amino acid can cause severe functional consequences, but can also be completely harmless. Understanding what determines the phenotypical impact is important both for planning targeted mutation experiments in the laboratory and for analyzing naturally occurring mutations found in patients. Common wisdom suggests using the extent of evolutionary conservation of a residue or a sequence motif as an indicator of its functional importance an...

  4. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    Wen-Hao Wei

    2015-03-01

    Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

  5. Microwave-Assisted Synthesis of New Substituted Anilides of Quinaldic Acid

    Josef Jampilek

    2012-01-01

    Full Text Available In this study a one step method for the preparation of substituted anilides of quinoline-2-carboxylic acid was developed. This efficient innovative approach is based on the direct reaction of an acid or ester with substituted anilines using microwave irradiation. The optimized method was used for the synthesis of a series of eighteen substituted quinoline-2-carboxanilides. The molecular structure of N-(4-bromophenylquinoline-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. It crystallizes in the monoclinic space group with four molecules within the unit cell and the total structure of the compound can be described as “a slightly screwed boat”.

  6. Rh(III)-Catalyzed Oxidative Coupling of Benzoic Acids with Geminal-Substituted Vinyl Acetates: Synthesis of 3-Substituted Isocoumarins.

    Zhang, Mingliang; Zhang, Hui-Jun; Han, Tiantian; Ruan, Wenqing; Wen, Ting-Bin

    2015-01-01

    The Rh(III)-catalyzed C-H activation initiated cyclization of benzoic acids with electron-rich geminal-substituted vinyl acetates was described. The reaction was employed to prepare a range of 3-aryl and 3-alkyl substituted isocoumarins selectively. PMID:25436434

  7. QSBR study of substituted phenols and benzoic acids

    2003-01-01

    The biodegradability of 30 substituted phenols and benzoic acids was determined by BOD technique. The molecular weight (MW), heat of formation (Hf) and the energy of the highest occupied molecular orbital (EHOMO) of the studied compounds were calculated by the quantum chemical method MOPAC6.0-AM1. The quantitative structure-biodegradability relationships (QSBRs) were developed by the linear regression method and neural network approach, respectively. It has been shown that the neural network method is able to provide a superior fit to the training set data and test se t data and produce a lower prediction error than the linear regression method.

  8. An effective synthesis of β-aryl substituted isotetronic acids via Suzuki coupling

    Huan Sheng Chen; Xia Ping Ma; Zhi Ming Li; Quan Rui Wang; Feng Gang Tao

    2008-01-01

    lsotetronic acids are of great agricultural and pharmacological relevance and occur in a number of natural products.A convenient synthetic pathway to β-aryl substituted isotetronic acid derivatives was developed via Suzuki cross-coupling of the corresponding β-bromo substituted isotetronic acid derivatives with arylboronic acids under palladium acetate catalysis.Good to excellent yields have been achieved.

  9. Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans.

    Shmuel Sattath

    Full Text Available In Drosophila, multiple lines of evidence converge in suggesting that beneficial substitutions to the genome may be common. All suffer from confounding factors, however, such that the interpretation of the evidence-in particular, conclusions about the rate and strength of beneficial substitutions-remains tentative. Here, we use genome-wide polymorphism data in D. simulans and sequenced genomes of its close relatives to construct a readily interpretable characterization of the effects of positive selection: the shape of average neutral diversity around amino acid substitutions. As expected under recurrent selective sweeps, we find a trough in diversity levels around amino acid but not around synonymous substitutions, a distinctive pattern that is not expected under alternative models. This characterization is richer than previous approaches, which relied on limited summaries of the data (e.g., the slope of a scatter plot, and relates to underlying selection parameters in a straightforward way, allowing us to make more reliable inferences about the prevalence and strength of adaptation. Specifically, we develop a coalescent-based model for the shape of the entire curve and use it to infer adaptive parameters by maximum likelihood. Our inference suggests that ∼13% of amino acid substitutions cause selective sweeps. Interestingly, it reveals two classes of beneficial fixations: a minority (approximately 3% that appears to have had large selective effects and accounts for most of the reduction in diversity, and the remaining 10%, which seem to have had very weak selective effects. These estimates therefore help to reconcile the apparent conflict among previously published estimates of the strength of selection. More generally, our findings provide unequivocal evidence for strongly beneficial substitutions in Drosophila and illustrate how the rapidly accumulating genome-wide data can be leveraged to address enduring questions about the genetic basis

  10. Analysis of amino acid substitutions in AraC variants that respond to triacetic acid lactone.

    Frei, Christopher S; Wang, Zhiqing; Qian, Shuai; Deutsch, Samuel; Sutter, Markus; Cirino, Patrick C

    2016-04-01

    The Escherichia coli regulatory protein AraC regulates expression of ara genes in response to l-arabinose. In efforts to develop genetically encoded molecular reporters, we previously engineered an AraC variant that responds to the compound triacetic acid lactone (TAL). This variant (named "AraC-TAL1") was isolated by screening a library of AraC variants, in which five amino acid positions in the ligand-binding pocket were simultaneously randomized. Screening was carried out through multiple rounds of alternating positive and negative fluorescence-activated cell sorting. Here we show that changing the screening protocol results in the identification of different TAL-responsive variants (nine new variants). Individual substituted residues within these variants were found to primarily act cooperatively toward the gene expression response. Finally, X-ray diffraction was used to solve the crystal structure of the apo AraC-TAL1 ligand-binding domain. The resolved crystal structure confirms that this variant takes on a structure nearly identical to the apo wild-type AraC ligand-binding domain (root-mean-square deviation 0.93 Å), suggesting that AraC-TAL1 behaves similar to wild-type with regard to ligand recognition and gene regulation. Our results provide amino acid sequence-function data sets for training and validating AraC modeling studies, and contribute to our understanding of how to design new biosensors based on AraC. PMID:26749125

  11. Annonaceae substitution rates: a codon model perspective

    Lars Willem Chatrou

    2014-01-01

    Full Text Available The Annonaceae includes cultivated species of economic interest and represents an important source of information for better understanding the evolution of tropical rainforests. In phylogenetic analyses of DNA sequence data that are used to address evolutionary questions, it is imperative to use appropriate statistical models. Annonaceae are cases in point: Two sister clades, the subfamilies Annonoideae and Malmeoideae, contain the majority of Annonaceae species diversity. The Annonoideae generally show a greater degree of sequence divergence compared to the Malmeoideae, resulting in stark differences in branch lengths in phylogenetic trees. Uncertainty in how to interpret and analyse these differences has led to inconsistent results when estimating the ages of clades in Annonaceae using molecular dating techniques. We ask whether these differences may be attributed to inappropriate modelling assumptions in the phylogenetic analyses. Specifically, we test for (clade-specific differences in rates of non-synonymous and synonymous substitutions. A high ratio of nonsynonymous to synonymous substitutions may lead to similarity of DNA sequences due to convergence instead of common ancestry, and as a result confound phylogenetic analyses. We use a dataset of three chloroplast genes (rbcL, matK, ndhF for 129 species representative of the family. We find that differences in branch lengths between major clades are not attributable to different rates of non-synonymous and synonymous substitutions. The differences in evolutionary rate between the major clades of Annonaceae pose a challenge for current molecular dating techniques that should be seen as a warning for the interpretation of such results in other organisms.

  12. Synthesis and antiulcer activity studies of 2-(1′-iminothioimido substituted-1′-substituted phenylbenzoic acids

    Subudhi B

    2008-01-01

    Full Text Available Certain 2-(1′-iminothioimido substituted-1′-substituted phenybenzoic acids (P 1-9 were synthesized by reaction of phthalic anhydride with benzotriazole, 2-mercapto benzothiazole and 2-p-amino phenyl benzimidazole, respectively (A 1-3 followed by imine formation with Schiff bases of thiourea with salicylaldehyde, furfuraldehyde and 1-phenyl-3-methyl-5-pyrazolone. Antiulcer activity was evaluated using reduction in total acidity, free acidity and ulcer index as parameters. Compounds P 3 , P 6 , P 7 and P 9 (100 mg/kg showed significant (P< 0.001 antiulcer action compared to control and omeprazole (40 mg/kg.

  13. Substitution of aspartic acid with glutamic acid increases the unfolding transition temperature of a protein

    Proteins from thermophiles are more stable than those from mesophiles. Several factors have been suggested as causes for this greater stability, but no general rule has been found. The amino acid composition of thermophile proteins indicates that the content of polar amino acids such as Asn, Gln, Ser, and Thr is lower, and that of charged amino acids such as Arg, Glu, and Lys is higher than in mesophile proteins. Among charged amino acids, however, the content of Asp is even lower in thermophile proteins than in mesophile proteins. To investigate the reasons for the lower occurrence of Asp compared to Glu in thermophile proteins, Glu was substituted with Asp in a hyperthermophile protein, MjTRX, and Asp was substituted with Glu in a mesophile protein, ETRX. Each substitution of Glu with Asp decreased the Tm of MjTRX by about 2 deg. C, while each substitution of Asp with Glu increased the Tm of ETRX by about 1.5 deg. C. The change of Tm destabilizes the MjTRX by 0.55 kcal/mol and stabilizes the ETRX by 0.45 kcal/mol in free energy

  14. Correlated mutations: a hallmark of phenotypic amino acid substitutions.

    Andreas Kowarsch

    Full Text Available Point mutations resulting in the substitution of a single amino acid can cause severe functional consequences, but can also be completely harmless. Understanding what determines the phenotypical impact is important both for planning targeted mutation experiments in the laboratory and for analyzing naturally occurring mutations found in patients. Common wisdom suggests using the extent of evolutionary conservation of a residue or a sequence motif as an indicator of its functional importance and thus vulnerability in case of mutation. In this work, we put forward the hypothesis that in addition to conservation, co-evolution of residues in a protein influences the likelihood of a residue to be functionally important and thus associated with disease. While the basic idea of a relation between co-evolution and functional sites has been explored before, we have conducted the first systematic and comprehensive analysis of point mutations causing disease in humans with respect to correlated mutations. We included 14,211 distinct positions with known disease-causing point mutations in 1,153 human proteins in our analysis. Our data show that (1 correlated positions are significantly more likely to be disease-associated than expected by chance, and that (2 this signal cannot be explained by conservation patterns of individual sequence positions. Although correlated residues have primarily been used to predict contact sites, our data are in agreement with previous observations that (3 many such correlations do not relate to physical contacts between amino acid residues. Access to our analysis results are provided at http://webclu.bio.wzw.tum.de/~pagel/supplements/correlated-positions/.

  15. Correlated mutations: a hallmark of phenotypic amino acid substitutions.

    Kowarsch, Andreas; Fuchs, Angelika; Frishman, Dmitrij; Pagel, Philipp

    2010-01-01

    Point mutations resulting in the substitution of a single amino acid can cause severe functional consequences, but can also be completely harmless. Understanding what determines the phenotypical impact is important both for planning targeted mutation experiments in the laboratory and for analyzing naturally occurring mutations found in patients. Common wisdom suggests using the extent of evolutionary conservation of a residue or a sequence motif as an indicator of its functional importance and thus vulnerability in case of mutation. In this work, we put forward the hypothesis that in addition to conservation, co-evolution of residues in a protein influences the likelihood of a residue to be functionally important and thus associated with disease. While the basic idea of a relation between co-evolution and functional sites has been explored before, we have conducted the first systematic and comprehensive analysis of point mutations causing disease in humans with respect to correlated mutations. We included 14,211 distinct positions with known disease-causing point mutations in 1,153 human proteins in our analysis. Our data show that (1) correlated positions are significantly more likely to be disease-associated than expected by chance, and that (2) this signal cannot be explained by conservation patterns of individual sequence positions. Although correlated residues have primarily been used to predict contact sites, our data are in agreement with previous observations that (3) many such correlations do not relate to physical contacts between amino acid residues. Access to our analysis results are provided at http://webclu.bio.wzw.tum.de/~pagel/supplements/correlated-positions/. PMID:20862353

  16. 40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

    2010-07-01

    ... amines with a substituted benzenesulfonic acid and sulfuric acid (generic name). 721.9220 Section 721... Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric acid... benzenesulfonic acid and sulfuric acid (PMNs P-89-703, P-89-755, and P-89-756) are subject to reporting under...

  17. A model-independent approach to infer hierarchical codon substitution dynamics

    Jacobi Martin

    2010-04-01

    Full Text Available Abstract Background Codon substitution constitutes a fundamental process in molecular biology that has been studied extensively. However, prior studies rely on various assumptions, e.g. regarding the relevance of specific biochemical properties, or on conservation criteria for defining substitution groups. Ideally, one would instead like to analyze the substitution process in terms of raw dynamics, independently of underlying system specifics. In this paper we propose a method for doing this by identifying groups of codons and amino acids such that these groups imply closed dynamics. The approach relies on recently developed spectral and agglomerative techniques for identifying hierarchical organization in dynamical systems. Results We have applied the techniques on an empirically derived Markov model of the codon substitution process that is provided in the literature. Without system specific knowledge of the substitution process, the techniques manage to "blindly" identify multiple levels of dynamics; from amino acid substitutions (via the standard genetic code to higher order dynamics on the level of amino acid groups. We hypothesize that the acquired groups reflect earlier versions of the genetic code. Conclusions The results demonstrate the applicability of the techniques. Due to their generality, we believe that they can be used to coarse grain and identify hierarchical organization in a broad range of other biological systems and processes, such as protein interaction networks, genetic regulatory networks and food webs.

  18. Synthesis and Hydrolytic Degradation of Substituted Poly(DL-Lactic Acids

    Hideto Tsuji

    2011-08-01

    Full Text Available Non-substituted racemic poly(DL-lactic acid (PLA and substituted racemic poly(DL-lactic acids or poly(DL-2-hydroxyalkanoic acids with different side-chain lengths, i.e., poly(DL-2-hydroxybutanoic acid (PBA, poly(DL-2-hydroxyhexanoic acid (PHA, and poly(DL-2-hydroxydecanoic acid (PDA were synthesized by acid-catalyzed polycondensation of DL-lactic acid (LA, DL-2-hydroxybutanoic acid (BA, DL-2-hydroxyhexanoic acid (HA, and DL-2-hydroxydecanoic acid (DA, respectively. The hydrolytic degradation behavior was investigated in phosphate-buffered solution at 80 and 37 °C by gravimetry and gel permeation chromatography. It was found that the reactivity of monomers during polycondensation as monitored by the degree of polymerization (DP decreased in the following order: LA > DA > BA > HA. The hydrolytic degradation rate traced by DP and weight loss at 80 °C decreased in the following order: PLA > PDA > PHA > PBA and that monitored by DP at 37 °C decreased in the following order: PLA > PDA > PBA > PHA. LA and PLA had the highest reactivity during polymerization and hydrolytic degradation rate, respectively, and were followed by DA and PDA. BA, HA, PBA, and PHA had the lowest reactivity during polymerization and hydrolytic degradation rate. The findings of the present study strongly suggest that inter-chain interactions play a major role in the reactivity of non-substituted and substituted LA monomers and degradation rate of the non-substituted and substituted PLA, along with steric hindrance of the side chains as can be expected.

  19. Colorimetric Sugar Sensing Using Boronic Acid-Substituted Azobenzenes

    Yuya Egawa; Ryotaro Miki; Toshinobu Seki

    2014-01-01

    In association with increasing diabetes prevalence, it is desirable to develop new glucose sensing systems with low cost, ease of use, high stability and good portability. Boronic acid is one of the potential candidates for a future alternative to enzyme-based glucose sensors. Boronic acid derivatives have been widely used for the sugar recognition motif, because boronic acids bind adjacent diols to form cyclic boronate esters. In order to develop colorimetric sugar sensors, boronic acid-conj...

  20. Liquid Membrane Transport Behavior of Functional Substituted Crown Ethers for Amino Acids

    2002-01-01

    Three functional substituted crown ethers were synthesized as liquid membrane transport carriers for amino acids. The result obtained shows that this kind of ditopic ligands can transport sodium salt of amino acids in good rate value especially the one with two pyridinyl groups as binding site outside the macrocycle.

  1. 40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.

    2010-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.7770 Alkylphenoxypoly(oxyethylene) sulfuric acid...) The chemical substance identified as alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkylphenoxypoly(oxyethylene)...

  2. Effect of Lateral Substitution on the Electronics and Phase Transitions of Stilbazoles, Benzoic Acids, Phenols, and Hydrogen Bonded Mixtures

    Jeremy R. Wolf

    2015-01-01

    The preparation and characterization of laterally substituted 4-alkoxy-stilbazoles, 4-alkoxy-benzoic acids, and 4-alkoxy phenols and hydrogen bonded heterodimeric mixtures of these compounds are reported. Lateral substitution has a minimal effect on the ring electronics of 4-alkoxy benzoic acids and 4-alkoxy phenols; however the ring electronics of stilbazole units is extremely sensitive to lateral substitution. While lateral substitution is an effective technique for lowering the melting poi...

  3. Synthesis, characterization, antifungal evaluation and 3D-QSAR study of phenylhydrazine substituted tetronic acid derivatives.

    Hu, Ying; Wang, Junjun; Lu, Aimin; Yang, Chunlong

    2014-08-15

    A series of 3-(1-(2-(substituted phenyl)hydrazinyl)alkylidene)furan-2,4(3H,5H)-diones were designed and prepared using two synthetic routes. Their structures were confirmed by FT-IR, (1)H NMR, (13)C NMR, MS, elemental analysis and single-crystal X-ray diffraction. Their bioactivity was evaluated against Botrytis cinerea in vitro. Most target compounds exhibited remarkable antifungal activity. Two compounds 7f and 7h were highly effective and their EC50 values were 0.241 μg/mL and 0.167 μg/mL, respectively, close to that of the control drug procymidone. 3D-QSAR studies of CoMFA and CoMSIA were carried out. Models with good predictive ability were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.565 and 0.823. Conventional r(2) values were 0.983 and 0.945, respectively. The results provided a practical tool for guiding the design and synthesis of novel and more potent tetronic acid derivatives containing substituted phenylhydrazine moiety. PMID:25042337

  4. Twelve positions in a β-lactamase that can expand its substrate spectrum with a single amino acid substitution.

    Hyojeong Yi

    Full Text Available The continuous evolution of β-lactamases resulting in bacterial resistance to β-lactam antibiotics is a major concern in public health, and yet the underlying molecular basis or the pattern of such evolution is largely unknown. We investigated the mechanics of the substrate fspectrum expansion of the class A β-lactamase using PenA of Burkholderia thailandensis as a model. By analyzing 516 mutated enzymes that acquired the ceftazidime-hydrolyzing activity, we found twelve positions with single amino acid substitutions (altogether twenty-nine different substitutions, co-localized at the active-site pocket area. The ceftazidime MIC (minimum inhibitory concentration levels and the relative frequency in the occurrence of substitutions did not correlate well with each other, and the latter appeared be largely influenced by the intrinsic mutational biases present in bacteria. Simulation studies suggested that all substitutions caused a congruent effect, expanding the space in a conserved structure called the omega loop, which in turn increased flexibility at the active site. A second phase of selection, in which the mutants were placed under increased antibiotic pressure, did not result in a second mutation in the coding region, but a mutation that increased gene expression arose in the promoter. This result suggests that the twelve amino acid positions and their specific substitutions in PenA may represent a comprehensive repertoire of the enzyme's adaptability to a new substrate. These mapped substitutions represent a comprehensive set of general mechanical paths to substrate spectrum expansion in class A β-lactamases that all share a functional evolutionary mechanism using common conserved residues.

  5. Banana-shaped molecules derived from substituted isophthalic acids

    H T Nguyen; J P Bedel; J C Rouillon; J P Marcerou; M F Achard

    2003-08-01

    In this paper we present a review of five-rings banana-shaped molecules derived from isophthalic acids. This study deals with about a hundred compounds and most of them have not been published. By a combination of several linking groups and different selected substituents either on the outer rings or on the central core, several mesophases with switching properties are induced. The study of homologous series underlines the importance of the length and nature of the terminal chains. X-ray analysis reveals several new structures.

  6. Substitution of trans fatty acids in foods on the Danish market

    Bysted, Anette; Mikkelsen, Aase Ærendahl; Leth, Torben

    2009-01-01

    , in 68% of the products (e.g. sweets, cakes and cookies as well as fast food such as pie and tortilla), IP-TFA were mainly substituted with saturated fatty acids (SFA). In some cases, the SFA source was coconut fat, whereas in other products, palm oil was added instead of partially hydrogenated oils...

  7. A UNIFORM SUBSTITUTE DEMAND MODEL WITH VARYING COEFFICIENTS

    Mark G. Brown; Lee, Jonq-Ying

    2000-01-01

    This study extends Barten's synthetic demand modeling approach to increase the flexibility of the uniform substitute specification of the Rotterdam demand system. Marginal propensities to consume (MPC) vary with budget shares and Slutsky coefficients are defined in terms of varying MPCs. An application of the model to orange-juice products shows that the pattern of income and price elasticities over time is much different than when MPCs are restricted to be constant.

  8. Rapid formation of β-allyl substituted isotetronic acid derivatives via Claisen rearrangement using a microfludic device

    Xia Ping Ma; Zhi Ming Li; Quan Rui Wang

    2011-01-01

    The thermal Claisen rearrangement of O-allyl substituted isotetronic acids 1 was successfully carried out within a glass microreactor operated with temperature at 150 ℃ and a flow rate of 1 mL/h. The strategy provides an efficient alternative way to β-allyl substituted isotetronic acid derivatives 2 in high yields with much accelerated reaction speed.

  9. Synthesis and Structural Characterization of 1- and 2-Substituted Indazoles: Ester and Carboxylic Acid Derivatives

    Isabel Bento; Teresa Duarte, M.; M. João M. Curto; Inês F. Antunes; Hélène Ramos; Fátima C. Teixeira

    2006-01-01

    A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2)nCO2R of different lengths (n = 0-6, 9, 10) are described.Nucleophilic substitution reactions on halo esters (X(CH2)nCO2R) by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomerpredominates. Basic hydrolysis of the ester derivatives allowed the synthesis of thecorresponding indazole carboxylic acids. All compounds were fully characterised bymultin...

  10. Natural derivatives of diphenolic acid as substitutes for bisphenol-A

    Ertl, Johanna; Cerri, Elisa; Rizzuto, Matteo; Caretti, Daniele

    2014-05-01

    Diphenolic acid had been originally used in the first epoxy resins and was later on forgotten as it was substituted by the cheaper bisphenol A. But in the recent years major health concerns have been raised as bisphenol A has a pseudo-hormonal effect on the body, playing the role of estrogen it can cause a severe impact on the organism, especially in males. Moreover it is produced from acetone and phenol, both from fossil, and thus limited resources. On the contrary, diphenolic acid is synthesized from levulinic acid and phenol. Levulinic acid being directly produced by hydrolysis of biomass. By substituting the fossil phenol with natural phenols from lignin or plant extraction we are able to synthesize a fully renewable substitute for bisphenol A. The reactions to yield an epoxy resin have been examined and the reactivity with epichlorohydrin is satisfying. Moreover, some of the derivatives of diphenolic acid have interesting curing properties and preliminary results show excellent properties of the cured resin, including thermal stability and pencil hardness.

  11. Dielectric Relaxation Studies of Alkylacrylates with Ortho-Substituted Benzoic acids in 1, 4 - Dioxane

    F. Liakath Ali Khan*,1

    2014-07-01

    Full Text Available Dielectric absorption studies of Hydrogen bonded complexes of alkyl acrylates with ortho substituted benzoic acid (2 - Fluro benzoic acid, 2 - Iodo benzoic acid, 2 - Chloro benzoic acid, 2 - Bromo benzoic acid, and 2 - Nitro benzoic acid were studied at microwave frequency 9.43GHz in dilute solution of 1,4 - Dioxane at room temperature. Different dielectric parameters like dielectric constant ( and dielectric loss ( at microwave frequency, and static dielectric constant (0 and dielectric constant ( at optical frequency were determined. The validity of the single frequency equation proposed by Higasi et.al., for multiple relaxation time (1 was found to be a function of the hydrogen bonding strength in benzoic acid, whereas the group rotation relaxation time (2 was a function of the steric interaction of proton donor. The relaxation time was maximum at 1:1 molar ratios of alky acrylates with ortho substituted benzoic acid.

  12. Phenylalanine Aminomutase-Catalyzed Addition of Ammonia to Substituted Cinnamic Acids : a Route to Enantiopure alpha- and beta-Amino Acids

    Szymanski, Wiktor; Wu, Bian; Weiner, Barbara; Wildeman, Stefaan de; Feringa, Ben L.; Janssen, Dick B.

    2009-01-01

    An approach is described for the synthesis of aromatic alpha- and beta-amino acids that Uses phenylalanine aminomutase to catalyze a highly enantioselective addition of ammonia to substituted cinnamic acids. The reaction has a broad scope and yields Substituted alpha- and beta-phenylalanines with ex

  13. Mechanical Models of the Dynamics of Vitreous Substitutes

    Krystyna Isakova

    2014-01-01

    Full Text Available We discuss some aspects of the fluid dynamics of vitreous substitutes in the vitreous chamber, focussing on the flow induced by rotations of the eye bulb. We use simple, yet not trivial, theoretical models to highlight mechanical concepts that are relevant to understand the dynamics of vitreous substitutes and also to identify ideal properties for vitreous replacement fluids. We first recall results by previous authors, showing that the maximum shear stress on the retina grows with increasing viscosity of the fluid up to a saturation value. We then investigate how the wall shear stress changes if a thin layer of aqueous humour is present in the vitreous chamber, separating the retina from the vitreous replacement fluid. The theoretical predictions show that the existence of a thin layer of aqueous is sufficient to substantially decrease the shear stress on the retina. We finally discuss a theoretical model that predicts the stability conditions of the interface between the aqueous and a vitreous substitute. We discuss the implications of this model to understand the mechanisms leading to the formation of emulsion in the vitreous chamber, showing that instability of the interface is possible in a range of parameters relevant for the human eye.

  14. Omega-3 Fatty Acid Formulations in Cardiovascular Disease: Dietary Supplements are Not Substitutes for Prescription Products.

    Fialkow, Jonathan

    2016-08-01

    Omega-3 fatty acid products are available as prescription formulations (icosapent ethyl, omega-3-acid ethyl esters, omega-3-acid ethyl esters A, omega-3-carboxylic acids) and dietary supplements (predominantly fish oils). Most dietary supplements and all but one prescription formulation contain mixtures of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Products containing both EPA and DHA may raise low-density lipoprotein cholesterol (LDL-C). In clinical trials, the EPA-only prescription product, icosapent ethyl, did not raise LDL-C compared with placebo. To correct a common misconception, it is important to note that omega-3 fatty acid dietary supplements are not US FDA-approved over-the-counter drugs and are not required to demonstrate safety and efficacy prior to marketing. Conversely, prescription products are supported by extensive clinical safety and efficacy investigations required for FDA approval and have active and ongoing safety monitoring programs. While omega-3 fatty acid dietary supplements may have a place in the supplementation of diet, they generally contain lower levels of EPA and DHA than prescription products and are not approved or intended to treat disease. Perhaps due to the lack of regulation of dietary supplements, EPA and DHA levels may vary widely within and between brands, and products may also contain unwanted cholesterol or fats or potentially harmful components, including toxins and oxidized fatty acids. Accordingly, omega-3 fatty acid dietary supplements should not be substituted for prescription products. Similarly, prescription products containing DHA and EPA should not be substituted for the EPA-only prescription product, as DHA may raise LDL-C and thereby complicate the management of patients with dyslipidemia. PMID:27138439

  15. Synthesis and Structural Characterization of 1- and 2-Substituted Indazoles: Ester and Carboxylic Acid Derivatives

    Isabel Bento

    2006-11-01

    Full Text Available A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2nCO2R of different lengths (n = 0-6, 9, 10 are described.Nucleophilic substitution reactions on halo esters (X(CH2nCO2R by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomerpredominates. Basic hydrolysis of the ester derivatives allowed the synthesis of thecorresponding indazole carboxylic acids. All compounds were fully characterised bymultinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; theNMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers.The molecular structure of indazol-2-yl-acetic acid (5b was determined by X-raydiffraction, which shows a supramolecular architecture involving O2-H...N1intermolecular hydrogen bonds.

  16. Novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids as calcium activated chloride channel inhibitors

    Kumar, Satish; Namkung, Wan; A S Verkman; Sharma, Pawan K

    2012-01-01

    Transmembrane protein 16A (TMEM16A) channels are recently discovered membrane proteins that functions as a calcium activated chloride channel (CaCC). CaCCs are major regulators of various physiological processes, such as sensory transduction, epithelial secretion, smooth muscle contraction and oocyte fertilization. Thirty novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids (B01–B30) were synthesized and evaluated for their TMEM16A inhibitory activity by using short circuit curre...

  17. Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity

    Katarina Kralova; Jiri Kunes; Miroslav Miletin; Martin Dolezal

    2002-01-01

    Condensation of 6-chloro-, 5-tert-butyl- or 6-chloro-5-tert-butylpyrazine-2-carboxylic acid chloride with ring substituted anilines yielded a series of amides, which were tested for their in vitro antimycobacterial, antifungal and photosynthesis-inhibiting activities. The highest antituberculotic activity (72% inhibition) against Mycobacterium tuberculosis and the highest lipophilicity (log P = 6.85) were shown by the 3,5-bistrifluoromethylphenyl amide of 5-tert-butyl-6-chloropyrazine-2-carbo...

  18. Lewis acid free high speed synthesis of nimesulide-based novel N-substituted cyclic imides

    The first synthesis of nimesulide-based novel cyclic imides has been accomplished via the reaction of an amine prepared from nimesulide with appropriate anhydrides in the presence of sodium acetate. Using this process a variety of N-substituted cyclic imides was prepared in good yields in glacial acetic acid. Some of the compounds synthesized showed anti-inflammatory activities when tested in vivo. (author)

  19. Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses

    Harvey, William T.; Benton, Donald J.; Gregory, Victoria; Hall, James P. J.; Daniels, Rodney S.; Bedford, Trevor; Haydon, Daniel T.; Hay, Alan J.; McCauley, John W.; Reeve, Richard

    2016-01-01

    Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. PMID:27057693

  20. Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains

    Branislava Gemovic

    2013-01-01

    Full Text Available There are more than 500 amino acid substitutions in each human genome, and bioinformatics tools irreplaceably contribute to determination of their functional effects. We have developed feature-based algorithm for the detection of mutations outside conserved functional domains (CFDs and compared its classification efficacy with the most commonly used phylogeny-based tools, PolyPhen-2 and SIFT. The new algorithm is based on the informational spectrum method (ISM, a feature-based technique, and statistical analysis. Our dataset contained neutral polymorphisms and mutations associated with myeloid malignancies from epigenetic regulators ASXL1, DNMT3A, EZH2, and TET2. PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than expected, with especially low sensitivity. On the other hand, only ISM algorithm showed statistically significant classification of these sequences. It outperformed PolyPhen-2 and SIFT by 15% and 13%, respectively. These results suggest that feature-based methods, like ISM, are more suitable for the classification of amino acid substitutions outside CFDs than phylogeny-based tools.

  1. Computational models of the single substitutional nitrogen atom in diamond

    The single substitutional nitrogen atom in diamond is apparently a very simple defect in a very simple elemental solid. It has been modelled by a range of computational models, few of which either agree with each other, or with the experimental data on the defect. If the computational models of less well understood defects in this and more complex materials are to be reliable, we should understand why the discrepancies arise and how they can be avoided in future modelling. This paper presents an all-electron, augmented plane-wave (APW) density functional theory (DFT) calculation using the modern APW with local orbitals full potential periodic approximation. This is compared to DFT, finite cluster pseudopotential calculations and a semi-empirical Hartree-Fock model. Comparisons between the results of these and previous models allow us to discuss the reliability of computational methods of this and similar defects

  2. Electrochemical oxidation of substituted benzylamines in aquo-acetic acid medium: substituent and solvent effects

    A Thirumoorthi; K P Elango

    2007-07-01

    Electrochemical oxidation of nine para- and meta-substituted benzylamines in varying mole fractions of acetic acid in water has been investigated in the presence of 0.1 M sulphuric acid as supporting electrolyte. The oxidation potentials correlate well with Hammett’s substituent constants affording negative reaction constants. The correlation of potential values with macroscopic solvent parameters is non-linear suggesting that the operation of both specific and non-specific solvent-solvent-solute interaction mechanisms. Multiple correlation analysis of the experimental data with Kamlet-Taft solvatochromic parameters is employed.

  3. Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors

    Bräuner-Osborne, Hans; Nielsen, B; Stensbøl, T B; Johansen, T N; Skjaerbaek, N; Krogsgaard-Larsen, P

    The pharmacology of (2S,4R)-4-methylglutamic acid, (2S,4S)-4-methylglutamic acid and (S)- and (R)-4-methyleneglutamic acids (obtained in high chemical and enantiomeric purity from racemic 4-methyleneglutamic acid by chiral HPLC using a Crownpak CR(+) column), was examined in binding experiments u...

  4. Phenological modelling: Can spatial data substitute temporal data?

    Jochner, Susanne; Caffarra, Amelia; Menzel, Annette

    2014-05-01

    Not only long-term information, but also urbanisation gradients may be supportive to assess phenological responses to global warming. A substitution of phenological data collected over a longer period with data collected over a spatial gradient might be appropriate if plant phenology responds to climate change over time similarly as climate variability over space. However, the inherent methodological, spatial and temporal peculiarities of different data sources could hinder generalisations. We investigated whether phenological responses of birch (Betula pendula Roth) assessed by temperature variations are comparable over time and space and whether spatially calibrated models can predict long-term phenological data adequately. Therefore, we used flowering data sampled along urbanisation gradients in Germany in 2010 and 2011 and long-term data (1991-2010) in Bavaria. These data was explored using linear regression models based on mean temperature as well as process-based models (DORMPHOT model) incorporating forcing and chilling temperatures and photoperiod. A time-for-space substitution might not always be suitable since models calibrated on spatial data were only found to be useful to predict spatial data, but not to predict long-term data. This finding was also confirmed by a comparison of temperature response rates. The temperature response derived from spatial data (-4.4 days/°C) was significantly higher than the response calculated from the long-term data (-1.9 days/°C). Furthermore, the predictive performance of the linear model was comparable to that of the DORMPHOT model. A possible explanation might be that the process-based DORMPHOT model also includes the description of the responses of trees to chilling and photoperiod and to their interaction, but there is not enough information in only two study years to adequately model this response. Consequently, models calibrated on spatial data cannot necessarily reflect changes that occur in phenological

  5. Synthesis of novel N1-substituted bicyclic pyrazole amino acids and evaluation of their interaction with glutamate receptors

    Conti, Paola; Grazioso, Giovanni; di Ventimiglia, Samuele Joppolo;

    2005-01-01

    N1-substituted bicyclic pyrazole amino acids (S)-9a-9c and (R)-9a-9c, which are conformationally constrained analogues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested for activity at ionotropic and metabotropic glutamate receptors...

  6. Co-metabolic formation of substituted phenylacetic acids by styrene-degrading bacteria

    Michel Oelschlägel

    2015-06-01

    The styrene-degrading strains Rhodococcus opacus 1CP, Pseudomonas fluorescens ST, and the novel isolates Sphingopyxis sp. Kp5.2 and Gordonia sp. CWB2 were investigated with respect to their applicability to co-metabolically produce substituted phenylacetic acids. Isolates were found to differ significantly in substrate tolerance and biotransformation yields. Especially, P. fluorescens ST was identified as a promising candidate for the production of several phenylacetic acids. The biotransformation of 4-chlorostyrene with cells of strain ST was shown to be stable over a period of more than 200 days and yielded about 38 mmolproduct gcelldryweight−1 after nearly 350 days. Moreover, 4-chloro-α-methylstyrene was predominantly converted to the (S-enantiomer of the acid with 40% enantiomeric excess.

  7. Accelerated hydrolysis of substituted cellulose for potential biofuel production: kinetic study and modeling.

    Mu, Bingnan; Xu, Helan; Yang, Yiqi

    2015-11-01

    In this work, kinetics of substitution accelerated cellulose hydrolysis with multiple reaction stages was investigated to lay foundation for mechanism study and molecular design of substituting compounds. High-efficiency hydrolysis of cellulose is critical for cellulose-based bioethanol production. It is known that, substitution could substantially decrease activation energy and increase reaction rate of acidic hydrolysis of glycosidic bonds in cellulose. However, reaction kinetics and mechanism of the accelerated hydrolysis were not fully revealed. In this research, it was proved that substitution therefore accelerated hydrolysis only occurred in amorphous regions of cellulose fibers, and was a process with multiple reaction stages. With molar ratio of substitution less than 1%, the overall hydrolysis rate could be increased for around 10 times. We also quantified the relationship between the hydrolysis rate of individual reaction stage and its major influences, including molar ratio of substitution, activation energy of acidic hydrolysis, pH and temperature. PMID:26253917

  8. Amino acid esters substituted phosphorylated emtricitabine and didanosine derivatives as antiviral and anticancer agents.

    Sekhar, Kuruva Chandra; Janardhan, Avilala; Kumar, Yellapu Nanda; Narasimha, Golla; Raju, Chamarthi Naga; Ghosh, S K

    2014-07-01

    Owing to the promising antiviral activity of amino acid ester-substituted phosphorylated nucleosides in the present study, a series of phosphorylated derivatives of emtricitabine and didanosine substituted with bioactive amino acid esters at P-atom were synthesized. Initially, molecular docking studies were screened to predict their molecular interactions with hemagglutinin-neuraminidase protein of Newcastle disease virus and E2 protein of human papillomavirus. The title compounds were screened for their antiviral ability against Newcastle disease virus (NDV) by their in ovo study in embryonated chicken eggs. Compounds 5g and 9c exposed well mode of interactions with HN protein and also exhibited potential growth of NDV inhibition. The remaining compounds exhibited better growth of NDV inhibition than their parent molecules, i.e., emtricitabine (FTC) and didanosine (ddI). In addition, the in vitro anticancer activity of all the title compounds were screenedagainst HeLa cell lines at 10 and 100 μg/mL concentrations. The compounds 5g and 9c showed an effective anticancer activity than that of the remaining title compounds with IC50 values of 40 and 60 μg/mL, respectively. The present in silico and in ovo antiviral and in vitro anticancer results of the title compounds are suggesting that the amino acid ester-substituted phosphorylated FTC and ddI derivatives, especially 5g and 9c, can be used as NDV inhibitors and anticancer agents for the control and management of viral diseases with cancerous condition. PMID:24789416

  9. Stability constants of mixed ligand complexes of lanthanide(III) and yttrium(III) with complexone and substituted salicylic acids

    Salicylic acid and substituted salicylic acids are potential antimicrobial agents. Binary complexes of salicylic acid and its substituted derivatives with lanthanide(III) and yttrium(III) metal ions have been reported. There are reports on the ternary metal complexing equilibria with some lanthanide(III) and yttrium(III) metal ions involving aminopolycarboxylic acid as one ligand and salicylic acid (SA) and other related compounds as the second ligands. Ethylene glycol bis(2-aminoethylether)- N, N, N', N'-tetraacetic acid (EGTA) is an important member of aminopolycarboxylic acid and finds many applications in medicine and biology. Recently, few ternary complexes have been reported using EGTA as ligand. In view of biological importance of simple and mixed ligand complexes EGTA, SA and DNSA (3,5-dinitrosalicylic acid), a systematic study has been undertaken for the determination of stability constant and the results are reported. (author). 6 refs., 1 fig., 2 tabs

  10. Controlling electron emission from the photoactive yellow protein chromophore by substitution at the coumaric acid group.

    Parkes, Michael A; Phillips, Ciara; Porter, Michael J; Fielding, Helen H

    2016-04-21

    Understanding how the interactions between a chromophore and its surrounding protein control the function of a photoactive protein remains a challenge. Here, we present the results of photoelectron spectroscopy measurements and quantum chemistry calculations aimed at investigating how substitution at the coumaryl tail of the photoactive yellow protein chromophore controls competing relaxation pathways following photoexcitation of isolated chromophores in the gas phase with ultraviolet light in the range 350-315 nm. The photoelectron spectra are dominated by electrons resulting from direct detachment and fast detachment from the 2(1)ππ* state but also have a low electron kinetic energy component arising from autodetachment from lower lying electronically excited states or thermionic emission from the electronic ground state. We find that substituting the hydrogen atom of the carboxylic acid group with a methyl group lowers the threshold for electron detachment but has very little effect on the competition between the different relaxation pathways, whereas substituting with a thioester group raises the threshold for electron detachment and appears to 'turn off' the competing electron emission processes from lower lying electronically excited states. This has potential implications in terms of tuning the light-induced electron donor properties of photoactive yellow protein. PMID:27025529

  11. Effect of amino acid substitution in the hydrophobic face of amphiphilic peptides on membrane curvature and perturbation: N-terminal helix derived from adenovirus internal protein VI as a model.

    Murayama, Tomo; Pujals, Sílvia; Hirose, Hisaaki; Nakase, Ikuhiko; Futaki, Shiroh

    2016-11-01

    The N-terminal amphipathic helical segment of adenovirus internal protein VI (AdVpVI) plays a critical role in viral infection. Here, we report that the peptide segment corresponding to AdVpVI (positions 33-55) can induce positive membrane curvature together with membrane perturbation. The enhanced perturbation ability of the peptide was observed for membranes containing negatively charged phospholipids. Based on the liposome leakage assay, substitution of leucine at position 40 to other aliphatic (isoleucine) and aromatic (phenylalanine and tryptophan) residues yielded a similar degree of membrane perturbation by the peptides, which was considerably diminished by the substitution to glutamine. Further studies using the wild-type AdVpVI (33-55) (WT) and phenylalanine-substituted peptides (L40F) demonstrated that both peptides have positive membrane-curvature-inducing ability. These peptides showed higher binding affinity to 50-nm large unilamellar vesicles (LUVs) than to 200-nm LUVs. However, no enhanced perturbation by these peptides was observed for 50-nm LUVs compared to 200-nm LUVs, suggesting that both the original membrane curvature and the additional strain due to peptide insertion affect the membrane perturbation ability of these peptides. In the case of L40F, this peptide rather had a lower membrane perturbation ability for 50-nm LUVs than for 200-nm LUVs, which can be attributed to possible shallower binding of L40F on membranes. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 430-439, 2016. PMID:27271816

  12. Synthesis, Characterization, and Antifungal Activity of Phenylpyrrole-Substituted Tetramic Acids Bearing Carbonates.

    Xu, Wen-Qin; Chen, Min; Wang, Kun-Yao; Ren, Zheng-Jiao; Lu, Ai-Min; Yang, Chun-Long

    2016-01-01

    For the aim of discovering new fungicide, a series of phenylpyrrole-substituted tetramic acid derivatives bearing carbonates 6a-q were designed and synthesized via 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(phenylamino)butanoic acids 4a-k and the cyclized products 1',3,4,5'-tetrahydro-[2,3'-bipyrrolylidene]-2',4',5(1H)-triones 5a-k. The compounds were characterized using IR, ¹H- and (13)C-NMR spectroscopy, mass spectrometry (EI-MS), and elemental analysis. The structure of 6b was confirmed by X-ray diffraction crystallography. The title compounds 6a-q were bioassayed in vitro against the phytopathogenic fungi Fusarium graminearum, Botrytis cinerea and Rhizoctonia solani at a concentration of 100 μg/mL, respectively. Most compounds displayed good inhibitory activity. PMID:27007370

  13. Stearic acid: a possible substitute for trans fatty acids from industrial origin

    Tavella, Marcelo

    2011-06-01

    Full Text Available Trans isomers, contained in partially hydrogenated oils, which are used in the food industry, have been questioned and nowadays trends are heading towards reducing their consumption. The food industry is facing a dilemma, since in order to remove trans fatty acids, hydrogenated fats should be eliminated and replaced by fats rich in saturated fatty acids. Scientific research has shown that saturated fatty acids have negative effects on the lipid profile and its consumption is associated with a higher cardiovascular risk. Therefore it is recommended to avoid their consumption. Nevertheless, not all fatty acids behave in the same way, with stearic acid (18:0 the exception. Stearic acid has a low level of intestinal absorption and its intake does not negatively modify the lipid profile. For this reason, it is considered a “neutral” fatty acid with regard to cardiovascular health. B-100 apolipoprotein, whose levels determine plasma VLDL and LDL concentration (triglycerides and cholesterol carriers, respectively, is not modified by diets which provide up to 7% of the energy as stearic acid. Markers of cardiovascular risk, such as activation of platelet aggregation factors or C-reactive protein levels, are not modified by diets providing stearic acid, as occurs with other saturated fatty acids. The confirmation of the “neutral” effect of stearic acid represents a perspective for the development of fats with high contents of this fatty acid to replace hydrogenated fats containing trans isomers. The present review discusses these aspects.Los isómeros trans que contienen los aceites parcialmente hidrogenados de origen industrial, han sido cuestionados y la recomendación es reducir su consumo. La industria de alimentos se enfrenta a un dilema, ya que para disminuir los isómeros trans debe reducir los aceites parcialmente hidrogenados y reemplazarlos por grasas ricas en ácidos grasos saturados. La investigación ha demostrado que los

  14. Acid-base thermochemistry of gaseous oxygen and sulfur substituted amino acids (Ser, Thr, Cys, Met)

    Riffet, Vanessa; Frison, Gilles; Bouchoux, Guy

    2011-01-01

    Acid-base thermochemistry of isolated amino acids containing oxygen or sulfur in their side chain (serine, threonine, cysteine and methionine) have been examined by quantum chemical computations. Density functional theory (DFT) was used, with B3LYP, B97-D and M06-2X functionals using the 6-31+G(d,p) basis set for geometry optimizations and the larger 6-311++G(3df,2p) basis set for energy computations. Composite methods CBS-QB3, G3B3, G4MP2 and G4 were applied to large sets of neutral, protona...

  15. Preparation of a nitro-substituted tris(indolyl)methane modified silica in deep eutectic solvents for solid-phase extraction of organic acids.

    Wang, Na; Wang, Jiamin; Liao, Yuan; Shao, Shijun

    2016-05-01

    A new sorbent for solid-phase extraction was synthesized by chemical immobilization of nitro-substituted tris(indolyl)methane on silica in new and green deep eutectic solvents. Elemental analysis results indicated that deep eutectic solvents could be an alternative to the traditional solvents in preparing nitro-substituted tris(indolyl)methane modified silica. Coupled with high performance liquid chromatography, the extraction performance of the sorbent was evaluated by using four organic acids as model analytes. The rebinding experiments results showed that the nitro-substituted tris(indolyl)methane modified silica sorbent had a good adsorption capacity towards the selected organic acids. Under the appropriate experimental conditions, good precision and wide linear ranges with coefficient of determination (R(2)) of higher than 0.9957 were obtained, and the limits of detection were in the range of 0.50-2.0μgL(-1) for the organic acids tested. The developed solid-phase extraction-high performance liquid chromatography-diode array detection (SPE-HPLC-DAD) method was successfully applied for the determination of organic acids in two drinking samples with recoveries ranging from 76.7% to 110.0% and 67.7% to 104.0% for all the selected organic acids, respectively. PMID:26946003

  16. Iodine 125-phenylpentadecanoic acid and its beta-methyl substitute metabolism in cultured mouse embryonal myocytes

    Iodine-labelled fatty acids have been proposed as new tracers of cardiac metabolisms. However, it is not clear how these tracers would reflect the intracellular metabolism. Therefore, we measured the uptake and release of iodine 125-labelled phenylpentadecanoic acid (IPPA), its β-methyl substitute (BMIPP) and 201Tl in cultured myocytes of mouse embryos, and compared these values to intracellular adenosine triphosphate (ATP) content after metabolic inhibitions of oxidative phosphorylation by sodium cyanide (CN), glycolysis by 2-deoxyglucose (2-DG) or fatty acid β-oxidation by lactate. The uptake and release of BMIPP was not changed by any inhibitors suggesting BMIPP would not be metabolized in the myocytes. The uptake of IPPA was significantly reduced by 2DG and 60-80% of IPPA was metabolized to hydrophilic catabolites. The correlation of BMIPP and IPPA uptake to intracellular ATP content were high (r=0.89, p201Tl to ATP values (r=0.53, n.s.). These results suggested that iodine-labelled fatty acids could be used as better tracers of myocardial metabolism than 201Tl. (author)

  17. Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity

    Katarina Kralova

    2002-03-01

    Full Text Available Condensation of 6-chloro-, 5-tert-butyl- or 6-chloro-5-tert-butylpyrazine-2-carboxylic acid chloride with ring substituted anilines yielded a series of amides, which were tested for their in vitro antimycobacterial, antifungal and photosynthesis-inhibiting activities. The highest antituberculotic activity (72% inhibition against Mycobacterium tuberculosis and the highest lipophilicity (log P = 6.85 were shown by the 3,5-bistrifluoromethylphenyl amide of 5-tert-butyl-6-chloropyrazine-2-carboxylic acid (2o. The 3-methylphenyl amides of 6-chloro- and 5-tert-butyl-6-chloro-pyrazine-2-carboxylic acid (2d and 2f exhibited only a poor in vitro antifungal effect (MIC = 31.25-500 μmol·dm-3 against all strains tested, although the latter was the most active antialgal compound (IC50 = 0.063 mmol·dm-3. The most active inhibitor of oxygen evolution rate in spinach chloroplasts was the (3,5-bis-trifluoromethylphenylamide of 6-chloropyrazine-2-carboxylic acid (2m, IC50 = 0.026 mmol·dm-3.

  18. Acid-base thermochemistry of gaseous oxygen and sulfur substituted amino acids (Ser, Thr, Cys, Met).

    Riffet, Vanessa; Frison, Gilles; Bouchoux, Guy

    2011-11-01

    Acid-base thermochemistry of isolated amino acids containing oxygen or sulfur in their side chain (serine, threonine, cysteine and methionine) have been examined by quantum chemical computations. Density functional theory (DFT) was used, with B3LYP, B97-D and M06-2X functionals using the 6-31+G(d,p) basis set for geometry optimizations and the larger 6-311++G(3df,2p) basis set for energy computations. Composite methods CBS-QB3, G3B3, G4MP2 and G4 were applied to large sets of neutral, protonated and deprotonated conformers. Conformational analysis of these species, based on chemical approach and AMOEBA force field calculations, has been used to identify the lowest energy conformers and to estimate the population of conformers expected to be present at thermal equilibrium at 298 K. It is observed that G4, G4MP2, G3B3, CBS-QB3 composite methods and M06-2X DFT lead to similar conformer energies. Thermochemical parameters have been computed using either the most stable conformers or equilibrium populations of conformers. Comparison of experimental and theoretical proton affinities and Δ(acid)H shows that the G4 method provides the better agreement with deviations of less than 1.5 kJ mol(-1). From this point of view, a set of evaluated thermochemical quantities for serine, threonine, cysteine and methionine may be proposed: PA = 912, 919, 903, 938; GB = 878, 886, 870, 899; Δ(acid)H = 1393, 1391, 1396, 1411; Δ(acid)G = 1363, 1362, 1367, 1382 kJ mol(-1). This study also confirms that a non-negligible ΔpS° is associated with protonation of methionine and that the most acidic hydrogen of cysteine in the gas phase is that of the SH group. In several instances new conformers were identified thus suggesting a re-examination of several IRMPD spectra. PMID:21947236

  19. Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase.

    Buček, Aleš; Matoušková, Petra; Vogel, Heiko; Šebesta, Petr; Jahn, Ullrich; Weißflog, Jerrit; Svatoš, Aleš; Pichová, Iva

    2015-10-13

    For sexual communication, moths primarily use blends of fatty acid derivatives containing one or more double bonds in various positions and configurations, called sex pheromones (SPs). To study the molecular basis of novel SP component (SPC) acquisition, we used the tobacco hornworm (Manduca sexta), which uses a blend of mono-, di-, and uncommon triunsaturated fatty acid (3UFA) derivatives as SP. We identified pheromone-biosynthetic fatty acid desaturases (FADs) MsexD3, MsexD5, and MsexD6 abundantly expressed in the M. sexta female pheromone gland. Their functional characterization and in vivo application of FAD substrates indicated that MsexD3 and MsexD5 biosynthesize 3UFAs via E/Z14 desaturation from diunsaturated fatty acids produced by previously characterized Z11-desaturase/conjugase MsexD2. Site-directed mutagenesis of sequentially highly similar MsexD3 and MsexD2 demonstrated that swapping of a single amino acid in the fatty acyl substrate binding tunnel introduces E/Z14-desaturase specificity to mutated MsexD2. Reconstruction of FAD gene phylogeny indicates that MsexD3 was recruited for biosynthesis of 3UFA SPCs in M. sexta lineage via gene duplication and neofunctionalization, whereas MsexD5 representing an alternative 3UFA-producing FAD has been acquired via activation of a presumably inactive ancestral MsexD5. Our results demonstrate that a change as small as a single amino acid substitution in a FAD enzyme might result in the acquisition of new SP compounds. PMID:26417103

  20. An amino acid substitution (L925V associated with resistance to pyrethroids in Varroa destructor.

    Joel González-Cabrera

    Full Text Available The Varroa mite, Varroa destructor, is an important pest of honeybees and has played a prominent role in the decline in bee colony numbers over recent years. Although pyrethroids such as tau-fluvalinate and flumethrin can be highly effective in removing the mites from hives, their intensive use has led to many reports of resistance. To investigate the mechanism of resistance in UK Varroa samples, the transmembrane domain regions of the V. destructor voltage-gated sodium channel (the main target site for pyrethroids were PCR amplified and sequenced from pyrethroid treated/untreated mites collected at several locations in Central/Southern England. A novel amino acid substitution, L925V, was identified that maps to a known hot spot for resistance within the domain IIS5 helix of the channel protein; a region that has also been proposed to form part of the pyrethroid binding site. Using a high throughput diagnostic assay capable of detecting the mutation in individual mites, the L925V substitution was found to correlate well with resistance, being present in all mites that had survived tau-fluvalinate treatment but in only 8 % of control, untreated samples. The potential for using this assay to detect and manage resistance in Varroa-infected hives is discussed.

  1. Flash vacuum pyrolysis of methoxy-substituted lignin model compounds.

    Britt, P F; Buchanan, A C; Cooney, M J; Martineau, D R

    2000-03-10

    The flash vacuum pyrolysis (FVP) of methoxy-substituted beta-O-4 lignin model compounds has been studied at 500 degrees C to provide mechanistic insight into the primary reaction pathways that occur under conditions of fast pyrolysis. FVP of PhCH(2)CH(2)OPh (PPE), a model of the dominant beta-O-4 linkage in lignin, proceeds by C-O and C-C cleavage, in a 37:1 ratio, to produce styrene plus phenol as the dominant products and minor amounts of toluene, bibenzyl, and benzaldehyde. From the deuterium isotope effect in the FVP of PhCD(2)CH(2)OPh, it was shown that C-O cleavage occurs by homolysis and by 1,2-elimination in a ratio of 1.4:1, respectively. Methoxy substituents enhance the homolysis of the beta-O-4 linkage, relative to PPE, in o-CH(3)O-C(6)H(4)OCH(2)CH(2)Ph (o-CH(3)O-PPE) and (o-CH(3)O)(2)-C(6)H(3)OCH(2)CH(2)Ph ((o-CH(3)O)(2)-PPE) by a factor of 7.4 and 21, respectively. The methoxy-substituted phenoxy radicals undergo a complex series of reactions, which are dominated by 1,5-, 1,6-, and 1,4-intramolecular hydrogen abstraction, rearrangement, and beta-scission reactions. In the FVP of o-CH(3)O-PPE, the dominant product, salicylaldehyde, forms from the methoxyphenoxy radical by a 1,5-hydrogen shift to form 2-hydroxyphenoxymethyl radical, 1,2-phenyl shift, and beta-scission of a hydrogen atom. The 2-hydroxyphenoxymethyl radical can also cleave to form formaldehyde and phenol in which the ratio of 1, 2-phenyl shift to beta-scission is ca. 4:1. In the FVP of o-CH(3)O-PPE and (o-CH(3)O)(2)-PPE, products (ca. 20 mol %) are also formed by C-O homolysis of the methoxy group. The resulting phenoxy radicals undergo 1,5- and 1,6-hydrogen shifts in a ratio of ca. 2:1 to the aliphatic or benzylic carbon, respectively, of the phenethyl chain. In the FVP of (o-CH(3)O)(2)-PPE, o-cresol was the dominant product. It was formed by decomposition of 2-hydroxy-3-hydroxymethylbenzaldehyde and 2-hydroxybenzyl alcohol, which are formed from a complex series of reactions from the 2

  2. Radioimmunoassay for anileridine, meperidine, and other N-substituted phenylpiperidine carboxylic acid esters

    Van Vunakis, H.; Freeman, D.S.; Gjika, H.B.

    1975-10-01

    Antibodies that bind an /sup 125/I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50 percent inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 10/sup 4/, major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay.

  3. Radioimmunoassay for anileridine, meperidine, and other N-substituted phenylpiperidine carboxylic acid esters

    Antibodies that bind an 125I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50 percent inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 104, major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay

  4. [Influence of the degree of substitution on the absorptivity of acidic carboxymethyl cellulose in the form of nonwoven fabric].

    Masteiková, Ruta; Vinklárková, Lenka; Muselík, Jan; Vetchý, David; Bernatoniene, Jurga; Sopuch, Tomáš

    2013-04-01

    Modern wound treatment is based on the creation of moist wound environment which accelerates healing. For these purposes some devices and materials may be used, including carboxymethyl cellulose (CMC). Wound dressings currently available on the market contain CMC in the form of sodium salt. CMC in the acidic form has not been used in wound healing therapy yet. Likewise, there are only a few papers describing the acidic CMC preparation and properties, which are inter alia dependent on the degree of substitution (DS). Therefore, the aim of the study was to evaluate the influence of DS on absorptivity, which is one of the main features of dressings after application on the wound. Samples with DS from 0.1 to 0.45 were examined using five media: purified water, normal saline, buffer solution with pH 7.4, physiological buffer solution with pH 7.2, and solution A. Absorptivity was evaluated using a model wound created by us. It has been found that from the viewpoint of absorptivity the optimal DS of acidic CMC in the form of nonwoven fabric lies in the range from 0.25 to 0.35. Below or above these values the absorptivity is worse. PMID:23822574

  5. Computational Modeling of Degradation of Substituted Benzyltrimethyl Ammonium: Preprint

    Long, H.; Pivovar, B. S.

    2014-09-01

    The degradation of cations on the alkaline exchange membranes is the major challenge for alkaline membrane fuel cells. In this paper, we investigated the degradation barriers by density functional theory for substituted benzyltrimethyl ammonium (BTMA+) cations, which is one of the most commonly used cations for alkaline exchange membranes. We found that substituted cations with electron-releasing substituent groups at meta-position of the benzyl ring could result in improved degradation barriers. However, after investigating more than thirty substituted BTMA+ cations with ten different substituent groups, the largest improvement of degradation barriers is only 1.6 kcal/mol. This implies that the lifetime of alkaline membrane fuel cells could increase from a few months to a few years by using substituted BTMA+ cations, an encouraging but still limited improvement for real-world applications.

  6. Modelling substitution between domestic and outbound tourism in Australia: a system-of-equations approach

    Athanasopoulos, George; Deng, Minfeng; Li, Gang

    2014-01-01

    This study uses a system-of-equations approach to model the substitution relationship between Australian domestic and outbound tourism demand. A new price variable based on relative ratios of purchasing power parity index is developed for the substitution analysis. Short-run demand elasticities are calculated based on the estimated error correction almost ideal demand systems. The empirical results reveal significant substitution relationships between Australian domestic tourism and outbound ...

  7. Meso-ester and carboxylic acid substituted BODIPYs with far-red and near-infrared emission for bioimaging applications

    Ni, Yong

    2014-01-21

    A series of meso-ester-substituted BODIPY derivatives 1-6 are synthesized and characterized. In particular, dyes functionalized with oligo(ethylene glycol) ether styryl or naphthalene vinylene groups at the α positions of the BODIPY core (3-6) become partially soluble in water, and their absorptions and emissions are located in the far-red or near-infrared region. Three synthetic approaches are attempted to access the meso-carboxylic acid (COOH)-substituted BODIPYs 7 and 8 from the meso-ester-substituted BODIPYs. Two feasible synthetic routes are developed successfully, including one short route with only three steps. The meso-COOH-substituted BODIPY 7 is completely soluble in pure water, and its fluorescence maximum reaches around 650 nm with a fluorescence quantum yield of up to 15 %. Time-dependent density functional theory calculations are conducted to understand the structure-optical properties relationship, and it is revealed that the Stokes shift is dependent mainly on the geometric change from the ground state to the first excited singlet state. Furthermore, cell staining tests demonstrate that the meso-ester-substituted BODIPYs (1 and 3-6) and one of the meso-COOH-substituted BODIPYs (8) are very membrane-permeable. These features make these meso-ester- and meso-COOH-substituted BODIPY dyes attractive for bioimaging and biolabeling applications in living cells. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Amino-acid substitution in alpha-spectrin commonly coinherited with nondominant hereditary spherocytosis.

    Tse, W T; Gallagher, P G; Jenkins, P B; Wang, Y; Benoit, L; Speicher, D; Winkelmann, J C; Agre, P; Forget, B G; Marchesi, S L

    1997-03-01

    Nondominant hereditary spherocytosis (ndHS) is a disorder characterized in some patients by severe hemolytic anemia and marked deficiency of erythrocyte spectrin. This report describes the identification of a variant spectrin chain, alpha-spectrin Bughill or alpha(BH), that is associated with this disorder in a number of patients. Tryptic maps of spectrin from affected individuals revealed an acidic shift in isoelectric point of the alphaII domain peptides at 46 kD and 35 kD. A point mutation at codon 970 of the alpha-spectrin gene (GCT-->GAT), that changes the encoded amino acid from an alanine to an aspartic acid, was identified in genomic DNA of affected patients. The alpha(BH) variant was present in 8 patients with ndHS from five different kindreds but was absent in 4 patients from two other kindreds. The 8 ndHS patients with the alpha(BH) variant appeared to be homozygous for the alpha(BH) variant by analysis of peptide maps of limited tryptic digests of erythrocyte spectrin. However, following genomic DNA analysis, only 2 of these patients were true homozygotes, whereas 6 were found to be doubly heterozygous for the alpha(BH) allele and a second, presumably abnormal, alpha-spectrin gene. These results suggest that, in these 6 patients, the second alpha-spectrin allele is in fact associated with one or more genetic defect(s), causing decreased accumulation of alpha-spectrin. The pattern of transmission of the alpha(BH) allele in certain families suggests that the alpha(BH) amino-acid substitution is not itself responsible for ndHS but is more likely a polymorphic variant that, in some but not all cases, is in linkage disequilibrium with another uncharacterized alpha-spectrin gene defect that itself is a cause of ndHS. PMID:9067503

  9. Role of a single amino acid substitution of VP3 H142D for increased acid resistance of foot-and-mouth disease virus serotype A.

    Biswal, Jitendra K; Das, Biswajit; Sharma, Gaurav K; Khulape, Sagar A; Pattnaik, Bramhadev

    2016-04-01

    Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their dissociation into pentamers at pH value below 6.5. After the uptake of FMDV by receptor-mediated endocytosis, the acid-dependent dissociation process is required for the release of FMDV genome inside endosomes. Nevertheless, dissociation of FMDV particles in mildly acidic conditions renders the inactivated FMD vaccine less effective. To improve the acid stability of inactivated FMD vaccine during the manufacturing process, a serotype A IND 40/2000 (in-use vaccine strain) mutant with increased resistance to acid inactivation was generated through reverse genetics approach. Based upon the earlier reports, the crucial amino acid residue, H142 of VP3 capsid protein was substituted separately to various amino acid residues Arg (R), Phe (F), Ala (A), and Asp (D) on the full-genome length cDNA clone. While the H142 → R or H142 → F or H142 → A substitutions resulted in non-infectious FMDV, H142 → D mutation on VP3 protein (H3142D) resulted in the generation of mutant virus with enhanced resistance to acid-induced inactivation. In addition, H3142D substitution did not alter the replication ability and antigenicity of mutant as compared to the parental virus. However, the virus competition experiments revealed that the H3142D substitution conferred a loss of fitness for the mutant virus. Results from this study demonstrate that the H3142D substitution is the molecular determinant of acid-resistant phenotype in FMDV serotype A. PMID:26873406

  10. N-substituted aminomethanephosphonic and aminomethane-P-methylphosphinic acids as inhibitors of ureases.

    Berlicki, Lukasz; Bochno, Marta; Grabowiecka, Agnieszka; Białas, Arkadiusz; Kosikowska, Paulina; Kafarski, Paweł

    2012-05-01

    Small unextended molecules based on the diamidophosphate structure with a covalent carbon-to-phosphorus bond to improve hydrolytic stability were developed as a novel group of inhibitors to control microbial urea decomposition. Applying a structure-based inhibitor design approach using available crystal structures of bacterial urease, N-substituted derivatives of aminomethylphosphonic and P-methyl-aminomethylphosphinic acids were designed and synthesized. In inhibition studies using urease from Bacillus pasteurii and Canavalia ensiformis, the N,N-dimethyl derivatives of both lead structures were most effective with dissociation constants in the low micromolar range (Ki=13±0.8 and 0.62±0.09 μM, respectively). Whole-cell studies on a ureolytic strain of Proteus mirabilis showed the high efficiency of N,N-dimethyl and N-methyl derivatives of aminomethane-P-methylphosphinic acids for urease inhibition in pathogenic bacteria. The high hydrolytic stability of selected inhibitors was confirmed over a period of 30 days using NMR technique. PMID:21559954

  11. Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function

    Xi, T; Jones, I M; Mohrenweiser, H W

    2003-11-03

    Over 520 different amino acid substitution variants have been previously identified in the systematic screening of 91 human DNA repair genes for sequence variation. Two algorithms were employed to predict the impact of these amino acid substitutions on protein activity. Sorting Intolerant From Tolerant (SIFT) classified 226 of 508 variants (44%) as ''Intolerant''. Polymorphism Phenotyping (PolyPhen) classed 165 of 489 amino acid substitutions (34%) as ''Probably or Possibly Damaging''. Another 9-15% of the variants were classed as ''Potentially Intolerant or Damaging''. The results from the two algorithms are highly associated, with concordance in predicted impact observed for {approx}62% of the variants. Twenty one to thirty one percent of the variant proteins are predicted to exhibit reduced activity by both algorithms. These variants occur at slightly lower individual allele frequency than do the variants classified as ''Tolerant'' or ''Benign''. Both algorithms correctly predicted the impact of 26 functionally characterized amino acid substitutions in the APE1 protein on biochemical activity, with one exception. It is concluded that a substantial fraction of the missense variants observed in the general human population are functionally relevant. These variants are expected to be the molecular genetic and biochemical basis for the associations of reduced DNA repair capacity phenotypes with elevated cancer risk.

  12. The Effect of Synthesis Conditions and Nature of Heteroelement on Acidic Properties of Isomorphously Substituted UTL Zeolites

    Shamzhy, Mariya; Shvets, O. V.; Opanasenko, Maksym; Vitvarová, Dana; Nachtigall, P.; Čejka, Jiří

    2013-01-01

    Roč. 1, č. 1 (2013), s. 103-113. ISSN 2327-3941 R&D Projects: GA ČR GBP106/12/G015; GA ČR GAP106/11/0819 Institutional support: RVO:61388955 Keywords : Extra-Large Pore Zeolite * Isomorphous Substitution * Brønsted and Lewis Acidity Subject RIV: CF - Physical ; Theoretical Chemistry

  13. Probing structural features of Alzheimer's amyloid-β pores in bilayers using site-specific amino acid substitutions.

    Capone, Ricardo; Jang, Hyunbum; Kotler, Samuel A; Kagan, Bruce L; Nussinov, Ruth; Lal, Ratnesh

    2012-01-24

    A current hypothesis for the pathology of Alzheimer's disease (AD) proposes that amyloid-β (Aβ) peptides induce uncontrolled, neurotoxic ion flux across cellular membranes. The mechanism of ion flux is not fully understood because no experiment-based Aβ channel structures at atomic resolution are currently available (only a few polymorphic states have been predicted by computational models). Structural models and experimental evidence lend support to the view that the Aβ channel is an assembly of loosely associated mobile β-sheet subunits. Here, using planar lipid bilayers and molecular dynamics (MD) simulations, we show that amino acid substitutions can be used to infer which residues are essential for channel structure. We created two Aβ(1-42) peptides with point mutations: F19P and F20C. The substitution of Phe19 with Pro inhibited channel conductance. MD simulation suggests a collapsed pore of F19P channels at the lower bilayer leaflet. The kinks at the Pro residues in the pore-lining β-strands induce blockage of the solvated pore by the N-termini of the chains. The cysteine mutant is capable of forming channels, and the conductance behavior of F20C channels is similar to that of the wild type. Overall, the mutational analysis of the channel activity performed in this work tests the proposition that the channels consist of a β-sheet rich organization, with the charged/polar central strand containing the mutation sites lining the pore, and the C-terminal strands facing the hydrophobic lipid tails. A detailed understanding of channel formation and its structure should aid studies of drug design aiming to control unregulated Aβ-dependent ion fluxes. PMID:22242635

  14. Color reactions between indium and reagents of chromotropic acid 2,7-bisazo substituted derivatives in water - organic media

    Colour reactions between indium and six 2,7-bisazo substituted chromotropic acid derivatives have been studied in organo-aqueous solutions containing propanol and isopropanol. The reactions between indium and picramin S or picramin M in the organo-aqueous solutions are more sensitive and contrast than in aqueous media. New highly sensitive reactions for the reagents, whose benzene rings contain carboxy groups, have been found. Significant amounts of some complexing substances and acids do not interfere with the reaction between indium and picramin M although their application does not improve the reaction selectivity. The selectivity can be dramatically improved if the reaction proceeds directly in an organic extract after indium extraction by diisopropyl ether from a solution containing H2SO4 and KI. The possibility has been shown of photometric determining indium in gallium compounds using a model mixture of In and Ga (1:2400). Multiple by mass quantities of Ga (3700), Ca (3600), Fe (2500), Al (1700) do not interfere with indium determination

  15. Substitution in Markusen’s Classic Trade and Factor Movement Complementarity Models

    Schiff, Maurice

    2006-01-01

    Mundell and Markusen each wrote classic papers on the relationship between trade and factor movement. Mundell showed that substitution holds in the Heckscher-Ohlin model. Markusen challenged the substitution result and showed in five different models that removing barriers to factor movement results in complementarity under free trade, identical factor endowments, and a change in any one of the other assumptions underlying the Heckscher-Ohlin model. The author generalizes Markusen's analysis ...

  16. Space-for-Time Substitution Works in Everglades Ecological Forecasting Models

    Banet, Amanda I.; Trexler, Joel C.

    2013-01-01

    Space-for-time substitution is often used in predictive models because long-term time-series data are not available. Critics of this method suggest factors other than the target driver may affect ecosystem response and could vary spatially, producing misleading results. Monitoring data from the Florida Everglades were used to test whether spatial data can be substituted for temporal data in forecasting models. Spatial models that predicted bluefin killifish (Lucania goodei) population respons...

  17. Acid rain: Mesoscale model

    Hsu, H. M.

    1980-01-01

    A mesoscale numerical model of the Florida peninsula was formulated and applied to a dry, neutral atmosphere. The prospective use of the STAR-100 computer for the submesoscale model is discussed. The numerical model presented is tested under synoptically undisturbed conditions. Two cases, differing only in the direction of the prevailing geostrophic wind, are examined: a prevailing southwest wind and a prevailing southeast wind, both 6 m/sec at all levels initially.

  18. Selective oxidation of glycerol to formic acid in highly concentrated aqueous solutions with molecular oxygen using V-substituted phosphomolybdic acids

    Zhang, Jizhe

    2014-01-01

    Formic acid is an important commodity chemical as well as a promising medium for hydrogen storage and hydrogen production. In this paper, we report that formic acid can be produced through selective oxidation of glycerol, a low-cost by-product of biodiesel, by using vanadium-substituted phosphomolybdic acids as catalysts and molecular oxygen as the oxidant. Significantly, this catalytic system allows for high-concentration conversions and thus leads to exceptional efficiency. Specifically, 3.64 g of formic acid was produced from 10 g of glycerol/water (50/50 in weight) solution. © 2014 the Partner Organisations.

  19. Whole-cell biocatalytic production of variously substituted β-aryl- and β-heteroaryl-β-amino acids.

    Ratnayake, Nishanka Dilini; Theisen, Chelsea; Walter, Tyler; Walker, Kevin D

    2016-01-10

    Biologically-active β-peptides and pharmaceuticals that contain key β-amino acids are emerging as target therapeutics; thus, synthetic strategies to make substituted, enantiopure β-amino acids are increasing. Here, we use whole-cell Escherichia coli (OD600 ∼ 35) engineered to express a Pantoea agglomerans phenylalanine aminomutase (PaPAM) biocatalyst. In either 5 mL, 100mL, or 1L of M9 minimal medium containing α-phenylalanine (20mM), the cells produced ∼ 1.4 mg mL(-1) of β-phenylalanine in each volume. Representative pilot-scale 5-mL cultures, fermentation reactions converted 18 variously substituted α-arylalanines to their (S)-β-aryl-β-amino acids in vivo and were not toxic to cells at mid- to late-stage growth. The β-aryl-β-amino acids made ranged from 0.043 mg (p-nitro-β-phenylalanine, 4% converted yield) to 1.2mg (m-bromo-β-phenylalanine, 96% converted yield) over 6h in 5 mL. The substituted β-amino acids made herein can be used in redox and Stille-coupling reactions to make synthetic building blocks, or as bioisosteres in drug design. PMID:26528624

  20. Acid rain: Microphysical model

    Dingle, A. N.

    1980-01-01

    A microphysical model was used to simulate the case of a ground cloud without dilution by entrainment and without precipitation. The numerical integration techniques of the model are presented. The droplet size spectra versus time and the droplet molalities for each value of time are discussed.

  1. Amino acid substitutions in malate dehydrogenases of piezophilic bacteria isolated from intestinal contents of deep-sea fishes retrieved from the abyssal zone.

    Saito, Rie; Kato, Chiaki; Nakayama, Akihiko

    2006-02-01

    To examine the occurrence in other deep-sea bacteria of two amino acid substitutions (Ala-180 and His-229) in malate dehydrogenase (MDH) found previously in the deep-sea piezophilic Moritella sp. strain 2D2, we cloned and sequenced MDH genes of deep-sea piezophilic Moritella and Shewanella strains isolated from intestinal contents of deep-sea fishes, as well as other Moritella species from deep-sea water and sediments: M. marina, M. japonica, and M. yayanosii. The piezophilic Moritella strains had a Val residue or an Ala residue at position 180 and all the Moritella strains except for one had a His residue at position 229. However, four piezophilic-strain-specific substitutions at positions 103, 111, 229, and 283 were found to be completely conserved in the MDH of the intestinal Moritella strains of deep-sea fishes, indicating the substitutions may be habitat-specific. The piezophilic Shewanella strains had a Val residue and a Gln residue at positions 180 and 229, respectively. However, the MDHs of the Shewanella strains had five piezophilic-strain-specific substitutions at positions 61, 65, 107, 161, and 202. Therefore, the enzymatic strategies for responding to deep-sea high pressure environments of the MDHs between the genera Moritella and Shewanella are potentially different. Moreover, homology modeling shows these substitutions found in the MDHs of both genera except for position 229 in the subunit interface are located on the exposed region of the MDH molecules, indicating the substitutions may be related to the hydration state of the molecules. PMID:16598154

  2. Vapor pressures of substituted polycarboxylic acids are much lower than previously reported

    A. J. Huisman

    2013-07-01

    Full Text Available The partitioning of compounds between the aerosol and gas phase is a primary focus in the study of the formation and fate of secondary organic aerosol. We present measurements of the vapor pressure of 2-methylmalonic (isosuccinic acid, 2-hydroxymalonic (tartronic acid, 2-methylglutaric acid, 3-hydroxy-3-carboxy-glutaric (citric acid and DL-2,3-dihydroxysuccinic (DL-tartaric acid, which were obtained from the evaporation rate of supersaturated liquid particles levitated in an electrodynamic balance. Our measurements indicate that the pure component liquid vapor pressures at 298.15 K for tartronic, citric and tartaric acids are much lower than the same quantity that was derived from solid state measurements in the only other room temperature measurement of these materials (made by Booth et al., 2010. This strongly suggests that empirical correction terms in a recent vapor pressure estimation model to account for the inexplicably high vapor pressures of these and similar compounds should be revisited, and that due caution should be used when the estimated vapor pressures of these and similar compounds are used as inputs for other studies.

  3. High-Temperature Decomposition of Brønsted Acid Sites in Gallium-Substituted Zeolites

    K Al-majnouni; N Hould; W Lonergan; D Vlachos; R Lobo

    2011-12-31

    The dehydroxylation of Broensted acid sites (BAS) in Ga-substituted zeolites was investigated at temperatures up to 850 C using X-ray absorption spectroscopy (XAS), Fourier transform infrared spectroscopy (FTIR), and mass spectrometry-temperature programmed desorption (MS-TPD). X-ray absorption near-edge spectroscopy (XANES) revealed that the majority of gallium has tetrahedral coordination even after complete dehydroxylation. The interatomic gallium-oxygen distance and gallium coordination number determined by extended X-ray absorption fine structure (EXAFS) are consistent with gallium in tetrahedral coordination at low T (< 550 C). Upon heating Ga-Beta and Ga-ZSM5 to 850 C, analysis of the EXAFS showed that 70 and 80% of the gallium was still in tetrahedral coordination. The remainder of the gallium was found to be in octahedral coordination. No trigonal Ga atoms were observed. FTIR measurements carried out at similar temperatures show that the intensity of the OH vibration due to BAS has been eliminated. MS-TPD revealed that hydrogen in addition to water evolved from the samples during dehydroxylation. This shows that dehydrogenation in addition to dehydration is a mechanism that contributes to BAS decomposition. Dehydrogenation was further confirmed by exposing the sample to hydrogen to regenerate some of the BAS as monitored by FTIR and MS-TPD.

  4. Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues – precursors for dyes and drugs

    Enas M. Malik

    2015-11-01

    Full Text Available Anthraquinone (AQ derivatives play a prominent role in medicine and also in textile industry. Bromaminic acid (1-amino-4-bromoanthraquinone-2-sulfonic acid is an important precursor for obtaining dyes as well as biologically active compounds through the replacement of the C4-bromo substituent with different (aralkylamino residues. Here we report methods for the synthesis of bromaminic acid analogues bearing different substituents at the 2-position of the anthraquinone core. 1-Aminoanthraquinone was converted to its 2-hydroxymethyl-substituted derivative which, under different reaction conditions, yielded the corresponding carbaldehyde, carboxylic acid, and nitrile derivatives. The latter was further reacted to obtain 1-amino-2-tetrazolylanthraquinone. Subsequent bromination using bromine in DMF led to the corresponding bromaminic acid derivatives in excellent isolated yields (>90% and high purities. Alternatively, 1-amino-4-bromo-2-hydroxymethylanthraquinone could be directly converted to the desired 2-substituted bromaminic acid analogues in high yields (85–100%. We additionally report the preparation of bromaminic acid sodium salt and 1-amino-2,4-dibromoanthraquinone directly from 1-aminoanthraquinone in excellent yields (94–100% and high purities. The synthesized brominated AQs are valuable precursors for the preparation of AQ drugs and dyes.

  5. A unified approach to the transition matrices of DNA substitution models.

    Yap, Von Bing

    2013-04-01

    For a reversible finite-state continuous-time Markov chain containing similar states, the computation of the transition matrix can be expressed quite elegantly in terms of the transition matrix of an associated lumped Markov chain. This result is immensely useful for obtaining explicit transition matrices for many DNA substitution models, without diagonalizing a matrix or solving a differential equation. Furthermore, the technique works for the analogous problem in the discrete-time DNA substitution models. PMID:23313463

  6. Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite.

    Friederichs, Robert J; Chappell, Helen F; Shepherd, David V; Best, Serena M

    2015-07-01

    Experimental chemistry and atomic modelling studies were performed here to investigate a novel ionic co-substitution in hydroxyapatite (HA). Zinc, silicate co-substituted HA (ZnSiHA) remained phase pure after heating to 1100 °C with Zn and Si amounts of 0.6 wt% and 1.2 wt%, respectively. Unique lattice expansions in ZnSiHA, silicate Fourier transform infrared peaks and changes to the hydroxyl IR stretching region suggested Zn and silicate co-substitution in ZnSiHA. Zn and silicate insertion into HA was modelled using density functional theory (DFT). Different scenarios were considered where Zn substituted for different calcium sites or at a 2b site along the c-axis, which was suspected in singly substituted ZnHA. The most energetically favourable site in ZnSiHA was Zn positioned at a previously unreported interstitial site just off the c-axis near a silicate tetrahedron sitting on a phosphate site. A combination of experimental chemistry and DFT modelling provided insight into these complex co-substituted calcium phosphates that could find biomedical application as a synthetic bone mineral substitute. PMID:26040597

  7. Growth and nitrogen metabolism of sea bass fed graded levels of nucleic acid nitrogen from yeast or RNA extract as partial substitute for protein nitrogen from fish meal

    S. Kaushik

    2010-01-01

    Full Text Available Some studies carried out in mammalian models have shown de novo synthesis and salvage of nucleotides to be a costly metabolic process and a dietary supplementation with nucleic acids (NA or nucleotides has been suggested to result in a protein sparing action (Sanderson and He, 1994. On the other hand, high levels of dietary NA could have toxic effects and lead to disturbance in protein, lipid and carbohydrate metabolism in monogastric animals lacking uricase activity, an enzyme involved in NA degradation (Clifford and Story, 1976. So far, there is no clear indication of such effects in fish fed nucleic acid-enriched diets (Tacon and Cooke, 1980; Rumsey et al., 1992; Fournier et al., 2002. The aim of this experiment was to investigate growth response and N metabolism in juvenile sea bass (D. labrax fed diets supplying graded levels of nucleic acid N from dry brewer's yeast or RNA extract as partial substitutes for protein nitrogen provided by fish meal.

  8. Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite

    Friederichs, Robert J.; Chappell, Helen F.; Shepherd, David V.; Best, Serena M.

    2015-01-01

    Experimental chemistry and atomic modelling studies were performed here to investigate a novel ionic co-substitution in hydroxyapatite (HA). Zinc, silicate co-substituted HA (ZnSiHA) remained phase pure after heating to 1100°C with Zn and Si amounts of 0.6 wt% and 1.2 wt%, respectively. Unique lattice expansions in ZnSiHA, silicate Fourier transform infrared peaks and changes to the hydroxyl IR stretching region suggested Zn and silicate co-substitution in ZnSiHA. Zn and silicate insertion in...

  9. Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

    E2, along with Erns and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, 818CPIGWTGVIEC828, containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP 818CPIGWTGVIEC828 indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion

  10. Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

    Fernández-Sainz, I.J. [Plum Island Animal Disease Center, ARS, USDA (United States); Largo, E. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Gladue, D.P.; Fletcher, P. [Plum Island Animal Disease Center, ARS, USDA (United States); O’Donnell, V. [Plum Island Animal Disease Center, ARS, USDA (United States); Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Holinka, L.G. [Plum Island Animal Disease Center, ARS, USDA (United States); Carey, L.B. [Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), E-08003 Barcelona (Spain); Lu, X. [Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Nieva, J.L. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Borca, M.V., E-mail: manuel.borca@ars.usda.gov [Plum Island Animal Disease Center, ARS, USDA (United States)

    2014-05-15

    E2, along with E{sup rns} and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, {sup 818}CPIGWTGVIEC{sup 828}, containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP {sup 818}CPIGWTGVIEC{sup 828} indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion.

  11. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

    Nengyi Zhang

    Full Text Available BACKGROUND: Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system. METHODOLOGY/PRINCIPAL FINDINGS: We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41, in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

  12. Mass Spectrometry Analysis Coupled with de novo Sequencing Reveals Amino Acid Substitutions in Nucleocapsid Protein from Influenza A Virus

    Zijian Li

    2014-02-01

    Full Text Available Amino acid substitutions in influenza A virus are the main reasons for both antigenic shift and virulence change, which result from non-synonymous mutations in the viral genome. Nucleocapsid protein (NP, one of the major structural proteins of influenza virus, is responsible for regulation of viral RNA synthesis and replication. In this report we used LC-MS/MS to analyze tryptic digestion of nucleocapsid protein of influenza virus (A/Puerto Rico/8/1934 H1N1, which was isolated and purified by SDS poly-acrylamide gel electrophoresis. Thus, LC-MS/MS analyses, coupled with manual de novo sequencing, allowed the determination of three substituted amino acid residues R452K, T423A and N430T in two tryptic peptides. The obtained results provided experimental evidence that amino acid substitutions resulted from non-synonymous gene mutations could be directly characterized by mass spectrometry in proteins of RNA viruses such as influenza A virus.

  13. Amino acid substitutions at the major insertion loop of Candida albicans sterol 14alpha-demethylase are involved in fluconazole resistance.

    Nidia Alvarez-Rueda

    Full Text Available BACKGROUND: In the fungal pathogen Candida albicans, amino acid substitutions of 14alpha-demethylase (CaErg11p, CaCYP51 are associated with azole antifungals resistance. This is an area of research which is very dynamic, since the stakes concern the screening of new antifungals which circumvent resistance. The impact of amino acid substitutions on azole interaction has been postulated by homology modeling in comparison to the crystal structure of Mycobacterium tuberculosis (MT-CYP51. Modeling of amino acid residues situated between positions 428 to 459 remains difficult to explain to date, because they are in a major insertion loop specifically present in fungal species. METHODOLOGY/PRINCIPAL FINDING: Fluconazole resistance of clinical isolates displaying Y447H and V456I novel CaErg11p substitutions confirmed in vivo in a murine model of disseminated candidiasis. Y447H and V456I implication into fluconazole resistance was then studied by site-directed mutagenesis of wild-type CaErg11p and by heterogeneously expression into the Pichia pastoris model. CLSI modified tests showed that V447H and V456I are responsible for an 8-fold increase in fluconazole MICs of P. pastoris mutants compared to the wild-type controls. Moreover, mutants showed a sustained capacity for producing ergosterol, even in the presence of fluconazole. Based on these biological results, we are the first to propose a hybrid homology structure-function model of Ca-CYP51 using 3 different homology modeling programs. The variable position of the protein insertion loop, using different liganded or non-liganded templates of recently solved CYP51 structures, suggests its inherent flexibility. Mapping of recognized azole-resistant substitutions indicated that the flexibility of this region is probably enhanced by the relatively high glycine content of the consensus. CONCLUSIONS/SIGNIFICANCE: The results highlight the potential role of the insertion loop in azole resistance in the human

  14. Infrared study of some 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. Correlation with MO-calculations

    Juranic, Ivan O.; BRATISLAV Z. JOVANOVIC; UBAVKA B. MIOC; LJUBINKA J. BOGUNOVIC

    2000-01-01

    The IR spectra of a series of 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids (substituent = OH, SH, CH3, CH3S and NH2) were studied from the aspect of the influence of the subsitutent on the polarizability of some bonds, keto-enol tautomerism and hydrogen bond formation. The spectra were taken using solids due to the low solubility of the acids. Theoretical calculations were done using the MNDO-AM1 semiempirical molecular-orbital method. The stabilities of various tautomers were calcul...

  15. Synthesis of substituted gamma-lactams through petasis-type addition of boronic acids to N-acyliminium lons

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas Eiland

    2014-01-01

    remains the most widely utilized appro ach. Even though hydroxylactams are important precursors of cyclic N -acyliminium ions, few approaches for their synthesis hav e been reported so far. By implementing a reductive cyc lization reaction, linear L -malic acid derivatives were rapidly converted into cycl...... ic N -acyliminium ions. Under the optimized conditions, entail ing the use of HFIP as solvent, both electron-rich and electron -deficient boronic acids were successfully added to a ran ge of cyclic N -acyliminium ions, thereby obtaining a collection of phar maceutically relevant substituted g...

  16. The extraction of uranium (VI) and plutonium (IV) from nitric acid solutions with N,N-dialkyl substituting amides

    The use of N,N-di-2-methylheptyl acetamide (DMHAA),N,N-di-butylbutylamide(DBBA) and N,N-di-butylheptylamide(DBHA) as extractants for the extraction of nitric acid, U(VI) and Pu(IV) from the nitric acid solution has been investigated. The molar ratios of DBHA-HNO3 and DBHA-UO2(NO3)2 complexes are found to be 1:1 and 2:1 respectively. The complexes of both nitric acid and uranyl nitrate with these amides are highly soluble in aromatic diluent such as toluene without any formation of the third phase. The results show that, by modifying the length of the substitute chain and the degree of branch chain, some substituted amides might be found with which U(VI) and Pu(IV) could be co-extracted at moderate nitric acid solution and Pu(IV) could be preferably stripped at low acidity, and the separation of U(VI) and Pu(IV) could be accomplished without reductant of U(VI) and Pu(IV) in amide extraction

  17. Computer-assisted automated synthesis. III. Synthesis of substituted N-(carboxyalkyl) amino-acid tert-butyl ester derivatives.

    Hayashi, N; Sugawara, T; Kato, S

    1991-01-01

    A versatile automated synthesis apparatus, equipped with a chemical artificial intelligence, was developed to prepare and isolate a wide variety of compounds. The apparatus was to the synthesis of substituted N-(carboxyalkyl)amino-acids. The apparatus [1,2] is composed of units for performing various tasks,for example reagent supply, reaction, purification and separation, each linked to a control system. All synthetic processes, including washing and drying of the apparatus after each synthetic run, were automatically performed from the mixing of the reactants to the isolation of the products as powders or crystals. The reaction of an amino-acid tertbutyl ester acetic acid salt with a 2-keto acid sodium salt produces an unstable intermediate, Schiff base, which is reduced with sodum cyanoborohydride to give a substituted N-(carboxyalkyl)aminoacid tert-butyl ester sodium salt. The equilibrium and the consecutive reactions were controlled by adding sodium cyanoborohydride using the artificial intelligence software, which contained novel kinetic equations [3] and substituent effects [4].Substitued N-(carboxyalkyl)amino-acid tert-butyl esters, 90 derivatives, were automatically synthesized using the computerassisted automated synthesis apparatus. The syntheses were performed unattended 24 hours a day, except for supplying the raw materials, reagents and solvents. The apparatus is extremely valuable for synthesizing many derivatives of a particular compound. The configurations of the products were determined by circular dichroism measurements. PMID:18924904

  18. Design and Synthesis of p/m-[p-(un)Substituted Phenylsulfonamido]phenyl β-Diketo Acids and Quinoxalone Derivatives

    ZENG,Cheng-Chu; LI,Xue-Mei; YAN,Hong; ZHONG,Ru-Gang

    2007-01-01

    Diketo acid derivatives are potent and selective HIV-1 integrase inhibitors. To investigate the detailed synthesis of those derivatives, a series of p/m-[p-(un)substituted phenylsulfonamido]phenyl β-diketo acid derivatives have been designed and synthesized. The quinoxalone derivatives as the potential bioisosteres of the biologically labile β-diketoacid pharmacophores have also been synthesized from reactions of the corresponding diketo acids with o-phenylenediamine. The structures of all diketo acid (ester) and quinoxalone derivatives were confirmed by 1H NMR, 13C NMR, IR, HRMS and/or MS (ESI). X-ray crystallographic analysis of 11b demonstrates a similar arrangement of the side chain of quinoxalone derivatives with the parent diketoacids due to the intramolecular hydrogen bond (O…H-N) and the sp2 hybridization configuration of the two nitrogen atoms of the quinoxalone ring.

  19. Electro-membrane reactor for separation and in situ ion substitution of glutamic acid from its sodium salt

    Kumar, Mahendra; Tripathi, Bijay P. [Electro-Membrane Processes Division, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), G. B. Marg, Bhavnagar 364002, Gujarat (India); Shahi, Vinod K. [Electro-Membrane Processes Division, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), G. B. Marg, Bhavnagar 364002, Gujarat (India)], E-mail: vkshahi@csmcri.org

    2009-08-30

    An electro-membrane reactor with four compartments (EMR-4) (anolyte, catholyte and comp. 1 and 2) based on in-house-prepared cation- and anion-exchange membrane (CEM and AEM, respectively) was developed to achieve separation and recovery of glutamic acid (GAH) from its sodium salt by in situ ion substitution and acidification. The physicochemical and electrochemical properties of CEM and AEM were characterized and its suitability was assessed in operating environment. The separation of GA{sup -} from the mixture of nonionic organic compounds and further ion substitution was achieved by EMR-4. But the higher energy consumption (5.75 kWh/kg of GAH produced), low current efficiency (50.5%) and recovery of GAH (57.2%) in this process were main obstacles for the industrial exploration of the process. Latter, electro-membrane reactor with three compartments (EMR-3) (anolyte, catholyte and central compartment) was developed based on CEMs for only in situ ion substitution of GANa to achieve GAH, in which GA{sup -} was not allowed for electro-migration from its feed compartment. CE and recovery of GAH were close to 73% and 96% that indicate the suitability of the EMR-3 process for industrial application over the EMR-4. It was concluded that EMR-3 was efficient as compared to EMR-4 for separation and recovery of GAH from fermentation broth by in situ ion substitution in eco-friendly manner.

  20. Substitution of a single amino acid in the 2b protein of Pea early-browning virus affects nematode transmission.

    Vellios, Evangelos; Brown, Derek J F; MacFarlane, Stuart A

    2002-07-01

    The 2b protein of Pea early-browning virus (PEBV) is required for transmission of the virus by nematodes. Comparison of the 2b proteins of highly transmissible (TpA56) and poorly transmissible (SP5) isolates of PEBV identified two amino acid substitutions (G90S and G177R) that might be responsible for the poor transmission of isolate SP5. Hybrid viruses were created in which the TpA56 2b protein carried SP5-specific substitutions at residue 90 or 177, and in which the SP5 2b protein carried TpA56-specific substitutions at these positions. Transmission tests showed that the G177R substitution is sufficient to prevent nematode transmission of the virus. Examination of the 2b proteins from PEBV and other tobraviruses predicted the presence of a coiled-coil domain in the central region of the protein. This structural element is important for the association of interacting proteins and, thus, might mediate interaction of the 2b protein with the virus coat protein or with the vector nematode. PMID:12075098

  1. Electro-membrane reactor for separation and in situ ion substitution of glutamic acid from its sodium salt

    An electro-membrane reactor with four compartments (EMR-4) (anolyte, catholyte and comp. 1 and 2) based on in-house-prepared cation- and anion-exchange membrane (CEM and AEM, respectively) was developed to achieve separation and recovery of glutamic acid (GAH) from its sodium salt by in situ ion substitution and acidification. The physicochemical and electrochemical properties of CEM and AEM were characterized and its suitability was assessed in operating environment. The separation of GA- from the mixture of nonionic organic compounds and further ion substitution was achieved by EMR-4. But the higher energy consumption (5.75 kWh/kg of GAH produced), low current efficiency (50.5%) and recovery of GAH (57.2%) in this process were main obstacles for the industrial exploration of the process. Latter, electro-membrane reactor with three compartments (EMR-3) (anolyte, catholyte and central compartment) was developed based on CEMs for only in situ ion substitution of GANa to achieve GAH, in which GA- was not allowed for electro-migration from its feed compartment. CE and recovery of GAH were close to 73% and 96% that indicate the suitability of the EMR-3 process for industrial application over the EMR-4. It was concluded that EMR-3 was efficient as compared to EMR-4 for separation and recovery of GAH from fermentation broth by in situ ion substitution in eco-friendly manner.

  2. Supramolecular complex formation of β-cyclodextrin polymer with substituted salicylic acid or 3-hydroxy-2-naphthoic acid and their electrorheological behaviors

    GAO Ziwei; ZHAO Xiaopeng; SUN Ping; SI Gang

    2004-01-01

    According to the chemical design, electrorheological properties of supramolecular complex from β-cyclodextrin polymer (β -CDP) were discussed. Six supramolecular complexes of β-cyclodextrin polymer with substituted salicylic acid and 3-hydroxy-2-naphthoic acid were synthesized by the solid-phase self-assembly method, and their component and structure were characterized by NMR, FT-IR, UV-vis and the fluorescence analysis. Then the electrorheological properties of their suspensions in silicone oil were investigated under DC electric fields. It was found that the yield stresses of these supramolecular complex ER fluids were 7.3-9.8 kPa at 4kV/mm in DC electric field, which were enhanced by 34%-72% compared with that of pure β-CDP. Among them, that of β-CDP/3-hydroxy-2-naphthoic acid ER fluid was the highest. It was also found that the ER effect of supramolecular complexes can be controlled by changing different guests. When the substituted group is at phenyl ring, ER behavior can be slightly adjusted by the different substituted groups, their number as well as their position at phenyl ring. This can be proved by the measurement of dielectric properties.

  3. Using the cre-lox recombination system to assess functional impairment caused by amino acid substitutions in yeast proteins

    Shirley Renee L.

    2004-01-01

    Full Text Available A method was developed to assess the functional significance of a sequence motif in yeast Upf3p, a protein required for nonsense-mediated mRNA decay (NMD. The motif lies at the edge of the Upf3p-Upf2p interaction domain, but at the same time resembles the canonical leucine-rich nuclear export sequence (NES found in proteins that bind Crm1p exportin. To test the function of the putative NES, site-directed mutations that cause substitutions of conserved NES-A residues were first selected to identify hypermorphic alleles. Next, a portable Crm1p-binding NES from HIV-1 Rev protein that functions in yeast was fused en masse to the C-terminus of variant Upf3 proteins using loxP sites recognized by bacterial cre-recombinase. Finally, variant Upf3-Rev proteins that were functional in NMD were selected and examined for the types of amino acid substitutions present in NES-A. The mutational analysis revealed that amino acid substitutions in the Upf3 NES impair both nuclear export and the Upf2p-Upf3p interaction, both of which are required for Upf3p to function in NMD. The method described in this report could be modified for the genetic analysis of a variety of portable protein domains.

  4. 2-substituted thiazolidine-4(R)-carboxylic acids as prodrugs of L-cysteine. Protection of mice against acetaminophen hepatotoxicity

    A number of 2-alkyl- and 2-aryl-substituted thiazolidine-4(R)-carboxylic acids were evaluated for their protective effect against hepatotoxic deaths produced in mice by LD90 doses of acetaminophen. 2(RS)-Methyl-, 2(RS)-n-propyl-, and 2(RS)-n- pentylthiazolidine -4(R)-carboxylic acids (compounds 1b,d,e, respectively) were nearly equipotent in their protective effect based on the number of surviving animals at 48 h as well as by histological criteria. 2(RS)-Ethyl-, 2(RS)-phenyl-, and 2(RS)-(4-pyridyl)thiazolidine-4(R)-carboxylic acids (compounds 1c,f,g) were less protective. The enantiomer of 1b, viz., 2(RS)- methylthiazolidine -4(S)-carboxylic acid (2b), was totally ineffective in this regard. Thiazolidine-4(R)-carboxylic acid (1a), but not its enantiomer, 2a, was a good substrate for a solubilized preparation of rat liver mitochondrial proline oxidase [K/sub m/ 1.1 x 10(-4) M; V/sub max/ . 5.4 mumol min-1 (mg of protein)-1]. Compound 1b was not a substrate for proline oxidase but dissociated to L-cysteine in this system. At physiological pH and temperature, the hydrogens on the methyl group of 1b underwent deuterium exchange with solvent D2O (k1 . 2.5 X 10(-5) s), suggesting that opening of the thiazolidine ring must have taken place. Indeed, 1b labeled with 14C in the 2 and methyl positions was rapidly metabolized by the rat to produce 14CO2, 80% of the dose being excreted in this form in the expired air after 24 h. It is suggested that these 2-substituted thiazolidine-4(R)-carboxylic acids are prodrugs of L-cysteine that liberate this sulfhydryl amino acid in vivo by nonenzymatic ring opening, followed by solvolysis

  5. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Ye Li

    2015-07-01

    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  6. Durability of Concrete Using Rice Husk Ash as Cement Substitution Exposed To Acid Rain

    I. A. Ahmad

    2014-05-01

    Full Text Available The acidity of rainfall in major areas of Indonesia is under neutral pH. Average pH of rainfall is between 3 and 5. Free lime within concrete will react with acid and cause a decrease in the strength of concrete. A means to anticipate the damage is to reduce the content of free lime within concrete. Silicon oxide contained in rice husk ash can react with free lime to form a new compound that is harder and denser. It became the basis for the use of rice husk ash in concrete mixtures. The mixtures were prepared by replacing 5% and 10% of cement with rice husk ash and the results were compared with a reference mix with 100% cement. This paper presents the results of an experimental investigation on the mechanical characteristics of concrete specimens as durability parameters. Then to evaluate the mechanical characteristics, microstructure test was conducted. The lower the mechanical properties of the concrete, the higher the level of gypsum contained within concrete. The percentage of 5% rice husk ash of the cement weight has a lower compressive strength decrease than the 10% rice husk ash. In addition, the proposed durability model is a model of polynomial equation with two variables.

  7. College Chemistry Students' Mental Models of Acids and Acid Strength

    McClary, LaKeisha; Talanquer, Vicente

    2011-01-01

    The central goal of this study was to characterize the mental models of acids and acid strength expressed by advanced college chemistry students when engaged in prediction, explanation, and justification tasks that asked them to rank chemical compounds based on their relative acid strength. For that purpose we completed a qualitative research…

  8. Path to facilitate the prediction of functional amino acid substitutions in red blood cell disorders--a computational approach.

    Rajith B

    Full Text Available BACKGROUND: A major area of effort in current genomics is to distinguish mutations that are functionally neutral from those that contribute to disease. Single Nucleotide Polymorphisms (SNPs are amino acid substitutions that currently account for approximately half of the known gene lesions responsible for human inherited diseases. As a result, the prediction of non-synonymous SNPs (nsSNPs that affect protein functions and relate to disease is an important task. PRINCIPAL FINDINGS: In this study, we performed a comprehensive analysis of deleterious SNPs at both functional and structural level in the respective genes associated with red blood cell metabolism disorders using bioinformatics tools. We analyzed the variants in Glucose-6-phosphate dehydrogenase (G6PD and isoforms of Pyruvate Kinase (PKLR & PKM2 genes responsible for major red blood cell disorders. Deleterious nsSNPs were categorized based on empirical rule and support vector machine based methods to predict the impact on protein functions. Furthermore, we modeled mutant proteins and compared them with the native protein for evaluation of protein structure stability. SIGNIFICANCE: We argue here that bioinformatics tools can play an important role in addressing the complexity of the underlying genetic basis of Red Blood Cell disorders. Based on our investigation, we report here the potential candidate SNPs, for future studies in human Red Blood Cell disorders. Current study also demonstrates the presence of other deleterious mutations and also endorses with in vivo experimental studies. Our approach will present the application of computational tools in understanding functional variation from the perspective of structure, expression, evolution and phenotype.

  9. Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1

    Hussin, Ainulkhir; Nor, Norefrina Shafinaz Md; Ibrahim, Nazlina

    2013-11-01

    Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovir-resistant HSV-1 was selected at high concentration (2.0 - 4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphism-associated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TK-gene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene.

  10. In vitro and in vivo antitumor effects of novel actinomycin D analogs with amino acid substituted in the cyclic depsipeptides.

    Zhang, Bang-zhi; Wang, Kai-rong; Yan, Jie-xi; Zhang, Wei; Song, Jing-jing; Ni, Jing-man; Wang, Rui

    2010-04-01

    The actinomycin D (AMD) analogs in which the D-valine residues (the second amino acid residue in the cyclic depsipeptide of AMD) and the N-methyl-L-valine residues (the fifth amino acid residue in the cyclic depsipeptide of AMD) were replaced with D-Phe or l- and D-forms N-methylvalines, N-methylisoleucine, N-methylleucine, N-methylphenylalanine, N-methylalanine, and sarcosine were synthesized. The antimicrobial activity and cytotoxic activities of these compounds in vitro were investigated. The results showed that most D-valine substituted analogs had much lower antimicrobial activity and cytotoxic activities in vitro than AMD itself, but three N-methyl-L-valine substituted analogs had comparable or even more remarkable cytotoxic activities in vitro than AMD. Acute toxicities and antitumor effects of the N-methyl-L-valine substituted analogs in mice were also examined. The result showed that the acute toxicity of compound 4 L-methylleucine(5)-AMD analog is comparable to AMD itself and that of compound 3(L-Methylisoleucine(5)-AMD analog) is slightly more toxic, about 1.25-fold than AMD. However, the acute toxicity of compound 5 D-methylleucine5-AMD analog is about 2-fold lower than AMD. This suggested that the N-methyl-D-amino acid replacement in the cyclic ring might play a vital role in their decreased acute toxicities, and perhaps the N-methyl-D-leucine substituent is more favorable, though there may be a slight loss of antitumor activity. This finding may be helpful for the design and development of more potent antitumor agents together with low acute toxicity, and suggests that the N-methyl-D-leucine substituent has the potential to be used as antitumor drug lead. PMID:20045716

  11. Space-for-time substitution works in everglades ecological forecasting models.

    Amanda I Banet

    Full Text Available Space-for-time substitution is often used in predictive models because long-term time-series data are not available. Critics of this method suggest factors other than the target driver may affect ecosystem response and could vary spatially, producing misleading results. Monitoring data from the Florida Everglades were used to test whether spatial data can be substituted for temporal data in forecasting models. Spatial models that predicted bluefin killifish (Lucania goodei population response to a drying event performed comparably and sometimes better than temporal models. Models worked best when results were not extrapolated beyond the range of variation encompassed by the original dataset. These results were compared to other studies to determine whether ecosystem features influence whether space-for-time substitution is feasible. Taken in the context of other studies, these results suggest space-for-time substitution may work best in ecosystems with low beta-diversity, high connectivity between sites, and small lag in organismal response to the driver variable.

  12. Modeling primary energy substitution in the Asia Pacific

    Highlights: • We model the market shares (i.e. energy mix) of gases, liquids and solids in the Asia Pacific. • The model matches the historical energy mix and projects three scenarios of the future mix to 2030. • We then model the past and future hydrogen to carbon ratio (a proxy for environmental quality). • Importance of natural gas in the region could increase significantly, depending on policy and tech progress. - Abstract: A Global Energy Market model (GEM) is used to analyze the market shares (i.e. the primary energy mix) of gases, liquids and solids in the Asia Pacific. The model is successful in matching the historical energy mix from 1850 to 2009. The model also provides a good match of the hydrogen to carbon ratio, which is a proxy for environmental quality. Given these validations, the GEM is then used to present scenarios of the Asia Pacific energy mix and hydrogen to carbon ratio until the year 2030. Three energy mix scenarios are presented – reference case; alternative case 1; alternative case 2. The reference case assumes limited divergence from current policies and technologies. It indicates that Asia Pacific energy needs will be met by approximately 46% solids, 34% liquids, and 20% gases by 2030. Alternative cases 1 and 2 represent policies and technologies that either encourage or discourage the use of gases. The good matches observed for historical data suggest the GEM can be used cautiously for evaluating outcomes and opportunities in the region. Although the model can be used for projecting far into the future, it is currently calibrated to what we consider a reasonable time horizon – until the year 2030. Given appropriate energy policies and sufficient technological advancement, the importance of natural gas in the region could increase significantly

  13. 40 CFR 721.10107 - Naphthalenedisulfonic acid, [amino-hydroxy-[(substituted)azo-sulfo-naphthaleneyl]azo]-hydroxy...

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Naphthalenedisulfonic acid, azo... Significant New Uses for Specific Chemical Substances § 721.10107 Naphthalenedisulfonic acid, azo]-hydroxy... chemical substance identified generically as naphthalenedisulfonic acid, azo]-hydroxy- , metal salt (PMN...

  14. A Diffusion Theory Model of Adoption and Substitution for Successive Generations of High-Technology Products

    John A. Norton; Frank M. Bass

    1987-01-01

    This study deals with the dynamic sales behavior of successive generations of high-technology products. New technologies diffuse through a population of potential buyers over time. Therefore, diffusion theory models are related to this demand growth. Furthermore, successive generations of a technology compete with earlier ones, and that behavior is the subject of models of technological substitution. Building upon the Bass (Bass, F. M. 1969. A new-product growth model for consumer durables. M...

  15. Non-Extensive Entropy Econometrics: New Statistical Features of Constant Elasticity of Substitution-Related Models

    Second Bwanakare

    2014-01-01

    Power-law (PL) formalism is known to provide an appropriate framework for canonical modeling of nonlinear systems. We estimated three stochastically distinct models of constant elasticity of substitution (CES) class functions as non-linear inverse problem and showed that these PL related functions should have a closed form. The first model is related to an aggregator production function, the second to an aggregator utility function (the Armington) and the third to an aggregator technical tra...

  16. Demand for orange-juice products: an application of the uniform substitute model

    Brown, Mark G.; Lee, Jonq-Ying

    1991-01-01

    The differential demand model for uniform substitutes is used to analyze demand for orange-juice products. Consumption trends are examined by allowing the marginal propensities to consume to vary with time. Results indicate ready-to-serve (frozen concentrated) orange juice has become more (less) sensitive to expenditure and prices.

  17. Correlation between Ka/Ks and Ks is related to substitution model and evolutionary lineage

    Li, Jun; Zhang, Zhang; Vang, Søren;

    2009-01-01

    calculation of Ka and Ks using six different algorithms on three cross-species orthologous data sets and found a highly variable correlation among the algorithms and lineages. Algorithms based on the GY-HKY substitution model exhibit a weaker positive correlation or a stronger negative correlation than those...

  18. Synthesis of a Stable Primary-Alkyl-Substituted Selenenyl Iodide and Its Hydrolytic Conversion to the Corresponding Selenenic Acid.

    Sase, Shohei; Kakimoto, Ryo; Kimura, Ryutaro; Goto, Kei

    2015-01-01

    A primary-alkyl-substituted selenenyl iodide was successfully synthesized through oxidative iodination of a selenol with N-iodosuccinimide by taking advantage of a cavity-shaped steric protection group. The selenenyl iodide exhibited high thermal stability and remained unchanged upon heating at 100 °C for 3 h in [D₈]toluene. The selenenyl iodide was reduced to the corresponding selenol by treatment with dithiothreitol. Hydrolysis of the selenenyl iodide under alkaline conditions afforded the corresponding selenenic acid almost quantitatively, corroborating the chemical validity of the recent proposal that hydrolysis of a selenenyl iodide to a selenenic acid is potentially involved in the catalytic mechanism of an iodothyronine deiodinase. PMID:26633336

  19. Synthesis of a Stable Primary-Alkyl-Substituted Selenenyl Iodide and Its Hydrolytic Conversion to the Corresponding Selenenic Acid

    Shohei Sase

    2015-12-01

    Full Text Available A primary-alkyl-substituted selenenyl iodide was successfully synthesized through oxidative iodination of a selenol with N-iodosuccinimide by taking advantage of a cavity-shaped steric protection group. The selenenyl iodide exhibited high thermal stability and remained unchanged upon heating at 100 °C for 3 h in [D8]toluene. The selenenyl iodide was reduced to the corresponding selenol by treatment with dithiothreitol. Hydrolysis of the selenenyl iodide under alkaline conditions afforded the corresponding selenenic acid almost quantitatively, corroborating the chemical validity of the recent proposal that hydrolysis of a selenenyl iodide to a selenenic acid is potentially involved in the catalytic mechanism of an iodothyronine deiodinase.

  20. Self-assembled structure of alkyloxy substituted benzoic acid methyl ester on HOPG:An STM study

    YUAN Qunhui; LU Jun; WAN Lijun; BAI Chunli

    2004-01-01

    Self-assembled structures of 3,4,5-tris-dodecy- loxy benzoic acid methyl ester (E12), 3,4,5-tris-tetradecy- loxy-benzoic acid methyl ester (E14) and their mixture (E12/E14) have been studied on HOPG by scanning tunneling microscopy (STM). Dimer-like patterns induced by dipole-dipole interaction are observed in E12 and E14 monolayers. The molecules form close-packed rows and interdigitate with the alkyl chains in adjacent molecules. The structural differences are proposed to be from the different length of substituted alkyl chains. Owing to similar adsorption energy, phase separation is observed in the E12 and E14 mixed adlayer with different domains.

  1. Computer-assisted automatic synthesis II. Development of a fully automated apparatus for preparing substituted N-(carboxyalkyl)amino acids.

    Hayashi, N; Sugawara, T; Shintani, M; Kato, S

    1989-01-01

    A versatile automated apparatus, equipped with an artificial intelligence has been developed which may be used to prepare and isolate a wide variety of compounds. The prediction of the optimum reaction conditions and the reaction control in real time, are accomplished using novel kinetic equations and substituent effects in an artificial intelligence software which has already reported [1]. This paper deals with the design and construction of the fully automated system, and its application to the synthesis of a substituted N-(carboxyalkyl)amino acid. The apparatus is composed of units for perfoming various tasks, e.g. reagent supply, reaction, purification and separation, each linked to a control system. All synthetic processes including washing and drying of the apparatus after each synthetic run were automatically performed from the mixing of the reactants to the isolation of the products as powders with purities of greater than 98%. The automated apparatus has been able to run for 24 hours per day, and the average rate of synthesis of substituted N-(carboxyalkyl)amino acids has been three compounds daily. The apparatus is extremely valuable for synthesizing many derivatives of one particular compound structure. Even if the chemical yields are low under the optimum conditions, it is still possible to obtain a sufficient amount of the desired product by repetition of the reaction. Moreover it was possible to greatly reduce the manual involvement of the many syntheses which are a necessary part of pharmaceutical research. PMID:18924679

  2. Computer-assisted automatic synthesis II. Development of a fully automated apparatus for preparing substituted N–(carboxyalkyl)amino acids

    Hayashi, Nobuyoshi; Sugawara, Tohru; Shintani, Motoaki; Kato, Shinji

    1989-01-01

    A versatile automated apparatus, equipped with an artificial intelligence has been developed which may be used to prepare and isolate a wide variety of compounds. The prediction of the optimum reaction conditions and the reaction control in real time, are accomplished using novel kinetic equations and substituent effects in an artificial intelligence software which has already reported [1]. This paper deals with the design and construction of the fully automated system, and its application to the synthesis of a substituted N-(carboxyalkyl)amino acid. The apparatus is composed of units for perfoming various tasks, e.g. reagent supply, reaction, purification and separation, each linked to a control system. All synthetic processes including washing and drying of the apparatus after each synthetic run were automatically performed from the mixing of the reactants to the isolation of the products as powders with purities of greater than 98%. The automated apparatus has been able to run for 24 hours per day, and the average rate of synthesis of substituted N-(carboxyalkyl)amino acids has been three compounds daily. The apparatus is extremely valuable for synthesizing many derivatives of one particular compound structure. Even if the chemical yields are low under the optimum conditions, it is still possible to obtain a sufficient amount of the desired product by repetition of the reaction. Moreover it was possible to greatly reduce the manual involvement of the many syntheses which are a necessary part of pharmaceutical research. PMID:18924679

  3. Infrared study of some 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. Correlation with MO-calculations

    IVAN O. JURANIC

    2000-06-01

    Full Text Available The IR spectra of a series of 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids (substituent = OH, SH, CH3, CH3S and NH2 were studied from the aspect of the influence of the subsitutent on the polarizability of some bonds, keto-enol tautomerism and hydrogen bond formation. The spectra were taken using solids due to the low solubility of the acids. Theoretical calculations were done using the MNDO-AM1 semiempirical molecular-orbital method. The stabilities of various tautomers were calculated simulating the dielectric continuum using the COSMO facility of the MOPAC program package. Theoretical calculations were made for all the possible tautomers of the 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. For the most stable isomers, the vibrational spectra were calculated. For the majority of the compounds the most stable isomer was identified having the structure 2-Y-6-oxo-4-carboxy-3H-pyrimidine. Besides this structure, for the 2-amino-, and 2-methyl- derivatives the zwitterionic forms have very similar stability. The 2-hydroxy compound is most stable as the 2,6-dioxo-1H, 3H isomer. The calculated vibrations for the compounds with a single stable structure correlate very well with the experimental frequencies. For the 2-methyl- and 2-amino- compounds the correlation is considerably less satisfactory. The most probable reason for this deviation is the existence of two or more tautomets in equilibrium. The correlation of the measured frequencies and the pKa values of the acids, indicate that the same tautomers exist in the solid state and in the solution.

  4. A modified rabbit ulna defect model for evaluating periosteal substitutes in bone engineering: a pilot study.

    El Backly, Rania M; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2014-01-01

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX(®)) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12-16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX(®)) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute. PMID:25610828

  5. Response of Substituted Indoleacetic Acids in the Indolo-alpha-pyrone Fluorescence Determination

    Engvild, Kjeld Christensen; Böttger, M.; Kaiser, P.

    1978-01-01

    The method of indolo-.alpha.-pyrone fluorescence-determination of IAA was investigated to study possible interference from 4-chloro-indoleacetic acid and 5-hydroxyindoleacetic acid, which occur naturally. Both compounds show about 40% of the fluorescence of IAA after conversion into their .alpha.......-pyrones. Other halogenated indoleacetic acids show between zero and 60% of the fluorescence of IAA. Apparently the concentration of IAA cannot be determined in crude extracts in the presence of 4-chloro- or 5-hydroxy-indoleacetic acid, because separate determinations of each of these compounds are not possible...

  6. 4-Substituted anilinomethylpropionate: New and efficient corrosion inhibitors for mild steel in hydrochloric acid solution

    4-substituted anilinomethylpropionate namely 3-anilinomethylpropionate (Inh-1), 3-(4-methylanilino)methylpropionate (Inh-2) and 3-(4-chloroanilino) methylpropionate (Inh-3) were synthesized and investigated as corrosion inhibitors of mild steel in 1 N HCl solution using weight loss, polarization resistance, Tafel polarization and electrochemical Impedance spectroscopy techniques. The inhibition efficiency of the synthesized inhibitors followed the order Inh3 > Inh2 > Inh1. The inhibiting action of the all inhibitors was found to depend on electronic nature of functional groups present in inhibitors. Potentiodynamic polarizations suggest that all inhibitors are mixed type in nature. Electrochemical impedance spectroscopy was also used to investigate the mechanism of corrosion inhibition.

  7. A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study

    El Backly, Rania M.; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2015-01-01

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked ...

  8. Molecular modeling of nucleic acid structure

    Galindo-Murillo, Rodrigo; Bergonzo, Christina; Cheatham, Thomas E

    2001-01-01

    This unit is the first in a series of four units covering the analysis of nucleic acid structure by molecular modeling. This unit provides an overview of computer simulation of nucleic acids. Topics include the static structure model, computational graphics and energy models, generation of an initial model, and characterization of the overall three-dimensional structure.

  9. L-dehydroascorbic acid can substitute l-ascorbic acid as dietary vitamin C source in guinea pigs.

    Frikke-Schmidt, Henriette; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-04-01

    Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA)-commonly found in vitamin C containing food products prone to oxidation-was studied. Our aim was to compare tissue accumulation of vitamin C in guinea pigs receiving different oral doses of either ascorbate or DHA. In all tissues tested (plasma, liver, spleen, lung, adrenal glands, kidney, muscle, heart, and brain), only sporadic differences in vitamin C accumulation from ascorbate or DHA were observed except for the lowest dose of DHA (0.25mg/ml in the drinking water), where approximately half of the tissues had slightly yet significantly less vitamin C accumulation than from the ascorbate source. As these results contradicted data from rats, we continued to explore the ability to recycle DHA in blood, liver and intestine in guinea pigs, rats and mice. These investigations revealed that guinea pigs have similar recycling capacity in red blood cells as observed in humans, while rats and mice do not have near the same ability to reduce DHA in erythrocytes. In liver and intestinal homogenates, guinea pigs also showed a significantly higher ability to recycle DHA compared to rats and mice. These data demonstrate that DHA in guinea pigs-as in humans-is almost as effective as ascorbate as vitamin C source when it comes to taking up and storing vitamin C and further suggest that the guinea pig is superior to other rodents in modeling human vitamin C homeostasis. PMID:26609560

  10. l-dehydroascorbic acid can substitute l-ascorbic acid as dietary vitamin C source in guinea pigs

    Henriette Frikke-Schmidt

    2016-04-01

    Full Text Available Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA—commonly found in vitamin C containing food products prone to oxidation—was studied. Our aim was to compare tissue accumulation of vitamin C in guinea pigs receiving different oral doses of either ascorbate or DHA. In all tissues tested (plasma, liver, spleen, lung, adrenal glands, kidney, muscle, heart, and brain, only sporadic differences in vitamin C accumulation from ascorbate or DHA were observed except for the lowest dose of DHA (0.25 mg/ml in the drinking water, where approximately half of the tissues had slightly yet significantly less vitamin C accumulation than from the ascorbate source. As these results contradicted data from rats, we continued to explore the ability to recycle DHA in blood, liver and intestine in guinea pigs, rats and mice. These investigations revealed that guinea pigs have similar recycling capacity in red blood cells as observed in humans, while rats and mice do not have near the same ability to reduce DHA in erythrocytes. In liver and intestinal homogenates, guinea pigs also showed a significantly higher ability to recycle DHA compared to rats and mice. These data demonstrate that DHA in guinea pigs—as in humans—is almost as effective as ascorbate as vitamin C source when it comes to taking up and storing vitamin C and further suggest that the guinea pig is superior to other rodents in modeling human vitamin C homeostasis.

  11. An environmentally benign one pot synthesis of substituted quinolines catalysed by fluoroboric acid based ionic liquid

    A Rajendran; C Karthikeyan; K Rajathi; D Ragupathy

    2012-07-01

    Organic synthesis generally required large amount of solvent, avoiding the use of organic solvents in synthesis is a paradigm shift directed at developing more benign chemistry, and with ionic liquids surprisingly can lead to access to new compounds. An elegant one-pot synthesis of quinoline derivatives has been achieved by reaction of substituted anilines with -ketoester at 60°C in ethanol using an ionic liquid [Et3NH]+[BF4]−as catalyst. All the reactions gave products with high degree of purity and excellent yield (78-93%) within the shorter span of time (20-65 min) than those reactions with conventional methods. The screening of solvents as well as the reuse of ionic liquid has been evaluated. The structure of the products has been elucidated by spectral and analytical data. The present scope and potential economic impact of the reaction are demonstrated by the synthesis of substituted quinolines. Remaining challenges and future perspectives of the new transformation are discussed.

  12. Transformation of Tri-Titanium(IV)-Substituted α-Keggin Polyoxometalate (POM) into Tetra-Titanium(IV)-Substituted POMs : Reaction Products of Titanium(IV) Sulfate with the Dimeric Keggin POM Precursor under Acidic Conditions

    Kenji Nomiya; Shoko Yoshida; Yoshitaka Kobayashi; Yoshitaka Sakai; Yuki Mouri

    2010-01-01

    Reaction products of titanium(IV) sulfate in HCl-acidic aqueous solution with the dimeric species linked through three intermolecular Ti-O-Ti bonds of the two tri-titanium(IV)-substituted α-Keggin polyoxometalate (POM) subunits are described. Two novel titanium(IV)-containing α-Keggin POMs were obtained under different conditions. One product was a dimeric species through two intermolecular Ti-O-Ti bonds of the two tetra-titanium(IV)-substituted α-Keggin POM subunits, i.e., [[{Ti(H2O)3}2(μ-O)...

  13. Are the modern computer simulations a substitute for physical models? The SKA case

    Tingay, Steven J

    2012-01-01

    I consider the question posed to me by the scientific organisers of the conference, "Are the modern computer simulations a substitute for physical models? The SKA case." I briefly consider the current knowledge of computer simulations and of physical prototypes in the context of understanding interferometric radio telescopes. My conclusion is that, "no, computer simulations are not a substitute for physical models when it comes to understanding the SKA.....furthermore, physical models are not much help either." This conclusion is intentionally provocative, designed to promote some discussion at the conference, which it did. However, the conclusion reflects my belief that we do not have a deep enough understanding, theoretical or practical, of how interferometry works, to determine if the SKA will meet the stated specifications or not. I conclude that we need to adopt a qualitatively different approach to dealing with interferometric data. I note that some good work is being done on this front, but it is likel...

  14. Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids.

    Misra, Ankita; Anil Kumar, K S; Jain, Manish; Bajaj, Kirti; Shandilya, Shyamali; Srivastava, Smriti; Shukla, Pankaj; Barthwal, Manoj K; Dikshit, Madhu; Dikshit, Dinesh K

    2016-03-01

    N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular, the compound 4j offered significant protection against collagen epinephrine induced pulmonary thromboembolism as well as ferric chloride induced arterial thrombosis, without affecting bleeding tendency in mice. Therefore, the present study suggests that the compound 4j displays a remarkable antithrombotic efficacy much better than aspirin and clopidogrel. PMID:26807542

  15. Analyzing the Impact of Beach Closures, Intersite Substitution and Intertemporal Substitution Via a Model of Attendance at Five Orange County Beaches

    Busch, Christopher B.; Hanemann, W. Michael

    2001-01-01

    This paper explores the impact on beach attendance of beach closures and the intersite and intertemporal substitution that may follow beach closures. A model of beach attendance is developed that builds on a model constructed by Paul Ruud to support the State of California's claim to damages after the American Trader oil spill off the coast of Orange County, southern California. Newly gathered data on beach closures is combined with data on daily attendance from 1985-1993. Variables are const...

  16. Evaluation of dermal substitute in a novel co-transplantation model with autologous epidermal sheet.

    Guofeng Huang

    Full Text Available The development of more and more new dermal substitutes requires a reliable and effective animal model to evaluate their safety and efficacy. In this study we constructed a novel animal model using co-transplantation of autologous epidermal sheets with dermal substitutes to repair full-thickness skin defects. Autologous epidermal sheets were obtained by digesting the basement membrane (BM and dermal components from rat split-thickness skins in Dispase II solution (1.2 u/ml at 4 °C for 8, 10 and 12 h. H&E, immunohistochemical and live/dead staining showed that the epidermal sheet preserved an intact epidermis without any BM or dermal components, and a high percentage of viable cells (92.10 ± 4.19% and P63 positive cells (67.43 ± 4.21% under an optimized condition. Porcine acellular dermal matrixes were co-transplanted with the autologous epidermal sheets to repair full-thickness skin defects in Sprague-Dawley rats. The epidermal sheets survived and completely re-covered the wounds within 3 weeks. Histological staining showed that the newly formed stratified epidermis attached directly onto the dermal matrix. Inflammatory cell infiltration and vascularization of the dermal matrix were not significantly different from those in the subcutaneous implantation model. Collagen IV and laminin distributed continuously at the epidermis and dermal matrix junction 4 weeks after transplantation. Transmission electron microscopy further confirmed the presence of continuous lamina densa and hemidesmosome structures. This novel animal model can be used not only to observe the biocompatibility of dermal substitutes, but also to evaluate their effects on new epidermis and BM formation. Therefore, it is a simple and reliable model for evaluating the safety and efficacy of dermal substitutes.

  17. A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin-hemoglobin receptor abolishes TLF-1 binding.

    E DeJesus

    Full Text Available Critical to human innate immunity against African trypanosomes is a minor subclass of human high-density lipoproteins, termed Trypanosome Lytic Factor-1 (TLF-1. This primate-specific molecule binds to a haptoglobin-hemoglobin receptor (HpHbR on the surface of susceptible trypanosomes, initiating a lytic pathway. Group 1 Trypanosoma brucei gambiense causes human African Trypanosomiasis (HAT, escaping TLF-1 killing due to reduced uptake. Previously, we found that group 1 T. b. gambiense HpHbR (TbgHpHbR mRNA levels were greatly reduced and the gene contained substitutions within the open reading frame. Here we show that a single, highly conserved amino acid in the TbgHpHbR ablates high affinity TLF-1 binding and subsequent endocytosis, thus evading TLF-1 killing. In addition, we show that over-expression of TbgHpHbR failed to rescue TLF-1 susceptibility. These findings suggest that the single substitution present in the TbgHpHbR directly contributes to the reduced uptake and resistance to TLF-1 seen in these important human pathogens.

  18. A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin-hemoglobin receptor abolishes TLF-1 binding.

    DeJesus, E; Kieft, R; Albright, B; Stephens, N A; Hajduk, S L

    2013-01-01

    Critical to human innate immunity against African trypanosomes is a minor subclass of human high-density lipoproteins, termed Trypanosome Lytic Factor-1 (TLF-1). This primate-specific molecule binds to a haptoglobin-hemoglobin receptor (HpHbR) on the surface of susceptible trypanosomes, initiating a lytic pathway. Group 1 Trypanosoma brucei gambiense causes human African Trypanosomiasis (HAT), escaping TLF-1 killing due to reduced uptake. Previously, we found that group 1 T. b. gambiense HpHbR (TbgHpHbR) mRNA levels were greatly reduced and the gene contained substitutions within the open reading frame. Here we show that a single, highly conserved amino acid in the TbgHpHbR ablates high affinity TLF-1 binding and subsequent endocytosis, thus evading TLF-1 killing. In addition, we show that over-expression of TbgHpHbR failed to rescue TLF-1 susceptibility. These findings suggest that the single substitution present in the TbgHpHbR directly contributes to the reduced uptake and resistance to TLF-1 seen in these important human pathogens. PMID:23637606

  19. Physicochemical and acid gelation properties of commercial UHT-treated plant-based milk substitutes and lactose free bovine milk.

    Mäkinen, Outi E; Uniacke-Lowe, Thérèse; O'Mahony, James A; Arendt, Elke K

    2015-02-01

    Physicochemical and acid gelation properties of UHT-treated commercial soy, oat, quinoa, rice and lactose-free bovine milks were studied. The separation profiles were determined using a LUMiSizer dispersion analyser. Soy, rice and quinoa milks formed both cream and sediment layers, while oat milk sedimented but did not cream. Bovine milk was very stable to separation while all plant milks separated at varying rates; rice and oat milks being the most unstable products. Particle sizes in plant-based milk substitutes, expressed as volume mean diameters (d4.3), ranged from 0.55μm (soy) to 2.08μm (quinoa) while the average size in bovine milk was 0.52μm. Particles of plant-based milk substitutes were significantly more polydisperse compared to those of bovine milk. Upon acidification with glucono-δ-lactone (GDL), bovine, soy and quinoa milks formed structured gels with maximum storage moduli of 262, 187 and 105Pa, respectively while oat and rice milks did not gel. In addition to soy products currently on the market, quinoa may have potential in dairy-type food applications. PMID:25172757

  20. Substitution and price elasticity estimates using inter-countrypooled data in a translog cost model

    Roy, Joyashree; Sanstad, Alan H.; Sathaye, Jayant A.; Khaddaria,Raman

    2006-06-01

    Pooled data across several developing countries and the U.S. were used to estimate long-run substitution and price elasticities ina translog framework for the paper, iron and steel, and aggregatemanufacturing industries. While the quality of the estimates variesacross the several industry-specific models, the results suggest highervalues for these elasticities than appear commonly used in integratedassessment models. Estimates of own-price elasticities of energy rangefrom - 0.80 to - 1.76 and are comparable to estimates from previouseconometric studies in the context of developed countries (- 0.77 to -0.87). Substitution elasticities show wider variation across countriesand industries. For energy and capital they range from -1.96 to 9.80, forlabor and energy from 2.61 to 7.11, and for energy and material from -0.26 to 2.07.

  1. DNA and RNA "traffic lights": synthetic wavelength-shifting fluorescent probes based on nucleic acid base substitutes for molecular imaging.

    Holzhauser, Carolin; Wagenknecht, Hans-Achim

    2013-08-01

    The DNA base substitute approach by the (S)-3-amino-1,2-propanediol linker allows placing two fluorophores in a precise way inside a given DNA framework. The double helical architecture around the fluorophores, especially the DNA-induced twist, is crucial for the desired photophysical interactions. Excitonic, excimer, and energy transfer interactions yield fluorescent DNA and RNA probes with dual emission color readout. Especially, our DNA and RNA "traffic light" that combines the green emission of TO with the red emission of TR represents an important tool for molecular imaging and can be applied as aptasensors and as probes to monitor the siRNA delivery into cells. The concept can be extended to the synthetically easier to access postsynthetic 2'-modifications and the NIR range. Thereby, the pool of tailor-made fluorescent nucleic acid conjugates can be extended. PMID:23796243

  2. A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5α

    Shioda Tatsuo

    2010-07-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 productively infects only humans and chimpanzees but not Old World monkeys, such as rhesus and cynomolgus (CM monkeys. To establish a monkey model of HIV-1/AIDS, several HIV-1 derivatives have been constructed. We previously reported that efficient replication of HIV-1 in CM cells was achieved after we replaced the loop between α-helices 6 and 7 (L6/7 of the capsid protein (CA with that of SIVmac239 in addition to the loop between α-helices 4 and 5 (L4/5 and vif. This virus (NL-4/5S6/7SvifS was supposed to escape from host restriction factors cyclophilin A, CM TRIM5α, and APOBEC3G. However, the replicative capability of NL-4/5S6/7SvifS in human cells was severely impaired. Results By long-term cultivation of human CEMss cells infected with NL-4/5S6/7SvifS, we succeeded in rescuing the impaired replicative capability of the virus in human cells. Sequence analysis of the CA region of the adapted virus revealed a G-to-E substitution at the 116th position of the CA (G116E. Introduction of this substitution into the molecular DNA clone of NL-4/5S6/7SvifS indeed improved the virus' replicative capability in human cells. Although the G116E substitution occurred during long-term cultivation of human cells infected with NL-4/5S6/7SvifS, the viruses with G116E unexpectedly became resistant to CM, but not human TRIM5α-mediated restriction. The 3-D model showed that position 116 is located in the 6th helix near L4/5 and L6/7 and is apparently exposed to the protein surface. The amino acid substitution at the 116th position caused a change in the structure of the protein surface because of the replacement of G (which has no side chain with E (which has a long negatively charged side chain. Conclusions We succeeded in rescuing the impaired replicative capability of NL-4/5S6/7SvifS and report a mutation that improved the replicative capability of the virus. Unexpectedly, HIV-1 with this

  3. Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase

    Buček, Aleš; Matoušková, P.; Vogel, H.; Šebesta, Petr; Jahn, Ullrich; Weissflog, J.; Svatoš, Aleš; Pichová, Iva

    2015-01-01

    Roč. 112, č. 41 (2015), s. 12586-12591. ISSN 0027-8424 R&D Projects: GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : fatty acid desaturase * Manduca sexta * sex pheromone biosynthesis * pheromone evolution * substrate specificity Subject RIV: CC - Organic Chemistry Impact factor: 9.674, year: 2014

  4. A Cornea Substitute Derived from Fish Scale: 6-Month Followup on Rabbit Model

    Fei Yuan; Liyan Wang; Chien-Chen Lin; Cheng-Hung Chou; Lei Li

    2014-01-01

    A fish scale-derived cornea substitute (Biocornea) is proposed as an alternative for human donor corneal tissue. We adopt a regenerative medicine approach to design a primary alternative to the use of fish scale for restoring sight by corneal replacement. Biocornea with corneal multilayer arrangement collagen was implanted to rabbits by pocket implantation. Our study demonstrated the safety and detailed morphologic and physiologic results from the 6 months of followup of rabbit model. In the ...

  5. Determining the optimal model for role-substitution in NHS dental services in the United Kingdom

    Brocklehurst, Paul; Birch, Stephen; McDonald, Ruth; Tickle, Martin

    2013-01-01

    Background Role-substitution describes a model of dental care where Dental Care Professionals (DCPs) provide some of the clinical activity previously undertaken by General Dental Practitioners. This has the potential to increase technical efficiency, the capacity to care and reduce costs. Technical efficiency is defined as the production of the maximum amount of output from a given amount of input so that the service operates at the production frontier i.e. optimal level of productivity. Acad...

  6. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Ye Li; Shu-Kui Chen; Long Li; Ling Qin; Xin-Luan Wang; Yu-Xiao Lai

    2015-01-01

    Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for...

  7. Durability of Concrete Using Rice Husk Ash as Cement Substitution Exposed To Acid Rain

    I. A. Ahmad; Parung, H.

    2014-01-01

    The acidity of rainfall in major areas of Indonesia is under neutral pH. Average pH of rainfall is between 3 and 5. Free lime within concrete will react with acid and cause a decrease in the strength of concrete. A means to anticipate the damage is to reduce the content of free lime within concrete. Silicon oxide contained in rice husk ash can react with free lime to form a new compound that is harder and denser. It became the basis for the use of rice husk ash in concrete mix...

  8. Synthesis of Novel N-9-Substituted Purine Derivatives from Polymer Supported alpha-Amino Acids

    Vanda, D.; Jorda, Radek; Lemrová, B.; Volná, T.; Kryštof, Vladimír; McMaster, C.; Soural, M.

    2015-01-01

    Roč. 17, č. 7 (2015), s. 426-432. ISSN 2156-8952 R&D Projects: GA MŠk(CZ) LO1204; GA MŠk(CZ) LO1304 Institutional support: RVO:61389030 Keywords : alpha-amino acids * solid-phase synthesis * purine derivatives Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.032, year: 2014

  9. Separation of Cs from acid radwaste solutions using substituted tetraphenyl borates

    It was the aim of this study to selectively separate active caesium (Cs-134 and Cs-137) from acid, radioactive waste solutions (especially MAW and HAWC). The following strategy was designed for a separating process: synthesis of acid-resistant reagents selective to caesium; precipitation of Cs+ and separation of the precipitates by filtration or centrifugation; precipitation of Cs+ and separation of the precipitates by flotation; caesium separation by means of liquid-liquid extraction. Different fluorophenyl derivatives of sodium tetraborate were synthesized and tested with regard to acid stability and selectivity with regards to caesium ions. Furthermore, the solubility products of the caesium salts of these compounds also in dependence on the concentration of NaNO3, were determined. With regard to the separation of precipitates the best result for the MAW was obtained with sodium tetrakis (2,4 difluorophenyl) by which inactive Cs+ can be used as carrier. The pentafluorophenyl derivative, however, is the most suitable for the highly active waste concentrates (5M HNO3) due to its better acid stability; because of its comparatively high solubility the quantity of precipitants to be used is larger. In the pH range 7-10 the liquid-liquid extractions of these precipitates showed very good separation results with nitrobenzene. Apart from process-oriented aspects, also the physical and chemical processes are discussed. (orig./RB)

  10. Development of mild and efficient method for synthesis of substituted flavones using oxalic acid catalyst

    Abhay S.Zambare; Jaiprakash N.Sangshetti; Nagnnath D.Kokare; Devanand B.Shinde

    2009-01-01

    Oxalic acid has been used as a catalyst for intramolecular cyclisation of 2-hydroxyehalcones to form flavones in good yields.The efficiency of the catalyst was proved with a variety of substrates ranging from electron-deficient to electron-rich aryl aldehydes and 2-hydroxychalcone.

  11. Bent-shaped liquid crystals based on 4-substituted 3-hydroxybenzoic acid central core

    Kohout, M.; Kozmík, V.; Slabochová, M.; Tůma, J.; Svoboda, J.; Novotná, Vladimíra; Pociecha, D.

    2015-01-01

    Roč. 42, č. 1 (2015), s. 87-103. ISSN 0267-8292 R&D Projects: GA ČR GA13-14133S Institutional support: RVO:68378271 Keywords : liquid crystals * bent-shaped mesogens * hydroxybenzoic acid Subject RIV: JJ - Other Materials Impact factor: 2.486, year: 2014

  12. Substitution-Inert Trinuclear Platinum Complexes Efficiently Condense/Aggregate Nucleic Acids and Inhibit Enzymatic Activity

    Malina, Jaroslav; Farrell, N. P.; Brabec, Viktor

    2014-01-01

    Roč. 53, č. 47 (2014), s. 12812-12816. ISSN 1433-7851 R&D Projects: GA ČR(CZ) GA13-08273S Institutional support: RVO:68081707 Keywords : DNA condensation * nucleic acids * platinum Subject RIV: BO - Biophysics Impact factor: 11.261, year: 2014

  13. Biobased furandicarboxylic acids (FDCAs): effects of isomeric substitution on polyester synthesis and properties

    Thiyagarajan, S.; Vogelzang, W.; Knoop, J.R.I.; Frissen, A.E.; Haveren, van J.; Es, van D.S.

    2014-01-01

    In this study we present the application of different isomers of furandicarboxylic acid, or FDCA, obtained from agro-residues, in polyester synthesis. New polyesters based on 2,4-FDCA and 3,4-FDCA isomers with (linear) diols were thoroughly characterised and compared with their as-synthesised 2,5-FD

  14. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects

  15. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

    Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.; Krylov, Petr S. [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation); Ilyushina, Natalia A., E-mail: Natalia.Ilyushina@fda.hhs.gov [FDA CDER, 29 Lincoln Drive, Bethesda, MD 20892 (United States); Kaverin, Nikolai V., E-mail: nik.kaverin@gmail.com [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation)

    2013-12-15

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects.

  16. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein.

    Zhang, Xinsheng; Wallace, Olivia L; Domi, Arban; Wright, Kevin J; Driscoll, Jonathan; Anzala, Omu; Sanders, Eduard J; Kamali, Anatoli; Karita, Etienne; Allen, Susan; Fast, Pat; Gilmour, Jill; Price, Matt A; Parks, Christopher L

    2015-08-01

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. PMID:25880113

  17. Composite electrolytes composed of Cs-substituted phosphotungstic acid and sulfonated poly(ether-ether ketone) for fuel cell systems

    Oh, Song-Yul, E-mail: ms089203@tutms.tut.ac.jp [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan); Yoshida, Toshihiro; Kawamura, Go [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan); Muto, Hiroyuki [Department of Materials Science and Engineering, Kurume National College of Technology, 1-1-1 Komorino, Kurume, Fukuoka 830-8555 (Japan); Sakai, Mototsugu [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan); Matsuda, Atsunori, E-mail: matsuda@tutms.tut.ac.jp [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan)

    2010-10-15

    Composite electrolytes composed of cesium hydrogen sulfate containing phosphotungstic acids (CsHSO{sub 4}-H{sub 3}PW{sub 12}O{sub 40}) and sulfonated poly(ether-ether ketone) (SPEEK) were prepared by casting the corresponding precursor for application in fuel cells. Partially Cs-substituted phosphotungstic acids (Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40}) were formed in the CsHSO{sub 4}-H{sub 3}PW{sub 12}O{sub 40} system by mechanochemical treatment. SPEEK was prepared from PEEK by sulfonation using concentrated sulfuric acid. Flexible composite electrolytes were obtained and their electrochemical properties were markedly improved with the addition of Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40}, into the SPEEK matrix. A maximum power density of 213 mW cm{sup -2} was obtained from the single cell test for 50H{sub 3}PW{sub 12}O{sub 40}-50CsHSO{sub 4} in SPEEK (1/5 by weight) composite electrolyte at 80 deg. C and at 80 RH%. Electrochemical properties and transmission electron microscopy (TEM) results suggest that three-dimensional cluster particles were formed and homogeneously distributed in the SPEEK matrix. The mechanochemically synthesized Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40} incorporated into the SPEEK matrix increased the number of protonate sites in the electrolyte. The composite electrolytes were successfully formed with Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40}, which consist of hydrogen bonding between surface of inorganic solid acids and not only -HSO{sub 4}{sup -} dissociated from CsHSO{sub 4} but also -SO{sub 3}H groups in the SPEEK.

  18. Electron inductive effects in the radiolysis of substituted phenylboronic acid solutions

    The pulse radiolysis of aqueous solutions of phenylboronic acid PhB(OH)2 and its m-nitro and m-amino derivatives has been investigated. The transient optical absorption spectra indicate the presence of three intermediate species absorbing with independent maxima at 297, 317 and 400 nm. The 297-nm band has been assigned to the anion formed in an electron capture reaction, i.e. PhB(OH)2+epsilonsub(aq)- → PhB(OH)2-and the 317-nm band to cyclohexadienyl radicals formed from OH and H attack on OhB(OH)2. Hydroxyphenylboronic acid has been identified as the major stable radiation product. For each of the systems studied the respective yield and reactivity of observed intermediate species can be interpreted relative to the inductive effects of substituent groups in agreement with the Hammett relationship. (author)

  19. A stable enol from a 6-substituted benzanthrone and its unexpected behaviour under acidic conditions

    Marc Debeaux

    2009-06-01

    Full Text Available Treatment of benzanthrone (1 with biphenyl-2-yl lithium leads to the surprisingly stable enol 4, which is converted by dehydrogenation into the benzanthrone derivative 7. Under acidic conditions 4 isomerises to the spiro compound 11 and the bicyclo[4.3.1]decane derivative 12. Furthermore, the formation of 7 and the hydrogenated compound 13 is observed. A mechanism for the formation of the reaction products is proposed and supported by DFT calculations.

  20. Single amino acid substitutions in the enzyme acetolactate synthase confer resistance to the herbicide sulfometuron methyl

    Yadav, Narendra; McDevitt, Raymond E.; Benard, Susan; Falco, S. Carl

    1986-01-01

    Sulfometuron methyl, a sulfonylurea herbicide, blocks growth of bacteria, yeast, and higher plants by inhibition of acetolactate synthase (EC 4.1.3.18), the first common enzyme in the biosynthesis of branched-chain amino acids. Spontaneous mutations that confer increased resistance to the herbicide were obtained in cloned genes for acetolactate synthase from Escherichia coli and Saccharomyces cerevisiae. The DNA sequence of a bacterial mutant gene and a yeast mutant gene revealed single nucle...

  1. Exotoxin A of Pseudomonas aeruginosa: substitution of glutamic acid 553 with aspartic acid drastically reduces toxicity and enzymatic activity.

    Douglas, C M; Collier, R J

    1987-01-01

    Glutamic acid 553 of Pseudomonas aeruginosa exotoxin A (ETA) has been identified by photoaffinity labeling as a residue within the NAD binding site (S.F. Carroll and R.J. Collier, J. Biol. Chem. 262:8707-8711, 1987). To explore the function of Glu-553 we used oligonucleotide-directed mutagenesis to replace this residue with Asp in cloned ETA and expressed the mutant gene in Escherichia coli K-12. ADP-ribosylation activity of Asp-553 ETA in cell extracts was about 1,800-fold lower and toxicity...

  2. Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature.

    Morio, Florent; Loge, Cedric; Besse, Bernard; Hennequin, Christophe; Le Pape, Patrice

    2010-04-01

    For several years, azole antifungal drugs have been a treatment option for potentially life-threatening Candida infections. However, azole resistance can occur through various mechanisms such as alterations in ERG11, encoding lanosterol 14alpha-demethylase (CYP51). In this study, we investigated the antifungal susceptibility to fluconazole, itraconazole, and voriconazole of 73 clinical isolates of Candida albicans. Screening for amino acid substitutions in Erg11 was performed on each of the 73 isolates. Twenty isolates displayed a marked decrease in azole susceptibility. Amino acid substitutions were detected in more than two-thirds of the strains. In all, 23 distinct substitutions were identified. Four have not been described previously, among which N136Y and Y447H are suspected to be involved in azole resistance. We suggest that the high genetic polymorphism of ERG11 must be considered in the rationale design of new azole compounds targeting lanosterol 14alpha-demethylase. A review of all Erg11 amino acid polymorphisms described to date is given. PMID:20226328

  3. The nucleotide sequence of HLA-B{sup *}2704 reveals a new amino acid substitution in exon 4 which is also present in HLA-B{sup *}2706

    Rudwaleit, M.; Bowness, P.; Wordsworth, P. [John Radcliffe Hospital, Oxford (United Kingdom)

    1996-12-31

    The HLA-B27 subtype HLA-B{sup *}2704 is virtually absent in Caucasians but common in Orientals, where it is associated with ankylosing spondylitis. The amino acid sequence of HLA-B{sup *}2704 has been established by peptide mapping and was shown to differ by two amino acids from HLA-B{sup *}2705, HLA-B{sup *}2704 is characterized by a serine for aspartic acid substitution at position 77 and glutamic acid for valine at position 152. To date, however, no nucleotide sequence confirming these changes at the DNA level has been published. 13 refs., 2 figs.

  4. Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.

    Nielsen, R.; Z. Yang

    1998-01-01

    Several codon-based models for the evolution of protein-coding DNA sequences are developed that account for varying selection intensity among amino acid sites. The "neutral model" assumes two categories of sites at which amino acid replacements are either neutral or deleterious. The "positive-selection model" assumes an additional category of positively selected sites at which nonsynonymous substitutions occur at a higher rate than synonymous ones. This model is also used to identify target s...

  5. Structural investigation of liquid formic acid by neutron diffraction. II: Isotopic substitution for DCOO[H/D

    New measurements of neutron diffraction data for four samples involving H/D isotopic substitution on the hydroxyl hydrogen of liquid formic acid at 20 deg C are reported. The results are combined with earlier measurements on [H/D]COOD to provide a full range of data. The determination of molecular conformation and bond-lengths has been made with a partial form-factor formalism and also using the 'Monte Carlo determination of g(r)' technique. The partial real-space correlation functions, RR, RH and HH are evaluated in each case and compared with existing computer simulations. The results confirm the strongly hydrogen-bonded nature of the liquid, but show that current molecular dynamics predictions based on transferable potentials do not give a very good representation of the structure. The observations provide a basis for a more detailed investigation and work is currently in progress. Ab initio quantum chemical calculations showed that the non-planar configuration suggested by Bertagnolli et al. [Ber. Bunsen. Phys. Chem. 88 (1984) 977; Ber. Bunsen. Phys. Chem. 89 (1985) 500], is very unlikely both for formic acid dimers and monomers

  6. A new proof for the convergence of an individual based model to the Trait substitution sequence

    Gupta, Ankit; Tran, Viet Chi

    2012-01-01

    We consider a stochastic individual based model for a population structured by a vector trait and with logistic interactions. We consider its limit in a context from adaptive dynamics: the population is large, the mutations are rare and we view the process in the timescale of mutations. Using averaging techniques due to Kurtz (1992), we give a new proof of the convergence of the individual based model to the Trait substitution sequence of Metz et al. (1992) and rigorously proved by Champagnat (2006): assuming that "invasion implies fixation", we obtain in the limit a process that jumps from one population equilibrum to another one when mutations occur and invade the population.

  7. Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A

    The C4B isotype of the fourth component of human complement (C4) displays 3- to 4-fold greater hemolytic activity than does its other isotype C4A. This correlates with differences in their covalent binding efficiencies to erythrocytes coated with antibody and complement C1. C4A binds to a greater extent when C1 is on IgG immune aggregates. The differences in covalent binding properties correlate only with amino acid changes between residues 1101 and 1106 (pro-C4 numbering)-namely, Pro-1101, Cys-1102, Leu-1105, and Asp-1106 in C4A and Leu-1101, Ser-1102, Ile-1105, and His-1106 in C4B, which are located in the C4d region of the α chain. To more precisely identify the residues that are important for the functional differences, C4A-C4B hybrid proteins were constructed by using recombinant DNA techniques. Comparison of these by hemolytic assay and binding to IgG aggregates showed that the single substitution of aspartic acid for histidine at position 1106 largely accounted for the change in functional activity and nature of theformed. Surprisingly, substitution of a neutral residue, alanine, for histidine at position 1106 resulted in an increase in binding to immune aggregates without subsequent reduction in the hemolytic activity. This result strongly suggests that position 1106 is not catalytic as previously proposed but interacts sterically/electrostatically with potential acceptor sites and serves to select binding sites on potential acceptor molecules

  8. Amino acid substitutions of cysteine residues near the amino terminus of Wheat streak mosaic virus HC-Pro abolishes virus transmission by the wheat curl mite

    The amino-terminal half of HC-Pro of Wheat streak mosaic virus (WSMV) is required for semi-persistent transmission by the wheat curl mite (Aceria tosichella Keifer). The amino-proximal region of WSMV HC-Pro is cysteine-rich with a zinc finger-like motif. Amino acid substitutions were made in this re...

  9. Aqueous solubility study of salts of benzylamine derivatives and p-substituted benzoic acid derivatives using X-ray crystallographic analysis

    Parshad, Henrik; Frydenvang, Karla Andrea; Liljefors, Tommy; Sorensen, Henning Osholm; Larsen, Claus

    2004-01-01

    Twenty two p-substituted benzoic acid derivates were used to prepare salts of N-methylbenzylamine (II) and N,N-dimethylbenzylamine (III), respectively. Only five salts of (II) and two salts of (III) were obtained in a crystalline state. The solubility of these salts was orders of magnitude higher...

  10. Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles.

    Rajaguru, Kandasamy; Mariappan, Arumugam; Suresh, Rajendran; Manivannan, Periasamy; Muthusubramanian, Shanmugam

    2015-01-01

    The reaction of α-azidochalcones with carboxylic acids has been investigated resulting in the formation of α-amido-1,3-diketones under microwave irradiation via in situ formation of 2H-azirine intermediates. An interesting reaction is described wherein, with trifluoroacetic acid at lower temperature, it affords highly substituted 2-(trifluoromethyl)oxazoles. These flexible transformations proceed under solvent free conditions in good to excellent yields without any catalyst. PMID:26664623

  11. Characterization of the inflammatory response to four commercial bone graft substitutes using a murine biocompatibility model

    Markel DC

    2012-01-01

    Full Text Available David C Markel1, S Trent Guthrie2, Bin Wu3, Zheng Song4, Paul H Wooley41Department of Orthopaedics, Providence Hospital and Medical Centers, Southfield, MI, 2Henry Ford Hospital, Detroit, MI, 3Department of Biomedical Engineering, Wayne State University, Detroit, MI, 4Orthopaedic Research Institute, Wichita, KS, USAAbstract: Bone grafting is utilized in nearly all orthopedic subspecialties and in most anatomic regions. Bone graft substitutes have the potential to offer similar efficacy as autogenous grafts without the morbidity of harvest. Several studies have noted the efficacy of new-generation bone substitute products, but few studies have evaluated their safety. This study characterizes and quantifies the inflammatory reaction to four different commercially available bone graft substitutes, which were examined using the in vivo murine air pouch biocompatibility model. One coralline hydroxyapatite product was chosen as an example of a purely osteoconductive material. Three demineralized bone matrix products were chosen to represent products that are both osteoconductive and osteoinductive. Samples were implanted in a murine air pouch and harvested after 14 days in situ. Pouch fluid was extracted, mRNA isolated, and reverse transcription polymerase chain reactions carried out to detect interleukin-1 gene expression as a marker for inflammation. In addition, multiple histological characteristics were examined to quantify cellular responses to the implanted materials. All bone graft substitutes induced a significant inflammatory response compared with negative controls. Histology and polymerase chain reaction data indicated that the level of inflammatory reaction was elevated in materials with a higher demineralized bone matrix to carrier proportion. The hydroxyapatite product generated a low inflammatory reaction. In conclusion, this study used an in vivo model of biocompatibility to demonstrate that a significant inflammatory reaction occurs

  12. Analysis of substitution experiments in ZED-2 with physically realistic model adjustments

    Substitution experiments involve several types of reactor simulation. When an experiment on a power reactor is impracticable, such as a loss-of-coolant accident, a simulation of its lattice must be set up in a lattice-testing reactor, such as ZED-2. A full core of such a test lattice may not go critical, because of the size limitation, and/or may be expensive. A substitution experiment simulates such a full-core, by setting up a few channels of the experimental lattice, surrounded by a 'driving' lattice, to make a critical assembly. A corresponding 'reference' experiment, with a pure driver lattice, permits the characteristics of the experimental lattice to be inferred by comparison of the two experiments. This inference requires mathematical modelling of the experiments. Measurements of the flux distributions should enable refinement of the model. However, previous analyses have required that the model of outer parts of the reactor, such as the graphite reflector, be replaced by arbitrary extrapolation lengths, so that these can be varied to correspondingly adjust the calculated fluxes. This arbitrary replacement may lose more accuracy than the adjustment of the model gains. The FITEXPTS family of substitution experiment simulation programs permits the adjustment to consist instead of variations of the modelling of small, unknown details of the experiment, the best choice of which depends on the experiment. Examples are: the flux depression inside the support structures in the bottom ends of the channels; the effective thicknesses of the irregular graphite reflectors; the reactivity of ring of 'booster rods', which are sometimes necessary around the periphery of the driver lattice; and the extrapolation length used of necessity at the unreflected top of the core. This flexibility leads to improved accuracy. The paper expands on techniques and testing. (author). 8 refs., 5 figs

  13. Destabilization of pea lectin by substitution of a single amino acid in a surface loop.

    Hoedemaeker, F J; van Eijsden, R R; Díaz, C L; de Pater, B S; Kijne, J W

    1993-09-01

    Legume lectins are considered to be antinutritional factors (ANF) in the animal feeding industry. Inactivation of ANF is an important element in processing of food. In our study on the stability of Pisum sativum L. lectin (PSL), a conserved hydrophobic amino acid (Val103) in a surface loop was replaced with alanine. The mutant lectin, PSL V103A, showed a decrease in unfolding temperature (Tm) by some 10 degrees C in comparison with wild-type (wt) PSL, and the denaturation energy (delta H) is only about 55% of that of wt PSL. Replacement of an adjacent amino acid (Phe104) with alanine did not result in a significant difference in stability in comparison with wt PSL. Both mutations did not change the sugar-binding properties of the lectin, as compared with wt PSL and with PSL from pea seeds, at ambient temperatures. The double mutant, PSL V103A/F104A, was produced in Escherichia coli, but could not be isolated in an active (i.e. sugar-binding) form. Interestingly, the mutation in PSL V103A reversibly affected sugar-binding at 37 degrees C, as judged from haemagglutination assays. These results open the possibility of production of lectins that are active in planta at ambient temperatures, but are inactive and possibly non-toxic at 37 degrees C in the intestines of mammals. PMID:8400124

  14. 1,2,3-Triazole-Substituted Oleanolic Acid Derivatives: Synthesis and Antiproliferative Activity

    Guillermo Schmeda-Hirschmann

    2013-07-01

    Full Text Available Hybrid compounds are relevant products when searching for structure-activity relationships of natural products. Starting from the naturally occurring triterpene oleanolic acid, alkyl esters were prepared and treated with different aromatic azides using click chemistry to produce hybrid compounds. Some 18 new oleanolic acid derivatives were synthesized and the structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new derivatives was evaluated towards normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, promyelocytic leukemia (HL-60, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. The alkyne esters 1 and 3 showed activity on all cell lines but without selectivity (19.6–23.1 μM and 14.1–56.2 μM, respectively, their respective methyl esters were inactive. Compounds with a benzene and p-anisole attached to the triazole ring, showed no antiproliferative effect. Introduction of a chlorine atom into the benzene ring (compound 9 elicited a selective effect against AGS cells (IC50 value: 8.9 μM. The activity was lost when the COOH function at C-28 was methylated. Better antiproliferative effect was found for compounds 11 and 15 bearing a p-toluenesulphonyl group, with values in the range of 10.8–47.1 μM and 11.5–22.2 μM, respectively. The effect, however, was not associated with selectivity.

  15. A cornea substitute derived from fish scale: 6-month followup on rabbit model.

    Yuan, Fei; Wang, Liyan; Lin, Chien-Chen; Chou, Cheng-Hung; Li, Lei

    2014-01-01

    A fish scale-derived cornea substitute (Biocornea) is proposed as an alternative for human donor corneal tissue. We adopt a regenerative medicine approach to design a primary alternative to the use of fish scale for restoring sight by corneal replacement. Biocornea with corneal multilayer arrangement collagen was implanted to rabbits by pocket implantation. Our study demonstrated the safety and detailed morphologic and physiologic results from the 6 months of followup of rabbit model. In the peripheral Biocornea, the collagen fibrils were arranged in reticular fashion. Slit lamp examination showed that haze and an ulcer were not observed in all groups at 3 months postoperatively while all corneas with Biocornea were clear at both 3 months and 6 months postoperatively. The interface of Biocornea and stromal tissue were filled successfully and without observable immune cells at postoperative day 180. Moreover, the Biocornea was not dissolved and degenerated but remained transparent and showed no apparent fragmentation. Our study demonstrated that the Biocornea derived from fish scale as a good substitute had high biocompatibility and support function after a long-term evaluation. This revealed that the new approach of using Biocornea may yield an ideal artificial cornea substitute for long-term inlay placement. PMID:25089206

  16. A Cornea Substitute Derived from Fish Scale: 6-Month Followup on Rabbit Model

    Fei Yuan

    2014-01-01

    Full Text Available A fish scale-derived cornea substitute (Biocornea is proposed as an alternative for human donor corneal tissue. We adopt a regenerative medicine approach to design a primary alternative to the use of fish scale for restoring sight by corneal replacement. Biocornea with corneal multilayer arrangement collagen was implanted to rabbits by pocket implantation. Our study demonstrated the safety and detailed morphologic and physiologic results from the 6 months of followup of rabbit model. In the peripheral Biocornea, the collagen fibrils were arranged in reticular fashion. Slit lamp examination showed that haze and an ulcer were not observed in all groups at 3 months postoperatively while all corneas with Biocornea were clear at both 3 months and 6 months postoperatively. The interface of Biocornea and stromal tissue were filled successfully and without observable immune cells at postoperative day 180. Moreover, the Biocornea was not dissolved and degenerated but remained transparent and showed no apparent fragmentation. Our study demonstrated that the Biocornea derived from fish scale as a good substitute had high biocompatibility and support function after a long-term evaluation. This revealed that the new approach of using Biocornea may yield an ideal artificial cornea substitute for long-term inlay placement.

  17. Single substitutions to closely related amino acids contribute to the functional diversification of an insect-inducible, positively selected plant cystatin.

    Rasoolizadeh, Asieh; Goulet, Marie-Claire; Sainsbury, Frank; Cloutier, Conrad; Michaud, Dominique

    2016-04-01

    A causal link has been reported between positively selected amino acids in plant cystatins and the inhibitory range of these proteins against insect digestive cysteine (Cys) proteases. Here we assessed the impact of single substitutions to closely related amino acids on the contribution of positive selection to cystatin diversification. Cystatin sequence alignments, while confirming hypervariability, indicated a preference for related amino acids at positively selected sites. For example, the non-polar residues leucine (Leu), isoleucine (Ile) and valine (Val) were shown to predominate at positively selected site 2 in the N-terminal region, unlike selected sites 6 and 10, where polar residues are preferred. The model cystatin SlCYS8 and single variants with Leu, Ile or Val at position 2 were compared with regard to their ability to bind digestive proteases of the coleopteran pest Leptinotarsa decemlineata and to induce compensatory responses in this insect. A functional proteomics procedure to capture target Cys proteases in midgut extracts allowed confirmation of distinct binding profiles for the cystatin variants. A shotgun proteomics procedure to monitor whole Cys protease complements revealed protease family specific compensatory responses in the insect, dependent on the variant ingested. Our data confirm the contribution of closely related amino acids to the functional diversity of positively selected plant cystatins in a broader structure/function context imposing physicochemical constraints to primary structure alterations. They also underline the complexity of protease/inhibitor interactions in plant-insect systems, and the challenges still to be met in order to harness the full potential of ectopically expressed protease inhibitors in crop protection. PMID:26833679

  18. Examining the Competition for Forest Resources in Sweden Using Factor Substitution Analysis and Partial Equilibrium Modelling

    Olsson, Anna

    2011-07-01

    The overall objective of the thesis is to analyse the procurement competition for forest resources in Sweden. The thesis consists of an introductory part and two self-contained papers. In paper I a translog cost function approach is used to analyse the factor substitution in the sawmill industry, the pulp and paper industry and the heating industry in Sweden over the period 1970 to 2008. The estimated parameters are used to calculate the Allen and Morishima elasticities of substitution as well as the price elasticities of input demand. The utilisation of forest resources in the energy sector has been increasing and this increase is believed to continue. The increase is, to a large extent, caused by economic policies introduced to reduce the emission of greenhouse gases. Such policies could lead to an increase in the procurement competition between the forest industries and the energy sector. The calculated substitution elasticities indicate that it is easier for the heating industry to substitutes between by-products and logging residues than it is for the pulp and paper industry to substitute between by-products and roundwood. This suggests that the pulp and paper industry could suffer from an increase in the procurement competition. However, overall the substitutions elasticities estimated in our study are relatively low. This indicates that substitution possibilities could be rather limited due to rigidities in input prices. This result suggests that competition of forest resources also might be relatively limited. In paper II a partial equilibrium model is constructed in order to asses the effects an increasing utilisation of forest resources in the energy sector. The increasing utilisation of forest fuel is, to a large extent, caused by economic policies introduced to reduce the emission of greenhouse gases. In countries where forests already are highly utilised such policies will lead to an increase in the procurement competition between the forest sector and

  19. Effect of a bulky lateral substitution by chlorine atom and methoxy group on self-assembling properties of lactic acid derivatives

    Several chiral liquid crystalline materials derived from the lactic acid have been studied with the aim to establish the effect of bulky lateral substituents on their self-assembling properties. A chlorine atom and methoxy group have been used as lateral substituents in ortho position to ether group position on phenyl ring far from the chiral centre. All the studied materials possess tilted ferroelectric smectic C* phase in a broad temperature range. In dependence on the molecular structure namely type of lateral substituent and length of the chiral chain, the cholesteric mesophase, orthogonal paraelectric smectic A* and crystal mesophases have been detected. Lateral chlorine substitution results in decrease of both the clearing point and crystallisation temperature as well as in a distinct increase of spontaneous polarization. Bulky methoxy substitution slightly suppresses the spontaneous polarisation but strongly increases the melting point that results in monotropic peculiarity of the SmC* phase. Mesomorphic, spontaneous, structural and dielectric properties of the substituted compounds were established and compared to those of the non-substituted ones in order to contribute to better understanding of the structure–property relationship for such chiral self-assembling materials. - Highlights: • Chiral liquid crystalline materials derived from the lactic acid have been studied. • Effect of bulky lateral substituents on self-assembling properties has been established. • Bulky methoxy substitution suppresses spontaneous polarisation but increases the melting point. • The compounds might have a strong potential for many advanced electro-optic applications

  20. Effect of a bulky lateral substitution by chlorine atom and methoxy group on self-assembling properties of lactic acid derivatives

    Stojanović, Maja, E-mail: maja.stojanovic@df.uns.ac.rs [Department of Physics, Faculty of Sciences, University of Novi Sad, Trg D.Obradovića 4, 21000 Novi Sad (Serbia); Bubnov, Alexej [Institute of Physics, Academy of Sciences of the Czech Republic, Na Slovance 2, 182 21 Prague (Czech Republic); Obadović, Dušanka Ž. [Department of Physics, Faculty of Sciences, University of Novi Sad, Trg D.Obradovića 4, 21000 Novi Sad (Serbia); Hamplová, Věra [Institute of Physics, Academy of Sciences of the Czech Republic, Na Slovance 2, 182 21 Prague (Czech Republic); Cvetinov, Miroslav [Department of Physics, Faculty of Sciences, University of Novi Sad, Trg D.Obradovića 4, 21000 Novi Sad (Serbia); Kašpar, Miroslav [Institute of Physics, Academy of Sciences of the Czech Republic, Na Slovance 2, 182 21 Prague (Czech Republic)

    2014-07-01

    Several chiral liquid crystalline materials derived from the lactic acid have been studied with the aim to establish the effect of bulky lateral substituents on their self-assembling properties. A chlorine atom and methoxy group have been used as lateral substituents in ortho position to ether group position on phenyl ring far from the chiral centre. All the studied materials possess tilted ferroelectric smectic C* phase in a broad temperature range. In dependence on the molecular structure namely type of lateral substituent and length of the chiral chain, the cholesteric mesophase, orthogonal paraelectric smectic A* and crystal mesophases have been detected. Lateral chlorine substitution results in decrease of both the clearing point and crystallisation temperature as well as in a distinct increase of spontaneous polarization. Bulky methoxy substitution slightly suppresses the spontaneous polarisation but strongly increases the melting point that results in monotropic peculiarity of the SmC* phase. Mesomorphic, spontaneous, structural and dielectric properties of the substituted compounds were established and compared to those of the non-substituted ones in order to contribute to better understanding of the structure–property relationship for such chiral self-assembling materials. - Highlights: • Chiral liquid crystalline materials derived from the lactic acid have been studied. • Effect of bulky lateral substituents on self-assembling properties has been established. • Bulky methoxy substitution suppresses spontaneous polarisation but increases the melting point. • The compounds might have a strong potential for many advanced electro-optic applications.

  1. Amino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae.

    Cheng, Yi-Hsiang; Lin, Tzu-Lung; Lin, Yi-Tsung; Wang, Jin-Town

    2016-06-01

    Colistin is a last-resort antibiotic for treatment of carbapenem-resistant Klebsiella pneumoniae A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistant K. pneumoniae clinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study, crrAB sequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generate crrB loci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in colistin MICs. These crrB mutants showed increased accumulation of H239_3062, H239_3059, pmrA, pmrC, and pmrH transcripts by quantitative reverse transcription (qRT)-PCR. Deletion of H239_3062 (but not that of H239_3059) in the A4528 crrB(N141I) strain attenuated resistance to colistin, and H239_3062 was accordingly named crrC Similarly, accumulation of pmrA, pmrC, and pmrH transcripts induced by crrB(N141I) was significantly attenuated upon deletion of crrC Complementation of crrC restored resistance to colistin and accumulation of pmrA, pmrC, and pmrH transcripts in a crrB(N141I) ΔcrrC strain. In conclusion, novel individual CrrB amino acid substitutions (Y31H, W140R, N141I, P151S, and S195N) were shown to be responsible for colistin resistance. We hypothesize that CrrB mutations induce CrrC expression, thereby inducing elevated expression of the pmrHFIJKLM operon and pmrC (an effect mediated via the PmrAB two-component system) and yielding increased colistin resistance. PMID:27067316

  2. Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

    Tyurenkov, I N; Borodkina, L E; Bagmetova, V V; Berestovitskaya, V M; Vasil'eva, O S

    2016-02-01

    GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut. PMID:26906198

  3. Efficacious rat model displays non-toxic effect with Korean beechwood creosote: a possible antibiotic substitute

    Quynh, Anh Nguyen Thai; Sharma, Neelesh; Cho, Kwang Keun; Yeo, Tae Jong; Kim, Ki Beom; Jeong, Chul Yon; Min, Tae Sun; Young, Kim Jae; Kim, Jin Nam; Jeong, Dong-Kee

    2014-01-01

    Wood creosote, an herbal anti-diarrheal and a mixture of major volatile compounds, was tested for its non-toxicological effects, using a rat model, with the objective to use the creosote as an antibiotic substitute. A total of 30 Sprague-Dawley rats were studied to form five groups with 6 rats each. Korea beechwood creosote was supplemented into three test groups with 0.03 g/kg, 0.07 g/kg and 0.1 g/kg body weight/day without antibiotic support, along with a positive control of Apramycin sulph...

  4. Determination and structural correlation of the pKa values of p-substituted trans-2,3-epoxy-4-oxo-4-phenylbutanoic acids

    I. JURANIC

    2000-11-01

    Full Text Available The pKa values for a series of eight p-substituted trans-2,3-epoxy-4-phenyl butanoic acids (p-substituted trans-b-aroylepoxyacrylic acids have been determined potentiometrically in aqueous media at 25°C at an ionic strength of 0.1 mol/dm3 (NaCl. The transmission of polar effects from the substituents on the phenyl nucleus to the carboxylic group through the side chain involving a carbonyl group and an epoxide ring was investigated. The pKa values were correlated with structure using the Hammett, Taft and Yukawa-Tsuno approaches. The Hammett r constant (0.34 was compared with analogue values for structurally similar acids.

  5. Parvovirus B19 Genotype Specific Amino Acid Substitution in NS1 Reduces the Protein's Cytotoxicity in Culture

    Violetta Kivovich, Leona Gilbert, Matti Vuento, Stanley J. Naides

    2010-01-01

    Full Text Available A clinical association between idiopathic liver disease and parvovirus B19 infection has been observed. Fulminant liver failure, not associated with other liver-tropic viruses, has been attributed to B19 in numerous reports, suggesting a possible role for B19 components in the extensive hepatocyte cytotoxicity observed in this condition. A recent report by Abe and colleagues (Int J Med Sci. 2007;4:105-9 demonstrated a link between persistent parvovirus B19 genotype I and III infection and fulminant liver failure. The genetic analysis of isolates obtained from these patients demonstrated a conservation of key amino acids in the nonstructural protein 1 (NS1 of the disease-associated genotypes. In this report we examine a conserved residue identified by Abe and colleagues and show that substitution of isoleucine 181 for methionine, as occurs in B19 genotype II, results in the reduction of B19 NS1-induced cytotoxicity of liver cells. Our results support the hypothesis that in the setting of persistent B19 infection, direct B19 NS1-induced cytotoxicity may play a role in idiopathic fulminant liver failure.

  6. Improvement of the reverse tetracycline transactivator by single amino acid substitutions that reduce leaky target gene expression to undetectable levels.

    Roney, Ian J; Rudner, Adam D; Couture, Jean-François; Kærn, Mads

    2016-01-01

    Conditional gene expression systems that enable inducible and reversible transcriptional control are essential research tools and have broad applications in biomedicine and biotechnology. The reverse tetracycline transcriptional activator is a canonical system for engineered gene expression control that enables graded and gratuitous modulation of target gene transcription in eukaryotes from yeast to human cell lines and transgenic animals. However, the system has a tendency to activate transcription even in the absence of tetracycline and this leaky target gene expression impedes its use. Here, we identify single amino-acid substitutions that greatly enhance the dynamic range of the system in yeast by reducing leaky transcription to undetectable levels while retaining high expression capacity in the presence of inducer. While the mutations increase the inducer concentration required for full induction, additional sensitivity-enhancing mutations can compensate for this effect and confer a high degree of robustness to the system. The novel transactivator variants will be useful in applications where tight and tunable regulation of gene expression is paramount. PMID:27323850

  7. Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids.

    Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A; Silva, K Ishara; Huang, Zhentai; Amoscato, Andrew A; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E

    2014-06-01

    Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance and electron spin echo envelope modulation) we demonstrated that TPP-n-ISAs indeed were able to potently suppress CL-induced structural rearrangements in Cyt c, paving the way to its peroxidase competence. TPP-n-ISA analogs preserved the low-spin hexa-coordinated heme-iron state in Cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of Cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of Cyt c/CL complexes with a significant antiapoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all-atom molecular dynamics simulations. Based on the experimental data and computation predictions, we identified TPP-6-ISA as a candidate drug with optimized antiapoptotic potency. PMID:24631490

  8. Non-Extensive Entropy Econometrics: New Statistical Features of Constant Elasticity of Substitution-Related Models

    Second Bwanakare

    2014-05-01

    Full Text Available Power-law (PL formalism is known to provide an appropriate framework for canonical modeling of nonlinear systems. We estimated three stochastically distinct models of constant elasticity of substitution (CES class functions as non-linear inverse problem and showed that these PL related functions should have a closed form. The first model is related to an aggregator production function, the second to an aggregator utility function (the Armington and the third to an aggregator technical transformation function. A q-generalization of K-L information divergence criterion function with a priori consistency constraints is proposed. Related inferential statistical indices are computed. The approach leads to robust estimation and to new findings about the true stochastic nature of this class of nonlinear—up until now—analytically intractable functions. Outputs from traditional econometric techniques (Shannon entropy, NLLS, GMM, ML are also presented.

  9. AN EOQ MODEL WITH PRICE AND TIME DEPENDENT DEMAND UNDER THE INFLUENCE OF COMPLEMENT AND SUBSTITUTE PRODUCT'S SELLING PRICES

    ,

    2010-01-01

    Demand for a product is affected by its own selling price. In many situations it has also been affected by its Complement's as well as substitute's selling prices. This effect can be observed in many retailed items all over the markets. In this paper, we developed finite replenishment inventory model while considering that demand is sensitive to changes in time, its selling price and prices of complementary and substitute good's. Numerical example and sensitivity analysis have been performed ...

  10. An evaluation of Substitute natural gas production from different coal gasification processes based on modeling

    Coal and lignite will play a significant role in the future energy production. However, the technical options for the reduction of CO2 emissions will define the extent of their share in the future energy mix. The production of synthetic or substitute natural gas (SNG) from solid fossil fuels seems to be a very attractive process: coal and lignite can be upgraded into a methane rich gas which can be transported and further used in high efficient power systems coupled with CO2 sequestration technologies. The aim of this paper is to present a modeling analysis comparison between substitute natural gas production from coal by means of allothermal steam gasification and autothermal oxygen gasification. In order to produce SNG from syngas several unit operations are required such as syngas cooling, cleaning, potential compression and, of course, methanation reactors. Finally the gas which is produced has to be conditioned i.e. removal of unwanted species, such as CO2 etc. The heat recovered from the overall process is utilized by a steam cycle, producing power. These processes were modeled with the computer software IPSEpro™. An energetic and exergetic analysis of the coal to SNG processes have been realized and compared. -- Highlights: ► The production of SNG from coal is examined. ► The components of the process were simulated for integrated autothermal or allothermal coal gasification to SNG. ► The energetic and exergetic evaluation of the two processes is presented.

  11. Effects of the substitution of amino acid residues, through chemical synthesis, on the conformation and activity of antimicrobial peptides

    Regina C. Adão

    2012-06-01

    Full Text Available Antimicrobial peptides make up an assorted group of molecules which contain from 12 to 50 amino acid residues and which may be produced by microorganisms, plants and animals. From the discovery that these biomolecules are lethal to bacteria, inhibiting the pathogenic organism’s growth, and are also related to innate and adapted defense mechanisms, the investigation of such molecules came to be an emergent research field, in which more than 1800 antimicrobial peptides have so far been discovered throughout the last three decades. These molecules are potential representatives of a new generation of antibiotic agents and the main motivation for such use is their activity against a wide variety of pathogens, including Gram-positive and Gram-negative bacteria as well as fungi and viruses. An important class of comprising some of these peptides may be found in anurans, from which it has been isolated, a considerable number of antimicrobial peptides with diverse sequences and structures, including linear and dimeric ones. In this work monomeric chains (CH1 e CH2 of the heterodimeric antimicrobial peptide distinctin (isolated in 1999 from Phyllomedusa distincta anurans, as well as its mutated monomers (CH1-S and CH2-S and the heterodimer itself were synthesized. The distinctin is the peptide with two chains of different sequences (Table 1 bound each other by disulfide bond from the cystein residues constituting the heterodimer. To investigate the effects on the biological activity by amino acids substitution at normal distinctin CH1 and CH2 chains, both were synthesized as well as their similar chains (CH1-S and CH2-S in which the cystein (Fig.1 a residues of each chain were changed by serin residues (Fig. 1 b. The new chains were named mutants. The synthesis was carried out in solid phase, using Fmoc strategy. The heterodimer distinctin was obtained from CH1 and CH2 chains coupling through cystein residues air oxidation. The results from HPLC

  12. FASTSUBS: An Efficient Admissible Algorithm for Finding the Most Likely Lexical Substitutes Using a Statistical Language Model

    Yuret, Deniz

    2012-01-01

    Lexical substitutes have found use in the context of word sense disambiguation, unsupervised part-of-speech induction, paraphrasing, machine translation, and text simplification. Using a statistical language model to find the most likely substitutes in a given context is a successful approach, but the cost of a naive algorithm is proportional to the vocabulary size. This paper presents the Fastsubs algorithm which can efficiently and correctly identify the most likely lexical substitutes for a given context based on a statistical language model without going through most of the vocabulary. The efficiency of Fastsubs makes large scale experiments based on lexical substitutes feasible. For example, it is possible to compute the top 10 substitutes for each one of the 1,173,766 tokens in Penn Treebank in about 6 hours on a typical workstation. The same task would take about 6 days with the naive algorithm. An implementation of the algorithm and a dataset with the top 100 substitutes of each token in the WSJ secti...

  13. Optimization of immunoglobulin substitution therapy by a stochastic immune response model.

    Marc Thilo Figge

    Full Text Available BACKGROUND: The immune system is a complex adaptive system of cells and molecules that are interwoven in a highly organized communication network. Primary immune deficiencies are disorders in which essential parts of the immune system are absent or do not function according to plan. X-linked agammaglobulinemia is a B-lymphocyte maturation disorder in which the production of immunoglobulin is prohibited by a genetic defect. Patients have to be put on life-long immunoglobulin substitution therapy in order to prevent recurrent and persistent opportunistic infections. METHODOLOGY: We formulate an immune response model in terms of stochastic differential equations and perform a systematic analysis of empirical therapy protocols that differ in the treatment frequency. The model accounts for the immunoglobulin reduction by natural degradation and by antigenic consumption, as well as for the periodic immunoglobulin replenishment that gives rise to an inhomogeneous distribution of immunoglobulin specificities in the shape space. Results are obtained from computer simulations and from analytical calculations within the framework of the Fokker-Planck formalism, which enables us to derive closed expressions for undetermined model parameters such as the infection clearance rate. CONCLUSIONS: We find that the critical value of the clearance rate, below which a chronic infection develops, is strongly dependent on the strength of fluctuations in the administered immunoglobulin dose per treatment and is an increasing function of the treatment frequency. The comparative analysis of therapy protocols with regard to the treatment frequency yields quantitative predictions of therapeutic relevance, where the choice of the optimal treatment frequency reveals a conflict of competing interests: In order to diminish immunomodulatory effects and to make good economic sense, therapeutic immunoglobulin levels should be kept close to physiological levels, implying high

  14. Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

    Sándor B. Ötvös

    2013-07-01

    Full Text Available The preparation of novel multi-substituted 1,2,3-triazole-modified β-aminocyclohexanecarboxylic acid derivatives in a simple and efficient continuous-flow procedure is reported. The 1,3-dipolar cycloaddition reactions were performed with copper powder as a readily accessible Cu(I source. Initially, high reaction rates were achieved under high-pressure/high-temperature conditions. Subsequently, the reaction temperature was lowered to room temperature by the joint use of both basic and acidic additives to improve the safety of the synthesis, as azides were to be handled as unstable reactants. Scale-up experiments were also performed, which led to the achievement of gram-scale production in a safe and straightforward way. The obtained 1,2,3-triazole-substituted β-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects.

  15. Identification and analysis of 21 novel disease-causing amino acid substitutions in the conserved part of ATP7A

    Moller, L.B.; Bukrinsky, J.T.; Mølgaard, Anne; Paulsen, M.; Lund, C.; Tumer, Z.; Larsen, S.; Horn, N.

    2005-01-01

    ATP7A encodes a copper. translocating ATPase that belongs to the large family of P-type ATPases. Eight conserved regions define the core of the P-type ATPase superfamily. We report here the identification of 21 novel missense mutations in the conserved part of ATP7A that encodes the residues p.V842......-p.S1404. Using the coordinates of X-ray crystal structures of the sarcoplasmic reticulum Ca2+-ATPase, as determined in the presence and absence of Ca2+, we created structural homology models of ATP7A. By mapping the substituted residues onto the models, we found that these residues are more...... number of the mutated ATP7A protein variants was correct. In the absence of copper, they were located in perinuclear regions of the cells, just like the wild type. However, two of the mutated ATP7A variants showed only partly correct localization, and in five cultures no ATP7A protein could be detected...

  16. 6-Substituted 2-Oxo-2h-1-Benzopyran-3-Carboxylic Acid Derivatives in a New Approach of the Treatment of Cancer Cell Invasion and Metastasis

    Kempen, I; Hemmer, Marc; Counerotte, Stéphane; Pochet, L.; De Tullio, Pascal; Foidart, Jean-Michel; Blacher, Silvia; Noël, Agnès; Frankenne, Francis; Pirotte, Bernard

    2008-01-01

    Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were synthesized and their potency in reducing the invasive behaviour of HT 1080 fibrosarcoma cells was evaluated. Structure-activity relationships were deduced from biological results and will be used in further design of new active compounds. In particular, the acetoxymethyl substituent found at the 6-position of previously described active compounds can be replaced by an acetamidomethyl substituent without loss of pote...

  17. The R467K Amino Acid Substitution in Candida albicans Sterol 14α-Demethylase Causes Drug Resistance through Reduced Affinity

    Lamb, David C.; Kelly, Diane E.; White, Theodore C.; Kelly, Steven L.

    2000-01-01

    The cytochrome P450 sterol 14α-demethylase (CYP51) of Candida albicans is involved in an essential step of ergosterol biosynthesis and is the target for azole antifungal compounds. We have undertaken site-directed mutation of C. albicans CYP51 to produce a recombinant mutant protein with the amino acid substitution R467K corresponding to a mutation observed clinically. This alteration perturbed the heme environment causing an altered reduced-carbon monoxide difference spectrum with a maximum ...

  18. Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles

    Singh Jagbir; Michel Deborah; Chitanda Jackson M; Verrall Ronald E; Badea Ildiko

    2012-01-01

    Abstract Background Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted ge...

  19. Brøsted Acidic Ionic Liquid ([Bmim]Hso4 Promoted Cyclocodensation Reaction: Synthesis of 3,4,5-Substituted Furan-2(5h-Ones

    Sajjad Salahi

    2015-12-01

    Full Text Available 1-Butyl-3-methylimidazolium hydrogen sulfate [bmim]HSO4: an acidic ionic liquid was used as a catalyst for the synthesis of heterocyclic compounds 3,4,5-substituted furan-2(5H-ones from aniline derivatives, dialkyl acetylenedicarboxylates and aromatic aldehydes at 75 °C. Solvent-free conditions, shorter reaction time, and good yields (71-94% are some of advantages.

  20. Hydroxyapatite-calcium sulfate-hyaluronic acid composite encapsulated with collagenase as bone substitute for alveolar bone regeneration.

    Subramaniam, Sadhasivam; Fang, Yen-Hsin; Sivasubramanian, Savitha; Lin, Feng-Huei; Lin, Chun-pin

    2016-01-01

    Periodontitis is a very severe inflammatory condition of the periodontium that progressively damages the soft tissue and destroys the alveolar bone that supports the teeth. The bone loss is naturally irreversible because of limited reparability of the teeth. Advancement in tissue engineering provides an effective regeneration of osseous defects with suitable dental implants or tissue-engineered constructs. This study reports a hydroxyapatite, calcium sulfate hemihydrate and hyaluronic acid laden collagenase (HAP/CS/HA-Col) as a bone substitute for the alveolar bone regeneration. The composite material was mechanically tested and the biocompatibility was evaluated by WST-1 assay. The in vivo bone formation was assessed in rat with alveolar bone defects and the bone augmentation by the HAP/CS/HA-Col composite was confirmed by micro-CT images and histological examination. The mechanical strength of 6.69 MPa with excellent biocompatibility was obtained for the HAP/CS/HA-Col composite. The collagenase release profile had facilitated the acceleration of bone remodeling process and it was confirmed by the findings of micro-CT and H&E staining. The bone defects implanted with HAP/CS/HA composite containing 2 mg/mL type I collagenase have shown improved new bone formation with matured bone morphology in comparison with the HAP/CS/HA composite that lacks the collagenase and the porous hydroxyapatite (p-HAP) granules. The said findings demonstrated that the collagenase inclusion in HAP/CS/HA composite is a feasible approach for the alveolar bone regeneration and the same design can also be applied to other defective tissues. PMID:26454048

  1. Effects of Single Amino Acid Substitution on the Biophysical Properties and Biological Activities of an Amphipathic α-Helical Antibacterial Peptide Against Gram-Negative Bacteria

    Juanjuan Tan

    2014-07-01

    Full Text Available An antimicrobial peptide, known as V13K, was utilized as the framework to study the effects of charge, hydrophobicity and helicity on the biophysical properties and biological activities of α-helical peptides. Six amino acids (Lys, Glu, Gly, Ser, Ala, and Leu were individually used to substitute the original hydrophobic valine at the selected sixteenth location on the non-polar face of V13K. The results showed that the single amino acid substitutions changed the hydrophobicity of peptide analogs as monitored by RP-HPLC, but did not cause significant changes on peptide secondary structures both in a benign buffer and in a hydrophobic environment. The biological activities of the analogs exhibited a hydrophobicity-dependent behavior. The mechanism of peptide interaction with the outer membrane and cytoplasmic membrane of Gram-negative bacteria was investigated. We demonstrated that this single amino acid substitution method has valuable potential for the rational design of antimicrobial peptides with enhanced activities.

  2. Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels.

    Guo, Kai; Wang, Xianming; Gao, Guofeng; Huang, Congxin; Elmslie, Keith S; Peterson, Blaise Z

    2010-11-01

    We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149-1159, 2010). The short 17 amino acid extracellular NH(2)-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and Asp-12 significantly enhanced the ability of PLM to modulate Ca(V)1.2 gating. T10A exhibited a twofold enhancement of PLM-induced slowing of activation, whereas D12K and D12C dramatically enhanced PLM-induced increase of VDI. The PLM-induced slowing of channel closing was abrogated by D12A and D12C, whereas D12K and T10A failed to impact this effect. These studies demonstrate that the PFXYD motif is not necessary for the association of PLM with Ca(V)1.2. Instead, since altering the chemical and/or physical properties of the PFXYD segment alters the relative magnitudes of opposing PLM-induced effects on Ca(V)1.2 channel gating, PLM appears to play an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca(2+) dynamics in the heart. PMID:20720179

  3. Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus.

    Mateu, M G; Martínez, M A; Rocha, E.; Andreu, D; Parejo, J; Giralt, E.; Sobrino, F; Domingo, E

    1989-01-01

    We provide evidence that the quasispecies nature (extreme genetic heterogeneity) of foot-and-mouth disease virus is relevant to the virus evading an immune response. A monoclonal antibody neutralizing the viral infectivity (clone SD6) recognizes an epitope located around a highly conserved sequence (amino acid sequence Arg-Gly-Asp-Leu-Ala at positions 141-145) in the capsid protein VP1 of foot-and-mouth disease virus of serotype C1. The amino acid substitutions Ala-138----Thr and Leu-147----I...

  4. Molybdenum (VI) binded to humic and nitrohumic acid models in aqueous solutions salicylic, 3-nitrosalicylic, 5-nitrosalicylic and 3,5 dinitrosalicylic acids, Part 2

    In this work electrochemical and Ultraviolet-Visible studies were performed in solutions of salicylic acid models of humic and nitrohumic acids, a laboratory artifact, and molybdenum in order to determine the affinity of these models towards the metal ion. Molybdenum, which plays a very important role in the soil chemistry, and together with humic substances, impart fertility to soil and water and is a key element in the activity of nitrogenase. The obtained results showed that at least one complexed species is present at the pH range of 6.3 to 8.0, even for the less basic chosen models, the nitrosalicylic acids. Previous study showed that phthalic and nitrophthalic, also humic and nitrohumic acids model compounds, presented complexed species with molybdenum only till pH 6.5. The calculated formation constants showed that the substitution of the nitro group in the orto position was less favoured than in the para substitution, probably due to a steric hindrance in the former, which was clearly seen in the double substituted salicylic nitro derivative. The cyclic voltammetry as well as the Ultraviolet-Visible obtained spectra were able to show that the chemistry of molybdenum in aqueous solutions as the pH is increased is very complex, and the molybdate stops acting as an anion only after pH around 4, when it finally becomes a cation MoO22+ (M). (author)

  5. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  6. Amino acid residue Y196E substitution and C-terminal peptide synergistically alleviate the toxicity of Clostridium perfringens epsilon toxin.

    Yao, Wenwu; Kang, Lin; Gao, Shan; Zhuang, Xiangjin; Zhang, Tao; Yang, Hao; Ji, Bin; Xin, Wenwen; Wang, Jinglin

    2015-06-15

    Epsilon toxin (ETX) is produced by Clostridium perfringens type B and D strains, and is the causative agent of a lethal enterotoxemia in livestock animals and possibly in humans. However, many details of ETX structure and activity are not known. Therefore, it is important to clarify the relationship between ETX structure and activity. To explore the effect and mechanism of ETX amino acid residue Y196E substitution and C-terminal peptide on toxicity, four recombinant proteins, rETX (without 13 N-terminal peptides and 23 C-terminal peptides), rETX-C (rETX with 23 C-terminal peptides), rETX(Y196E) (rETX with an amino acid residue substitution at Y196) and rETX(Y196E)-C (rETX-C with a Y196E mutation), were constructed in this study. Both the amino acid residue Y196E substitution and the C-terminal peptide reduce ETX toxicity to a similar extent, and the two factors synergistically alleviate ETX toxicity. In addition, we demonstrated that the C-terminal peptides and Y196E amino acid mutation reduce the toxin toxicity in two different pathways: the C-terminal peptides inhibit the binding activity of toxins to target cells, and the Y196E amino acid mutation slightly inhibits the pore-forming or heptamer-forming process. Interaction between the two factors was not observed in pore-forming or binding assays but toxicity assays, which demonstrated that the relationship between domains of the toxin is more complicated than previously appreciated. However, the exact mechanism of synergistic action is not yet clarified. PMID:25912943

  7. Determination of small halogenated carboxylic acid residues in drug substances by high performance liquid chromatography-diode array detection following derivatization with nitro-substituted phenylhydrazines.

    Hou, Desheng; Fan, Jingjing; Han, Lingfei; Ruan, Xiaoling; Feng, Feng; Liu, Wenyuan; Zheng, Feng

    2016-03-18

    A method for the determination of small halogenated carboxylic acid (HCA) residues in drug substances is urgently needed because of the potential of HCAs for genotoxicity and carcinogenicity in humans. We have now developed a simple method, involving derivatization followed by high performance liquid chromatography-diode array detection (HPLC-DAD), for the determination of six likely residual HCAs (monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, 2-chloropropionic acid, 2-bromopropionic acid and 3-chloropropionic acid) in drug substances. Different nitro-substituted phenylhydrazines (NPHs) derivatization reagents were systematically compared and evaluated. 2-Nitrophenylhydrazine hydrochloride (2-NPH·HCl) was selected as the most suitable choice since its derivatives absorb strongly at 392 nm, a region of the spectrum where most drug substances and impurities absorb very weakly. During the derivatization process, the commonly used catalyst, pyridine, caused rapid dechlorination or chlorine substitution of α-halogenated derivatives. To avoid these unwanted side reactions, a reliable derivatization method that did not use pyridine was developed. Reaction with 2-NPH·HCl using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as coupling agent in acetonitrile-water (70:30) at room temperature for 2h gave complete reaction and avoided degradation products. The derivatives were analyzed, without any pretreatment, using gradient HPLC with detection in the near visible region. Organic acids commonly found in drug substances and other impurities did not interfere with the analysis. Good linearity (r>0.999) and low limits of quantitation (0.05-0.12 μg mL(-1)) were obtained. The mean recoveries were in the range of 80-115% with RSD <5.81% except for 3-CPA in ibuprofen which was 78.5%. The intra- and inter-day precisions were expressed as RSD <1.98% and <4.39%, respectively. Finally, the proposed method was successfully used for the residue

  8. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance

  9. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

    Zhang, Xinsheng, E-mail: xzhang@iavi.org [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY (United States); Wallace, Olivia L.; Domi, Arban; Wright, Kevin J.; Driscoll, Jonathan [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Anzala, Omu [Kenya AIDS Vaccine Initiative (KAVI)-Institute of Clinical Research, Nairobi (Kenya); Sanders, Eduard J. [Centre for Geographic Medicine Research, Kenya Medical Research Institute (KEMRI), Kilifi, Kenya & Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Headington (United Kingdom); Kamali, Anatoli [MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka and Entebbe (Uganda); Karita, Etienne [Projet San Francisco, Kigali (Rwanda); Allen, Susan [Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA (United States); Fast, Pat [Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY (United States); Gilmour, Jill [Human Immunology Laboratory, International AIDS Vaccine Initiative, London (United Kingdom); Price, Matt A. [Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY (United States); Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA (United States); Parks, Christopher L. [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY (United States)

    2015-08-15

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.

  10. Assessing the relative importance of the biophysical properties of amino acid substitutions associated with human genetic disease

    Terp, Bent N; Cooper, David N; Christensen, Inge T; Jørgensen, Flemming Steen; Bross, Peter Gerd; Gregersen, Niels; Krawczak, Michael

    2002-01-01

    five human genes encoding arylsulphatase A (ARSA), antithrombin III (SERPINC1), protein C (PROC), phenylalanine hydroxylase (PAH), and transthyretin (TTR). These proteins were chosen on the basis of 1) the availability of a crystallographic structure, and 2) a sufficiently large number of amino acid...... replacements being logged in HGMD. A total of 9,795 possible mutant structures were modeled and 20 different biophysical parameters assessed. Together with the HGMD-derived spectra of clinically detected mutations, these data allowed maximum likelihood estimation of RCOL profiles for the 20 parameters studied...

  11. PHOSPHORUS PENTOXIDE-METHANESULFONIC ACID CATALYZED EFFICIENT SYNTHESIS OF 5-SUBSTITUTED 1H-TETRAZOLE DERIVATIVES Phosphorpentoxid-Methansulfonsäure KATALYSIERTEN EFFICIENT Synthese von 5-substituierten 1H-Tetrazolderivate

    Amulrao U. Borse,Mahesh N. Patil, Nilesh L. Patil, and Sandesh R. Tetgure

    2012-01-01

    The mixture of phosphorus pentoxide-methanesulfonic acid (Eaton’s reagent) is prove to be an efficient protocol for the [3+2] cycloaddition reaction between sodium azide and organic nitriles to give the corresponding 5-substituted 1H-tetrazole derivatives in good to excellent yields. The in situ formation of hydrazoic acid helps for the [3+2] cycloaddition reaction providing 5- substituted 1H-tetrazole with short reaction time.

  12. PHOSPHORUS PENTOXIDE-METHANESULFONIC ACID CATALYZED EFFICIENT SYNTHESIS OF 5-SUBSTITUTED 1H-TETRAZOLE DERIVATIVES Phosphorpentoxid-Methansulfonsäure KATALYSIERTEN EFFICIENT Synthese von 5-substituierten 1H-Tetrazolderivate

    Amulrao U. Borse,Mahesh N. Patil, Nilesh L. Patil, and Sandesh R. Tetgure

    2012-07-01

    Full Text Available The mixture of phosphorus pentoxide-methanesulfonic acid (Eaton’s reagent is prove to be an efficient protocol for the [3+2] cycloaddition reaction between sodium azide and organic nitriles to give the corresponding 5-substituted 1H-tetrazole derivatives in good to excellent yields. The in situ formation of hydrazoic acid helps for the [3+2] cycloaddition reaction providing 5- substituted 1H-tetrazole with short reaction time.

  13. Modeling particulate matter concentrations measured through mobile monitoring in a deletion/substitution/addition approach

    Su, Jason G.; Hopke, Philip K.; Tian, Yilin; Baldwin, Nichole; Thurston, Sally W.; Evans, Kristin; Rich, David Q.

    2015-12-01

    Land use regression modeling (LUR) through local scale circular modeling domains has been used to predict traffic-related air pollution such as nitrogen oxides (NOX). LUR modeling for fine particulate matters (PM), which generally have smaller spatial gradients than NOX, has been typically applied for studies involving multiple study regions. To increase the spatial coverage for fine PM and key constituent concentrations, we designed a mobile monitoring network in Monroe County, New York to measure pollutant concentrations of black carbon (BC, wavelength at 880 nm), ultraviolet black carbon (UVBC, wavelength at 3700 nm) and Delta-C (the difference between the UVBC and BC concentrations) using the Clarkson University Mobile Air Pollution Monitoring Laboratory (MAPL). A Deletion/Substitution/Addition (D/S/A) algorithm was conducted, which used circular buffers as a basis for statistics. The algorithm maximizes the prediction accuracy for locations without measurements using the V-fold cross-validation technique, and it reduces overfitting compared to other approaches. We found that the D/S/A LUR modeling approach could achieve good results, with prediction powers of 60%, 63%, and 61%, respectively, for BC, UVBC, and Delta-C. The advantage of mobile monitoring is that it can monitor pollutant concentrations at hundreds of spatial points in a region, rather than the typical less than 100 points from a fixed site saturation monitoring network. This research indicates that a mobile saturation sampling network, when combined with proper modeling techniques, can uncover small area variations (e.g., 10 m) in particulate matter concentrations.

  14. Unique equilibria and substitution effects in a stochastic model of the marriage market

    Decker, Colin; McCann, Robert J; Stephens, Benjamin K

    2010-01-01

    Choo-Siow (2006) propose a very general model for the marriage market which allows for randomly identically distributed noise in the preferences of each of the participants. The randomness is McFadden-type, which permits an explicit resolution of the equilibrium preference probabilities. We prove existence and uniqueness of the resulting equilibrium marriage distribution, and find a representation of it in closed form. This allows us to derive smooth dependence of this distribution on exogenous preference and population parameters, and establish sign, symmetry, and size of the various substitution effects, making comparative statics possible. For example, we show that an increase in the population of men of any given type in this model leads to an increase in single men of each type, and a decrease in single women of each type. We show that an increase in the number of men of a given type increases the equilibrium transfer paid by such men to their spouses, and also increases the percentage of men of that typ...

  15. Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

    Rajendra Surasani

    2012-11-01

    Full Text Available Simple and efficient procedures for palladium-catalyzed cross-coupling reactions of N-substituted 4-bromo-7-azaindole (1H-pyrrole[2,3-b]pyridine, with amides, amines, amino acid esters and phenols through C–N and C–O bond formation have been developed. The C–N cross-coupling reaction of amides, amines and amino acid esters takes place rapidly by using the combination of Xantphos, Cs2CO3, dioxane and palladium catalyst precursors Pd(OAc2/Pd2(dba3. The combination of Pd(OAc2, Xantphos, K2CO3 and dioxane was found to be crucial for the C–O cross-coupling reaction. This is the first report on coupling of amides, amino acid esters and phenols with N-protected 4-bromo-7-azaindole derivatives.

  16. Enhancement of the Luminance Efficiency in Organic Light-Emitting Devices with p-Substituted Phenylphosphonic-Acid Self-Assembled Monolayers.

    Kim, Min Sung; Jeon, Young Pyo; Kim, Youngwoo; Noh, Jaegeun; Kim, Tae Whan

    2015-07-01

    Organic light-emitting devices (OLEDs) containing self-assembled monolayers (SAMs) prepared by using p-substituted phenylphosponic acids on indium-tin-oxide electrodes were fabricated and examined to understand the substituent effect of the SAMs on the device performance. OLEDs modified by using (4-methoxyphenyl)phosphonic acid (MOPPA) SAMs or (4-chlorophenyl)phosphonic acid (CPPA) SAMs, both with electron withdrawing groups, had enhanced hole injection, reduced operating voltage, and remarkably increased current density and luminance efficiency compared with those without SAMs. The luminance efficiency which was the ratio of luminous flux to power for OLEDs containing CPPA SAMs and that for the OLEDs containing MOPPA SAMs were enhanced 2.2 and 1.9 times, respectively, in comparison with that of OLEDs without SAMs. CPPA SAMs significantly reduced the operating voltage of OLED by 24.8% compared with OLEDs without SAMs. PMID:26373078

  17. A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice▿

    Jiao, Peirong; Tian, Guobin; Li, Yanbing; Deng, Guohua; Jiang, Yongping; Liu, Chang; Liu, Weilong; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2008-01-01

    In this study, we explored the molecular basis determining the virulence of H5N1 avian influenza viruses in mammalian hosts by comparing two viruses, A/Duck/Guangxi/12/03 (DK/12) and A/Duck/Guangxi/27/03 (DK/27), which are genetically similar but differ in their pathogenicities in mice. To assess the genetic basis for this difference in virulence, we used reverse genetics to generate a series of reassortants and mutants of these two viruses. We found that a single-amino-acid substitution of serine for proline at position 42 (P42S) in the NS1 protein dramatically increased the virulence of the DK/12 virus in mice, whereas the substitution of proline for serine at the same position (S42P) completely attenuated the DK/27 virus. We further demonstrated that the amino acid S42 of NS1 is critical for the H5N1 influenza virus to antagonize host cell interferon induction and for the NS1 protein to prevent the double-stranded RNA-mediated activation of the NF-κB pathway and the IRF-3 pathway. Our results indicate that the NS1 protein is critical for the pathogenicity of H5N1 influenza viruses in mammalian hosts and that the amino acid S42 of NS1 plays a key role in undermining the antiviral immune response of the host cell. PMID:18032512

  18. The structure and properties of free radicals: An electron spin resonance study of radiation damage to nucleic acid and protein components and to some sulfur-substituted derivitives

    When cellular systems are exposed to ionizing radiation the long-term effects may range from minor disturbances to such dramatic changes as mutations and cell death. The processes leading to these macroscopical injuries are primarily confined at the molecular level. In all models aimed at a description of the action of radiation at the molecular level the formation of free radicals (which are species containing unpaired electrons) is a central concept. The technique of ESR spectroscopy is uniquely suited to study free radicals, as it is based on resonance absorption of energy by unpaired electrons in a magnetic field. ESR spectroscopy makes it possible to detect free radicals and, in some cases, to identify them. In order to study free radicals by ESR it is necessary to build up a sufficient number of unpaired spins in the sample (approximately 1011 or more, depending on the shape of the resonance). This may be different techniques have been used to trap the induced radicals or to attain a sufficient steady state concentration level. A procedure which seems to contain a large amount of information is to irradiate at low temperatures, and, by subsequent heat-treatment of the sample to study the reactions and fate of the induced radicals. In this thesis single crystal studies of aromatic amino acids and pyrimidine derivitives together with some substituted purine derivitives are presented, and the results are discussed in relation to the present knowledge about radical formation in these classes of compounds. Single crystal studies of some sulfur-containing aromatic compounds have been presented with the purpose of shedding light on the electronic structure of sulfur-centred radicals. (JIW)

  19. No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

    There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women

  20. A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice▿

    Jiao, Peirong; Tian, Guobin; Li, Yanbing; Deng, Guohua; Jiang, Yongping; Liu, Chang; Liu, Weilong; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2007-01-01

    In this study, we explored the molecular basis determining the virulence of H5N1 avian influenza viruses in mammalian hosts by comparing two viruses, A/Duck/Guangxi/12/03 (DK/12) and A/Duck/Guangxi/27/03 (DK/27), which are genetically similar but differ in their pathogenicities in mice. To assess the genetic basis for this difference in virulence, we used reverse genetics to generate a series of reassortants and mutants of these two viruses. We found that a single-amino-acid substitution of s...

  1. Solid-phase synthesis of amidine-substituted phenylbenzimidazoles and incorporation of this DNA binding and recognition motif into amino acid and peptide conjugates.

    Garner, Matthew L; Georgiadis, Taxiarchis M; Li, Jessica Bo; Wang, Tianxiu; Long, Eric C

    2014-05-01

    Amidine-substituted phenylbenzimidazoles are well-established DNA-binding structural motifs that have contributed to the development of diverse classes of DNA-targeted agents; this ring system not only assists in increasing the overall DNA affinity of an agent, but can also influence its site selectivity. Seeking a means to conveniently exploit these attributes, a protocol for the on-resin synthesis of amino acid- and peptide-phenylbenzimidazole-amidine conjugates was developed to facilitate installation of phenylbenzimidazole-amidines into peptide chains during the course of standard solid-phase syntheses. Building from a resin-bound amino acid or peptide on Rink amide resin, 4-formyl benzoic acid was coupled to the resin-bound free amine followed by introduction of 3,4-diamino-N'-hydroxybenzimidamide (in the presence of 1,4-benzoquinone) to construct the benzimidazole heterocycle. Finally, the resin-bound N'-hydroxybenzimidamide functionality was reduced to an amidine via 1 M SnCl2·2H2O in DMF prior to resin cleavage to release final product. This procedure permits the straightforward synthesis of amino acids or peptides that are N-terminally capped by a phenylbenzimidazole-amidine ring system. Employing this protocol, a series of amino acid-phenylbenzimidazole-amidine (Xaa-R) conjugates was synthesized as well as dipeptide conjugates of the general form Xaa-Gly-R (where R is the phenylbenzimidazole-amidine and Xaa is any amino acid). PMID:24562478

  2. A model of substitution of non-tariff barriers for tariffs

    Zhihao Yu

    2000-01-01

    In this paper some coherent explanations are suggested for tariff reductions and substitution of non-tariff barriers for tariffs, taking into account both organized special interests and unorganized consumer interests. The focus is on how the presence of informed consumers affects the political equilibrium choice of trade policy. Three effects are identified that interact with each other as an incumbent government substitutes a NTB for a tariff, and, among other things, it is found that an in...

  3. A substitute model of two-dimensional dry friction exposed to dither generated by rolling contact of wheel and rail

    Piotrowski, Jerzy

    2012-10-01

    Dither generated by rolling contact of wheel and rail smoothes dry friction damping provided by the primary suspension dampers of freight wagons and it should be taken into account in numerical simulations. But numerically the problem is non-smooth and this leads to long execution time during simulation, especially when the vehicle with friction dampers is modelled in the environment of an multi-body system simulation program, whose solver has to cope with many strong non-linearities. The other difficulty is the necessity of handling within the code a number of big volume files of recorded dither sampled with high frequency. To avoid these difficulties, a substitute model of two-dimensional dry friction exposed to dither is proposed that does not need application of dither during simulation, but it behaves as if dither were applied. Due to this property of the model, the excitation of the vehicle model by track irregularities may be supplied as low-frequency input, which allows fast execution and, the necessity of handling high-volume files of recorded dither is avoided. The substitute model is numerically effective. To identify parameters of the substitute model, a pre-processing employing a sample of the realistic dither is carried-out on a simple two-degrees-of-freedom system. The substitute model is anisotropic, describing anisotropic properties of the two-dimensional friction arising in the presence of one-dimensional dither. The model may be applied in other branches of engineering, for example, in mechatronics and robotics, where application of dither may improve the accuracy of positioning devices.

  4. Modelling the ecotoxicity of naphthenic acids

    Oil sand-derived process water is comprised of mixtures of many different toxic compounds. Recent modelling studies have been developed to assess oil sand ecotoxicity caused by naphthenic acids (NA). The hydrocarbon block method was used to described the ecotoxicity of NA mixtures using a database of physico-chemical properties for individual hydrocarbons. Chemical speciation and biota partitioning models are used to characterize the toxicity of ionizable compounds. An analysis of model predictions has suggested that high MW and compounds from the higher Z families contribute significantly to the ecotoxicity of oil sand-derived process water. However, the current modelling method overpredicts the toxicity of the highest residual fractions, which suggests that the bioavailability of the highest MW compounds is limited. Further model refinement is needed to evaluate NA compounds across a wide range of MW and Z families.

  5. Arsenic Scavenging by Al-Substituted Ferrihydrites in a Circumneutral pH River Impacted by the Acid Mine Drainage of Carnoulès, Gard, France

    ADRA, A.; Morin, G.; ona-Nguema, G.; Maillot, F.; Casiot, C.; Bruneel, O.

    2013-12-01

    Ferrihydrite (Fh) is a nanocrystalline ferric oxyhydroxide involved in the retention of pollutants in natural systems and in water-treatment processes. The status and properties of major chemical impurities in natural Fh is however still scarcely documented. Here we investigated the structure and reactivity of aluminum-rich Fh from river-bed sediments collected in a circumneutral river (pH 6-7) impacted by an arsenic-rich acid mine drainage (AMD). Extended X-ray absorption fine structure (EXAFS) spectroscopy at the Fe K-edge shows that Fh is the predominant mineral phase forming after neutralization of the AMD, in association with minor amount of schwertmannite transported from the AMD. EXAFS analysis indicates that Al(III) substitutes for Fe(III) ions into the Fh structure in the natural sediment samples, with local aluminum concentration within the 20-37×7 mol%Al range, in agreement with bulk chemical compositions. Synthetic aluminous Fh analogues prepared in the present study are found to be less Al-substituted (14-18×4 mol%Al). Finally, EXAFS analysis at the arsenic K-edge indicates that As(V) form similar inner-sphere surface complexes on the natural and synthetic Al-substituted Fh studied. Our results provide direct evidences for the scavenging of arsenic by natural Al- Fh, with possible implications for other pollutants in natural or engineered systems.

  6. Synthesis of a Stable Primary-Alkyl-Substituted Selenenyl Iodide and Its Hydrolytic Conversion to the Corresponding Selenenic Acid

    Shohei Sase; Ryo Kakimoto; Ryutaro Kimura; Kei Goto

    2015-01-01

    A primary-alkyl-substituted selenenyl iodide was successfully synthesized through oxidative iodination of a selenol with N-iodosuccinimide by taking advantage of a cavity-shaped steric protection group. The selenenyl iodide exhibited high thermal stability and remained unchanged upon heating at 100 °C for 3 h in [D8]toluene. The selenenyl iodide was reduced to the corresponding selenol by treatment with dithiothreitol. Hydrolysis of the selenenyl iodide under alkaline conditions afforded the ...

  7. Modulating the electronic structure of amino acids: interaction of model lewis acids with anthranilic acid

    Tareq Irshaidat

    2014-01-01

    On the basis of theoretical B3LYP calculations, Yáñez and co-workers (J. Chem. Theory Comput. 2012, 8, 2293) illustrated that beryllium ions are capable of significantly modulating (changing) the electronic structures of imidazole. In this computational organic chemistry study, the interaction of this β-amino acid and five model Lewis acids (BeF1+, Be2+, AlF2(1+), AlF2+, and Al3+) were investigated. Several aspects were addressed: natural bond orbitals, including second order perturbation ana...

  8. Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles

    2012-01-01

    Background Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted gemini surfactants that showed higher transfection efficiency than their parent compound. In this study, we evaluated the mechanism of cellular uptake of the plasmid/gemini surfactant/helper lipid nanoparticles and their effect on the transfection efficiency. Results Nanoparticles were incubated with Sf 1 Ep cells in the presence of different endocytic inhibitors and gene expression (interferon-γ) was measured using ELISA. Clathrin-mediated and caveolae-mediated uptake were found to be equally contributing to cellular internalization of both P/12-7NH-12/L (parent gemini surfactant) and P/12-7NGK-12/L (amino acid-substituted gemini surfactant) nanoparticles. The plasmid and the helper lipid were fluorescently tagged to track the nanoparticles inside the cells, using confocal laser scanning microscopy. Transmission electron microscopy images showed that the P/12-7NGK-12/L particles were cylindrical while the P/12-7NH-12/L particles were spherical which may influence the cellular uptake behaviour of these particles. Dye exclusion assay and pH-titration of the nanoparticles suggested that high buffering capacity, pH-dependent increase in particle size and balanced DNA binding properties may be contributing to a more efficient endosomal escape of P/12-7NGK-12/L compared to the P/12-7NH-12/L nanoparticles, leading to higher gene expression. Conclusion Amino-acid substitution in the spacer of gemini surfactant did not alter the cellular uptake pathway, showing similar pattern to the

  9. Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles

    Singh Jagbir

    2012-02-01

    Full Text Available Abstract Background Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted gemini surfactants that showed higher transfection efficiency than their parent compound. In this study, we evaluated the mechanism of cellular uptake of the plasmid/gemini surfactant/helper lipid nanoparticles and their effect on the transfection efficiency. Results Nanoparticles were incubated with Sf 1 Ep cells in the presence of different endocytic inhibitors and gene expression (interferon-γ was measured using ELISA. Clathrin-mediated and caveolae-mediated uptake were found to be equally contributing to cellular internalization of both P/12-7NH-12/L (parent gemini surfactant and P/12-7NGK-12/L (amino acid-substituted gemini surfactant nanoparticles. The plasmid and the helper lipid were fluorescently tagged to track the nanoparticles inside the cells, using confocal laser scanning microscopy. Transmission electron microscopy images showed that the P/12-7NGK-12/L particles were cylindrical while the P/12-7NH-12/L particles were spherical which may influence the cellular uptake behaviour of these particles. Dye exclusion assay and pH-titration of the nanoparticles suggested that high buffering capacity, pH-dependent increase in particle size and balanced DNA binding properties may be contributing to a more efficient endosomal escape of P/12-7NGK-12/L compared to the P/12-7NH-12/L nanoparticles, leading to higher gene expression. Conclusion Amino-acid substitution in the spacer of gemini surfactant did not alter the cellular uptake pathway, showing similar

  10. Expression, purification, crystallization and preliminary X-ray analysis of a novel N-substituted branched-chain l-amino-acid dioxygenase from Burkholderia ambifaria AMMD

    Diffraction data were collected to a limiting resolution of 2.4 Å from a crystal of selenomethionyl-labelled SadA, an l-amino-acid dioxygenase. Ferrous ion- and α-ketoglutarate-dependent dioxygenase from Burkholderia ambifaria AMMD (SadA) catalyzes the C3-hydroxylation of N-substituted branched-chain l-amino acids, especially N-succinyl-l-leucine, coupled to the conversion of α-ketoglutarate to succinate and CO2. SadA was expressed in Escherichia coli, purified and crystallized using the sitting-drop vapour-diffusion method at 293 K. Crystals of selenomethionine-substituted SadA were obtained using a reservoir solution containing PEG 3000 as the precipitant at pH 9.5 and diffracted X-rays to 2.4 Å resolution. The crystal belonged to space group P212121, with unit-cell parameters a = 49.3, b = 70.9, c = 148.2 Å. The calculated Matthews coefficient (VM = 2.1 Å3 Da−1, 41% solvent content) suggested that the crystal contains two molecules per asymmetric unit

  11. Synthesis, structure-activity, and structure-stability relationships of 2-substituted-N-(4-oxo-3-oxetanyl) N-acylethanolamine acid amidase (NAAA) inhibitors.

    Vitale, Romina; Ottonello, Giuliana; Petracca, Rita; Bertozzi, Sine Mandrup; Ponzano, Stefano; Armirotti, Andrea; Berteotti, Anna; Dionisi, Mauro; Cavalli, Andrea; Piomelli, Daniele; Bandiera, Tiziano; Bertozzi, Fabio

    2014-02-01

    N-Acylethanolamine acid amidase (NAAA) is a cysteine amidase that preferentially hydrolyzes saturated or monounsaturated fatty acid ethanolamides (FAEs), such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are endogenous agonists of nuclear peroxisome proliferator-activated receptor-α (PPAR-α). Compounds that feature an α-amino-β-lactone ring have been identified as potent and selective NAAA inhibitors and have been shown to exert marked anti-inflammatory effects that are mediated through FAE-dependent activation of PPAR-α. We synthesized and tested a series of racemic, diastereomerically pure β-substituted α-amino-β-lactones, as either carbamate or amide derivatives, investigating the structure-activity and structure-stability relationships (SAR and SSR) following changes in β-substituent size, relative stereochemistry at the α- and β-positions, and α-amino functionality. Substituted carbamate derivatives emerged as more active and stable than amide analogues, with the cis configuration being generally preferred for stability. Increased steric bulk at the β-position negatively affected NAAA inhibitory potency, while improving both chemical and plasma stability. PMID:24403170

  12. Properties of Rhodobacter sphaeroides photosynthetic reaction center with double amino acid substitution I(L177)H+H(M182)L.

    Fufina, T Yu; Vasilieva, L G; Khatypov, R A; Shuvalov, V A

    2011-04-01

    Histidine M182 in the reaction center (RC) of Rhodobacter sphaeroides serves as the fifth ligand of the bacteriochlorophyll (BChl) B(B) Mg atom. When this His is substituted by an amino acid that is not able to coordinate Mg, bacteriopheophytin appears in the B(B) binding site instead of BChl (Katilius, E., et al. (1999) J. Phys. Chem. B, 103, 7386-7389). We have shown that in the presence of the additional mutation I(L177)H the coordination of the BChl B(B) Mg atom in the double mutant I(L177)H+H(M182)L RC still remains. Changes in the double mutant RC absorption spectrum attributed to BChl absorption suggest that BChl B(B) Mg atom axial ligation might be realized not from the usual α-side of the BChl macrocycle, but from the opposite, β-side. Weaker coordination of BChl B(B) Mg atom compared to the other mutant RC BChl molecules suggests that not an amino acid residue but a water molecule might be a possible ligand. The results are discussed in the light of the structural changes that occurred in the RC upon Ile/His substitution in the L177 position. PMID:21585320

  13. Organic acid modeling and model validation: Workshop summary

    Sullivan, T.J.; Eilers, J.M.

    1992-08-14

    A workshop was held in Corvallis, Oregon on April 9--10, 1992 at the offices of E S Environmental Chemistry, Inc. The purpose of this workshop was to initiate research efforts on the entitled Incorporation of an organic acid representation into MAGIC (Model of Acidification of Groundwater in Catchments) and testing of the revised model using Independent data sources.'' The workshop was attended by a team of internationally-recognized experts in the fields of surface water acid-bass chemistry, organic acids, and watershed modeling. The rationale for the proposed research is based on the recent comparison between MAGIC model hindcasts and paleolimnological inferences of historical acidification for a set of 33 statistically-selected Adirondack lakes. Agreement between diatom-inferred and MAGIC-hindcast lakewater chemistry in the earlier research had been less than satisfactory. Based on preliminary analyses, it was concluded that incorporation of a reasonable organic acid representation into the version of MAGIC used for hindcasting was the logical next step toward improving model agreement.

  14. Organic acid modeling and model validation: Workshop summary. Final report

    Sullivan, T.J.; Eilers, J.M.

    1992-08-14

    A workshop was held in Corvallis, Oregon on April 9--10, 1992 at the offices of E&S Environmental Chemistry, Inc. The purpose of this workshop was to initiate research efforts on the entitled ``Incorporation of an organic acid representation into MAGIC (Model of Acidification of Groundwater in Catchments) and testing of the revised model using Independent data sources.`` The workshop was attended by a team of internationally-recognized experts in the fields of surface water acid-bass chemistry, organic acids, and watershed modeling. The rationale for the proposed research is based on the recent comparison between MAGIC model hindcasts and paleolimnological inferences of historical acidification for a set of 33 statistically-selected Adirondack lakes. Agreement between diatom-inferred and MAGIC-hindcast lakewater chemistry in the earlier research had been less than satisfactory. Based on preliminary analyses, it was concluded that incorporation of a reasonable organic acid representation into the version of MAGIC used for hindcasting was the logical next step toward improving model agreement.

  15. Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

    Malik, Enas M; Younis Baqi; Müller, Christa E.

    2015-01-01

    Anthraquinone (AQ) derivatives play a prominent role in medicine and also in textile industry. Bromaminic acid (1-amino-4-bromoanthraquinone-2-sulfonic acid) is an important precursor for obtaining dyes as well as biologically active compounds through the replacement of the C4-bromo substituent with different (ar)alkylamino residues. Here we report methods for the synthesis of bromaminic acid analogues bearing different substituents at the 2-position of the anthraquinone core. 1-Aminoanthraqu...

  16. Organophosphonotungstic HPA of Keggin Type with Sulfo, Taurine and Glycine Substituted Ethylphosphonic Acids as the Coordinate Center

    2003-01-01

    The title compounds 2a-c were synthesized and characterized for the first time.Their proton numbers are around 3.2±0.15 and are not in proportion with the valid acidity-basicity of the central phosphonic acids.The entirety of phosphonic acids 1a-c is as the coordinate center of heteropoly anions of 2a-c.

  17. Long-Term Persistence of Infection in Chimpanzees Inoculated with an Infectious Hepatitis C Virus Clone Is Associated with a Decrease in the Viral Amino Acid Substitution Rate and Low Levels of Heterogeneity

    Fernandez, Javier; Taylor, Deborah; Morhardt, Duncan R.; Mihalik, Kathleen; Puig, Montserrat; Rice, Charles M.; Feinstone, Stephen M.; Major, Marian E.

    2004-01-01

    Two chimpanzees, 1535 and 1536, became persistently infected following inoculation with RNA transcripts from cDNA clones of hepatitis C virus (HCV). Analysis of the HCV genomes from both animals showed an accumulation of amino acid substitutions over time. The appearance of substitutions in the envelope genes was associated with increased antienvelope antibody titers. However, extensive mutations were not incorporated into hypervariable region 1 (HVR1). A comparison of the nonsynonymous subst...

  18. Cotton Chromosome Substitution Lines Crossed with Cultivars: Genetic Model Evaluation and Seed Trait Analyses

    Seed from Upland cotton, Gossypium hirsutum L., provides a desirable and important nutrition profile. In this study, six seed traits (protein content, oil content, seed hull fiber content, seed index, seed volume, embryo percentage) for F3 hybrids of 13 cotton chromosome substitution lines crossed w...

  19. Synthesis and biological activity of some new 3-and 6-substituted coumarin amino acid derivatives. Part I

    A. M. El-naggar; Ahmed, F. S. M.; El-Salam, A. M. A.; Radi, M. A.; Latif, M. S. A.

    1981-01-01

    The synthesis of 6-nitrocouarrain-3-CO-amino acids and their corresponding methyl esters (II-XVII) and some dipeptide methyl esters (XVIII-XXVI) are described. 6-(N-Tosyl- or N-phthalylaminoacyl)aminocoumarin-3-carboxylic acid methyl esters (XXXIV-XL) and 3-(N-phthalyl- or N-tosylaminoacytyaminocoumarins (XLV-LVI) have been prepared via the carbodiimide and acid chloride methods. Hydrazinolysis of 3- or 6-(N-phthalylaminoacyl)aminocoumarin derivatives in tetraline gave the corresponding 3- an...

  20. Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling.

    Satoko Uraki

    Full Text Available It has been suggested that amino acid (aa substitution at position 70 from arginine (70R to glutamine (70Q in the genotype 1b hepatitis C virus (HCV core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The aim of this study was to investigate the impact of the substitution at position 70 in HCV core protein on adipokine production by murine and human adipocytes.The influence of treatment with HCV core protein (70R or 70Q on adipokine production by both 3T3-L1 and human adipocytes were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA, and triglyceride content was also analyzed. The effects of toll-like receptor (TLR2/4 inhibition on IL-6 production by 3T3-L1 induced by HCV core protein were examined.IL-6 production was significantly increased and adiponectin production was reduced without a change in triglyceride content by treatment with 70Q compared to 70R core protein in both murine and human adipocytes. IL-6 induction of 3T3-L1 cells treated by 70Q HCV core protein was significantly inhibited with anti-TLR2 antibody by 42%, and by TLR4 inhibitor by 40%.Our study suggests that extracellular HCV core protein with substitution at position 70 enhanced IL-6 production and reduced adiponectin production from visceral adipose tissue, which can cause insulin resistance, hepatic steatosis, and ultimately development of HCC.

  1. Identification of robust synthon in the molecular salts of 2-aminothiazole with substituted benzoic acids: A case stu

    Madhavi Oruganti; Raghavaiah Pallepogu; Darshak R Trivedi

    2014-09-01

    Six new salts of an API intermediate 2-aminothiazole with different carboxylic acid coformers were synthesized and characterized by IR (Infrared spectroscopy), 1H-NMR, DSC (Differential scanning calorimetry), XRPD (X-ray powder diffraction) and single crystal XRD. The crystal structure of the salts with benzoic acid, 2,3-, 2,4-, 2,5-, 2,6- dihydroxybenzoic acids and 2,4-dinitrobenzoic acid were determined. The thiazole moiety exhibited solvent (polarity) assisted tautomerism in all reported salts and proton transfer was noticed to the ring N of thiazole due to which two point supramolecular synthon N+−H(thiazole)…O−(acid), N−H(amine)…O−(acid) was observed. The crystal structures were studied with respect to the positional effect of the competing functional groups like hydroxyl (−OH) and nitro (−NO2) as well as their donor and acceptor abilities for hydrogen bonding. The presence of the non-conventional hydrogen bond (C−H…O) has been found to play a critical role in the formation of secondary supramolecular architectures.

  2. Antimicrobial and antioxidant screening of N¢-substituted sulphonyl and benzoyl derivatives of 4-Pyridine carboxylic acid hydrazide.

    Naeem, Sabahat; Akhtar, Shamim; Asghar, Nadia; Sherwani, Sikander Khan; Mushtaq, Nousheen; Kamil, Arfa; Zafar, Shaista; Arif, Mohammad; Saify, Zafar Saeed

    2015-11-01

    In this research program, the antibacterial, antifungal and antioxidant activities of six N'-substituted sulfonyl and benzoyl derivatives of lead molecule PCH were reported. Out of these compounds, sulphonyl derivatives 2,3 and benzoyl derivative 5 showed moderate to good activity against different strains of gram-positive and gram-negative bacteria including B. cereus, B. subtilis, B. thruingiensis and S. pyogenes, S. fecalis and E. coli ATCC 8739. Moreover, upon antifungal screening, the compound, N¢-[(2,4,6-trimethylbenzene) sulfonyl]pyridine-4-carbohydrazide possessed good antifungal activity against Candida species, a causative agent of systemic fungal infections. Antioxidant study demonstrated more than 50% inhibition in DPPH assay for sulphonyl derivative 2 indicating its potential as antioxidant while the other derivatives expressed low level of radical scavenging property. PMID:26639506

  3. Alteration of alpha 1 Na+,K(+)-ATPase 86Rb+ influx by a single amino acid substitution

    The sodium- and potassium-dependent adenosine triphosphatase (Na+,K(+)-ATPase) maintains the transmembrane Na+ gradient to which is coupled all active cellular transport systems. The R and S alleles of the gene encoding the Na+,K(+)-ATPase alpha 1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats, respectively. Characterization of the S allele-specific Na+,K(+)-ATPase alpha 1 complementary DNA identified a leucine substitution of glutamine at position 276. This mutation alters the hydropathy profile of a region in proximity to T3(Na), the trypsin-sensitive site that is only detected in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx of S allele-specific sodium pumps, thus marking a domain in the Na+,K(+)-ATPase alpha subunit important for K+ transport, and supporting the hypothesis of a putative role of these pumps in hypertension

  4. Quantum network architecture of tight-binding models with substitution sequences

    Kim, ILki; Mahler, Guenter

    2000-01-01

    We study a two-spin quantum Turing architecture, in which discrete local rotations \\alpha_m of the Turing head spin alternate with quantum controlled NOT-operations. Substitution sequences are known to underlie aperiodic structures. We show that parameter inputs \\alpha_m described by such sequences can lead here to a quantum dynamics, intermediate between the regular and the chaotic variant. Exponential parameter sensitivity characterizing chaotic quantum Turing machines turns out to be an ad...

  5. Effect of surface acidity and pore size of Al-substituted plugs-containing SBA-15 and MCM-41 silicas on the polymerization of THF

    Zhi Qi Jia; Ming Zhao; Chun Guang Gao; Yong Xiang Zhao

    2011-01-01

    We reported here the simultaneous influence of surface acidity and pore size of Al-substituted hexagonal mesoporous silicas (Aldoped plugs-containing SBA-15 and Al-doped MCM-41) on polymerization of THF.These materials were directly synthesized by introduced aluminum isopropoxide into reaction mixture including surfactant and siliceous precursor.Al-doped plugs-containing SBA-15 (denotes as PAS) samples not only possess typical two-step desorption isotherms,which implied PAS materials generated plugs in their mesochannel,but also exhibit larger pore size and thicker wall than that of Al-doped MCM-41 (denotes as ACM),which implied PAS would have a great advantage on catalytic reaction involving large molecular (e.g.polymer of TI-IF) in industrial point'of view.To investigate catalytic activity of PAS and ACM with moderate acidic sites the polymerization of THF in the presence of acetic anhydride was carded out.The results showed PAS exhibiting good performance on polymerization of THF.Such result could be related to the large pore size and moderate acidic sites.

  6. Analytical Enantioseparation of β-Substituted-2-Phenylpropionic Acids by High-Performance Liquid Chromatography with Hydroxypropyl-β-Cyclodextrin as Chiral Mobile Phase Additive.

    Tong, Shengqiang; Zhang, Hu; Yan, Jizhong

    2016-04-01

    Analytical enantioseparation of five β-substituted-2-phenylpropionic acids by high-performance liquid chromatography with hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral mobile phase additive was established in this paper, and chromatographic retention mechanism was studied. The effects of various factors such as the organic modifier, different ODS C18 columns and concentration of HP-β-CD were investigated. The chiral mobile phase was composed of methanol or acetonitrile and 0.5% triethylamine acetate buffer at pH 3.0 added with 25 mmol L(-1) of HP-β-CD, and baseline separations could be reached for all racemates. As for chromatographic retention mechanism, it was found that there was a negative correlation between the concentration of HP-β-CD in mobile phase and the retention factor under constant pH value and column temperature. PMID:26755500

  7. Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone.

    Jin, Xin; Zheng, Chang-Ji; Song, Ming-Xia; Wu, Yan; Sun, Liang-Peng; Li, Yin-Jing; Yu, Li-Jun; Piao, Hu-Ri

    2012-10-01

    Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL. PMID:22982124

  8. Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

    Sudipta Pathak

    2013-11-01

    Full Text Available A convenient and efficient methodology for the synthesis of densely substituted pyrrole-fused isocoumarins, which employs solid-supported silica sulfuric acid (SSA as catalyst, has been developed. When the mixture of ninhydrin adducts of acetylacetone/ethyl acetoacetate and primary amines was heated on the solid surface of SSA under solvent-free conditions, the pyrrole-fused isocoumarins were formed in good yields. This synthetic method has several advantages such as the employment of solvent-free reaction conditions without the use of any toxic reagents and metal catalysts, the ease of product isolation, the use of a recyclable catalyst, the low cost, the easy availability of the starting materials, and the excellent yields of products.

  9. LASER BIOLOGY AND MEDICINE: Application of laser fluorimetry for determining the influence of a single amino-acid substitution on the individual photophysical parameters of a fluorescent form of a fluorescent protein mRFP1

    Banishev, A. A.; Vrzheshch, E. P.; Shirshin, E. A.

    2009-03-01

    Individual photophysical parameters of the chromophore of a fluorescent protein mRFP1 and its two mutants (amino-acid substitution at position 66 - mRFP1/ Q66C and mRFP1/Q66S proteins) are determined. For this purpose, apart from conventional methods of fluorimetry and spectrophotometry, nonlinear laser fluorimetry is used. It is shown that the individual extinction coefficients of the chromophore of proteins correlate (correlation coefficient above 0.9) with the volume of the substituted amino-acid residue at position 66 (similar to the positions of the absorption, fluorescence excitation and emission maxima).

  10. Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands

    Høg, Signe; Wellendorph, Petrine; Nielsen, Birgitte; Frydenvang, Karla; Dahl, Ivar F; Bräuner-Osborne, Hans; Brehm, Lotte; Frølund, Bente; Clausen, Rasmus P

    2008-01-01

    Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in...

  11. Substitutional analysis

    Rutherford, Daniel Edwin

    2013-01-01

    Classic monograph, suitable for advanced undergraduates and graduate students. Topics include calculus of permutations and tableaux, semi-normal representation, orthogonal and natural representations, group characters, and substitutional equations. 1968 edition.

  12. Modeling the continuous lactic acid production process from wheat flour.

    Gonzalez, Karen; Tebbani, Sihem; Lopes, Filipa; Thorigné, Aurore; Givry, Sébastien; Dumur, Didier; Pareau, Dominique

    2016-01-01

    A kinetic model of the simultaneous saccharification, protein hydrolysis, and fermentation (SSPHF) process for lactic acid production from wheat flour has been developed. The model describes the bacterial growth, substrate consumption, lactic acid production, and maltose hydrolysis. The model was fitted and validated with data from SSPHF experiments obtained under different dilution rates. The results of the model are in good agreement with the experimental data. Steady state concentrations of biomass, lactic acid, glucose, and maltose as function of the dilution rate were predicted by the model. This steady state analysis is further useful to determine the operating conditions that maximize lactic acid productivity. PMID:26399412

  13. Different self-assembly behaviors of mono-modified β-cyclodextrin substituted by benzoic acid derivatives

    2010-01-01

    The mono-modified β-cyclodextrin derivative,6-O-(4-aminobenzoyl)-β-cyclodextrin(1) ,was synthesized and characterized. We compared its self-assembling behavior with structurally related β-cyclodextrin derivative,6-O-(4-hydroxybenzoyl)-βcyclodextrin(2) ,in aqueous solution and in the solid state using NMR spectroscopy and single crystal X-ray structure analysis. The two complexes displayed different self-assembling behaviors.Complex 1 formed a head-to-tail helical columnar superstructure in which the substituent group penetrated deeply into the hydrophobic cavity of the adjacent β-cyclodextrin from the second side and aligned along the screw axis,whereas 2 exhibited a channel superstructure with a tail-to-tail dimer as the repeating motif.Further NMR studies in aqueous solution supported the result of the solid state.The influence of substituent groups on the self-assembly behavior was examined in mono-modified β-cyclodextrins by means of substituting an amino group for a hydroxyl group,which indicates that the weak intermolecular interaction is a critical factor in determining the self-assembling behavior.

  14. Preparation of a graphene oxide/silica composite modified with nitro-substituted tris(indolyl)methane as a solid-phase extraction sorbent for the extraction of organic acids.

    Wang, Na; Yu, Hui; Shao, Shijun

    2016-05-01

    This paper describes the use of graphene oxide/silica modified with nitro-substituted tris(indolyl)methane as a solid-phase extraction sorbent for the determination of organic acids. The resultant graphene oxide/silica modified with nitro-substituted tris(indolyl)methane was characterized by FTIR spectroscopy and adsorption experiments. Solid-phase extraction parameters such as sorbent type, sample solution pH, sample loading rate, eluent salt concentration, eluent methanol concentration, elution rate, sample loading, and elution volume were optimized. The method showed good precision, accuracy, sensitivity, and linear response for organic acids analysis over a concentration range of 1-100 μg/L for benzoic acid, p-methoxybenzoic acid, and salicylic acid and 5-100 μg/L for the remaining organic acids (cinnamic acid, p-chlorobenzoic acid, and p-bromobenzoic acid) with coefficients of determination (r(2) ) of higher than 0.9957. Limits of detection from 0.50 to 1.0 μg/L for six organic acids were achieved. The developed method was successfully applied to determine organic acids in real samples. PMID:26969351

  15. Development of Quantitative Structure-Activity Relationship Models for Predicting Chronic Toxicity of Substituted Benzenes to Daphnia Magna.

    Fan, Deling; Liu, Jining; Wang, Lei; Yang, Xianhai; Zhang, Shenghu; Zhang, Yan; Shi, Lili

    2016-05-01

    The chronic toxicity of anthropogenic molecules such as substituted benzenes to Daphnia magna is a basic eco-toxicity parameter employed to assess their environmental risk. As the experimental methods are laborious, costly, and time-consuming, development in silico models for predicting the chronic toxicity is vitally important. In this study, on the basis of five molecular descriptors and 48 compounds, a quantitative structure-property relationship model that can predict the chronic toxicity of substituted benzenes were developed by employing multiple linear regressions. The correlation coefficient (R (2)) and root-mean square error (RMSE) for the training set were 0.836 and 0.390, respectively. The developed model was validated by employing 10 compounds tested in our lab. The R EXT (2) and RMSE EXT for the validation set were 0.736 and 0.490, respectively. To further characterizing the toxicity mechanism of anthropogenic molecules to Daphnia, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were developed. PMID:27016939

  16. Correlation of acid-base properties of substituted polystyrene-azo-pyrocatechol and characteristics of their chelates with zirconium

    Acid-base and complexing properties of new synthesized polymeric chelate-forming sorbents (PCS) - substituents of polystyrene-azo-pyrocatechol - are investigated and quantitative correlations between pKOH of functional analytical group (FAG) of sorbent and Hammet constants for para-substituent and ΔpKOH-ΔpK50 correlations of zirconium chelate-forming and pKOH-lgKstb (Kstb - constant of stability of PCS complexes with zirconium) of polychelates to study regularities of effect of peculiarities of structure and acid-base properties of FAG on parameters of zirconium chemical sorption. Established correlations make it possible to predict quantitative physicochemical parameters of sorbents and zirconium chemisorption process with the aim of directed synthesis and application of PCS in concentrating processes

  17. Quantum network architecture of tight-binding models with substitution sequences

    Kim, I; Kim, Ilki; Mahler, Guenter

    2000-01-01

    We study a two-spin quantum Turing architecture, in which discrete local rotations \\alpha_m of the Turing head spin alternate with quantum controlled NOT-operations. Substitution sequences are known to underlie aperiodic structures. We show that parameter inputs \\alpha_m described by such sequences can lead here to a quantum dynamics, intermediate between the regular and the chaotic variant. Exponential parameter sensitivity characterizing chaotic quantum Turing machines turns out to be an adequate criterion for induced quantum chaos in a quantum network.

  18. Emergence of antigenic variants within serotype A FMDV in the Middle East with antigenically critical amino acid substitutions

    Mahapatra, Mana; Statham, Bob; Li, Yanmin; Hammond, Jef; Paton, David; Parida, Satya

    2016-01-01

    Highlights • The recent A-Iran-05 viruses circulating in the Middle East do not match with the existing vaccines. • Full capsid sequence of 13 SIS-10 and SIS-12 viruses was generated. • The r 1-values generated using antisera raised against two existing vaccines and a new vaccine. • Amino acid changes in neutralizing antigenic sites 1, 2 and 4 were observed.

  19. A Single Amino Acid Substitution in the Activation Loop Defines the Decoy Characteristic of VEGFR-1/FLT-1*

    Meyer, Rosana D.; Mohammadi, Moosa; Rahimi, Nader

    2005-01-01

    VEGFR-1 is a kinase-defective receptor tyrosine kinase (RTK) and negatively modulates angiogenesis by acting as a decoy receptor. The decoy characteristic of VEGFR-1 is required for normal development and angiogenesis. To date, there is no molecular explanation for this unusual characteristic of VEGFR-1. Here we show that the molecular mechanisms underlying the decoy characteristic of VEGFR-1 is linked to the replacement of a highly conserved amino acid residue in the activation loop. This am...

  20. Modelling intra- and extra-area trade substitution and exchange rate pass-through in the euro area

    Dieppe, Alistair; Warmedinger, Thomas

    2007-01-01

    The paper proposes a modelling approach for euro area goods and services trade volumes and prices on the basis of a break-down of trade data into their intra- and extra-area components. Using the evidence from the newly estimated trade equations, the paper gives new insights into two important issues. The first issue concerns the exchange-rate pass-through (ERPT) to euro area import prices. The second issue relates to substitution effects between intra- and extra-area trade. These issues are ...

  1. Modelling and simulation of photocatalytic oxidation mechanism of chlorohalogenated substituted phenols in batch systems: Langmuir-Hinshelwood approach.

    Khuzwayo, Z; Chirwa, E M N

    2015-12-30

    This study investigated, modelled and simulated the influence of multi-chlorohalogenation in heterogeneous photocatalytic degradation of substituted phenols (pentachlorophenol (PCP), trichlorophenol (TCP), dichlorophenol (DCP), and monochlorophenol (CP)). The Langmuir-Hinshelwood approach was applied to determine oxidation kinetics. Aquasim 2.0 computational software was used to model, simulate and estimate model parameters of the different chlorophenols. Chemical adsorption equilibrium isotherms for the four chlorophenols and phenol were studied and modelled for adsorption onto titanium dioxide (TiO2) semiconductor catalyst. Langmuir adsorption parameters were determined and used to calculate adsorption constant and maximum adsorption capacity. The adsorption of chloride phenolics onto titanium dioxide catalyst increased in the order of 4 - CP TCP > DCP ≥ 4 - CP. Photocatalytic parameters were calculated and estimated along with sensitivity and uncertainty analyses. PMID:26223020

  2. Molecular evolution of B6 enzymes: Binding of pyridoxal-5'-phosphate and Lys41Arg substitution turn ribonuclease A into a model B6 protoenzyme

    Marra Ersilia

    2008-06-01

    Full Text Available Abstract Background The pyridoxal-5'-phosphate (PLP-dependent or vitamin B6-dependent enzymes that catalyze manifold reactions in the metabolism of amino acids belong to no fewer than four evolutionarily independent protein families. The multiple evolutionary origin and the essential mechanistic role of PLP in these enzymes argue for the cofactor having arrived on the evolutionary scene before the emergence of the respective apoenzymes and having played a dominant role in the molecular evolution of the B6 enzyme families. Here we report on an attempt to re-enact the emergence of a PLP-dependent protoenzyme. The starting protein was pancreatic ribonuclease A (RNase, in which active-site Lys41 or Lys7 readily form a covalent adduct with PLP. Results We screened the PLP adduct of wild-type RNase and two variant RNases (K7R and K41R for catalytic effects toward L- and D-amino acids. RNase(K41R-PLP, in which the cofactor is bound through an imine linkage to Lys7, qualifies for a model proto-B6 enzyme by the following criteria: (1 covalent linkage of PLP (internal aldimine; (2 catalytic activity toward amino acids that depends on formation of an imine linkage with the substrate (external aldimine; (3 adjoining binding sites for the cofactor and amino acid moiety that facilitate the transimination reaction of the internal to the external aldimine and stabilize the resulting noncovalent complex of the coenzyme-substrate adduct with the protein; (4 reaction specificity, the only detectable reactions being racemization of diverse amino acids and β-decarboxylation of L-aspartate; (5 acceleration factors for racemization and β-decarboxylation of >103 over and above that of PLP alone; (6 ribonuclease activity that is 103-fold lower than that of wild-type RNase, attenuation of a pre-existing biological activity being indispensable for the further evolution as a PLP-dependent protoenzyme. Conclusion A single amino acid substitution (Lys41Arg and covalent

  3. Straightforward and effective synthesis of γ-aminobutyric acid transporter subtype 2-selective acyl-substituted azaspiro[4.5]decanes.

    Ma, Xiaofeng; Lubin, Hodney; Ioja, Enikő; Kékesi, Orsolya; Simon, Ágnes; Apáti, Ágota; Orbán, Tamás I; Héja, László; Kardos, Julianna; Markó, István E

    2016-01-15

    Supply of major metabolites such as γ-aminobutyric acid (GABA), β-alanine and taurine is an essential instrument that shapes signalling, proper cell functioning and survival in the brain and peripheral organs. This background motivates the synthesis of novel classes of compounds regulating their selective transport through various fluid-organ barriers via the low-affinity γ-aminobutyric acid (GABA) transporter subtype 2 (GAT2). Natural and synthetic spirocyclic compounds or therapeutics with a range of structures and biological activity are increasingly recognised in this regard. Based on pre-validated GABA transport activity, straightforward and efficient synthesis method was developed to provide an azaspiro[4.5]decane scaffold, holding a variety of charge, substituent and 3D constrain of spirocyclic amine. Investigation of the azaspiro[4.5]decane scaffold in cell lines expressing the four GABA transporter subtypes led to the discovery of a subclass of a GAT2-selective compounds with acyl-substituted azaspiro[4.5]decane core. PMID:26706177

  4. Substitution of Ala564 in the first zinc cluster of the deoxyribonucleic acid (DNA)-binding domain of the androgen receptor by Asp, Asn, or Leu exerts differential effects on DNA binding

    H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); J.M. Lobaccaro; L. Chiche; C. Sultan; J. Trapman (Jan); A.O. Brinkmann (Albert)

    1998-01-01

    textabstractIn the androgen receptor of a patient with androgen insensitivity, the alanine residue at position 564 in the first zinc cluster of the DNA-binding domain was substituted by aspartic acid. In other members of the steroid receptor family, either valine or ala

  5. Silica-based sulfonic acid (MCM-41-SO3H: a practical and efficient catalyst for the synthesis of highly substituted quinolines under solvent-free conditions at ambient temperature

    Ali Maleki

    2014-06-01

    Full Text Available In this work, a variety of highly substituted quinolines were readily synthesized via Friedlander annulation using Brönsted acid silica-based sulfonic acid as a modified catalyst under solvent-free conditions at room temperature. This efficient procedure has the advantages of giving the target compounds in high yields, short reaction times, simple workup procedure, reusability of the catalyst, and environmentally benign conditions.

  6. Market power, fuel substitution and infrastructure – A large-scale equilibrium model of global energy markets

    Assessing and quantifying the impacts of technological, economic, and policy shifts in the global energy system require large-scale numerical models. We propose a dynamic multi-fuel market equilibrium model that combines endogenous fuel substitution within demand sectors and in power generation, detailed infrastructure capacity constraints and investment, as well as strategic behaviour and market power aspects by suppliers in a unified framework. This model is the first of its kind in which market power is exerted across several fuels. Using a data set based on the IEA (International Energy Agency) World Energy Outlook 2013 (New Policies scenario, time horizon 2010–2050, 30 regions, 10 fuels), we illustrate the functionality of the model in two scenarios: a reduction of shale gas availability in the US relative to current projections leads to an even stronger increase of power generation from natural gas in the European Union relative to the base case; this is due to a shift in global fossil fuel trade. In the second scenario, a tightening of the EU ETS emission cap by 80% in 2050 combined with a stronger biofuel mandate spawns a renaissance of nuclear power after 2030 and a strong electrification of the transportation sector. We observe carbon leakage rates from the unilateral mitigation effort of 60–70%. - Highlights: • We propose a spatially disaggregated dynamic equilibrium model for energy markets. • The model combines fuel substitution, market power and detailed infrastructure constraints. • Market power by suppliers can be exerted “across” multiple fuels or resources. • The model includes seasonality and storage to capture short-term operational constraints. • Investment in production, transportation, transformation and storage infrastructure is endogenous

  7. Synthesis, Antiproliferative and Antifungal Activities of 1,2,3-Triazole-Substituted Carnosic Acid and Carnosol Derivatives

    Mariano Walter Pertino

    2015-05-01

    Full Text Available Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1–3 were the most active antiproliferative compounds of the series, with IC50 values in the range of 43.4–46.9 μM and 39.2–48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL−1. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition at 250 µg∙mL−1 In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL−1.

  8. Substituted Pyrazinecarboxamides: Synthesis and Biological Evaluation

    Katarina Kralova; Josef Jampilek; Vladimir Buchta; Jarmila Vinsova; Lukas Palek; Martin Dolezal

    2006-01-01

    Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2-carboxylic acid, 5-tert-butylpyrazine-2-carboxylic acid or 5-tert-butyl-6-chloropyrazine-2-carboxylic acid) withvarious ring-substituted aminothiazoles or anilines yielded a series of amides. Thesyntheses, analytical and spectroscopic data of thirty newly prepared compounds arepresented. Structure-activity relationships between the chemical structures and...

  9. FASTSUBS: An Efficient and Exact Procedure for Finding the Most Likely Lexical Substitutes Based on an N-gram Language Model

    Yüret, Deniz

    2012-01-01

    arXiv:1205.5407v2 [cs.CL] 1 Sep 2012 IEEE SIGNAL PROCESSING LETTERS, VOL. 0, NO. 0, JANUARY 0000 1 FASTSUBS: An Efficient and Exact Procedure for Finding the Most Likely Lexical Substitutes Based on an N-gram Language Model Deniz Yuret Abstract—Lexical substitutes have found use in areas such as paraphrasing, text simplification, machine translation, word sense disambiguation, and part of speech induction. However the computational complexity of accurately identifyi...

  10. A Generalized Nash-Cournot Model for the North-Western European Natural Gas Markets with a Fuel Substitution Demand Function: The GaMMES Model

    This article presents a dynamic Generalized Nash-Cournot model to describe the evolution of the natural gas markets. The major players along the gas chain are depicted including: producers, consumers, storage and pipeline operators, as well as intermediate local traders. Our economic structure description takes into account market power and the demand representation tries to capture the possible fuel substitution that can be made between the consumption of oil, coal, and natural gas in the overall fossil energy consumption. We also take into account long-term contracts in an endogenous way, which makes the model a Generalized Nash Equilibrium problem. We discuss some means to solve such problems. Our model has been applied to represent the European natural gas market and forecast, until 2030, after a calibration process, consumption, prices, production, and natural gas dependence. A comparison between our model, a more standard one that does not take into account energy substitution, and the European Commission natural gas forecasts is carried out to analyze our results. Finally, in order to illustrate the possible use of fuel substitution, we studied the evolution of the natural gas price as compared to the coal and oil prices. (authors)

  11. Identification and biological activity of 6-alkyl-substituted 3-methyl-pyridine-2-carbonyl amino dimethyl-benzoic acid EP4 antagonists.

    Blanco, Maria-Jesus; Vetman, Tatiana; Chandrasekhar, Srinivasan; Fisher, Matthew J; Harvey, Anita; Kuklish, Steven L; Chambers, Mark; Lin, Chaohua; Mudra, Daniel; Oskins, Jennifer; Wang, Xu-Shan; Yu, Xiao-Peng; Warshawsky, Alan M

    2016-05-01

    Continued SAR optimization of a series of 3-methylpyridine-2-carbonyl amino-2,4-dimethyl-benzoic acid led to the selection of compound 4f for clinical studies. Compound 4f showed an IC50 of 123nM for inhibition of PGE2-induced TNFα reduction in an ex vivo LPS-stimulated human whole blood assay (showing >10-fold increase over clinical compound CJ-023,423). Pharmacokinetic profile, selectivity and in vivo efficacy comparing 4f to NSAID diclofenac in the monoiodoacetic acid (MIA) pain model and adjuvant induced arthritis (AIA) inflammatory model are included. PMID:27020304

  12. Antibody-Specific Model of Amino Acid Substitution for Immunological Inferences from Alignments of Antibody Sequences

    Mirsky, Alexander; Kazandjian, Linda; Anisimova, Maria

    2014-01-01

    Antibodies are glycoproteins produced by the immune system as a dynamically adaptive line of defense against invading pathogens. Very elegant and specific mutational mechanisms allow B lymphocytes to produce a large and diversified repertoire of antibodies, which is modified and enhanced throughout all adulthood. One of these mechanisms is somatic hypermutation, which stochastically mutates nucleotides in the antibody genes, forming new sequences with different properties and, eventually, hig...

  13. Solvent substitution

    1990-01-01

    The DOE Environmental Restoration and Waste Management Office of Technology Development and the Air Force Engineering and Services Center convened the First Annual International Workshop on Solvent Substitution on December 4--7, 1990. The primary objectives of this joint effort were to share information and ideas among attendees in order to enhance the development and implementation of required new technologies for the elimination of pollutants associated with industrial use of hazardous and toxic solvents; and to aid in accelerating collaborative efforts and technology transfer between government and industry for solvent substitution. There were workshop sessions focusing on Alternative Technologies, Alternative Solvents, Recovery/Recycling, Low VOC Materials and Treatment for Environmentally Safe Disposal. The 35 invited papers presented covered a wide range of solvent substitution activities including: hardware and weapons production and maintenance, paint stripping, coating applications, printed circuit boards, metal cleaning, metal finishing, manufacturing, compliance monitoring and process control monitoring. This publication includes the majority of these presentations. In addition, in order to further facilitate information exchange and technology transfer, the US Air Force and DOE solicited additional papers under a general Call for Papers.'' These papers, which underwent review and final selection by a peer review committee, are also included in this combined Proceedings/Compendium. For those involved in handling, using or managing hazardous and toxic solvents, this document should prove to be a valuable resource, providing the most up-to-date information on current technologies and practices in solvent substitution. Individual papers are abstracted separated.

  14. Solvent substitution

    The DOE Environmental Restoration and Waste Management Office of Technology Development and the Air Force Engineering and Services Center convened the First Annual International Workshop on Solvent Substitution on December 4--7, 1990. The primary objectives of this joint effort were to share information and ideas among attendees in order to enhance the development and implementation of required new technologies for the elimination of pollutants associated with industrial use of hazardous and toxic solvents; and to aid in accelerating collaborative efforts and technology transfer between government and industry for solvent substitution. There were workshop sessions focusing on Alternative Technologies, Alternative Solvents, Recovery/Recycling, Low VOC Materials and Treatment for Environmentally Safe Disposal. The 35 invited papers presented covered a wide range of solvent substitution activities including: hardware and weapons production and maintenance, paint stripping, coating applications, printed circuit boards, metal cleaning, metal finishing, manufacturing, compliance monitoring and process control monitoring. This publication includes the majority of these presentations. In addition, in order to further facilitate information exchange and technology transfer, the US Air Force and DOE solicited additional papers under a general ''Call for Papers.'' These papers, which underwent review and final selection by a peer review committee, are also included in this combined Proceedings/Compendium. For those involved in handling, using or managing hazardous and toxic solvents, this document should prove to be a valuable resource, providing the most up-to-date information on current technologies and practices in solvent substitution. Individual papers are abstracted separated

  15. First principles calculations of hyperfine parameters on the Ca manganite with substitutional Cd-modeling of a PAC experiment

    Goncalves, JN; Lopes, A M L; Haas, H; Amaral, V S; Goncalves, J N

    2010-01-01

    The APW + lo (augmented plane waves + local orbitals) method of density functional theory, as implemented in the Wien2k code, is applied to calculate the electric field gradient of manganites. We report the first principles calculations on CaMnO3, and modeling of a perturbed angular correlation experiment with implanted Cd-111m isotope. To model the experiment we additionally calculate in Ca1-xCdxMnO3, where we substitute Cd at the Ca site. Increasing Cd dilution is done with the use of supercells. We find that the experimental CaMnO3 low-temperature value V-zz approximate to 6 x 10(-21) V/m(2) is reproduced, whenoptimizinginternalparameters. The analysis of the EFG tensor at the Ca atoms, with different electric field gradients at inequivalent positions, reveals that the convergence of the calculations is obtained. (C) 2009 Elsevier B.V. All rights reserved.

  16. Thioureides of 2-(phenoxymethyl)benzoic acid 4-R substituted: a novel class of anti-parasitic compounds.

    Müller, Joachim; Limban, Carmen; Stadelmann, Britta; Missir, Alexandru Vasile; Chirita, Ileana Cornelia; Chifiriuc, Mariana Carmen; Nitulescu, George Mihai; Hemphill, Andrew

    2009-06-01

    Fifty members of a novel class of antimicrobial compounds, 2-(4-R-phenoxymethyl)benzoic acid thioureides, were synthesized and characterized with respect to their activities against three parasites of human relevance, namely the protozoa Giardia lamblia and Toxoplasma gondii, and the larval (metacestode) stage of the tapeworm Echinococcus multilocularis. To determine the selective toxicity of these compounds, the human colon cancer cell line Caco2 and primary cultures of human foreskin fibroblasts (HFF) were also investigated. The new thioureides were obtained in a three-step-reaction process and subsequently characterized by their physical constants (melting point, solubility). The chemical structures were elucidated by (1)H NMR, (13)C NMR, IR spectral methods and elemental analysis. The analyses confirmed the final and intermediate compound structures and the synthesis. The compounds were then tested on the parasites in vitro. All thioureides, except two compounds with a nitro group, were totally ineffective against Giardia lamblia. 23 compounds inhibited the proliferation of T. gondii, three of them with an IC(50) of approximately 1 microM. The structural integrity of E. multilocularis metacestodes was affected by 22 compounds. In contrast, HFF were not susceptible to any of these thioureides, while Caco2 cells were affected by 17 compounds, two of them inhibiting proliferation with an IC(50) in the micromolar range. Thioureides may thus present a promising class of anti-infective agents. PMID:19162220

  17. Chemically modified konjac glucomannan with high colloid osmotic pressure: physiological evaluation in a rabbit model as a plasma substitute.

    Li, Suping; Hu, Tao; Chen, Yali; Wang, Xianwei; Liu, Tao; Ma, Guanghui; Su, Zhiguo

    2010-08-01

    Carboxylmethylated konjac glucomannan (CKGM) is a carboxylmethylated polymer of mannose and glucose that is derived from the plant Amorphophallus konjac cultivated in East Asia. The CKGM solution had a high volume-expanding efficacy and was evaluated as a plasma substitute in the present study. Ameliorative hemorrhagic shock rabbits were used as the model animals. The in vivo hemodynamic and hemorheologic properties, including blood pressure, blood viscosity, hematocrit, erythrocyte deformation index and erythrocyte aggregation index, were measured in animals treated in the CKGM solution. The in vitro colloid osmotic pressure (COP) of the CKGM solution was measured to estimate its plasma-expanding efficacy. These parameters of the CKGM-treated group were compared with groups exposed to four other treatments: human serum albumin (HSA), hydroxyethyl starch (HES), polygeline and normal saline. The CKGM solution showed an exceptionally higher COP than other therapy solutions. For example, the COP of 1% (weight in volume [w/v]) CKGM solution is comparable to those of 6% (w/v) HES solution and 5% (w/v) HSA solution. Accordingly, the CKGM solution can be transfused in a much lower dosage while maintaining its plasma-expanding efficacy. The CKGM-treated group showed an improved intravascular persistence and good hemodynamic and hemorheological properties. Biopsy analysis suggested no organ dysfunction in the group treated in CKGM solution. Moreover, the high plasma-expanding efficacy and inexpensive availability of the CKGM solution may facilitate its clinical application as a potential plasma substitute. PMID:20466646

  18. Coralline hydroxyapatite bone graft substitutes in a canine diaphyseal defect model: Radiographic features of failed and successful union

    Radiographic and densitometric evaluation of a new type of bone graft substitute derived from reef-building sea coral via a hydrothermal chemical exchange process was undertaken in a canine diaphyseal defect model. Comparably sized blocks of this material and autogenous iliac cortical-cancellous graft were implanted into the respective radial diaphyses of seven dogs. Qualitative and quantitative radiographic assessment was performed during the immediate postoperative period and at 3 months following surgery. Significant complications were observed radiographically in over half of the coralline implanted limbs, including failed union, graft fracture, and loosening of internal fixation hardware. No significant difference was noted in degree of native osseous ingrowth between the implants and the autografts, and the latter exhibited a higher success rate. Radiographic film densitometry was found not to be reliably predictive of coralline implant behavior in the individual case. It is concluded that coralline hydroxyapatite bone graft substitutes appear to offer no particular advantage over autogenous grafts in the management of diaphyseal defects, although further investigation is warranted since other factors may be responsible for the unfavorable findings in this study. (orig.)

  19. Molecular Modeling of Trifluoromethanesulfonic Acid for Solvation Theory

    Paddison, S J; Zawodzinski, T; Reagor, D W; Paddison, Stephen J.; Pratt, Lawrence R.; Zawodzinski, Thomas; Reagor, David W.

    1997-01-01

    Reported here are theoretical calculations on the triflic acid and water, establishing molecular scale information necessary to modeling of the structure, thermodynamics, and ionic transport of Nafion membranes. To characterize side chain flexibility and accessibility of the acid proton, free energies for rotation of both carbon-sulfur and sulfur-oxygen (hydroxyl) bonds are presented. The energetic barrier to rotation of the acid proton away from the sulfonic acid oxygen plane is substantially flattened, with barrier less than one kcal/mol, by electrostatic solvation. The activation free energy for acid-water proton interchange is about 4.7 kcal/mol.

  20. Thermodynamic assessment of the Mg-Pb and Mg-Bi systems using substitutional solution and associate models for the liquid phase

    Zhang F.

    2014-01-01

    Full Text Available By means of CALPHAD approach, thermodynamic assessments of the Mg-Pb and Mg-Bi systems were carried out based on the available experimental data including thermodynamic properties and phase equilibrium data. The liquid phase was described with both the substitutional solution model and the associate model, and two sets of self-consistent thermodynamic parameters for the Mg-Pb and Mg-Bi systems were obtained, respectively. It was found that the associate model can account for the experimental data more satisfactorily than the substitutional solution one, especially for the liquid phase with the short-range order behavior.

  1. Dipyrrolidinyl-substituted perylene diimide as additive for poly(3-hexylthiophene): [6,6]-Phenyl C61 butyric acid methylester bulk-heterojunction blends

    The effects of the addition of 1,7-dipyrrolidinyl-substituted perylene diimide (1,7-PyPDI) to a traditional poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C61-butyric acid methylester (PCBM) bulk-heterojunction blend on the performance of organic solar cells, are described. When the 1,7-PyPDI amount in the mixture is accurately tuned, the power conversion efficiency (η) of the 1,7-PyPDI-doped cells is enhanced compared to a reference non-doped device. Cells fabricated by spin-coating blends from chloroform solution with P3HT (monomer):PCBM:1,7-PyPDI molar ratio of 6.85:1:0.03 resulted in 39.6% higher power conversion efficiency than P3HT:PCBM blend. The efficiency improvement is attributed to possible photochemical interactions between the three components of the blend, which contribute to enhance the charge separation, and minimize the charge recombination processes. Moreover, the increased absorption and the microstructural implications induced by the introduction of 1,7-PyPDI contribute to explain the enhancement of the solar cell performance. - Highlights: • The solar cell active layer is doped with perylene derivative in different ratios. • The addition of the dopant significantly enhances the solar cell efficiency. • The possible role of the dopant in the heart of the solar cell is discussed

  2. Requirement for Asn298 on D1 protein for oxygen evolution: analyses by exhaustive amino acid substitution in the green alga Chlamydomonas reinhardtii.

    Kuroda, Hiroshi; Kodama, Natsumi; Sun, Xiao-Yu; Ozawa, Shin-ichiro; Takahashi, Yuichiro

    2014-07-01

    PSII generates strong oxidants used for water oxidation. The secondary electron donor, Y(Z), is Tyr161 on PSII reaction center D1 protein and mediates electron transfer from the oxygen-evolving Mn(4)CaO(5) cluster to the primary electron donor, P680. The latest PSII crystal structure revealed the presence of a hydrogen bond network around Y(Z), which is anticipated to play important roles in the electron and proton transfer reactions. Y(Z) forms a hydrogen bond with His190 which in turn forms a hydrogen bond with Asn298 on D1 protein. Although functional roles of Y(Z) and His190 have already been characterized, little is known about the functional role of Asn298. Here we have generated 19 mutants from a green alga Chlamydomonas reinhardtii, in which the Asn298 has been substituted by each of the other 19 amino acid residues. All mutants showed significantly impaired or no photosynthetic growth. Seven mutants capable of photosynthetic growth showed oxygen-evolving activity although at a significantly reduced rate. Interestingly the oxygen-evolving activity of these mutants was markedly photosensitive. The 19 mutants accumulated PSII at variable levels and showed a light-induced electron transfer reaction from 1,5-diphenylcarbazide (DPC) to 2,6-dichlorophenolindophenol (DCIP), suggesting that Asn298 is important for the function and photoprotection of the Mn(4)CaO(5) cluster. PMID:24853102

  3. Dipyrrolidinyl-substituted perylene diimide as additive for poly(3-hexylthiophene): [6,6]-Phenyl C61 butyric acid methylester bulk-heterojunction blends

    Vivo, Paola, E-mail: paola.vivo@tut.fi [Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere (Finland); Dubey, Rajeev; Lehtonen, Elina; Kivistö, Hannele [Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere (Finland); Vuorinen, Tommi [VTT Technical Research Centre of Finland, P.O. Box 1300, FI-33101 Tampere (Finland); Lemmetyinen, Helge [Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere (Finland)

    2013-12-02

    The effects of the addition of 1,7-dipyrrolidinyl-substituted perylene diimide (1,7-PyPDI) to a traditional poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C61-butyric acid methylester (PCBM) bulk-heterojunction blend on the performance of organic solar cells, are described. When the 1,7-PyPDI amount in the mixture is accurately tuned, the power conversion efficiency (η) of the 1,7-PyPDI-doped cells is enhanced compared to a reference non-doped device. Cells fabricated by spin-coating blends from chloroform solution with P3HT (monomer):PCBM:1,7-PyPDI molar ratio of 6.85:1:0.03 resulted in 39.6% higher power conversion efficiency than P3HT:PCBM blend. The efficiency improvement is attributed to possible photochemical interactions between the three components of the blend, which contribute to enhance the charge separation, and minimize the charge recombination processes. Moreover, the increased absorption and the microstructural implications induced by the introduction of 1,7-PyPDI contribute to explain the enhancement of the solar cell performance. - Highlights: • The solar cell active layer is doped with perylene derivative in different ratios. • The addition of the dopant significantly enhances the solar cell efficiency. • The possible role of the dopant in the heart of the solar cell is discussed.

  4. Genetic and functional analyses of the oeX174 DNA binding protein: the effects of substitutions for amino acid residues that spatially organize the two DNA binding domains

    The oeX174 DNA binding protein contains two DNA binding domains, containing a series of DNA binding basic amino acids, separated by a proline-rich linker region. Within each DNA binding domain, there is a conserved glycine residue. Glycine and proline residues were mutated and the effects on virion structure were examined. Substitutions for glycine residues yield particles with similar properties to previously characterized mutants with substitutions for DNA binding residues. Both sets of mutations share a common extragenic second-site suppressor, suggesting that the defects caused by the mutant proteins are mechanistically similar. Hence, glycine residues may optimize DNA-protein contacts. The defects conferred by substitutions for proline residues appear to be fundamentally different. The properties of the mutant particles along with the atomic structure of the virion suggest that the proline residues may act to guide the packaged DNA to the adjacent fivefold related asymmetric unit, thus preventing a chaotic packaging arrangement

  5. Exploring the Validity of Valproic Acid Animal Model of Autism

    Darine Froy N. Mabunga; Gonzales, Edson Luck T.; Kim, Ji-Woon; Kim, Ki Chan; Shin, Chan Young

    2015-01-01

    The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmenta...

  6. Evaluation of injectable silica-embedded nanohydroxyapatite bone substitute in a rat tibia defect model

    Xu W

    2011-08-01

    Full Text Available Weiguo Xu1, Cornelia Ganz2, Ulf Weber2, Martin Adam2, Gerd Holzhüter2, Daniel Wolter3, Bernhard Frerich3, Brigitte Vollmar1, Thomas Gerber21Institute for Experimental Surgery, 2Institute of Physics, 3Department of Oral, Maxillofacial and Plastic Surgery, University of Rostock, Rostock, GermanyAbstract: In clinical practice, vertebral compression fractures occur after trauma and osteoporosis. Kyphoplasty is a minimally invasive procedure using bone filler material for the treatment of such fractures. A full synthetic injectable bone substitute (SIBS was manufactured by means of spray drying. The aim of this study was to characterize the SIBS and to analyze the remodelling process during degradation of the biomaterial and new bone formation after implantation. SIBS is an aqueous suspension of donut-like microparticles. These microparticles consist of nanocrystallites of synthetic hydroxyapatite embedded in amorphous silica gel. After implantation of SIBS in a proximal tibial diaphyseal defect in 52 rats, grafts were harvested for subsequent analysis on different days. Newly formed bone originating from endosteum was observed on day 6. Hematomas in the medullary space and cortical wounds disappeared on day 12. The wound region was completely replaced by a composite of newly formed cancellous bone, extracellular matrix, and SIBS. At day 63 the cortical defect was fully healed by bone, while newly formed bone in the medullary space almost disappeared and was replaced with bone marrow. In conclusion, SIBS demonstrated a unique structure with osteoinductive and bioresorbable properties, which induced fast bone regeneration. Therefore, a clinical application of SIBS for kyphoplasty is promising.Keywords: bone remodelling, electron microscopy, histomorphometry, nanotechnology, tissue engineering

  7. Skin Substitutes

    Zavan, Barbara; Vindigni, Vincenzo; Cortivo, Roberta; Abatangelo, Giovanni

    2010-01-01

    The many studies conducted so far reveal that Tissue Engineering of the skin is only at the beginning of its use in human applications. Burns patients were the first targets for such tissue substitutes, then chronic diseases, such as venous ulcers, have followed. The more experience is gained from the surgeon, the more feedback for the basic scientist to improve the product and to broaden clinical indications. Nowadays, progress in cell culture and biomedical material technologies have added ...

  8. Substitution of carcinogenic solvent dichloromethane for the extraction of volatile compounds in a fat-free model food system.

    Cayot, Nathalie; Lafarge, Céline; Bou-Maroun, Elias; Cayot, Philippe

    2016-07-22

    Dichloromethane is known as a very efficient solvent, but, as other halogenated solvents, is recognized as a hazardous product (CMR substance). The objective of the present work is to propose substitution solvent for the extraction of volatile compounds. The most important physico-chemical parameters in the choice of an appropriate extraction solvent of volatile compounds are reviewed. Various solvents are selected on this basis and on their hazard characteristics. The selected solvents, safer than dichloromethane, are compared using the extraction efficiency of volatile compounds from a model food product able to interact with volatile compounds. Volatile compounds with different hydrophobicity are used. High extraction yields were positively correlated with high boiling points and high Log Kow values of volatile compounds. Mixtures of solvents such as azeotrope propan-2-one/cyclopentane, azeotrope ethyl acetate/ethanol, and mixture ethyl acetate/ethanol (3:1, v/v) gave higher extraction yields than those obtained with dichloromethane. PMID:27320380

  9. Design, Synthesis, and Crystal Structures of 6-Alkylidene-2 -Substituted Penicillanic Acid Sulfones as Potent Inhibitors of Acinetobacter baumannii OXA-24 Carbapenemase

    Bou, G.; Santillana, E; Sheri, A; Beceiro, A; Sampson, J; Kalp, M; Bethel, C; Distler, A; Drawz, S; et. al.

    2010-01-01

    Class D {beta}-lactamases represent a growing and diverse class of penicillin-inactivating enzymes that are usually resistant to commercial {beta}-lactamase inhibitors. As many such enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel {beta}-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2{prime}-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important {beta}-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 {beta}-lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to test the hypothesis that the hydrophobic tunnel formed by these residues influences inhibitor recognition. IC{sub 50} values against OXA-24 and two OXA-24 {beta}-lactamase variants ranged from 10 {+-} 1 (4 vs WT) to 338 {+-} 20 nM (5 vs Tyr112Ala, Met223Ala). Compound 4 possessed the lowest K{sub i} (500 {+-} 80 nM vs WT), and 1 possessed the highest inactivation efficiency (k{sub inact}/K{sub i} = 0.21 {+-} 0.02 {micro}M{sup -1}s{sup -1}). Electrospray ionization mass spectrometry revealed a single covalent adduct, suggesting the formation of an acyl-enzyme intermediate. X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 {angstrom}) reveal the formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in the oxyanion hole. These data provide the first structural evidence that 6-alkylidene-2{prime}-substituted penicillin sulfones are effective mechanism-based inactivators of class D {beta}-lactamases. Their unique chemistry makes them developmental candidates. Mechanisms for class D hydrolysis and inhibition are discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus aureus to the class D {beta}-lactamases is proposed.

  10. Modeling the adsorption of weak organic acids on goethite: the ligand and charge distribution model

    Filius, J.D.

    2001-01-01

    A detailed study is presented in which the CD-MUSIC modeling approach is used in a new modeling approach that can describe the binding of large organic molecules by metal (hydr)oxides taking the full speciation of the adsorbed molecule into account. Batch equilibration experiments were performed using the iron (hydr)oxide goethite to determine the adsorption of a series of weak organic acids (e.g. lactic acid, oxalic acid, malonic acid, phthalic acid, citric acid, and fulvic acid). In order t...

  11. Thr(118Met amino acid substitution in the peripheral myelin protein 22 does not influence the clinical phenotype of Charcot-Marie-Tooth disease type 1A due to the 17p11.2-p12 duplication

    W. Marques Jr.

    2003-10-01

    Full Text Available The Thr(118Met substitution in the peripheral myelin protein 22 (PMP22 gene has been detected in a number of families with demyelinating Charcot-Marie-Tooth (CMT1 neuropathy or with the hereditary neuropathy with liability to pressure palsy, but in none of them has it consistently segregated with the peripheral neuropathy. We describe here a CMT1 family (a 63-year-old man, his brother and his niece in which two mutations on different chromosomes were found in the PMP22 gene, the 17p duplication, detected by fluorescent semiquantitative polymerase chain reaction (PCR of microsatellite markers localized within the duplicated region on chromosome 17p11.2-p12, and the Thr(118Met substitution, detected by direct sequencing the four coding exons of the PMP22 gene. A genotype/phenotype correlation study showed that the neuropathy segregates with the duplication and that the amino acid substitution does not seem to modify the clinical characteristics or the severity of the peripheral neuropathy. We did not find any evidence to characterize this substitution as a polymorphism in the population studied and we propose that the high frequency reported for this point mutation in the literature suggests that the Thr(118Met substitution may be a hotspot for mutations in the PMP22 gene.

  12. Acidic deposition: State of science and technology. Report 4. The regional acid deposition model and engineering model. Final report

    The report describes the Regional Acid Deposition Model (RADM), a constantly evolving system of computational models that describe the major physical and chemical processes involved in acid deposition on a regional scale. RADM was developed by the Acid Deposition Modeling Project (ADMP), established at the National Center for Atmospheric Research (NCAR) in 1983 to design, develop, and implement a comprehensive modeling system suitable for assessment studies to be conducted as part of the National Acid Precipitation Assessment Program (NAPAP). The project was based at NCAR until 1987, when it moved to the Atmospheric Sciences Research Center (ASRC) of the State University of New York (SUNY) at Albany as the focus of its work moved into model testing and application. The ADMP team developed the RADM system, performed preliminary evaluation, transferred the system to the Environmental Protection Agency (EPA), and participated in NAPAP studies designed to test RADM and develop applications for the model

  13. Point substitutions in Japanese alloalbumins.

    Arai, K.; Madison, J; Huss, K; Ishioka, N; Satoh, C; Fujita, M.; Neel, J. V.; Sakurabayashi, I; Putnam, F W

    1989-01-01

    We have completed the structural study of five rare types of inherited albumin variants (alloalbumins) discovered in the Biochemical Genetics Study of 15,581 unrelated children in Hiroshima and Nagasaki. We have also identified the structural change in five other alloalbumin specimens detected during clinical electrophoresis of sera from Japanese living near Tokyo. Each of the five albumin variants from Nagasaki and Hiroshima has a single amino acid substitution. All of these substitutions di...

  14. Fluorine Substitution in Neurotransmitters: Microwave Spectroscopy and Modelling of the Conformational Space and Non Bonding Interactions

    Melandri, S.; Maris, A.; Merloni, A.

    2011-06-01

    Fluorine substitution in molecules is a common practice in bio-organic chemistry in order to modulate physicochemical properties and biological activity of molecules and an increasing number of drugs on the market contain fluorine, the presence of which is often of major importance to modify pharmacokinetics properties and molecular activity. The rationale for such a strategy is that fluorine is generally a stronger electron acceptor than the other halogen atoms and its size is intermediate between that of hydrogen and oxygen. We have studied two fluorinated analogs of 2-phenylethylamine (PEA), the prototype molecule for adrenergic neurotransmitters, namely: 4-Fluoro (4FPEA) and 2-Fluoro-2-phenylethylamine (2FPEA) by Molecular Beam Fourier Transform Microwave Spectroscopy in the frequency range 6-18 GHz and ab initio calculations at the MP2/6311++G** level. The aim is to obtain information on the spatial arrangement of the ethylamine side chain and the effects of fluorination on the energy landscape. The conformational space is dominated by low energy gauche conformations stabilized by weak interactions between the aminic hydrogens and the electron cloud of the benzene ring and anti conformations higher in energy. In 2FPEA the presence of the fluorine atom almost duplicate the number of possible conformation with respect to 4FPEA. We observed two conformers of 4FPEA and five conformers of 2FPEA which have been classified with the guide provided by accurate ab initio calculations. The identification of the conformational species was helped by the analysis of the quadrupole hyperfine pattern which is greatly influenced by the orientation of the amino group and acts as a fingerprint for each conformation. The orientation of the dipole moment within the principal axis frame and the order of stability of the different conformations are other independent pieces of evidence for the unambiguous assignment and identification of the conformers. The order of stability was

  15. Pharmacophore modeling and 3D-QSAR studies on substituted benzothiazole / benzimidazole analogues as DHFR inhibitors with antimycobacterial activity

    R. Priyadarsini

    2012-08-01

    Full Text Available The resurgence of tuberculosis and the emergence of multidrug-resistant strains of Mycobacteria drugs has propelled the development of new structural classes of antitubercular agents. The present study was undertaken to investigate the opportunities which the enzyme dihydrofolate reductase, a promising drug target for treatmentof Mycobacterial infections offers for the development of new TB drugs. Pharmacophore models were established by using the HipHop and HypoGen algorithms implemented in the Catalyst software package. Thebest quantitative pharmacophore model, consisted of two hydrogen bond acceptor, a hydrophobic aliphatic, and a ring aromatic feature which has the highest correlation coefficient (0.93, as well as enrichment factor of 1.75 and Goodness of hit score of 0.73. Based on the pharmacophore model some leads were optimized and some of its derivatives were synthesized and analysed by following QSAR studies. About 25 compounds of substituted benzothiazole/ benzimidazole derivatives were synthesized as potent DHFR inhibitors and screened for antimycobacterial activity. To further explore the structure-activity relationships of all newly synthesized compounds, 3D-QSAR analyses were developed. MFA studies were performed with the QSAR module of Cerius2 using genetic partial least squares (G/PLS algorithm. The predictive ability of the developed model was assessed using a training set of 25 and a test set of 5 compounds (r2pred = 0.924.The analyzed MF

  16. Of mental models, assumptions and heuristics: The case of acids and acid strength

    McClary, Lakeisha Michelle

    This study explored what cognitive resources (i.e., units of knowledge necessary to learn) first-semester organic chemistry students used to make decisions about acid strength and how those resources guided the prediction, explanation and justification of trends in acid strength. We were specifically interested in the identifying and characterizing the mental models, assumptions and heuristics that students relied upon to make their decisions, in most cases under time constraints. The views about acids and acid strength were investigated for twenty undergraduate students. Data sources for this study included written responses and individual interviews. The data was analyzed using a qualitative methodology to answer five research questions. Data analysis regarding these research questions was based on existing theoretical frameworks: problem representation (Chi, Feltovich & Glaser, 1981), mental models (Johnson-Laird, 1983); intuitive assumptions (Talanquer, 2006), and heuristics (Evans, 2008). These frameworks were combined to develop the framework from which our data were analyzed. Results indicated that first-semester organic chemistry students' use of cognitive resources was complex and dependent on their understanding of the behavior of acids. Expressed mental models were generated using prior knowledge and assumptions about acids and acid strength; these models were then employed to make decisions. Explicit and implicit features of the compounds in each task mediated participants' attention, which triggered the use of a very limited number of heuristics, or shortcut reasoning strategies. Many students, however, were able to apply more effortful analytic reasoning, though correct trends were predicted infrequently. Most students continued to use their mental models, assumptions and heuristics to explain a given trend in acid strength and to justify their predicted trends, but the tasks influenced a few students to shift from one model to another model. An

  17. The substitutability of reinforcers.

    Green, Leonard; Freed, Debra E

    1993-07-01

    Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

  18. Mathematical models for foam-diverted acidizing and their applications

    Li Songyan; Li Zhaomin; Lin Riyi

    2008-01-01

    Foam diversion can effectively solve the problem of uneven distribution of acid in layers of different permeabilities during matrix acidizing.Based on gas trapping theory and the mass conservation equation,mathematical models were developed for foam-diverted acidizing,which can be achieved by a foam slug followed by acid injection or by continuous injection of foamed acid.The design method for foam-diverted acidizing was also given.The mathematical models were solved by a computer program.Computed results show that the total formation skin factor,wellhead pressure and bottomhole pressure increase with foam injection,but decrease with acid injection.Volume flow rate in a highpermeability layer decreases,while that in a low-permeability layer increases,thus diverting acid to the low-permeability layer from the high-permeability layer.Under the same formation conditions,for foamed acid treatment the operation was longer,and wellhead and bottomhole pressures are higher.Field application shows that foam slug can effectively block high permeability layers,and improve intake profile noticeably.

  19. Evaluation of Osteoconductive and Osteogenic Potential of a Dentin-Based Bone Substitute Using a Calvarial Defect Model

    Ibrahim Hussain

    2012-01-01

    Full Text Available The aim of this study was to assess the osteoconductive and osteogenic properties of processed bovine dentin using a robust rabbit calvarial defect model. In total, 16 New Zealand White rabbits were operated to create three circular defects in the calvaria. One defect was left unfilled, one filled with collected autogenous bone, and the third defect was filled with the dentin-based bone substitute. Following surgery and after a healing period of either 1 or 6 weeks, a CT scan was obtained. Following sacrificing, the tissues were processed for histological examination. The CT data showed the density in the area grafted with the dentin-based material was higher than the surrounding bone and the areas grafted with autologous bone after 1 week and 6 weeks of healing. The area left unfilled remained an empty defect after 1 week and 6 weeks. Histological examination of the defects filled with the dentin product after 6 weeks showed soft tissue encapsulation around the dentin particles. It can be concluded that the rabbit calvarial model used in this study is a robust model for the assessment of bone materials. Bovine dentin is a biostable material; however, it may not be suitable for repairing large 4-wall defects.

  20. Theoretical modeling of iodine value and saponification value of biodiesel fuels from their fatty acid composition

    Gopinath, A.; Puhan, Sukumar; Nagarajan, G. [Internal Combustion Engineering Division, Department of Mechanical Engineering, Anna University, Chennai 600 025, Tamil Nadu (India)

    2009-07-15

    Biodiesel is an alternative fuel consisting of alkyl esters of fatty acids from vegetable oils or animal fats. The properties of biodiesel depend on the type of vegetable oil used for the transesterification process. The objective of the present work is to theoretically predict the iodine value and the saponification value of different biodiesels from their fatty acid methyl ester composition. The fatty acid ester compositions and the above values of different biodiesels were taken from the available published data. A multiple linear regression model was developed to predict the iodine value and saponification value of different biodiesels. The predicted results showed that the prediction errors were less than 3.4% compared to the available published data. The predicted values were also verified by substituting in the available published model which was developed to predict the higher heating values of biodiesel fuels from their iodine value and the saponification value. The resulting heating values of biodiesels were then compared with the published heating values and reported. (author)

  1. Lifetime modelling of lead acid batteries

    Bindner, H.; Cronin, T.; Lundsager, P.;

    2005-01-01

    , therefore, lead to uncertainty in the viability of the system in the long term. This report details the work undertaken to investigate and develop two different battery life prediction methodologies withspecific reference to their use in hybrid renewable energy systems. Alongside this, results from battery...... been part of the European Union Benchmarking research project (ENK6-CT-2001-80576), funded by theEuropean Union, the United States and Australian governments together with other European states and other public and private financing bodies. The project has concentrated on lead acid batteries as this...

  2. Modelling of Sulfuric Acid Nanoparticles Growth

    Škrabalová, Lenka; Brus, D.; Antilla, T.; Ždímal, Vladimír; Lihavainen, H.

    Praha: Czech Aerosol Society, 2013 - (Zíková, N.), s. 95-100 ISBN 978-80-86186-52-8. [Výroční konference České aerosolové společnosti /14./. Nový Smokovec, High Tatras (SK), 23.10.2013-25.10.2013] R&D Projects: GA AV ČR IAA200760905 Grant ostatní: AFCE(FI) 1118615 Institutional support: RVO:67985858 Keywords : sulfuric acid * nanoparticles * particle growth Subject RIV: BJ - Thermodynamics

  3. Effect of Isotopic Substitution on Elementary Processes in Dye-Sensitized Solar Cells: Deuterated Amino-Phenyl Acid Dyes on TiO2

    Sergei Manzhos

    2013-03-01

    Full Text Available We present the first computational study of the effects of isotopic substitution on the operation of dye-sensitized solar cells. Ab initio molecular dynamics is used to study the effect of deuteration on light absorption, dye adsorption dynamics, the averaged over vibrations driving force to injection (∆Gi and regeneration (∆Gr, as well as on promotion of electron back-donation in dyes NK1 (2E,4E-2-cyano-5-(4-dimethylaminophenylpenta-2,4-dienoic acid and NK7 (2E,4E-2-cyano-5-(4-diphenylaminophenylpenta-2,4-dienoic acid adsorbed in monodentate molecular and bidentate bridging dissociative configurations on the anatase (101 surface of TiO2. Deuteration causes a red shift of the absorption spectrum of the dye/TiO2 complex by about 5% (dozens of nm, which can noticeably affect the overlap with the solar spectrum in real cells. The dynamics effect on the driving force to injection and recombination (the difference between the averaged <∆Gi,r> and ∆Gi,requil at the equilibrium configuration is strong, yet there is surprisingly little isotopic effect: the average driving force to injection <∆Gi> and to regeneration <∆Gr> changes by only about 10 meV upon deuteration. The nuclear dynamics enhance recombination to the dye ground state due to the approach of the electron-donating group to TiO2, yet this effect is similar for deuterated and non-deuterated dyes. We conclude that the nuclear dynamics of the C-H(D bonds, mostly affected by deuteration, might not be important for the operation of photoelectrochemical cells based on organic dyes. As the expectation value of the ground state energy is higher than its optimum geometry value (by up to 0.1 eV in the present case, nuclear motions will affect dye regeneration by recently proposed redox shuttle-dye combinations operating at low driving forces.

  4. Supramolecular complex formation of β-cyclodextrin polymer with substituted salicylic acid or 3-hydroxy-2-naphthoic acid and their electrorheological behaviors

    GAO; Ziwei; ZHAO; Xiaopeng; SUN; Ping; SI; Gang

    2004-01-01

    supramolecular systems (XXXV) --Synthesis of novel β-cyclodextrin derivative beating pyridinio group and its chiral discrimination of amino acids, Science in China, Ser. B, 2001, 44(3): 260-267.[13]Liu, Y., Yang, Y. W., Cao, R. et al., Thermodynamic origin of molecular selective binding of bile salts by aminated β-cyclodextrins,J. Phys. Chem. B, 2003: 14130-14139.[14]Liu, Y., Chen, G. S., Li, L. et al., Inclusion complexation and solubilization of paclitaxel by bridged bis(β-cyclodextrin)s containing a tetraethylenepentaamino spacer, J. Med. Chem., 2003,46(22): 4634-4637.[15]Yoshida, K., Shimomura, T., Ito, K. et al., Inclusion complex formation of cyclodextrin and polyaniline, Langmuir, 1999, 15(4):910-913.[16]Crini, G., Bertini, S., Torri, G. et al., Sorption of aromatic co-pounds in water using insoluble cyclodextrin polymers, J.Appllied Polymer Science, 1998, 68: 1973-1978.[17]Renard, E., Deratani, A., Volet, G. et al., Preparation and characterization of water soluble high molecular weight β-cyclodextrinepichlorohydrin polymers, Eur. Polym. J., 1997, 33(1): 49-57.[18]Gao, Z. W., Zhao, X. P., Electrorheological properties of inclusive complex of β-cyclodextrin polymer, Materials Letters, 2002, 57:615-618.[19]Gao, Z. W., Zhao, X. P., Enhancing electrorheological behaviors with formation of β-cyclodextrin supramolecular complex, Polymer, 2003, 44:4519-4526.[20]Su, X. D., Liu, L. Z., Shen, H. Y., Study on the absorbing enrichment of trace metals using α-pyridylaxo-β-naphthol inclusion complexes of cyclodextrin polymer resin, Analytical Chemistry (in Chinese), 1995, 23(12): 1361-1366.[21]Catena, G. C., Bright, F. V., Thermodynamic study on the effects of β-cyclodextrin inclusion with anilinonaphthalenesulfonates,Anal. Chem., 1989, 61: 905-909.[22]Kano, K., Tatsumi, M., Hashimoto, S., Cyclodextrin-induced conformational enantiomerism of dinaphthylmethanes, J. Org.Chem., 1991, 56: 6579-6585.

  5. Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Five-, Six-, and Seven-Membered β-Substituted Cyclic Enones: Enantioselective Construction of All-Carbon Quaternary Stereocenters

    Kikushima, Kotaro

    2011-05-11

    The first enantioselective Pd-catalyzed construction of all-carbon quaternary stereocenters via 1,4-addition of arylboronic acids to β-substituted cyclic enones is reported. Reaction of a wide range of arylboronic acids and cyclic enones using a catalyst prepared from Pd(OCOCF(3))(2) and a chiral pyridinooxazoline ligand yields enantioenriched products bearing benzylic stereocenters. Notably, this transformation is tolerant to air and moisture, providing a practical and operationally simple method of synthesizing enantioenriched all-carbon quaternary stereocenters.

  6. Conversion of NfsA, the Major Escherichia coli Nitroreductase, to a Flavin Reductase with an Activity Similar to That of Frp, a Flavin Reductase in Vibrio harveyi, by a Single Amino Acid Substitution

    Zenno, Shuhei; Kobori, Toshiro; Tanokura, Masaru; Saigo, Kaoru

    1998-01-01

    NfsA is the major oxygen-insensitive nitroreductase of Escherichia coli, similar in amino acid sequence to Frp, a flavin reductase of Vibrio harveyi. Here, we show that a single amino acid substitution at position 99, which may destroy three hydrogen bonds in the putative active center, transforms NfsA from a nitroreductase into a flavin reductase that is as active as the authentic Frp and a tartrazine reductase that is 30-fold more active than wild-type NfsA. PMID:9440535

  7. Mononuclear non-heme iron(III) complexes of linear and tripodal tridentate ligands as functional models for catechol dioxygenases: Effect of -alkyl substitution on regioselectivity and reaction rate

    Mallayan Palaniandavar; Kusalendiran Visvaganesan

    2011-03-01

    Catechol dioxygenases are responsible for the last step in the biodegradation of aromatic molecules in the environment. The iron(II) active site in the extradiol-cleaving enzymes cleaves the C-C bond adjacent to the hydroxyl group, while the iron(III) active site in the intradiol-cleaving enzymes cleaves the C-C bond in between two hydroxyl groups. A series of mononuclear iron(III) complexes of the type [Fe(L)Cl3], where L is the linear -alkyl substituted bis(pyrid-2-ylmethyl)amine, -alkyl substituted -(pyrid-2-ylmethyl)ethylenediamine, linear tridentate 3N ligands containing imidazolyl moieties and tripodal ligands containing pyrazolyl moieties have been isolated and studied as structural and functional models for catechol dioxygenase enzymes. All the complexes catalyse the cleavage of catechols using molecular oxygen to afford both intra- and extradiol cleavage products. The rate of oxygenation depends on the solvent and the Lewis acidity of iron(III) center as modified by the sterically demanding -alkyl groups. Also, our studies reveal that stereo-electronic factors like the Lewis acidity of the iron(III) center and the steric demand of ligands, as regulated by the -alkyl substituents, determine the regioselectivity and the rate of dioxygenation. In sharp contrast to all these complexes, the pyrazole-containing tripodal ligand complexes yield mainly the oxidized product benzoquinone.

  8. Discovery of potent aryl-substituted 3-[(3-methylpyridine-2-carbonyl) amino]-2,4-dimethyl-benzoic acid EP4 antagonists with improved pharmacokinetic profile.

    Blanco, Maria-Jesus; Vetman, Tatiana; Chandrasekhar, Srinivasan; Fisher, Matthew J; Harvey, Anita; Chambers, Mark; Lin, Chaohua; Mudra, Daniel; Oskins, Jennifer; Wang, Xu-Shan; Yu, Xiao-Peng; Warshawsky, Alan M

    2016-02-01

    Two new series of EP4 antagonists containing a 3-methylaryl-2-carbonyl core have been identified. One series has a 3-substituted-phenyl core, while the other one incorporates a 3-substituted pyridine. Both series led to compounds with potent activity in functional and human whole blood (hWB) assays. In the pyridine series, compound 7a was found to be a highly potent and selective EP4 antagonist, with suitable rat and dog pharmacokinetic profiles. PMID:26764191

  9. Ab initio and kinetic modeling studies of formic acid oxidation

    Marshall, Paul; Glarborg, Peter

    2015-01-01

    A detailed chemical kinetic model for oxidation of formic acid (HOCHO) in flames has been developed, based on theoretical work and data from literature. Ab initio calculations were used to obtain rate coefficients for reactions of HOCHO with H, O, and HO2. Modeling predictions with the mechanism...... on calculations with the kinetic model. Formic acid is consumed mainly by reaction with OH, yielding OCHO, which dissociates rapidly to CO2 + H, and HOCO, which may dissociate to CO + OH or CO2 + H, or react with H, OH, or O2 to form more stable products. The branching fraction of the HOCHO + OH...

  10. Lifetime modelling of lead acid batteries

    Bindner, H.; Cronin, T.; Lundsager, P.

    2005-04-01

    The performance and lifetime of energy storage in batteries are an important part of many renewable based energy systems. Not only do batteries impact on the system performance but they are also a significant expenditure when considering the whole life cycle costs. Poor prediction of lifetime can, therefore, lead to uncertainty in the viability of the system in the long term. This report details the work undertaken to investigate and develop two different battery life prediction methodologies with specific reference to their use in hybrid renewable energy systems. Alongside this, results from battery tests designed to exercise batteries in similar modes to those that they experience in hybrid systems have also been analysed. These have yielded battery specific parameters for use in the prediction software and the first results in the validation process of the software are also given. This work has been part of the European Union Benchmarking research project (ENK6-CT-2001-80576), funded by the European Union, the United States and Australian governments together with other European states and other public and private financing bodies. The project has concentrated on lead acid batteries as this technology is the most commonly used. Through this work the project partner institutions have intended to provide useful tools to improve the design capabilities of organizations, private and public, in remote power systems. (au)

  11. Super acid catalysed sequential hydrolysis/cycloisomerization of -(acetylenic)benzamides under microwave condition: Synthesis, antinociceptive and antiinflammatory activity of substituted isocoumarins

    Chandrasekaran Praveen; P Dheenkumar; P T Perumal

    2013-01-01

    Synthesis of isocoumarins and related compounds via triflic acid promoted hydrolysis/cyclization sequence of 2-(alkynyl)benzamides under microwave condition was achieved. The substrate scope of the reaction was broad to include not only aromatic but also polyaromatic and heteroaromatic motifs, thus highlighting the significance of this methodology. One-pot operation, short reaction time, good chemical yields and excellent regioselectivity are the advantages of this protocol. All the synthesized compounds were evaluated for their antinociceptive and antiinflammatory activities using in vivo rodent models.

  12. Using inverted autogenous veins to substitute arteries in a canine model

    Nikeghbalian Saman

    2010-01-01

    Full Text Available Aims : Rapid harvesting of autogenous graft over a wire is an optional way in trauma surgery and it places the inverted conduit so that its adventitial layer is within the lumen of the graft. Our aim of this study was to compare the patency of inverted autogenous graft vs noninverted graft in dogs. Settings and Design : Experimental animal models. Materials and Methods : In this experimental study, 12 dogs were anesthetized and 10 cm of the external jugular vein was excised. The vein was equally divided into two 5-cm sections. One section was inverted and the other was left intact. Afterward, 5 cm of both the femoral arteries were removed and the right (inverted and the left (not inverted arteries were grafted, respectively. The patency of the arteries was evaluated by Color Doppler ultrasonography immediately postoperation and up to 6 months thereafter. Statistical Analysis : Data were analyzed with Fisher′s exact test using SPSS version 15. P value below 0.05 was significant. Results: None of the 12 inverted vein grafts were patent at 3 rd to 14 th days follow-up with Doppler ultrasonography. All of them were completely obstructed by thrombosis. However, 11 (92% of the noninverted vein grafts were patent both at 3 and 6 months follow-up. One of the noninverted grafts was almost completely obstructed with thrombosis (90% and the other 2 were incompletely obstructed with intimal thickening. Conclusions : Despite many favorable results in the previous studies with regard to excellent patency of inverted vein graft, our results were disappointing and we recommend using the graft in the right direction and taking care to preserve the intima intact.

  13. Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

    Grabellus Florian

    2011-08-01

    Full Text Available Abstract Background Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice. Methods We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE particles in 10 C57BL/6J wild-type (WT mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1, WT with UHMWPE particles (Group 2, Calca -/- mice without UHMWPE particles (Group 3, Calca -/- mice with UHMWPE particles (Group 4, Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5, and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6. Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP + cells. Results Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin increased significantly after CT substitution. Conclusions As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

  14. N-(4-Substituted-benzoyl)-N'-(beta-d-glucopyranosyl)ureas as inhibitors of glycogen phosphorylase: Synthesis and evaluation by kinetic, crystallographic, and molecular modelling methods

    Veronika Nagy; Nora Felfoeldi; Balint Konya; Praly, Jean-Pierre; Tibor Docsa; Pal Gergely; Chrysina, Evangelia D.; Tiraidis, Costas; Kosmopoulou, Magda N.; Alexacou, Kyra-Melinda; Konstantakaki, Maria; Leonidas, Demetres D.; Zographos, Spyros E.; Oikonomakos, Nikos G.; Kozmon, Stanislav

    2012-01-01

    N-(4-Substituted-benzoyl)-N'-(beta-D-glucopyranosyl)ureas (substituents: Me, Ph, Cl, OH, OMe, NO2, NH2, COOH, and COOMe) were synthesised by ZnCl2 catalysed acylation of O-peracetylated beta-D-glucopyranosyl urea as well as in reactions of O-peracetylated or O-unprotected glucopyranosylamines and acyl-isocyanates. O-deprotections were carried out by base or acid catalysed transesterifications where necessary. Kinetic studies revealed that most of these compounds were low micromolar inhibitors...

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

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

    2008-01-01

    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 C, C-H2SO4 - 0.1-1 M, water hyacinth intake = 1-5 wt%). At high acid concentrations (> 0.5 M), LA was the major organic acid whereas at low acid concentrations (

  16. PERFORMANCE OF PULVERIZED SLAG-SUBSTITUTED CEMENT

    1999-01-01

    The Portland cement is equivalently substituted by slag micropowders with various specific areas. The workability,activity and acid-corrosion resistance of the slag-substituted cements are investigated,the activation of gypsum is discussed,also the porosity and pore distribution of mortars of the slag micropowders cement are determined by mercury intrusion porosimetry.

  17. Kinetic Modeling of Sunflower Grain Filling and Fatty Acid Biosynthesis.

    Durruty, Ignacio; Aguirrezábal, Luis A N; Echarte, María M

    2016-01-01

    Grain growth and oil biosynthesis are complex processes that involve various enzymes placed in different sub-cellular compartments of the grain. In order to understand the mechanisms controlling grain weight and composition, we need mathematical models capable of simulating the dynamic behavior of the main components of the grain during the grain filling stage. In this paper, we present a non-structured mechanistic kinetic model developed for sunflower grains. The model was first calibrated for sunflower hybrid ACA855. The calibrated model was able to predict the theoretical amount of carbohydrate equivalents allocated to the grain, grain growth and the dynamics of the oil and non-oil fraction, while considering maintenance requirements and leaf senescence. Incorporating into the model the serial-parallel nature of fatty acid biosynthesis permitted a good representation of the kinetics of palmitic, stearic, oleic, and linoleic acids production. A sensitivity analysis showed that the relative influence of input parameters changed along grain development. Grain growth was mostly affected by the specific growth parameter (μ') while fatty acid composition strongly depended on their own maximum specific rate parameters. The model was successfully applied to two additional hybrids (MG2 and DK3820). The proposed model can be the first building block toward the development of a more sophisticated model, capable of predicting the effects of environmental conditions on grain weight and composition, in a comprehensive and quantitative way. PMID:27242809

  18. Kinetic Modeling of Sunflower Grain Filling and Fatty Acid Biosynthesis

    Durruty, Ignacio; Aguirrezábal, Luis A. N.; Echarte, María M.

    2016-01-01

    Grain growth and oil biosynthesis are complex processes that involve various enzymes placed in different sub-cellular compartments of the grain. In order to understand the mechanisms controlling grain weight and composition, we need mathematical models capable of simulating the dynamic behavior of the main components of the grain during the grain filling stage. In this paper, we present a non-structured mechanistic kinetic model developed for sunflower grains. The model was first calibrated for sunflower hybrid ACA855. The calibrated model was able to predict the theoretical amount of carbohydrate equivalents allocated to the grain, grain growth and the dynamics of the oil and non-oil fraction, while considering maintenance requirements and leaf senescence. Incorporating into the model the serial-parallel nature of fatty acid biosynthesis permitted a good representation of the kinetics of palmitic, stearic, oleic, and linoleic acids production. A sensitivity analysis showed that the relative influence of input parameters changed along grain development. Grain growth was mostly affected by the specific growth parameter (μ′) while fatty acid composition strongly depended on their own maximum specific rate parameters. The model was successfully applied to two additional hybrids (MG2 and DK3820). The proposed model can be the first building block toward the development of a more sophisticated model, capable of predicting the effects of environmental conditions on grain weight and composition, in a comprehensive and quantitative way. PMID:27242809

  19. Novel Caffeic Acid Nanocarrier: Production, Characterization, and Release Modeling

    Milad Fathi

    2013-01-01

    Full Text Available This paper deals with the development of novel nanocarriers using layer by layer carbohydrate coating of caffeic acid loaded solid lipid nanoparticles (SLNs to improve stability and colon delivery of the poorly water-soluble caffeic acid. Three biopolymers (chitosan, alginate, and pectin in different concentrations (0.1, 0.25, and 0.5% were electrostatically coated over the SLN surface. The size and zeta potential of produced nanocarriers were measured using photon correlation spectroscopy. Mathematical models (i.e., zero-order, first-order, Higuchi, Ritger-Peppas, reciprocal powered time, Weibull, and quadratic models were used to describe the release and kinetic modeling in gastrointestinal solution (GIS. Also, antioxidant activity of caffeic acid during the release in GIS was investigated using DPPH and reducing activity methods. The prepared treatments coated by alginate-chitosan as well as pectin-chitosan coated SLN at the concentration of 0.1% showed nanosized bead; the latter efficiently retarded the release of caffeic acid in gastric media up to 2.5 times higher than that of SLN. Zeta potential values of coated samples were found to significantly increase in comparison to SLN indicating the higher stability of produced nanocarriers. Antioxidant activity of caffeic acid after gastric release did not result in the same trend as observed for caffeic acid release from different treatments; however, in line with less caffeic acid release in the intestine solution by the effect of coating, lower antioxidant activity was determined at the end stage of the experiment.

  20. Modelling Negative Binomial as a substitute model to Poisson for raters agreement on ordinal scales with sparse data

    Adejumo, A. O.; Heumann, Christian; Toutenburg, Helge

    2004-01-01

    The Poisson distribution has been widely used for modelling rater agreement using loglinear models. Mostly in all life or social science researches, subjects are being classified into categories by rater, interviewers or observers and most of these tables indicate that the cell counts are mixtures of either too big values and two small values or zeroes which are sparse data. We refer to sparse as a situation when a large number of cell frequencies are very small. For these kinds of tables, th...

  1. Force field modeling of amino acid conformational energies

    Kaminský, Jakub; Jensen, F.

    2007-01-01

    Roč. 3, č. 5 (2007), s. 1774-1788. ISSN 1549-9618 R&D Projects: GA AV ČR IAA400550702 Institutional research plan: CEZ:AV0Z40550506 Keywords : amino acids * modeling * MP2 * DFT Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.308, year: 2007

  2. Pharmacological characterization of LY233053: A structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action

    This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity

  3. Retinoic acid fails to reverse emphysema in adult mouse models

    Fujita, M; Ye, Q.; Ouchi, H.; Nakashima, N; Hamada, N; Hagimoto, N; Kuwano, K.; Mason, R.; Nakanishi, Y

    2004-01-01

    Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric ...

  4. A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid

    Liu, Huan-Guang; Ma, Yu; Meng, Da-Wei; Yang, An-Chao; Zhang, Jian-Guo

    2013-01-01

    Objective Secondary dystonia commonly presents as hemidystonia and is often refractory to current treatments. We aimed to establish an inducible rat model of hemidystonia utilizing 3-nitropropionic acid (3-NP) and to determine the pathophysiology of this model. Methods Two different doses of 3-NP were stereotactically administered into the ipsilateral caudate putamen (CPu) of Wistar rats. Behavioral changes and alterations in the neurotransmitter levels in the basal ganglia were analyzed. We ...

  5. Kinetic Modeling of Esterification of Ethylene Glycol with Acetic Acid

    The reaction kinetics of the esterification of ethylene glycol with acetic acid in the presence of cation exchange resin has been studied and kinetic models based on empirical and Langmuir approach has been developed. The Langmuir based model involving eight kinetic parameters fits experimental data much better compared to empirical model involving four kinetic parameters. The effect of temperature and catalyst loading on the reaction system has been analyzed. Further, the activation energy and frequency factor of the rate constants for Langmuir based model has been estimated.

  6. Exploring the Validity of Valproic Acid Animal Model of Autism.

    Mabunga, Darine Froy N; Gonzales, Edson Luck T; Kim, Ji-Woon; Kim, Ki Chan; Shin, Chan Young

    2015-12-01

    The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmental manipulation. The uncovering of these complex pathways resulted to the growing pool of potential therapeutic candidates addressing the core symptoms of ASD. Here, we summarize the validity points of VPA that may or may not qualify it as a valid animal model of ASD. PMID:26713077

  7. Probing for improved potency and in vivo bioavailability of excitatory amino acid transporter subtype 1 inhibitors UCPH-101 and UCPH-102: Design, synthesis and pharmacological evaluation of substituted 7-biphenyl analogs

    Erichsen, Mette Norman; Hansen, J; Artacho Ruiz, Jose; Demmer, Charles Sylvain; Abrahamsen, Bjarke; Bastlund, Jesper F; Bundgaard, C; Jensen, Anders A.; Bunch, Lennart

    2014-01-01

    Uptake of the major excitatory neurotransmitter in the CNS, (S)-glutamate, is mediated by a family of excitatory amino acid transporters (EAAT). Previously we have explored the structure-activity relationship (SAR) of a series of EAAT1 selective inhibitors, leading to the development of the potent...... different chloro, fluoro, methoxy, triflouromethyl and carboxy substitution patterns at the o-biphenyl group of 1d (1h-1s) and m- and p-pyridine analogs of 1d (1t and 1v). Unfortunately, all of the modifications resulted in substantial decreased EAAT1 inhibitory activity, which supports the notion of a very...

  8. Organometallic Enantiomeric Scaffolding: General Access to 2-Substituted Oxa- and Azabicyclo[3.2.1]octenes via a Brønsted Acid-catalyzed [5+2] Cycloaddition Reaction

    Garnier, Ethel C.; Liebeskind, Lanny S.

    2008-01-01

    6-Substituted TpMo(CO)2(η-2,3,4-pyranyl)- and TpMo(CO)2(η-2,3,4-pyridinyl) scaffolds (Tp = hydridotrispyrazolylborato) function as reaction partners in an efficient regio- and stereocontrolled synthesis of functionalized oxa- and azabicyclo[3.2.1]octenes through a novel Brønsted acid-catalyzed [5+2] cycloaddition reaction. Excellent exo-selectivities are obtained and the reaction gives products with complete retention of enantiomeric purity when carried out with chiral, non-racemic scaffolds....

  9. Geometrical criteria versus quantum chemical criteria for assessment of intramolecular hydrogen bond (IMHB) interaction: A computational comparison into the effect of chlorine substitution on IMHB of salicylic acid in its lowest energy ground state conformer

    Paul, Bijan Kumar [Department of Chemistry, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Guchhait, Nikhil, E-mail: nikhil.guchhait@rediffmail.com [Department of Chemistry, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India)

    2013-02-01

    Highlights: ► Intramolecular hydrogen bonding (IMHB) in salicylic acid and its chloro derivatives. ► A complex effect of +R and −I effect of chlorine substituents on IMHB energy. ► Interplay between IMHB energy and aromaticity. ► Directional nature of IMHB from quantum chemical assessment. ► Quantum chemical treatment vs. geometrical criteria to assess weak interaction. - Abstract: Density functional theory based computational study has been performed to characterize intramolecular hydrogen bonding (IMHB) interaction in a series of salicylic acid derivatives varying in chlorine substitution on the benzene ring. The molecular systems studied are salicylic acid, 5-chlorosalicylic acid, 3,5-dichlorosalicylic acid and 3,5,6-tricholorosalicylic acid. Major emphasis is rendered on the analysis of IMHB interaction by calculation of electron density ρ(r) and Laplacian ∇{sup 2}ρ(r) at the bond critical point using atoms-in-molecule theory. Topological features, energy densities based on ρ(r) through perturbing the intramolecular H-bond distances suggest that at equilibrium geometry the IMHB interaction develops certain characteristics typical of covalent interaction. The interplay between aromaticity and resonance-assisted hydrogen bonding (RAHB) is discussed using both geometrical and magnetic criteria as the descriptors of aromaticity. The optimized geometry features, molecular electrostatic potential map analysis are also found to produce a consensus view in relation with the formation of RAHB in these systems.

  10. Enhanced Stability of the Model Mini-protein in Amino Acid Ionic Liquids and Their Aqueous Solutions

    Chevrot, Guillaume; Chaban, Vitaly V

    2015-01-01

    Using molecular dynamics simulations, the structure of model mini-protein was thoroughly characterized in the imidazolium-based amino acid ionic liquids and their aqueous solutions. We report that the mini-protein is more stable when AAIL is added as a cosolvent. Complete substitution of water by organic cations and anions further results in hindered conformational flexibility of the mini-protein. This observation suggests that AAILs are able to defend proteins from thermally induced denaturation. We show by means of radial distributions that the mini-protein is efficiently solvated by both solvents due to agood mutual miscibility. However, amino acid based anions prevail in the first coordination sphere of the mini-protein.

  11. Testing Substitutability of Weak Preferences

    Aziz, Haris; Brill, Markus; Harrenstein, Paul

    2012-01-01

    In many-to-many matching models, substitutable preferences constitute the largest domain for which a pairwise stable matching is guaranteed to exist. In this note, we extend the recently proposed algorithm of Hatfield et al. [3] to test substitutability of weak preferences. Interestingly, the algorithm is faster than the algorithm of Hatfield et al. by a linear factor on the domain of strict preferences.

  12. Lead-acid battery model for hybrid energy storage

    BUTTERBACH,S; Vulturescu, Bogdan; FORGEZ, C; Coquery, Gérard; Friedrich, G.

    2011-01-01

    This paper deals with the design of hybrid energy storage for an electric waste collection vehicle. The hybrid storage is made of lead-acid batteries and supercapacitors. A detailed lead-acid model is proposed in order to take into account the charge of the battery during regenerative braking. The vehicle was simulated on an urban driving cycle for a full working day. The reduction of the consumed energy due to an increased recovery capacity is outlined in this paper as a main benefit of the ...

  13. The kinetics of the solidification of highly supersaturated solutions of palmitic acid in oleic acid: a comparison between two models

    RAMIRO RICO-MARTINEZ; JOSE ALBERTO GALLEGOS-INFANTE

    1999-01-01

    The crystallization of fatty acids is very important in industrial applications and biological systems. A comparison between theoretical models and experimental data helps in clarifying mechanistic aspects of these systems. In this contribution, we compare the performance of two models in fitting data from the crystallization of supersaturated solutions of palmitic acid in oleic acid. One of the models was developed by Avrami and the other is based on considering diffusion as limiting (the D-...

  14. Modeling acid-gas generation from boiling chloride brines

    Zhang, Guoxiang; Spycher, Nicolas; Sonnenthal, Eric; Steefel, Carl

    2009-11-16

    This study investigates the generation of HCl and other acid gases from boiling calcium chloride dominated waters at atmospheric pressure, primarily using numerical modeling. The main focus of this investigation relates to the long-term geologic disposal of nuclear waste at Yucca Mountain, Nevada, where pore waters around waste-emplacement tunnels are expected to undergo boiling and evaporative concentration as a result of the heat released by spent nuclear fuel. Processes that are modeled include boiling of highly concentrated solutions, gas transport, and gas condensation accompanied by the dissociation of acid gases, causing low-pH condensate. Simple calculations are first carried out to evaluate condensate pH as a function of HCl gas fugacity and condensed water fraction for a vapor equilibrated with saturated calcium chloride brine at 50-150 C and 1 bar. The distillation of a calcium-chloride-dominated brine is then simulated with a reactive transport model using a brine composition representative of partially evaporated calcium-rich pore waters at Yucca Mountain. Results show a significant increase in boiling temperature from evaporative concentration, as well as low pH in condensates, particularly for dynamic systems where partial condensation takes place, which result in enrichment of HCl in condensates. These results are in qualitative agreement with experimental data from other studies. The combination of reactive transport with multicomponent brine chemistry to study evaporation, boiling, and the potential for acid gas generation at the proposed Yucca Mountain repository is seen as an improvement relative to previously applied simpler batch evaporation models. This approach allows the evaluation of thermal, hydrological, and chemical (THC) processes in a coupled manner, and modeling of settings much more relevant to actual field conditions than the distillation experiment considered. The actual and modeled distillation experiments do not represent

  15. Modeling acid-gas generation from boiling chloride brines

    This study investigates the generation of HCl and other acid gases from boiling calcium chloride dominated waters at atmospheric pressure, primarily using numerical modeling. The main focus of this investigation relates to the long-term geologic disposal of nuclear waste at Yucca Mountain, Nevada, where pore waters around waste-emplacement tunnels are expected to undergo boiling and evaporative concentration as a result of the heat released by spent nuclear fuel. Processes that are modeled include boiling of highly concentrated solutions, gas transport, and gas condensation accompanied by the dissociation of acid gases, causing low-pH condensate. Simple calculations are first carried out to evaluate condensate pH as a function of HCl gas fugacity and condensed water fraction for a vapor equilibrated with saturated calcium chloride brine at 50-150 C and 1 bar. The distillation of a calcium-chloride-dominated brine is then simulated with a reactive transport model using a brine composition representative of partially evaporated calcium-rich pore waters at Yucca Mountain. Results show a significant increase in boiling temperature from evaporative concentration, as well as low pH in condensates, particularly for dynamic systems where partial condensation takes place, which result in enrichment of HCl in condensates. These results are in qualitative agreement with experimental data from other studies. The combination of reactive transport with multicomponent brine chemistry to study evaporation, boiling, and the potential for acid gas generation at the proposed Yucca Mountain repository is seen as an improvement relative to previously applied simpler batch evaporation models. This approach allows the evaluation of thermal, hydrological, and chemical (THC) processes in a coupled manner, and modeling of settings much more relevant to actual field conditions than the distillation experiment considered. The actual and modeled distillation experiments do not represent

  16. Modeling acid-gas generation from boiling chloride brines

    Sonnenthal Eric

    2009-11-01

    Full Text Available Abstract Background This study investigates the generation of HCl and other acid gases from boiling calcium chloride dominated waters at atmospheric pressure, primarily using numerical modeling. The main focus of this investigation relates to the long-term geologic disposal of nuclear waste at Yucca Mountain, Nevada, where pore waters around waste-emplacement tunnels are expected to undergo boiling and evaporative concentration as a result of the heat released by spent nuclear fuel. Processes that are modeled include boiling of highly concentrated solutions, gas transport, and gas condensation accompanied by the dissociation of acid gases, causing low-pH condensate. Results Simple calculations are first carried out to evaluate condensate pH as a function of HCl gas fugacity and condensed water fraction for a vapor equilibrated with saturated calcium chloride brine at 50-150°C and 1 bar. The distillation of a calcium-chloride-dominated brine is then simulated with a reactive transport model using a brine composition representative of partially evaporated calcium-rich pore waters at Yucca Mountain. Results show a significant increase in boiling temperature from evaporative concentration, as well as low pH in condensates, particularly for dynamic systems where partial condensation takes place, which result in enrichment of HCl in condensates. These results are in qualitative agreement with experimental data from other studies. Conclusion The combination of reactive transport with multicomponent brine chemistry to study evaporation, boiling, and the potential for acid gas generation at the proposed Yucca Mountain repository is seen as an improvement relative to previously applied simpler batch evaporation models. This approach allows the evaluation of thermal, hydrological, and chemical (THC processes in a coupled manner, and modeling of settings much more relevant to actual field conditions than the distillation experiment considered. The actual

  17. Metabotyping of docosahexaenoic acid - treated Alzheimer's disease cell model.

    Priti Bahety

    Full Text Available BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA in Alzheimer's disease (AD, the mechanism by which DHA affects amyloid-β precursor protein (AβPP-induced metabolic changes has not been studied. OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS. METHODS: The lysate and supernatant samples of CHO-wt and CHO-AβPP695 cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software. RESULTS: Both principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment. CONCLUSION: Our study shows that DHA plays a role in mitigating AβPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AβPP695 cells shed further mechanistic insights on its neuroprotective actions.

  18. Effects of Ascorbic Acid, Phytic Acid and Tannic Acid on Iron Bioavailability from Reconstituted Ferritin Measured by an In Vitro Digestion/Caco-2 Cell Model

    The effects of ascorbic acid, phytate and tannic acid on Fe bioavailability from Fe supplied as ferritin was compared to FeSO4 using an in vitro digestion/Caco-2 cell model. Horse spleen ferritin (HSF) was chemically reconstituted into a plant-type ferritin (P-HSF). In the presence of ascorbic acid...

  19. Commercial formalin substitutes for histopathology

    Prentø, P; Lyon, H

    1997-01-01

    We compared the performance of six commercial fixatives proposed to be formalin substitutes with the performance of buffered formalin, Clarke's ethanol-acetic acid, and ethanol, using rat liver, small intestine, and kidney. We investigated the rate of penetration, mode of fixation, extent of...... performed equally well on all tissues tested. While several of the commercial fixatives appeared to preserve liver tissue at 200x, the preservation of kidney, intestinal villi, and smooth muscle was unacceptable. Histological distortion, cell shrinkage and vacuolization were prominent when the substitutes...... was obtained by combining formalin fixation with antigen retrieval. We conclude that none of the proposed commercial substitutes for buffered formalin are adequate for critical histology or histopathology....

  20. Composites based on acylated cellulose fibers and low-density polyethylene: Effect of the fiber content, degree of substitution and fatty acid chain length on final properties

    Freire, Carmen S. R.; Silvestre, Armando J. D.; Neto, Carlos Pascoal; Gandini, Alessandro; Martin, Loli; Mondragon, Iñaki

    2008-01-01

    Low-density polyethylene was filled with unmodified and fatty acid (hexanoic, dodecanoic, octadecanoic and docosanoic acids) esterified cellulose fibers. The thermal and mechanical properties, morphology and the water absorption behavior of the ensuing composites were investigated. The chemical modification of the cellulose fibers with fatty acids clearly improved the interfacial adhesion with the matrix and hence the mechanical properties of the composites and decreased their water uptake ca...

  1. A Bilayer Engineered Skin Substitute for Wound Repair in an Irradiation-Impeded Healing Model on Rat

    Mohd Hilmi, A.B.; Hassan, Asma; Halim, Ahmad Sukari

    2015-01-01

    Objective: An engineered skin substitute is produced to accelerate wound healing by increasing the mechanical strength of the skin wound via high production of collagen bundles. During the remodeling stage of wound healing, collagen deposition is the most important event. The collagen deposition process may be altered by nutritional deficiency, diabetes mellitus, microbial infection, or radiation exposure, leading to impaired healing. This study describes the fabrication of an engineered bila...

  2. Modeling acid-gas generation from boiling chloride brines

    Sonnenthal Eric; Spycher Nicolas; Zhang Guoxiang; Steefel Carl

    2009-01-01

    Abstract Background This study investigates the generation of HCl and other acid gases from boiling calcium chloride dominated waters at atmospheric pressure, primarily using numerical modeling. The main focus of this investigation relates to the long-term geologic disposal of nuclear waste at Yucca Mountain, Nevada, where pore waters around waste-emplacement tunnels are expected to undergo boiling and evaporative concentration as a result of the heat released by spent nuclear fuel. Processes...

  3. Soil sorption of acidic pesticides: modeling pH effects.

    Spadotto, Claudio A; Hornsby, Arthur G

    2003-01-01

    A model of acidic pesticide sorption in soils was developed from theoretical modeling and experimental data, which initially considered a combination of a strongly acidic pesticide and a variable-charge soil with high clay content. Contribution of 2,4-D [(2,4-dichlorophenoxy) acetic acid] anionic-form sorption was small when compared with molecular sorption. Dissociation of 2,4-D was not sufficient to explain the variation in Kd as a function of pH. Accessibility of soil organic functional groups able to interact with the pesticide (conformational changes) as a function of organic matter dissociation was proposed to explain the observed differences in sorption. Experimental 2,4-D sorption data and K(oc) values from literature for flumetsulam [N-(2,6-difluorophenyl)-5-methyl [1,2,4] triazolo [1,5-a] pyrimidine-2-sulfonamide] and sulfentrazone [N-[2,4-dichloro-5-[4-(difluromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl] phenyl] methanesulfonamide] in several soils fit the model. PMID:12809295

  4. Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats

    The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute. The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

  5. Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats

    Ghanaati, Shahram; Orth, Carina; Barbeck, Mike; Kirkpatrick, Charles James [Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz (Germany); Willershausen, Ines [Institute for Dental Material Sciences and Technology, University Medical Center of the Johannes Gutenberg University Mainz, Anselm-Franz-von-Bentzel-Weg 14, 55128 Mainz (Germany); Thimm, Benjamin W [Institute for Biomechanics, ETH Zuerich, Wolfgang-Pauli-Str.10, 8093 Zuerich (Switzerland); Booms, Patrick [Leeds Institute of Molecular Medicine, Section of Medicine, Surgery and Anaesthesia, University of Leeds (United Kingdom); Stuebinger, Stefan; Landes, Constantin; Sader, Robert Anton, E-mail: ghanaati@uni-mainz.d [Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Theodor-Stein-Kai 7, 60596 Frankfurt am Main (Germany)

    2010-06-01

    The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute. The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

  6. Effects of organic acids, amino acids and ethanol on the radio-degradation of patulin in an aqueous model system

    The effects of organic acids, amino acids, and ethanol on the radio-degradation of patulin by gamma irradiation in an aqueous model system were investigated. The patulin, dissolved in distilled water at a concentration of 50 ppm, was practically degraded by the gamma irradiation at the dose of 1.0 kGy, while 33% of the patulin remained in apple juice. In the aqueous model system, the radio-degradation of patulin was partially inhibited by the addition of organic acids, amino acids, and ethanol. The proportions of remaining patulin after irradiation with the dose of 1.0 kGy in the 1% solution of malic acid, citric acid, lactic acid, acetic acid, ascorbic acid, and ethanol were 31.4%, 2.3%, 31.2%, 6.1%, 50.8%, and 12.5%, respectively. During 30 days of storage, the remaining patulin was reduced gradually in the solution of ascorbic acid and malic acid compared to being stable in other samples. The amino acids, serine, threonine, and histidine, inhibited the radio-degradation of patulin. In conclusion, it was suggested that 1 kGy of gamma irradiation (recommended radiation doses for radicidation and/or quarantine in fruits) is effective for the reduction of patulin, but the nutritional elements should be considered because the radio-degradation effects are environment dependent

  7. Effects of organic acids, amino acids and ethanol on the radio-degradation of patulin in an aqueous model system

    Yun, Hyejeong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of); Department of Food Science and Technology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lim, Sangyong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of); Jo, Cheorun [Department of Animal Science and Biotechnology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Chung, Jinwoo [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of); Kim, Soohyun [Glycomics Team, Korea Basic Science Institute, Daejeon 305-333 (Korea, Republic of); Kwon, Joong-Ho [Department of Food Science and Technology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Kim, Dongho [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of)], E-mail: fungikim@kaeri.re.kr

    2008-06-15

    The effects of organic acids, amino acids, and ethanol on the radio-degradation of patulin by gamma irradiation in an aqueous model system were investigated. The patulin, dissolved in distilled water at a concentration of 50 ppm, was practically degraded by the gamma irradiation at the dose of 1.0 kGy, while 33% of the patulin remained in apple juice. In the aqueous model system, the radio-degradation of patulin was partially inhibited by the addition of organic acids, amino acids, and ethanol. The proportions of remaining patulin after irradiation with the dose of 1.0 kGy in the 1% solution of malic acid, citric acid, lactic acid, acetic acid, ascorbic acid, and ethanol were 31.4%, 2.3%, 31.2%, 6.1%, 50.8%, and 12.5%, respectively. During 30 days of storage, the remaining patulin was reduced gradually in the solution of ascorbic acid and malic acid compared to being stable in other samples. The amino acids, serine, threonine, and histidine, inhibited the radio-degradation of patulin. In conclusion, it was suggested that 1 kGy of gamma irradiation (recommended radiation doses for radicidation and/or quarantine in fruits) is effective for the reduction of patulin, but the nutritional elements should be considered because the radio-degradation effects are environment dependent.

  8. Photoproduction of glyoxylic acid in model wine: Impact of sulfur dioxide, caffeic acid, pH and temperature.

    Grant-Preece, Paris; Schmidtke, Leigh M; Barril, Celia; Clark, Andrew C

    2017-01-15

    Glyoxylic acid is a tartaric acid degradation product formed in model wine solutions containing iron and its production is greatly increased by exposure to UV-visible light. In this study, the combined effect of sulfur dioxide, caffeic acid, pH and temperature on the light-induced (⩾300nm) production of glyoxylic acid in model wine containing tartaric acid and iron was investigated using a Box-Behnken experimental design and response surface methodology (RSM). Glyoxylic acid produced in the irradiated model wine was present in free and hydrogen sulfite adduct forms and the measured total, free and percentage free glyoxylic acid values were modeled using RSM. Sulfur dioxide significantly decreased the total amount of glyoxylic acid produced, but could not prevent its production, while caffeic acid showed no significant impact. The interaction between pH and temperature was significant, with low pH values and low temperatures giving rise to higher levels of total glyoxylic acid. PMID:27542478

  9. Towards Sustainable Aquafeeds: Complete Substitution of Fish Oil with Marine Microalga Schizochytrium sp. Improves Growth and Fatty Acid Deposition in Juvenile Nile Tilapia (Oreochromis niloticus)

    Sarker, Pallab K.; Kapuscinski, Anne R.; Lanois, Alison J.; Livesey, Erin D.; Bernhard, Katie P.; Coley, Mariah L.

    2016-01-01

    We conducted a 84-day nutritional feeding experiment with dried whole cells of DHA-rich marine microalga Schizochytrium sp. (Sc) to determine the optimum level of fish-oil substitution (partial or complete) for maximum growth of Nile tilapia. When we fully replaced fish oil with Schizochytrium (Sc100 diet), we found significantly higher weight gain and protein efficiency ratio (PER), and lower (improved) feed conversion ratio (FCR) and feed intake compared to a control diet containing fish oil (Sc0); and no significant change in SGR and survival rate among all diets. The Sc100 diet had the highest contents of 22:6n3 DHA, led to the highest DHA content in fillets, and consequently led to the highest DHA:EPA ratios in tilapia fillets. Schizochytrium sp. is a high quality candidate for complete substitution of fish oil in juvenile Nile tilapia feeds, providing an innovative means to formulate and optimize the composition of tilapia juvenile feed while simultaneously raising feed efficiency of tilapia aquaculture and to further develop environmentally and socially sustainable aquafeeds. Results show that replacing fish oil with DHA-rich marine Sc improves the deposition of n3 LC PUFA levels in tilapia fillet. These results support further studies to lower Schizochytrium production costs and to combine different marine microalgae to replace fish oil and fishmeal into aquafeeds. PMID:27258552

  10. Modelling of acid mine drainage (AMD in columns

    C. M. Bernardes de Souza

    2011-09-01

    Full Text Available A model is proposed in this paper to describe the generation of acid mine drainage (AMD in leaching columns. The model considers: (i Water flow through the column, which is calculated using the 1 - D analytic solution of the Richards' equation assuming the existence of a similarity relationship between the water retention function and the water content profiles at a given time; and (ii Pyrite oxidation weighted by microbiological effects occurring in spherical particles according to the shrinking core model. Mass balances of oxygen and pyrite were derived in order to evaluate the intrinsic oxidation rate and the pyrite fraction reacted with time and column position. The model was used to simulate a six month operation of a leaching column, which comprised successive weekly cycles of dry and wet periods. Simulation results demonstrated that AMD generation is strongly affected by the presence of microorganisms. A relative deviation of 5% between simulation and experimental data was obtained.

  11. Understanding atmospheric peroxyformic acid chemistry: observation, modeling and implication

    H. Liang

    2015-01-01

    Full Text Available The existence and importance of peroxyformic acid (PFA in the atmosphere has been under controversy. We present here, for the first time, the observation data for PFA from four field measurements carried out in China. These data provided powerful evidence that PFA can stay in the atmosphere, typically in dozens of pptv level. The relationship between PFA and other detected peroxides was examined. The results showed that PFA had a strong positive correlation with its homolog, peroxyacetic acid, due to their similar sources and sinks. Through an evaluation of PFA production and removal rates, we proposed that the reactions between peroxyformyl radical (HC(OO2 and formaldehyde or the hydroperoxyl radical (HO2 were likely to be the major source and degradation into formic acid (FA was likely to be the major sink for PFA. Based on a box model evaluation, we proposed that the HC(OO2 and PFA chemistry was a major source for FA under low NOx conditions. Furthermore, it is found that the impact of the HC(OO2 and PFA chemistry on radical cycling was dependent on the yield of HC(OO2 radical from HC(O + O2 reaction. When this yield exceeded 50%, the HC(OO2 and PFA chemistry should not be neglected for calculating the radical budget. To make clear the exact importance of HC(OO2 and PFA chemistry in the atmosphere, further kinetic, field and modeling studies are required.

  12. Do carboximide–carboxylic acid combinations form co-crystals? The role of hydroxyl substitution on the formation of co-crystals and eutectics

    Ramanpreet Kaur

    2015-05-01

    Full Text Available Carboxylic acids, amides and imides are key organic systems which provide understanding of molecular recognition and binding phenomena important in biological and pharmaceutical settings. In this context, studies of their mutual interactions and compatibility through co-crystallization may pave the way for greater understanding and new applications of their combinations. Extensive co-crystallization studies are available for carboxylic acid/amide combinations, but only a few examples of carboxylic acid/imide co-crystals are currently observed in the literature. The non-formation of co-crystals for carboxylic acid/imide combinations has previously been rationalized, based on steric and computed stability factors. In the light of the growing awareness of eutectic mixtures as an alternative outcome in co-crystallization experiments, the nature of various benzoic acid/cyclic imide combinations is established in this paper. Since an additional functional group can provide sites for new intermolecular interactions and, potentially, promote supramolecular growth into a co-crystal, benzoic acids decorated with one or more hydroxyl groups have been systematically screened for co-crystallization with one unsaturated and two saturated cyclic imides. The facile formation of an abundant number of hydroxybenzoic acid/cyclic carboximide co-crystals is reported, including polymorphic and variable stoichiometry co-crystals. In the cases where co-crystals did not form, the combinations are shown invariably to result in eutectics. The presence or absence and geometric disposition of hydroxyl functionality on benzoic acid is thus found to drive the formation of co-crystals or eutectics for the studied carboxylic acid/imide combinations.

  13. The Effect of Opsteoporotic Model Rats Induced by Retinoic Acid

    Xu Peng; Yao Jianfeng; Jin Weizhang; Cai Qiankun; Guo Xiong

    2005-01-01

    Objective: To study the effect of retinoic acid on inducing osteoporosis in female rat. Methods: 48SD female rats were divided randomly into experiment group and control group. Retinoic acid was administered orally to experiment group with 80mg.kg-1d-1 for 15 days. Then the rats were sacrificed on the 0th, 30th, 60th days after last administration. The serum concentration of Ca, P, BGP, E2, AKP and TRAP were detected. Components of collagen and proteoglycan in the bones and BMD were also assayed .The femoral morphometric change and epiphyseal plate cartilage histological changes were observed. Results: After a 15-day period treatment with retinoic acid, charateristics of experiment group were compared with control, it is shown that the concentration of serum E2 and BGP declined, the activity of AKP and TRAP increased while BMP decreased, the bone mass of both spongy bone and cortical bone reduced, the number of spongy bone osteoclasts and their activity increased, number of epiphyseal plate chondrocyte reduced, cartilage hypertrophic zone displayed dyscalcification, and no difference of other markers was found in the two groups. On the 30th day after the last administration, the experiment group appeared a declined number of cancellous bone osteoclast and level of serum AKP yet they were still higher than control. Number of epiphyseal chondrocyte, serum BGP and tibial BMD, though higher than before, were still lower than control. Other markers were no difference. On the 60th day after treatment, although the femoral cancellous bone mass was still less and cancellous osteoblast was more than control, the cortical bone mass, cancellous osteoclast number and level of serum Ca and P were all remained no different between two groups.Conclusion: Retinoic acid possessed a better short-term effect than long-term effect. Cancellous bone loss lasted much longer than cortical bone and more obviously; the bone matrix in this osteoporosis model was able to repair itself

  14. Investigating the effects of L- to D-amino acid substitution and deamidation on the activity and membrane interactions of antimicrobial peptide anoplin.

    Won, Amy; Khan, Mourin; Gustin, Sorin; Akpawu, Akuvi; Seebun, Deeptee; Avis, Tyler J; Leung, Bonnie O; Hitchcock, Adam P; Ianoul, Anatoli

    2011-06-01

    Isolated from the venom sac of solitary spider wasp, Anoplius samariensis, anoplin is the smallest linear α-helical antimicrobial peptide found naturally with broad spectrum activity against both Gram-positive and Gram-negative bacteria, and little hemolytic activity toward human erythrocytes. Deamidation was found to decrease the peptide's antibacterial properties. In the present work, interactions of amidated (Ano-NH2) and deamidated (Ano-OH) forms of anoplin as well as Ano-NH2 composed of all D-amino acids (D-Ano-NH2) with model cell membranes were investigated by means of Langmuir Blodgett (LB) technique, atomic force microscopy (AFM), X-ray photoemission electron microscopy (X-PEEM) and carboxyfluorescein leakage assay in order to gain a better understanding of the effect of these peptide modifications on membrane binding and lytic properties. According to LB, all three peptides form stable monolayers at the air/water interface with Ano-NH2 occupying a slightly greater area per molecule than Ano-OH. All three forms of the peptide interact preferentially with anionic 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DPPG), rather than zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer. Peptides form nanoscale clusters in zwitterionic but not in anionic monolayers. Finally, membrane lytic activity of all derivatives was found to depend strongly on membrane composition and lipid/peptide ratio. The results suggest that amidated forms of peptides are likely to possess higher membrane binding affinity due to the increased charge. PMID:21078293

  15. Protective effects of isolecanoric acid on neurodegenerative in vitro models.

    de Pedro, Nuria; Cantizani, Juan; Ortiz-López, Francisco Javier; González-Menéndez, Victor; Cautain, Bastien; Rodríguez, Lorena; Bills, Gerald F; Reyes, Fernando; Genilloud, Olga; Vicente, Francisca

    2016-02-01

    Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS), are neurodegenerative disorders characterized by loss of dopaminergic or motor neurons, respectively. Although understanding of the PD and ALS pathogenesis remains incomplete, increasing evidence from human and animal studies has suggested that aberrant GSK3β, oxidative stress and mitochondrial damage are involved in their pathogenesis. Using two different molecular models, treatment with L-BMAA for ALS and rotenone for PD the effect of isolecanoric acid, a natural product isolated from a fungal culture, was evaluated. Pre-treatment with this molecule caused inhibition of GSK3β and CK1, and a decrease in oxidative stress, mitochondrial damage, apoptosis and cell death. Taken together, these results indicated that isolecanoric acid might have a protective effect against the development of these neurodegenerative disorders. PMID:26455662

  16. Medicineringsfejl ved generisk substitution

    Rölfing, Jan

    2012-01-01

    Generic substitution is a major cause of medical mistakes in the general population. Danish legislation obligates pharmacies to substitute prescribed medicine with the cheapest equivalent formulation, despite variations in product name, packaging, shape and colour. Consequently, medical mistakes...

  17. A Single Amino Acid Substitution in the NS2A Protein of Japanese Encephalitis Virus Affects Virus Propagation In Vitro but Not In Vivo

    Takamatsu, Yuki; Morita, Kouichi; Hayasaka, Daisuke

    2015-01-01

    We identified a unique amino acid of NS2A113, phenylalanine, that affects the efficient propagation of two Japanese encephalitis virus strains, JaTH160 and JaOArS982, in neuroblastoma Neuro-2a cells but not in cell lines of extraneural origin. This amino acid did not affect viral loads in the brain or survival curves in mice. These findings suggest that virus propagation in vitro may not reflect the level of virus neuroinvasiveness in vivo.

  18. Field trial evaluation of the accumulation of omega-3 long chain polyunsaturated fatty acids in transgenic Camelina sativa: Making fish oil substitutes in plants

    Sarah Usher; Haslam, Richard P.; Noemi Ruiz-Lopez; Olga Sayanova; Napier, Johnathan A.

    2015-01-01

    The global consumption of fish oils currently exceeds one million tonnes, with the natural de novo source of these important fatty acids forming the base of marine foodwebs. Here we describe the first field-based evaluation of a terrestrial source of these essential nutrients, synthesised in the seeds of transgenic Camelina sativa plants via the heterologous reconstitution of the omega-3 long chain polyunsaturated fatty acid biosynthetic pathway. Our data demonstrate the robust nature of this...

  19. Synthesis, structure, antitumor activity of novel pharmaceutical co-crystals based on bispyridyl-substituted α, β-unsaturated ketones with gallic acid

    Liu, Lian-Dong; Liu, Shu-Lian; Liu, Zhi-Xian; Hou, Gui-Ge

    2016-05-01

    Three novel pharmaceutical co-crystals, (A)·(gallic acid) (1), (B)·(gallic acid) (2), and (C)·(gallic acid) (3) were generated based on 2,6-bis((pyridin-4-yl)methylene)cyclohexanone (A), N-methyl-3,5-bis((pyridin-3-yl)methylene)-4-piperidone (B), N-methyl-3,5-bis((pyridin-4-yl)methylene)-4-piperidone (C) with gallic acid, respectively. They are characterized by elemental analysis, FTIR spectroscopy, 1H NMR and single-crystal X-ray diffraction. Structural analysis reveals that two pharmaceutical ingredients link each other into H-bonding-driven 3D network in 1, 2, or 2D plane in 3. In addition, their antitumor activities against human neoplastic cell lines A549, SGC-7901, MCF-7, OVCA-433, HePG2 and cytotoxicity for HUVEC cell lines by CCK-8 method were evaluated primarily. Compared with gallic acid and free A, B and C, their antitumor activities have improved distinctly, while cytotoxicities have reduced markedly, especially for co-crystal 1. This is mainly because of the synergistic effect between pharmaceutical ingredients A, B, and C and gallic acid.

  20. Currency substitution, portfolio diversification, and money demand

    Freitas, Miguel Lebre de; Veiga, Francisco José

    2006-01-01

    We extend the Thomas (1985) dynamic optimising model of money demand and currency substitution to the case in which the individual has restricted or no access to foreign currency denominated bonds. In this case Currency Substitution decisions and Asset Substitution decisions are not separable. The results obtained suggest that the significance of an expected exchange rate depreciation term in the demand for domestic money provides a valid test for the presence of currency subst...

  1. Pre-clinical evaluation of soybean-based wound dressings and dermal substitute formulations in pig healing and non-healing in vivo models

    Rostislav V Shevchenko

    2014-10-01

    Full Text Available In the last decade, a new class of natural biomaterials derived from de-fatted soybean flour processed by either thermoset or extraction procedures has been developed. These biomaterials uniquely combine adaptability to various clinical applications to proven tissue regeneration properties. In the present work, the biomaterials were formulated either as hydrogel or as paste formulation and their potential as wound dressing material or as dermal substitute was assessed by two in vivo models in pig skin: The healing full-thickness punch biopsy model and the non-healing full-thickness polytetrafluoroethylene (PTFE chamber model. The results clearly show that collagen deposition is induced by the presence of these biomaterials. A unique pattern of early inflammatory response, eliciting neutrophils and controlling macrophage infiltration, is followed by tissue cell colonization of the wound bed with a significant deposition of collagen fibers. The study also highlighted the importance in the use of optimal formulations and appropriate handling upon implantation. In large size, non-healing wounds, wound dermis was best obtained with the paste formulation as hydrogels appeared to be too loose to ensure lasting scaffolding properties. On the contrary, packing of the granules during the application of paste reduced biomaterial degradation rate and prevent the penetration of newly vascularized tissue, thus impeding grafting of split-thickness autologous skin grafts on the dermal substitute base.

  2. An A643V amino acid substitution in Upc2p contributes to azole resistance in well-characterized clinical isolates of Candida albicans.

    Hoot, Samantha J; Smith, Adam R; Brown, Ryan P; White, Theodore C

    2011-02-01

    The Candida albicans Upc2p transcription factor regulates ERG11, encoding the target of azole drugs. Gain-of-function mutations that contribute to resistance were recently identified in a series of sequential clinical isolates (N. Dunkel, T. T. Liu, K. S. Barker, R. Homayouni, J. Morschhauser, and P. D. Rogers, Eukaryot. Cell 7:1180-1190, 2008). In the present study, UPC2 was sequenced from a matched set of 17 isolates. An A643V substitution was present in all of the isolates in the series that overexpressed ERG11. Azole susceptibility, ergosterol levels, and expression of ERG genes were elevated in the A643V clinical isolates and in reconstructed strains. PMID:21078937

  3. 允许重新进货情况下单周期可替代产品的库存模型%Single-period Two-product Inventory Model with Reorder and Substitution

    李小申; 高克权

    2006-01-01

    In market, excess demands for many products can be met by reorder even during one period, and retailers usually adopt substitution strategy for more benefit. Under the retailer's substitution strategy and permission of reorder, we develop the profits maximization model for the two-substitutable-product inventory problem with stochastic demands and proportional costs and revenues. We show that the objective function is concave and submodular, and therefore the optimal policy exists. We present the optimal conditions for order quantity and provide some properties of the optimal order quantities. Comparing our model with Netessine and Rudi's, we prove that reorder and adoption of the substitution strategy can raise the general profits and adjust down the general stock level.

  4. Substituted thiobenzoic acid S-benzyl esters as potential inhibitors of a snake venom phospholipase A2: Synthesis, spectroscopic and computational studies

    Henao Castañeda, I. C.; Pereañez, J. A.; Jios, J. L.

    2012-11-01

    4-Chlorothiobenzoic acid S-benzyl ester (I), 3-nitrothiobenzoic acid S-benzyl ester (II), 4-nitrothiobenzoic acid S-benzyl ester (III) and 4-methylthiobenzoic acid S-benzyl ester (IV) were prepared and characterized by 1H and 13C NMR, Mass spectrometry and IR spectroscopy. Quantum chemical calculations were performed with Gaussian 09 to calculate the geometric parameters and vibrational spectra. Phospholipase A2 (PLA2) was purified from Crotalus durissus cumanensis venom by molecular exclusion chromatography, followed by reverse phase-high performance liquid chromatography. Two studies of the inhibition of phospholipase A2 activity were performed using phosphatidilcholine and 4-nitro-3-octanoyloxybenzoic acid as substrates, in both cases compound II showed the best inhibitory ability, with 74.89% and 69.91% of inhibition, respectively. Average percentage of inhibition was 52.49%. Molecular docking was carried out with Autodock Vina using as ligands the minimized structures of compounds (I-IV) and as protein PLA2 (PDB code 2QOG). The results suggest that compounds I-IV could interact with His48 at the active site of PLA2. In addition, all compounds showed Van der Waals interactions with residues from hydrophobic channel of the enzyme. This interaction would impede normal catalysis cycle of the PLA2.

  5. Partitioning studies in China and the separation of americium and fission product rare earths with dialkyl phosphinic acid and its thio-substituted derivatives

    Studies on the TRPO extractions process for recovering actinides from highly active waste (HAW) and its application to the pretreatment of Chinese HAW are described. The removal of Sr by di-cyclohexyl 18 crown 6 and the removal of Cs by spherical titanium ferrous hexa-cyanate from acidic waste are also described. Results of the extraction of trivalent americium and fission product rare earths (FPREs) by dialkyl-phosphinic, dialkyl-mono-thio-phosphinic and dialkyl-di-thio-phosphinic acids are reported. Dialkyl-thio-phosphinic acid (commercial product Cyanex 301, alkyl =2, 4, 4-methyl-pentyl) shows very high selectivity towards Am. Using 1M Cyanex 301 -kerosene as extractant, 99.9 % Am can be separated from 0.5M(Pr+Nd)(NO3)3 solution with 3-4 extraction stages and 3-4 scrubbing stages. (authors)

  6. Kinetics and mechanism of the oxidation of some substituted aldonitrones by quinolinium chlorochromate in aqueous DMF medium in the absence and presence of oxalic acid

    GOVINDASAMY RAJARAJAN

    2009-02-01

    Full Text Available The kinetics of the oxidation of aldonitrones (nitrone by quinolinium chlorochromate (QCC was determined in 50 % DMF–water in the absence and presence of oxalic acid in order to study the effect of oxalic acid. It was considered worthwhile to investigate whether it undergoes co-oxidation or just functions as a catalyst in the reaction. The reaction was followed iodometrically. Under the employed experimental conditions, the reaction is first order each with respect to concentration of nitrone, QCC, and oxalic acid and fractional order with respect to H+ concentration. There was no discernible effect with increasing in ionic strength but the rate of oxidation decreased with decreasing dielectric constant of the medium. Addition of MnSO4 had a significant and acrylonitrile no effect on the reaction rate. A mechanism involving protonated nitrone and QCC as the reactive oxidant is proposed. The activation parameters were calculated and are presented.

  7. Site-specific antibodies distinguish single amino acid substitutions in position 57 in HLA-DQ beta-chain alleles associated with insulin-dependent diabetes

    Atar, D; Dyrberg, T; Michelsen, Birgitte;

    1989-01-01

    -chain alleles, we immunized rabbits with 12 to 13 amino acid long peptides representing HLA-DQw7 and -DQw8 allelic sequences, differing only by one amino acid in position 57 being aspartic acid (Asp) and alanine (Ala), respectively. Immunoblot analysis of lymphoblastoid cells showed that several antisera...... recognized a 29-kDa protein, equivalent to the expected molecular size of the HLA-DQ beta-chain to yield two antisera specific for HLA-DQw7 (pos. 57Asp) and three antisera for HLA-DQw8 (pos. 57Ala) positive cells. Analysis of HLA-DR 3/4 positive IDDM patients (n = 24) and controls (n = 19) showed that all...

  8. A neuro-inspired model-based closed-loop neuroprosthesis for the substitution of a cerebellar learning function in anesthetized rats

    Hogri, Roni; Bamford, Simeon A.; Taub, Aryeh H.; Magal, Ari; Giudice, Paolo Del; Mintz, Matti

    2015-02-01

    Neuroprostheses could potentially recover functions lost due to neural damage. Typical neuroprostheses connect an intact brain with the external environment, thus replacing damaged sensory or motor pathways. Recently, closed-loop neuroprostheses, bidirectionally interfaced with the brain, have begun to emerge, offering an opportunity to substitute malfunctioning brain structures. In this proof-of-concept study, we demonstrate a neuro-inspired model-based approach to neuroprostheses. A VLSI chip was designed to implement essential cerebellar synaptic plasticity rules, and was interfaced with cerebellar input and output nuclei in real time, thus reproducing cerebellum-dependent learning in anesthetized rats. Such a model-based approach does not require prior system identification, allowing for de novo experience-based learning in the brain-chip hybrid, with potential clinical advantages and limitations when compared to existing parametric ``black box'' models.

  9. Interference effects from coexisting fatty acids on elaidic acid separation by fractionating crystallization: A model study

    Jala, Ram Chandra Reddy; Guo, Zheng; Bjerring, Thomas;

    2010-01-01

    A multi-stage temperature-programmed fractionating crystallization process was carried out to examine the effects of the presence of stearic acid (SA), oleic acid (OA), and linoleic acid (LA) on the separation of elaidic acid (EA). The results showed that the efficiency of fractionating...

  10. Modeling of the charge acceptance of lead-acid batteries

    Thele, M.; Schiffer, J.; Sauer, D.U. [Electrochemical Energy Conversion and Storage Systems Group, Institute for Power Electronics and Electrical Drives (ISEA), RWTH Aachen University, Jaegerstrasse 17-19, D-52066 Aachen (Germany); Karden, E.; Surewaard, E. [Ford Research Center Aachen, Aachen (Germany)

    2007-05-25

    This paper presents a model for flooded and VRLA batteries that is parameterized by impedance spectroscopy and includes the overcharging effects to allow charge-acceptance simulations (e.g. for regenerative-braking drive-cycle profiles). The full dynamic behavior and the short-term charge/discharge history is taken into account. This is achieved by a detailed modeling of the sulfate crystal growth and modeling of the internal gas recombination cycle. The model is applicable in the full realistic temperature and current range of automotive applications. For model validation, several load profiles (covering the dynamics and the current range appearing in electrically assisted or hybrid cars) are examined and the charge-acceptance limiting effects are elaborately discussed. The validation measurements have been performed for different types of lead-acid batteries (flooded and VRLA). The model is therefore an important tool for the development of automotive power nets, but it also allows to analyze different charging strategies and energy gains which can be achieved during regenerative-braking. (author)

  11. Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

    Vida, Norbert; Václavík, Jiří; Beier, Petr

    2016-01-01

    Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic...

  12. What if oil is less substitutable? A New-Keynesian Model with Oil, Price and Wage Stickiness including Capital Accumulation

    Acurio Vásconez, Verónica

    2015-01-01

    La littérature récente sur énergie a déjà établit que le pétrole n'est pas parfaitement substituable aux autres facteurs, en considérant l'énergie fossile comme étant un facteur de production critique en différentes combinaisons. Cependant, les valeurs estimées de l'élasticité de substitution se trouvent dans un large rang, entre 0.004 et 0.64. Cet article évoque ce phénomène en élargissant le modèle DSGE développe en Acurio Vásconez et al. (2015) en modifiant les fonctions de production et c...

  13. 40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted pyridine azo substituted... Specific Chemical Substances § 721.8780 Substituted pyridine azo substituted phenyl. (a) Chemical substance... substituted pyridine azo substituted phenyl (PMNs P-96-767 and P-96-773) are subject to reporting under...

  14. Protonation of azines and purines as a model for the electrophilic aromatic substitution - rationalization by triadic formula.

    Vianello, Robert

    2011-09-01

    First gas-phase carbon proton affinities of eleven azines and purines (pyrrole, pyrazole, imidazole, pyridine, pyridazine, pyrimidine, pyrazine, bicyclic purine, pyridine-N-oxide, 2-aminopyrimidine and uracil) were calculated by a composite G3B3 methodology and used to probe their susceptibility to undergo electrophilic aromatic substitution (EAS), taking benzene as a reference molecule. The results revealed excellent agreement with the available experimental data and were interpreted using the triadic approach. We found out that pyrroles, which are more reactive towards EAS reaction than benzene, are stronger carbon bases than the latter compound, whereas pyridines exhibit lower carbon basicity, being at the same time less reactive toward substitution by electrophiles than benzene. In all of the investigated molecules the frontier orbital describing the corresponding p-electron density at the carbon atom to be protonated is HOMO as calculated by the HF/G3large//B3LYP/6-31G(d) level of theory. Our results are in a disagreement with the work by D'Auria (M. D'Auria, Tetrahedron Lett. 2005, 46, 6333-6336; Lett. Org. Chem. 2005, 2, 659-661), who at B3LYP/6-311+G(d, p) level found out that in some of systems investigated here the HOMO orbital is not of -symmetry, which was used to rationalize the lower reactivity of these systems towards EAS. It turned out that energies of HOMO orbitals alone correlate very poorly with carbon proton affinities, unlike the difference in proton affinities between the most basic carbon atom and thermodynamically the most favourable site of protonation, which performs much better. Triadic analysis demonstrated the importance of considering a complete picture of the protonation process and all three terms appearing in the triadic scheme individually when discussing trends in basicity/nucleophilicity of closely related molecules. PMID:24062111

  15. Aminosilane/oleic acid vesicles as model membranes of protocells.

    Douliez, Jean-Paul; Zhendre, Vanessa; Grélard, Axelle; Dufourc, Erick J

    2014-12-16

    Oleic acid vesicles represent good models of membrane protocells that could have existed in prebiotic times. Here, we report the formation, growth polymorphism, and dynamics of oleic acid spherical vesicles (1-10 μm), stable elongated vesicles (>50 μm length; 1-3 μm diameter), and chains of vesicles (pearl necklaces, >50 μm length; 1-3 μm diameter) in the presence of aminopropyl triethoxysilane and guanidine hydrochloride. These vesicles exhibit a remarkable behavior with temperature: spherical vesicles only are observed when keeping the sample at 4 °C for 2 h, and self-aggregated spherical vesicles occur upon freezing/unfreezing (-20/20 °C) samples. Rather homogeneous elongated vesicles are reformed upon heating samples at 80 °C. The phenomenon is reversible through cycles of freezing/heating or cooling/heating of the same sample. Deuterium NMR evidences a chain packing rigidity similar to that of phospholipid bilayers in cellular biomembranes. We expect these bilayered vesicles to be surrounded by a layer of aminosilane oligomers, offering a variant model for membrane protocells. PMID:25420203

  16. Displacement of DL-[3H]-2-amino-4-phosphonobutanoic acid ( [3H]APB) binding with methyl-substituted APB analogues and glutamate agonists

    The binding of the excitatory amino acid antagonist DL-2-amino-4-phosphonobutanoic acid (DL-APB) to rat brain synaptic plasma membranes was characterized. As determined by Scatchard analysis, the binding was saturable and homogeneous with a Kd = 6.0 microM and Bmax = 380 pmol/mg of protein. The binding was dependent on the presence of Ca2+ and Cl- ions and was diminished upon freezing. The association rate constant was 6.8 X 10(-3) microM-1 min-1, and the dissociation rate constant was 2.0 X 10(-2) min-1. The L isomers of APB, glutamate, and aspartate were more potent as displacers of APB binding than the D isomers. With the exception of kynurenic acid, all compounds examined in both systems were more potent as displacers of APB binding than as inhibitors of synaptic transmission. This difference in potency was most pronounced for agonists at dentate granule cells. L-Glutamate, D-glutamate, and L-glutamate tetrazole were between 140- and 7500-fold more potent as displacers of DL-APB binding than as inhibitors of synaptic transmission. D-2-Amino-5-phosphonopentanoic acid and alpha-methyl-APB were between 10- and 20-fold more potent as displacers of binding

  17. Trichloroisocyanuric acid as an efficient homogeneous catalyst for the chemoselective synthesis of 2-substituted oxazolines, imidazolines and thiazolines under solvent-free condition

    Hojati Fatemeh Seyedeh

    2012-01-01

    Full Text Available Trichloroisocyanuric acid as a commercially available and inexpensive catalyst has been used in a new, facile and efficient procedure for the synthesis of 2-oxazolines, 2-imidazolines and 2-thiazolines through the reaction of nitriles with 2-aminoethanol, ethylenediamine or 2-aminoethanthiol under solvent -free conditions.

  18. Studies on naturally occurring infectious bursal disease viruses suggest that a single amino acid substitution at position 253 in VP2 increases pathogenicity.

    Jackwood, D J; Sreedevi, B; LeFever, L J; Sommer-Wagner, S E

    2008-07-20

    Three classic IBDV strains were previously isolated from commercial layer chicken flocks and shown to be phylogenetically related to vaccine strains but pathogenic in susceptible chickens. In this study, their viral genomes were sequenced and compared to sequences of vaccines being used in those flocks. The vaccine strains examined were sequenced directly from the manufacturer and had identical genome segment B sequences. Compared to these vaccines, the GA-1, H-30 and CS-2-35 isolates each had one silent mutation in the gene that encodes VP1. Compared to the two vaccines used at the time CS-2-35 was isolated, the segment A sequence of CS-2-35 contained numerous nucleotide and amino acid mutations suggesting the CS-2-35 virus was not closely related to these vaccines. This virus however did have amino acid mutations in VP2 that are reported to be necessary for replication in cell culture and lacked two of the three amino acid mutations previously shown to be necessary for virulence. These data suggest that CS-2-35 was a descendant from an attenuated strain of IBDV. When the segment A genomic sequences of the GA-1 and H-30 viruses were compared to the vaccines being used in those flocks they were most closely related to the attenuated D78 vaccine strain. In genome segment A, three nucleotide mutations in GA-1 and four in H-30 were observed compared to the D78 classic vaccine. These nucleotide mutations caused one amino acid (H253N) change in the GA-1 virus and two amino acids (H253Q and G259D) were different in the H-30 virus. In addition, both the GA-1 and H-30 viruses had the amino acid G76 in VP2 that appears to be unique to the vaccine D78. The data suggest that GA-1 and H-30 are genetically related and have a common ancestor even though they were isolated from geographically distant flocks. The evidence also suggests that GA-1, H-30 and CS-2-35 could be reversions from attenuated vaccine viruses or by coincidence genetically resemble classic IBDV vaccines. It

  19. A Single Amino Acid Substitution Prevents Recognition of a Dominant Human Aquaporin-4 Determinant in the Context of HLA-DRB1*03:01 by a Murine TCR

    Arellano, Benjamine; Hussain, Rehana; Miller-Little, William A.; Herndon, Emily; Lambracht-Washington, Doris; Eagar, Todd N.; Lewis, Robert; Healey, Don; Vernino, Steven; Greenberg, Benjamin M.; Stüve, Olaf

    2016-01-01

    Background Aquaporin 4 (AQP4) is considered a putative autoantigen in patients with Neuromyelitis optica (NMO), an autoinflammatory disorder of the central nervous system (CNS). HLA haplotype analyses of patients with NMO suggest a positive association with HLA-DRB1* 03:01. We previously showed that the human (h) AQP4 peptide 281–300 is the dominant immunogenic determinant of hAQP4 in the context of HLA-DRB1*03:01. This immunogenic peptide stimulates a strong Th1 and Th17 immune response. AQP4281-300-specific encephalitogenic CD4+ T cells should initiate CNS inflammation that results in a clinical phenotype in HLA-DRB1*03:01 transgenic mice. Methods Controlled study with humanized experimental animals. HLA-DRB1*03:01 transgenic mice were immunized with hAQP4281-300, or whole-length hAQP4 protein emulsified in complete Freund’s adjuvant. Humoral immune responses to both antigens were assessed longitudinally. In vivo T cell frequencies were assessed by tetramer staining. Mice were followed clinically, and the anterior visual pathway was tested by pupillometry. CNS tissue was examined histologically post-mortem. Flow cytometry was utilized for MHC binding assays and to immunophenotype T cells, and T cell frequencies were determined by ELISpot assay. Results Immunization with hAQP4281-300 resulted in an in vivo expansion of antigen-specific CD4+ T cells, and an immunoglobulin isotype switch. HLA-DRB1*03:01 TG mice actively immunized with hAQP4281-300, or with whole-length hAQP4 protein were resistant to developing a neurological disease that resembles NMO. Experimental mice show no histological evidence of CNS inflammation, nor change in pupillary responses. Subsequent analysis reveals that a single amino acid substitution from aspartic acid in hAQP4 to glutamic acid in murine (m)AQP4 at position 290 prevents the recognition of hAQP4281-300 by the murine T cell receptor (TCR). Conclusion Induction of a CNS inflammatory autoimmune disorder by active immunization of

  20. Tax rates as strategic substitutes

    H. Vrijburg (Hendrik); R.A. de Mooij (Ruud)

    2016-01-01

    textabstractThis paper analytically derives conditions under which the slope of the tax-reaction function is negative in a classical tax competition model. If countries maximize welfare, a negative slope (reflecting strategic substitutability) occurs under relatively mild conditions. The strategic t

  1. Comparison of three calcium phosphate bone graft substitutes from biomechanical, histological, and crystallographic perspectives using a rat posterolateral lumbar fusion model.

    Hu, Ming-Hsien; Lee, Pei-Yuan; Chen, Wen-Cheng; Hu, Jin-Jia

    2014-12-01

    This study evaluated the effectiveness of three calcium phosphate bone graft substitutes with different chemical compositions on spinal fusion using a rat posterolateral lumbar fusion model. Specifically, two recently developed non-dispersive tetracalcium phosphate/dicalcium phosphate anhydrous-based calcium phosphate cements (CPCs), namely a CPC consisting of equimolar amounts of the two compounds (nd-CPC) and a CPC consisting of a two-fold greater amount of dicalcium phosphate anhydrous (DCP-rich CPC), were compared with a commercial calcium phosphate bone graft (c-CPG) consisting of hydroxyapatite (60%) and β-tricalcium phosphate (40%). Single-level posterolateral lumbar fusion was performed at the L4-L5 vertebrae in fifteen adult rats (n=5 for each group). Spinal fusion was evaluated with radiographs, manual palpation, mechanical testing, micro-CT, and histology 8 weeks post-surgery. In particular, the crystallographic phases in the three substitutes were identified before and 8 weeks after their implantation. Manual palpation revealed stable constructs in nearly all of the spine specimens. The stiffness and bending load of fused spines in the two CPC groups were comparable to those in the c-CPG group. The radiographs specifically revealed implant resorption and bone remodeling in the DCP-rich CPC group. Analysis of 3D micro-CT images revealed that the bone volume ratio in the DCP-rich CPC group was significantly greater than those in the nd-CPC and c-CPG groups. Histology showed that the DCP-rich CPC group exhibited the highest degree of bone regeneration and osseointegration. Notably, DCP-rich CPC led to a pronounced phase transformation, generating the greatest amount of poorly crystalline apatite among the three groups, which together with adequate resorption may explain the aforementioned positive findings. We therefore conclude that of the bone graft substitutes considered, DCP-rich CPC has the greatest potential to be used in spinal fusion. PMID

  2. The kinetics of the solidification of highly supersaturated solutions of palmitic acid in oleic acid: a comparison between two models

    RAMIRO RICO-MARTINEZ

    1999-08-01

    Full Text Available The crystallization of fatty acids is very important in industrial applications and biological systems. A comparison between theoretical models and experimental data helps in clarifying mechanistic aspects of these systems. In this contribution, we compare the performance of two models in fitting data from the crystallization of supersaturated solutions of palmitic acid in oleic acid. One of the models was developed by Avrami and the other is based on considering diffusion as limiting (the D-model. The D-model fitted the data better than the Avrami model in all cases. The D-model has a low value of the regression coefficient (r2, lower than 0.9 in only three cases. For these points, the thermodynamic force was smaller. Differences in the parameter n (an index of dimensionality were observed; these differences indicate that clusters were present previous to the crystallization process. Furthermore, there appears to be a difference in the mechanism of crystallization of pure solutions of palmitic acid and solutions with a small fraction of oleic acid. Thus, one is lead to the conclusion that the rate of crystallization of fatty acids at high concentrations is limited by diffusion.

  3. Comparison of three calcium phosphate bone graft substitutes from biomechanical, histological, and crystallographic perspectives using a rat posterolateral lumbar fusion model

    Hu, Ming-Hsien [Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Orthopedics, Show-Chwan Memorial Hospital, Changhua 50544, Taiwan (China); Department of Orthopedic Surgery, Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); Lee, Pei-Yuan [Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Orthopedics, Show-Chwan Memorial Hospital, Changhua 50544, Taiwan (China); Chen, Wen-Cheng, E-mail: wincheng0925@yahoo.com.tw [Department of Fiber and Composite Materials, College of Engineering, Feng Chia University, Taichung 40724, Taiwan (China); Hu, Jin-Jia, E-mail: jjhu@mail.ncku.edu.tw [Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan (China); Medical Device Innovation Center, National Cheng Kung University, Tainan 701, Taiwan (China)

    2014-12-01

    This study evaluated the effectiveness of three calcium phosphate bone graft substitutes with different chemical compositions on spinal fusion using a rat posterolateral lumbar fusion model. Specifically, two recently developed non-dispersive tetracalcium phosphate/dicalcium phosphate anhydrous-based calcium phosphate cements (CPCs), namely a CPC consisting of equimolar amounts of the two compounds (nd-CPC) and a CPC consisting of a two-fold greater amount of dicalcium phosphate anhydrous (DCP-rich CPC), were compared with a commercial calcium phosphate bone graft (c-CPG) consisting of hydroxyapatite (60%) and β-tricalcium phosphate (40%). Single-level posterolateral lumbar fusion was performed at the L4–L5 vertebrae in fifteen adult rats (n = 5 for each group). Spinal fusion was evaluated with radiographs, manual palpation, mechanical testing, micro-CT, and histology 8 weeks post-surgery. In particular, the crystallographic phases in the three substitutes were identified before and 8 weeks after their implantation. Manual palpation revealed stable constructs in nearly all of the spine specimens. The stiffness and bending load of fused spines in the two CPC groups were comparable to those in the c-CPG group. The radiographs specifically revealed implant resorption and bone remodeling in the DCP-rich CPC group. Analysis of 3D micro-CT images revealed that the bone volume ratio in the DCP-rich CPC group was significantly greater than those in the nd-CPC and c-CPG groups. Histology showed that the DCP-rich CPC group exhibited the highest degree of bone regeneration and osseointegration. Notably, DCP-rich CPC led to a pronounced phase transformation, generating the greatest amount of poorly crystalline apatite among the three groups, which together with adequate resorption may explain the aforementioned positive findings. We therefore conclude that of the bone graft substitutes considered, DCP-rich CPC has the greatest potential to be used in spinal fusion

  4. Comparison of three calcium phosphate bone graft substitutes from biomechanical, histological, and crystallographic perspectives using a rat posterolateral lumbar fusion model

    This study evaluated the effectiveness of three calcium phosphate bone graft substitutes with different chemical compositions on spinal fusion using a rat posterolateral lumbar fusion model. Specifically, two recently developed non-dispersive tetracalcium phosphate/dicalcium phosphate anhydrous-based calcium phosphate cements (CPCs), namely a CPC consisting of equimolar amounts of the two compounds (nd-CPC) and a CPC consisting of a two-fold greater amount of dicalcium phosphate anhydrous (DCP-rich CPC), were compared with a commercial calcium phosphate bone graft (c-CPG) consisting of hydroxyapatite (60%) and β-tricalcium phosphate (40%). Single-level posterolateral lumbar fusion was performed at the L4–L5 vertebrae in fifteen adult rats (n = 5 for each group). Spinal fusion was evaluated with radiographs, manual palpation, mechanical testing, micro-CT, and histology 8 weeks post-surgery. In particular, the crystallographic phases in the three substitutes were identified before and 8 weeks after their implantation. Manual palpation revealed stable constructs in nearly all of the spine specimens. The stiffness and bending load of fused spines in the two CPC groups were comparable to those in the c-CPG group. The radiographs specifically revealed implant resorption and bone remodeling in the DCP-rich CPC group. Analysis of 3D micro-CT images revealed that the bone volume ratio in the DCP-rich CPC group was significantly greater than those in the nd-CPC and c-CPG groups. Histology showed that the DCP-rich CPC group exhibited the highest degree of bone regeneration and osseointegration. Notably, DCP-rich CPC led to a pronounced phase transformation, generating the greatest amount of poorly crystalline apatite among the three groups, which together with adequate resorption may explain the aforementioned positive findings. We therefore conclude that of the bone graft substitutes considered, DCP-rich CPC has the greatest potential to be used in spinal fusion

  5. Proton binding to soil humic and fulvic acids: Experiments and NICA-Donnan modelling

    Tan, W.; Xiong, J.; Li, Y.; Wang, M.; Weng, L.; Koopal, L.K.

    2013-01-01

    Proton binding to one soil fulvic acid (JGFA), two soil humic acids (JGHA, JLHA) and a lignite-based humic acid (PAHA) was investigated. The results were fitted to NICA-Donnan model and compared directly with the predictions using the generic parameters. NICA-Donnan model can describe proton binding

  6. Field trial evaluation of the accumulation of omega-3 long chain polyunsaturated fatty acids in transgenic Camelina sativa: Making fish oil substitutes in plants

    Sarah Usher

    2015-12-01

    Full Text Available The global consumption of fish oils currently exceeds one million tonnes, with the natural de novo source of these important fatty acids forming the base of marine foodwebs. Here we describe the first field-based evaluation of a terrestrial source of these essential nutrients, synthesised in the seeds of transgenic Camelina sativa plants via the heterologous reconstitution of the omega-3 long chain polyunsaturated fatty acid biosynthetic pathway. Our data demonstrate the robust nature of this novel trait, and the feasibility of making fish oils in genetically modified crops. Moreover, to our knowledge, this is the most complex example of plant genetic engineering to undergo environmental release and field evaluation.

  7. One-pot synthesis of fully substituted 1,3,4-oxadiazole derivatives from aromatic carboxylic acids, cyclobutanone and N-isocyaniminotriphenylphosphorane

    HOLAGH, Mohsen VALIZADEH; MAHARRAMOV, Abel Mohammadali oglu

    2012-01-01

    Reactions of N-isocyaniminotriphenylphosphorane with cyclobutanone in the presence of aromatic (or heteroaromatic) carboxylic acids proceeded smoothly at room temperature and in neutral conditions to afford sterically congested 1-(5-aryl-1,3,4-oxadiazol-2-yl)- 1-cyclobutanol derivatives in high yields. The reaction proceeded smoothly and cleanly under mild conditions and no side reactions were observed. The structures of the products were deduced from their IR, 1HNMR, and 13CNMR spec...

  8. Aromatic substitution in the gas phase. On the mechanism of the dehalogenation reactions of halobenzenes and dihalobengenes promoted by gaseous Bronsted acids

    The attack of CH5+ and C2H5+ ions, obtained in the dilute gas state from the γ radiolysis of methane, on halo- and dihalobenzenes causes extensive dehalogenation via two distinct channels, leading respectively to protodehalogenated and methyldehalogenated products, whose relative rate depends primarily on the nature of the leaving halogen. Kinetic and mass spectrometric evidences suggest that direct attack of the Bronsted acid to the halogen substituent leads to formation of the correspondent arylium cation, via hydrogen halide elimination, at a rate which decreases in the order F much greater than Cl equal to or greater than Br. The subsequent electrophilic attack of the arylium cations on CH4, the bulk constituent of the system, yields methylated arenium ions, and eventually the observed methyldehalogenated products. On the other hand, attack of the Bronsted acid to the aromatic ring of halobenzenes promotes protodehalogenation, at a rate increasing in the order F much less than Cl < Br. Direct comparison of the rates of the two dehalogenation processes has been obtained from the study of dihalobenzenes containing different halogens. Furthermore, isolation of a mixture of m- and p-xylene among the dehalogenation products of p-fluorotoluene has provided direct evidence for the isomerization of the p-tolyl cation formed from the attack of the gaseous Bronsted acid to the n-type center of the substrate and/or of the xylenium ion formed from the attack of the tolyl ion to methane. The present results, and supporting mass spectrometric evidence, underline the typical ambident behavior of halobenzenes toward charged electprophiles, and allow a unified interpretation of the dehalogention processes promoted by different Bronsted acids. The gas-phase reactivity of halobenzenes is compared with their behavior in similar processes occuring in solution

  9. Lauric acid-rich medium-chain triglycerides can substitute for other oils in cooking applications and may have limited pathogenicity.

    McCarty, Mark F; DiNicolantonio, James J

    2016-01-01

    Recently, medium-chain triglycerides (MCTs) containing a large fraction of lauric acid (LA) (C12)-about 30%-have been introduced commercially for use in salad oils and in cooking applications. As compared to the long-chain fatty acids found in other cooking oils, the medium-chain fats in MCTs are far less likely to be stored in adipose tissue, do not give rise to 'ectopic fat' metabolites that promote insulin resistance and inflammation, and may be less likely to activate macrophages. When ingested, medium-chain fatty acids are rapidly oxidised in hepatic mitochondria; the resulting glut of acetyl-coenzyme A drives ketone body production and also provokes a thermogenic response. Hence, studies in animals and humans indicate that MCT ingestion is less obesogenic than comparable intakes of longer chain oils. Although LA tends to raise serum cholesterol, it has a more substantial impact on high density lipoprotein (HDL) than low density lipoprotein (LDL) in this regard, such that the ratio of total cholesterol to HDL cholesterol decreases. LA constitutes about 50% of the fatty acid content of coconut oil; south Asian and Oceanic societies which use coconut oil as their primary source of dietary fat tend to be at low cardiovascular risk. Since ketone bodies can exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential. As compared to traditional MCTs featuring C6-C10, laurate-rich MCTs are more feasible for use in moderate-temperature frying and tend to produce a lower but more sustained pattern of blood ketone elevation owing to the more gradual hepatic oxidation of ingested laurate. PMID:27547436

  10. Acid-resistant calcium silicate-based composite implants with high-strength as load-bearing bone graft substitutes and fracture fixation devices.

    Wei, Chung-Kai; Ding, Shinn-Jyh

    2016-09-01

    To achieve the excellent mechanical properties of biodegradable materials used for cortical bone graft substitutes and fracture fixation devices remains a challenge. To this end, the biomimetic calcium silicate/gelatin/chitosan oligosaccharide composite implants were developed, with an aim of achieving high strength, controlled degradation, and superior osteogenic activity. The work focused on the effect of gelatin on mechanical properties of the composites under four different kinds of mechanical stresses including compression, tensile, bending, and impact. The evaluation of in vitro degradability and fatigue at two simulated body fluid (SBF) of pH 7.4 and 5.0 was also performed, in which the pH 5.0 condition simulated clinical conditions caused by bacterial induced local metabolic acidosis or tissue inflammation. In addition, human mesenchymal stem cells (hMSCs) were sued to examine osteogenic activity. Experimental results showed that the appropriate amount of gelatin positively contributed to failure enhancement in compressive and impact modes. The 10wt% gelatin-containing composite exhibits the maximum value of the compressive strength (166.1MPa), which is within the reported compressive strength for cortical bone. The stability of the bone implants was apparently affected by the in vitro fatigue, but not by the initial pH environments (7.4 or 5.0). The gelatin not only greatly enhanced the degradation of the composite when soaked in the dynamic SBF solution, but effectively promoted attachment, proliferation, differentiation, and formation of mineralization of hMSCs. The 10wt%-gelatin composite with high initial strength may be a potential implant candidate for cortical bone repair and fracture fixation applications. PMID:27254281

  11. The sugar model: catalysis by amines and amino acid products

    Weber, A. L.

    2001-01-01

    Ammonia and amines (including amino acids) were shown to catalyze the formation of sugars from formaldehyde and glycolaldehyde, and the subsequent conversion of sugars to carbonylcontaining products under the conditions studied (pH 5.5 and 50 degrees C). Sterically unhindered primary amines were better catalysts than ammonia, secondary amines, and sterically hindered primary amines (i.e. alpha-aminoisobutyric acid). Reactions catalyzed by primary amines initially consumed formaldehyde and glycolaldehyde about 15-20 times faster than an uncatalyzed control reaction. The amine-catalyzed reactions yielded aldotriose (glyceraldehyde), ketotriose (dihydroxyacetone), aldotetroses (erythrose and threose), ketotetrose (erythrulose), pyruvaldehyde, acetaldehyde, glyoxal, pyruvate, glyoxylate, and several unindentified carbonyl products. The concentrations of the carbonyl products, except pyruvate and ketotetrose, initially increased and then declined during the reaction, indicating their ultimate conversion to other products (like larger sugars or pyruvate). The uncatalyzed control reaction yielded no pyruvate or glyoxylate, and only trace amounts of pyruvaldehyde, acetaldehyde and glyoxal. In the presence of 15 mM catalytic primary amine, such as alanine, the rates of triose and pyruvaldehyde of synthesis were about 15-times and 1200-times faster, respectively, than the uncatalyzed reaction. Since previous studies established that alanine is synthesized from glycolaldehyde and formaldehyde via pyruvaldehyde as its direct precursor, the demonstration that the alanine catalyzes the conversion of glycolaldehyde and formaldehyde to pyruvaldehyde indicates that this synthetic pathway is capable of autocatalysis. The relevance of this synthetic process, named the Sugar Model, to the origin of life is discussed.

  12. Novel 2,7-Substituted (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor γ Partial Agonists with Protein-Tyrosine Phosphatase 1B Inhibition.

    Otake, Kazuya; Azukizawa, Satoru; Takeda, Shigemitsu; Fukui, Masaki; Kawahara, Arisa; Kitao, Tatsuya; Shirahase, Hiroaki

    2015-01-01

    A novel series of 2,7-substituted 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and biologically evaluated. (S)-2-(2-Furylacryloyl)-7-[2-(2-methylindane-2-yl)-5-methyloxazol-4-yl]methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylamine salt (13jE) was identified as a potent human peroxisome proliferator-activated receptor γ (PPARγ)-selective agonist (EC50=85 nM) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC50=1.0 µM). Compound 13jE partially activated PPARγ, but not PPARα or PPARδ, and antagonized farglitazar, a full PPARγ agonist. Cmax after the oral administration of 13jE at 10 mg/kg was 28.6 µg/mL (53 µM) in male Sprague-Dawley (SD) rats. Repeated administration of 13jE and rosiglitazone for 14 d at 10 mg/kg/d decreased plasma glucose and triglyceride levels significantly in male KK-A(y) mice. Rosiglitazone, but not 13jE, significantly increased the plasma volume and liver weight. In conclusion, 13jE showed stronger hypoglycemic and hypolipidemic effects and weaker hemodilution and hepatotoxic effects than rosiglitazone, suggesting that its safer efficacy may be due to its partial PPARγ agonism and PTP-1B inhibition. PMID:26633022

  13. The effect of ligand substitution and water co-adsorption on the adsorption dynamics and energy level matching of amino-phenyl acid dyes on TiO2.

    Manzhos, Sergei; Segawa, Hiroshi; Yamashita, Koichi

    2012-02-01

    We perform a comparative theoretical analysis of adsorption of dyes NK1 (2E,4E-2-cyano-5-(4-dimethylaminophenyl)penta-2,4-dienoic acid) and NK7 (2E,4E-2-cyano-5-(4-diphenylaminophenyl)penta-2,4-dienoic acid) on clean and water-covered anatase (101) surfaces of TiO(2). Ligand substitution away from the anchoring group changes the energy level matching between the dye's LUMO and the oxide's conduction band. Monodentate binding and bidentate binding configurations of the dyes to TiO(2) are found to have similar adsorption energies even though the injection from the bidentate mode is found to dominate. Water has a strong effect on adsorption, inducing deprotonation and affecting strongly and differently between the dyes the energy level matching, leading to a shut-off of the injection from NK7 of bidentate adsorption configuration. Ab initio molecular dynamics simulations show a strong effect of nuclear motion on energy levels, specifically, increasing the driving force for injection in the monodentate regime. PMID:22194034

  14. Smart Phones and their Substitutes

    Bødker, Mads; Gimpel, Gregory; Hedman, Jonas

    2009-01-01

    Drawing on data from a longitudinal field study, this paper investigates the influence of existing, better and stand-alone technology substitutes on the use of smart phones. By applying prospect theory, media richness theory, and business model literature, the purpose of this paper is to improve...... our understanding of the role of substitutes, device content fit issues, and implications for business models by asking the question: What is an effective business model to address the relationship between user preference and the fit of the smart phone and everyday task? The field study data suggest...... the need for business models to recognize that adoption decisions are reference-dependent and strongly influenced by the fit between task and smart phone....

  15. Fractal dual substitution tilings

    Frank, Natalie Priebe; Webster, Samuel B. G.; Whittaker, Michael F.

    2014-01-01

    Starting with a substitution tiling, we demonstrate a method for constructing infinitely many new substitution tilings. Each of these new tilings is derived from a graph iterated function system and the tiles have fractal boundary. We show that each of the new tilings is mutually locally derivable to the original tiling. Thus, at the tiling space level, the new substitution rules are expressing geometric and combinatorial, rather than topological, features of the original. Our method is easy ...

  16. CTX-M-Type Extended-Spectrum β-Lactamase That Hydrolyzes Ceftazidime through a Single Amino Acid Substitution in the Omega Loop

    Poirel, Laurent; Naas, Thierry; Le Thomas, Isabelle; Karim, Amal; Bingen, Edouard; Nordmann, Patrice

    2001-01-01

    Escherichia coli ILT-1, Klebsiella pneumoniae ILT-2, and K. pneumoniae ILT-3 were isolated in May 1999 in Paris, France, from a rectal swab of a hospitalized 5-month-old girl. These isolates had a clavulanic acid-inhibited substrate profile that included expanded-spectrum cephalosporins. The MICs of cefotaxime were higher for E. coli ILT-1 and K. pneumoniae ILT-2 than for K. pneumoniae ILT-3, while the opposite was found for the MICs of ceftazidime. Genetic and biochemical analyses revealed t...

  17. Bile acid malabsorption or disturbed intestinal permeability in patients treated with enzyme substitution for exocrine pancreatic insufficiency is not caused by bacterial overgrowth

    Madsen, Jan Lysgård; Graff, Jesper; Philipsen, Else Kirstine; Scharff, Ole; Rumessen, Jüri Johannes

    2003-01-01

    INTRODUCTION: In some patients with severe exocrine pancreatic insufficiency, enzyme replacement therapy will not lead to clinical improvement or reduction of steatorrhea. Therefore, other mechanisms separately or in interplay with reduced enzyme secretion might be responsible for malabsorption in...... affected in patients with exocrine pancreatic insufficiency who receive treatment with enzyme supplementation. The prevalence of bacterial overgrowth seems to be low among these patients and does not explain the findings....... these patients. AIMS: To evaluate the prevalence of bacterial overgrowth, bile acid absorption capacity, and intestinal permeability in a group of patients with well-characterized exocrine pancreatic insufficiency. METHODOLOGY: Eleven men with severe exocrine pancreatic insufficiency, of whom 10 were...

  18. Acquisition of NFKB1-selective DNA binding by substitution of four amino acid residues from NFKB1 into RelA.

    Coleman, T A; Kunsch, C; Maher, M.; Ruben, S. M.; Rosen, C. A.

    1993-01-01

    The subunits of NF-kappa B, NFKB1 (formerly p50) and RelA (formerly p65), belong to a growing family of transcription factors that share extensive similarity to the c-rel proto-oncogene product. The homology extends over a highly conserved stretch of approximately 300 amino acids termed the Rel homology domain (RHD). This region has been shown to be involved in both multimerization (homo- and heterodimerization) and DNA binding. It is now generally accepted that homodimers of either subunit a...

  19. EFSA ; Scientific Opinion on Flavouring Group Evaluation 67, Revision 1 (FGE.67Rev.1): Consideration of 40 furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers evaluated by JECFA at the 65th meeting (JECFA, 2006

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister; Lund, Pia; Binderup, Mona-Lise

    evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 33 furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers evaluated by the JECFA. In the...

  20. Matrix models with Penner interaction inspired by interacting ribonucleic acid

    Pradeep Bhadola; N Deo

    2015-02-01

    The Penner interaction known in studies of moduli space of punctured Riemann surfaces is introduced and studied in the context of random matrix model of homo RNA. An analytic derivation of the generating function is given and the corresponding partition function is derived numerically. An additional dependence of the structure combinatorics factor on (related to the size of the matrix and the interaction strength) is obtained. This factor has a strong effect on the structure combinatorics in the low regime. Databases are scanned for real ribonucleic acid (RNA) structures and pairing information for these RNA structures is computationally extracted. Then the genus is calculated for every structure and plotted as a function of length. The genus distribution function is compared with the prediction from the nonlinear (NL) model. The specific heat and distribution of structure with temperature calculated from the NL model shows that the NL inter-action is biased towards planar structures. The second derivative of specific heat changes phase from a double peaked function for small to a single peak for large . Detailed analysis reveals the presence of the double peak only for genus 0 structures, the higher genii behave normally with . Comparable behaviour is found in studies involving interactions of RNA with osmolytes and monovalent cations in unfolding experiments.

  1. Syndeticity and independent substitutions

    Durand, Fabien

    2009-01-01

    We associate in a canonical way a substitution to any abstract numeration system built on a regular language. In relationship with the growth order of the letters, we define the notion of two independent substitutions. Our main result is the following. If a sequence $x$ is generated by two independent substitutions, at least one being of exponential growth, then the factors of $x$ appearing infinitely often in $x$ appear with bounded gaps. As an application, we derive an analogue of Cobham's theorem for two independent substitutions (or abstract numeration systems) one with polynomial growth, the other being exponential.

  2. Binary and ternary chelates of scandium (III), Yttrium (III) and lanthanum (III) with ethyleneglycol-bis(β-aminoethylether)-tetraacetic acid as primary and substituted salicylic acids as secondary ligands

    Formation constants of binary and ternary complexes of the systems of the type: M-L and M-egta-L (M = scandium(III), yttrium(III) and lanthanum(III), egta = ethylene glycol-bis(β-aminoethylether)-tetra acetic acid, L = o-cresotic acid (o-ca), m-cresotic acid (m-ca), 5-chlorosalicyclic acid(csa), and 3,5-dibromosalicylic acid (dbsa)) have been determined pH-metrically at 25deg and μ = 0.1M (KNO3) in 50% (v/v) aqueous-ethanol medium. The order of stabilities of ternary complexes has been compared with those of corresponding binary complexes, and results discussed on the basis of coulombic interactions. (auth.)

  3. Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein

    Agarwal, Sonya; Döring, Kristina; Gierusz, Leszek A.; Iyer, Pooja; Lane, Fiona M.; Graham, James F.; Goldmann, Wilfred; Pinheiro, Teresa J. T.; Gill, Andrew C.

    2015-10-01

    The β2-α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2-α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2-α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region.

  4. EFFECT OF SUBSTITUTION POSITION OF HYDROXY GROUP AT BENZOIC ACID ON THE LUMINESCENT AND DEGRADATION PROPERTIES OF POLY[DI(CARBOXYPHENYL) SUCCINATE-co-SEBACIC ANHYDRIDE]S

    Jun Fan; Hong-liang Jiang; Kang-jie Zhu

    2007-01-01

    In this work, two new diacids, di(m-carboxyphenyl) succinate (m-dCPS) and di(o-carboxyphenyl) succinate (o-dCPS), were synthesized by reaction of m-, o-hydroxy benzoic acid with succinic chloride, respectively. Their corresponding copolymers with sebacic acid (SA), P(m-dCPS:SA) and P(o-dCPS:SA), were prepared by melt copolycondensation and characterized by NMR, UV and DSC methods. Compared with inherently fluorescent poly[di(p-carboxyphenyl) succinateco-sebacic anhydride] (P(p-dCPS:SA)), P(m-dCPS:SA) and P(o-dCPS:SA) displayed different luminescent properties. P(m-dCPS:SA) could emit fluorescence under the excitation of both visible and UV light, while P(o-dCPS:SA) could only emit fluorescence when excited with UV light. Degradation rate of the two new copolyanhydrides increased with the increase of SA fraction in the copolymers. In addition, P(o-dCPS:SA) degraded more rapidly than P(m-dCPS:SA) with the same composition. Typical surface-degradation characteristics of these copolyanhydrides were observed.

  5. [Studies on the structure-activity relationship of allyl substituted oxopyrimidines searching for the novel antagonist or agonist of barbiturates to the sleep mechanism based on the uridine receptor theory--barbituric acid to uridine (part I)].

    Yamamoto, Ikuo

    2005-01-01

    Thirty-six allyl substituted oxopyrimidine analogues such as barbituric acid (BA), barbiturates, uracil, thymine, and related derivatives including 13 new compounds were synthesized and their pharmacologic effects ([hypnotic activity, anticonvulsant activity against pentylentetrazol (PTZ)-induced seizures, and LD(50)]) and interactions with the barbiturates were evaluated in mice and rats. The results are briefly and parially summarized as follows. BA prolonged pentobarbital (PB)-induced sleep and had some central depressant effects. N,5,5-triallyl-BA exhibited some hypnotic and anticonvulsant activities, although the other 5,N-allyl-compounds did not show any activity except for allobarbital (AlloB). N-allyl-BA, 5-allyl-BA, N(1),N(3),5-triallyl-BA, N,5,5-triallyl-BA, and N(1),N(3),5,5-tetraallyl-BA also prolonged PB-induced sleep. Interestingly, N,5,5-triallyl-BA was the most potent in the interaction with AlloB, phenobarbital (PheB), amobarbital (AB), PB, and thiopental (TP) but not barbital (B). N(1),N(3),5,5-tetraallyl-BA prolonged AlloB-, PB-, and AB-induced sleep but not B-, PheB-, and TP-induced sleep. N(1),N(3),5-triallyl-B prolonged only PB- and TP-induced sleep. 5,5-diallyl-BA prolonged PheB- and TP-induced sleep. N,5-diallyl-BA prolonged only TP-induced sleep. In contrast, BA and N(1),N(3),5-triallyl-AB tended to antagonize AlloB, AB, and B. N(1),N(3),5,5-tetraallyl-BA also slightly antagonized B, PheB, and TP. 5,5-diallyl-BA antagonized only AB. The prolonging effects of BA, N,5,5-triallyl-BA, and N(1),N(3),5,5-tetraallyl-BA on PB-induced sleep were dose dependent. These results indicate that the position and number of allyl groups substituted on the structure of BA play an important role in their depressant activities. This review deals with the structure-activity relationship of allyl-substituted oxopyrimidines as part of our search for antagonists and agonists of barbiturates as well as their mechanisms of action. PMID:15635282

  6. Asymmetric price responses and the underlying energy demand trend. Are they substitutes or complements? Evidence from modelling OECD aggregate energy demand

    A number of energy demand studies have considered the importance of modelling Asymmetric Price Responses (APR), for example, the often-cited work of Gately and Huntington (2002). Griffin and Schulman (2005) questioned the asymmetric approach arguing that this is only capturing energy saving technical progress. Huntington (2006), however, showed that for whole economy aggregate energy and oil demand there is a role statistically for both APR and exogenous energy saving technical change. In a separate strand of the literature the idea of the Underlying Energy Demand Trend (UEDT) has been developed, see for example Hunt et al. (2003a and 2003b) and Dimitropoulos et al. (2005). They argue that it is important, in time series energy demand models, to allow for stochastic trends (or UEDTs) based upon the structural time series/dynamic regression methodology recommended by Harvey (1989, 1997). This paper attempts to bring these strands of the literature together by proposing a testing procedure for the UEDT and APR in energy demand models within both a panel context (consistent with the Huntington, 2006 approach) and the structural time series modelling framework. A set of tests across a range of specifications using time-series and panel data are therefore suggested in order to try and ascertain whether energy saving technical change (or the more general UEDT) and APR are substitutes for each other when modelling energy demand or whether they are actually picking up different influences and are therefore complements. Using annual whole economy data for 17 OECD countries over the period 1960-2006 the results suggest that for most of the countries the UEDT is preferred to APR, whereas for another group the UEDT and APR are complements, and for another group they are substitutes. It is argued therefore that energy demand modellers should not assume at the outset that one method is superior to the other. Moreover, wherever possible, a general model (be it in a time series or

  7. Asymmetric price responses and the underlying energy demand trend: Are they substitutes or complements? Evidence from modelling OECD aggregate energy demand

    A number of energy demand studies have considered the importance of modelling Asymmetric Price Responses (APR), for example, the often-cited work of Gately and Huntington (2002). Griffin and Schulman (2005) questioned the asymmetric approach arguing that this is only capturing energy saving technical progress. Huntington (2006), however, showed that for whole economy aggregate energy and oil demand there is a role statistically for both APR and exogenous energy saving technical change. In a separate strand of the literature the idea of the Underlying Energy Demand Trend (UEDT) has been developed, see for example Hunt et al. (2003a and 2003b) and Dimitropoulos et al. (2005). They argue that it is important, in time series energy demand models, to allow for stochastic trends (or UEDTs) based upon the structural time series/dynamic regression methodology recommended by Harvey (1989, 1997). This paper attempts to bring these strands of the literature together by proposing a testing procedure for the UEDT and APR in energy demand models within both a panel context (consistent with the Huntington, 2006 approach) and the structural time series modelling framework. A set of tests across a range of specifications using time-series and panel data are therefore suggested in order to try and ascertain whether energy saving technical change (or the more general UEDT) and APR are substitutes for each other when modelling energy demand or whether they are actually picking up different influences and are therefore complements. Using annual whole economy data for 17 OECD countries over the period 1960-2006 the results suggest that for most of the countries the UEDT is preferred to APR, whereas for another group the UEDT and APR are complements, and for another group they are substitutes. It is argued therefore that energy demand modellers should not assume at the outset that one method is superior to the other. Moreover, wherever possible, a general model (be it in a time series or

  8. Binary and ternary chelates of Sc(III), Y(III) and La(III) with ethylenediamine tetraacetic acid as primary ligand and substituted salicylic acids as secondary ligands

    Study of ternary complex formation of several tripositive metal ions viz. Sc(III), Y(III) and La(III) with ethylenediamine tetraacetic acid (EDTA) as a primary ligand and 5-chlorosalicylic acid (CSA) or 3,5-dibromosalicylic acid (DBSA) as secondary ligands by pH-metric titration technique is reported. The stability order of metal chelates with respect to ligands is observed to be DBSA>CSA and with respect to metal ions Sc(III)>Y(III)>La(III). (B.G.W.)

  9. Antiproliferative, DNA cleavage, and ADMET study of substituted 2-(1-benzofuran-2-yl quinoline-4-carboxylic acid and its esters

    R. Anantacharya

    2016-12-01

    Full Text Available Synthesis, anti-proliferative, DNA cleavage, and in silico ADMET studies of 2-(1-benzofuran-2-yl quinoline-4-carboxylic acids and their resultant esters in acid catalyzed medium have been investigated. The synthesized compounds are characterized by UV, IR, 1H NMR, 13C NMR, and mass spectral analysis. The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest using agarose gel method and the antiproliferative activity was carried out by MTT assay on five different human cancer cell lines (Chronic Myelogenous Leukemia (K562, Breast Cancer (MCF-7, Cervical Cancer (HeLa, Colorectal Adino carcinoma (Colo 205, and Hepato cellular carcinoma (HepG2. Doxorubicin is taken as standard for comparison. The cleavage study indicated that molecules (3b–6a and 7b–8c did cleave the DNA completely with no trace of fragments. The molecules (6b, 6c and 7a have appeared to cleave DNA partially and assessed by comparing the bands appeared in control and test compounds at 100 μg concentration. The MTT antiproliferative activity of the synthesized derivatives at a concentration of 10 mM screened that out of the five cancer cell lines tested, the compounds 8b (25.97%, MCF-7, 7a (25.36%, Colo 205, and 7b (24.22%, HePG showed considerable degree of activity at a very low concentration. The molecules were active against MCF-7, Colo 205, and HepG. The molecules exhibited acceptable range in in silico ADMET prediction, significant DNA cleavage, and antiproliferative properties. The study further provides identification of possible lead moiety as an antiproliferative agent.

  10. Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers

    Kann, Nina

    2015-01-01

    © The Royal Society of Chemistry 2015. Peptidic foldamers have recently emerged as a novel class of artificial oligomers with properties and structural diversity similar to that of natural peptides, but possessing additional interesting features granting them great potential for applications in fields from nanotechnology to pharmaceuticals. Among these, foldamers containing 1,4- and 1,5-substitued triazole amino acids are easily prepared via the Cu- and Ru-catalyzed click reactions and may offer increased side chain variation, but their structural capabilities have not yet been widely explored. We here describe a systematic analysis of the conformational space of the two most important basic units, the 1,4-substitued (4Tzl) and the 1,5-substitued (5Tzl) 1,2,3-triazole amino acids, using quantum chemical calculations and NMR spectroscopy. Possible conformations of the two triazoles were scanned and their potential minima were located using several theoretical approaches (B3LYP/6-311++G(2d,2p), ωB97X-D/6-311++G(2d,2p), M06-2X/6-311++G(2d,2p) and MP2/6-311++G(2d,2p)) in different solvents. BOC-protected versions of 4Tzl and 5Tzl were also prepared via one step transformations and analyzed by 2D NOESY NMR. Theoretical results show 9 conformers for 5Tzl derivatives with relative energies lying close to each other, which may lead to a great structural diversity. NMR analysis also indicates that conformers preferring turn, helix and zig-zag secondary structures may coexist in solution. In contrast, 4Tzl has a much lower number of conformers, only 4, and these lack strong intraresidual interactions. This is again supported by NMR suggesting the presence of both extended and bent conformers. The structural information provided on these building units could be employed in future design of triazole foldamers. This journal is

  11. Egg substitutes: chemical and biologic evaluations.

    Childs, M T; Ostrander, J

    1976-03-01

    The total lipid, cholesterol, phospholipid, and fatty acid content of dried whole egg (DWE), a refrigerated liquid egg substitute, a powdered egg substitute, and a commercial egg yolk replacer (EYR) were compared. All substitutes contained less total lipid, cholesterol, and phospholipid than DWE. The powdered substitute contained only half the total lipid content reported by the producers and only a fifth of the cholesterol of DWE, while the percentage distribution of fatty acids was similar to that of DWE. The liquid substitute and EYR had fatty acid distributions similar to soybean oil. Rat growth and lipid response were compared for diets containing either DWE or a mixture of EYR and egg white. Both diets were fed with and without vitamin and mineral supplements. Rat growth response was greatest on the DWE diets, either with or without the supplements, was intermediate on the supplemented EYR diets, and was least on the unsupplemented EYR diets. The consumption of DWE-containing diets, when compared with the EYR-containing diets, caused greater liver weight, greater liver total lipid and total cholesterol content, and slightly higher serum cholesterol. PMID:942984

  12. N-(4-Substituted-benzoyl)-N'-(β-d-glucopyranosyl)ureas as inhibitors of glycogen phosphorylase: Synthesis and evaluation by kinetic, crystallographic, and molecular modelling methods.

    Nagy, Veronika; Felföldi, Nóra; Kónya, Bálint; Praly, Jean-Pierre; Docsa, Tibor; Gergely, Pál; Chrysina, Evangelia D; Tiraidis, Costas; Kosmopoulou, Magda N; Alexacou, Kyra-Melinda; Konstantakaki, Maria; Leonidas, Demetres D; Zographos, Spyros E; Oikonomakos, Nikos G; Kozmon, Stanislav; Tvaroška, Igor; Somsák, László

    2012-03-01

    N-(4-Substituted-benzoyl)-N'-(β-d-glucopyranosyl) ureas (substituents: Me, Ph, Cl, OH, OMe, NO(2), NH(2), COOH, and COOMe) were synthesised by ZnCl(2) catalysed acylation of O-peracetylated β-d-glucopyranosyl urea as well as in reactions of O-peracetylated or O-unprotected glucopyranosylamines and acyl-isocyanates. O-deprotections were carried out by base or acid catalysed transesterifications where necessary. Kinetic studies revealed that most of these compounds were low micromolar inhibitors of rabbit muscle glycogen phosphorylase b (RMGPb). The best inhibitor was the 4-methylbenzoyl compound (K(i)=2.3μM). Crystallographic analyses of complexes of several of the compounds with RMGPb showed that the analogues exploited, together with water molecules, the available space at the β-pocket subsite and induced a more extended shift of the 280s loop compared to RMGPb in complex with the unsubstituted benzoyl urea. The results suggest the key role of the water molecules in ligand binding and structure-based ligand design. Molecular docking study of selected inhibitors was done to show the ability of the binding affinity prediction. The binding affinity of the highest scored docked poses was calculated and correlated with experimentally measured K(i) values. Results show that correlation is high with the R-squared (R(2)) coefficient over 0.9. PMID:22325154

  13. Evaluation of polylactic acid nanoparticles safety using Drosophila model.

    Legaz, Sophie; Exposito, Jean-Yves; Lethias, Claire; Viginier, Barbara; Terzian, Christophe; Verrier, Bernard

    2016-10-01

    Cytotoxicity of nanoparticles and their sub-lethal effect on cell behavior and cell fate are a high topic of studies in the nanomaterial field. With an explosion of nanoparticle types (size, shape, polarity, stiffness, composition, etc.), Drosophila has become an attractive animal model for high throughput analysis of these nanocarriers in the drug delivery field with applications in cancer therapy, or simply to generate a fast and complete cytotoxic study of a peculiar nanoparticle. In respect to that, we have conducted an in cellulo study of poly(lactic acid) (PLA) nanoparticle cytotoxicity, and determined that near lethal nanoparticle doses, oxidative stress as well as P53 and ATP pathways may lead to cell cycle arrest at G1, and ultimately to cell death. Neither viability nor the development of Drosophila larvae are affected by the ingestion of PLA nanoparticles at sub-lethal concentrations. Drosophila will be a useful model to study PLA and PLA-modified nanoparticle toxicity, and nanoparticle fate after ingestion. PMID:27108761

  14. Optimization of Process of Methacrylic Acid Obtaining by Aldol Condensation of Propionic Acid with Formaldehyde Using a Kinetic Model

    Nebesnyi, Roman; Ivasiv, Volodymyr; Dmytruk, Yulia; Lapychak, Nazar

    2013-01-01

    Methacrylic acid is widely used industrial monomer. An alternative method of its obtaining is aldol condensation of propionic acid with formaldehyde in the gas phase. It has been found that catalyst based on oxides of boron and phosphorus and promoted by oxide of tungsten is effective for this process. The purpose of this work is to find out optimal parameters of this process (temperature and contact time) using a kinetic model. The optimal parameters of this process have been found and techn...

  15. Dysregulation of bile acid homeostasis in parenteral nutrition mouse model.

    Zhan, Le; Yang, Ill; Kong, Bo; Shen, Jianliang; Gorczyca, Ludwik; Memon, Naureen; Buckley, Brian T; Guo, Grace L

    2016-01-15

    Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12α-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-α (LXRα) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-α (RORα) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXRα function. Western blot showed significantly reduced nuclear migration of RORα protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver RORα signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD. PMID:26564717

  16. Elasticity of Substitution and Antidumping Measures

    Drud Hansen, Jørgen; Meinen, Philipp; Nielsen, Jørgen Ulff-Møller

    Abstract This paper analyzes the role of the elasticity of substitution for anti-dumping decisions across countries. In monopolistic competition models with cost heterogeneous firms across countries, price differences vary inversely with the elasticity of substitution. Anti-dumping duties should...... therefore also vary inversely with the elasticity of substitution at least for countries which have a strong focus on prices in the determination of their anti-dumping measures. We test this for ten countries from 1990 to 2009 using data on anti-dumping from Chad Bown (2010) and US-data at 8-digit level...... in our empirical investigation support the predicted role of the elasticity of substitution as we find a significant negative relation between the elasticity of substitution and the final anti-dumping duties for the ‘lesser duty rule’ group of countries. The countries which do not follow the ‘lesser duty...

  17. Substitution between cars within the household

    De Borger, Bruno; Mulalic, Ismir; Rouwendal, Jan

    2016-01-01

    In this paper we study the demand for car kilometres in two-car households, focusing on the substitution between cars of different fuel efficiency in response to fuel price changes. We use a large sample of detailed Danish data on two-car households to estimate – for each car owned by the household...... – own and cross-price effects of increases in fuel costs per kilometre. The empirical results show that failure to capture substitution between cars within the household can result in substantial misspecification biases. Ignoring substitution, the basic model yielded fuel price elasticities of 0.98 and...... 1.41 for the primary and secondary cars, respectively. Accounting for substitution effects, these figures reduce to, respectively, 0.32 and 0.45. Consistent with substitution behaviour, we find that the fuel price elasticity of fuel demand exceeds the elasticity of kilometre demands with respect to...

  18. 可替代产品库存模型的研究%Single-Period Two-Product Inventory Model with Reorder and Substitution

    李小申; 夏尊铨

    2008-01-01

    In market, many same or similar-characteristic products can substitute for each other, retailers usually adopt substitution strategy for more benefits, and excess demand for product can also be met by reorder. For single-period two-product inventory problem of this kind, we develop the profits maximization model with stochastic demands and proportional costs and revenues. We show that the objective function is concave and submodular, and therefore the optimal stock policy exists. We present the optimal conditions for stock quantities, and provide some properties of the optimal stock quantities. We explore the impacts of parameters on the profits and the optimal stock quantities. By comparison we prove that reorder, and adoption of the substitution strategy for special cases, can raise the profits and reduce the general stock level.%市场上,很多产品之间可相互替代,商家为了获得的更多的利润,经常会用一种产品替代另一种产品.不仅如此.某种产品缺货时,也可以重新进货以满足顾客的需求.我们从销售商的角度,讨论这两个因素对库存策略的影响,建立了这类问题有两个产品的单周期的利润最大化模型,证明了目标函数是凹的和子模的,从而问题的解是存在的,给出了最优订货量(原始库存)的必要条件,讨论了各参数对库存的影响.通过比较,证明了商家采取替代策略和允许再订货可以提高利润并且可减少库存总量.

  19. Reactive Transport Modeling of Acid Gas Generation and Condensation

    Pulvirenti et al. (2004) recently conducted a laboratory evaporation/condensation experiment on a synthetic solution of primarily calcium chloride. This solution represents one potential type of evaporated pore water at Yucca Mountain, Nevada, a site proposed for geologic storage of high-level nuclear waste. These authors reported that boiling this solution to near dryness (a concentration factor >75,000 relative to actual pore waters) leads to the generation of acid condensate (pH 4.5) presumably due to volatilization of HCl (and minor HF and/or HNO3). To investigate the various processes taking place, including boiling, gas transport, and condensation, their experiment was simulated by modifying an existing multicomponent and multiphase reactive transport code (TOUGHREACT). This code was extended with a Pitzer ion-interaction model to deal with high ionic strength. The model of the experiment was set-up to capture the observed increase in boiling temperature (143 C at ∼1 bar) resulting from high concentrations of dissolved salts (up to 8 m CaCl2). The computed HCI fugacity (∼ 10-4 bars) generated by boiling under these conditions is not sufficient to lower the pH of the condensate (cooled to 80 and 25 C) down to observed values unless the H2O mass fraction in gas is reduced below ∼10%. This is because the condensate becomes progressively diluted by H2O gas condensation. However, when the system is modeled to remove water vapor, the computed pH of instantaneous condensates decreases to ∼1.7, consistent with the experiment (Figure 1). The results also show that the HCl fugacity increases, and calcite, gypsum, sylvite, halite, MgCl24H2O and CaCl2 precipitate sequentially with increasing concentration factors

  20. Mechanistic aspects of ligand substitution on cis- diaqua-chloro-tris-(dimethyl sulfoxide)-ruthenium (II) complex by some amino acids in aqueous medium

    The kinetics of the interaction between cis-(RuCl (Me2 SO)3(H2O)2)+ and some selected amino acids such as glycine (L1H). L-value (L2H) and L-leucine (L3H) have been studied spectrophotometrically as a function (substrate complex), (ligand) and temperature at a particular pH (5.0), where the substrate complex exists predominantly as a diaqua species (in aqueous solution) and ligands as the zwitter ions. The reactions were found to proceed via two distinct consecutive steps: first one is (ligand) dependent but the second is (ligand) independent. The rate constants for the processes are: k1∼10-3 s-1 and k2∼10-5 s-1. The activation parameters, calculated from Eyring plots suggest an associative mode of activation for the interactions. From the temperature dependence of the outer sphere association equilibrium constants, the thermodynamic parameters were also calculated, which gives a negative ΔG0 value at all temperatures studied, supporting the spontaneous formation of an outer sphere association complex. (author)

  1. A single amino acid substitution in isozyme GST mu in Triclabendazole resistant Fasciola hepatica (Sligo strain) can substantially influence the manifestation of anthelmintic resistance.

    Fernández, V; Estein, S; Ortiz, P; Luchessi, P; Solana, V; Solana, H

    2015-12-01

    The helminth parasite Fasciola hepatica causes fascioliasis in human and domestic ruminants. Economic losses due to this infection are estimated in U$S 2000-3000 million yearly. The most common method of control is the use of anthelmintic drugs. However, there is an increased concern about the growing appearance of F. hepatica resistance to Triclabendazole (TCBZ), an anthelmintic with activity over adult and young flukes. F. hepatica has eight Glutathione S-Transferase (GST) isozymes, which are enzymes involved in the detoxification of a wide range of substrates through chemical conjugation with glutathione. In the present work we identified and characterized the GST mu gene isolated from the TCBZ-susceptible and TCBZ-resistant F. hepatica strains. Total RNA was transcribed into cDNA by reverse transcription and a 657 bp amplicon corresponding to the GST mu gene was obtained. The comparative genetic analysis of the GST mu gene of the TCBZ susceptible strain (Cullompton) and TCBZ resistant strain (Sligo) showed three nucleotide changes and one amino acid change at position 143 in the GST mu isozyme of the TCBZ-resistant strain. These results have potential relevance as they contribute better understand the mechanisms that generate resistance to anthelmintics. PMID:26542261

  2. Currency Substitution and Government Revenue from Inflation Currency Substitution and Government Revenue from Inflation

    C. Luis Ramírez-Rojas

    1986-03-01

    Full Text Available Currency Substitution and Government Revenue from Inflation The purpose of this paper is to show that in the case of an open economy the calculations of revenue-maximing rates of inflation have been made using a restrictive model that assumes that domestic residents can only substitute between domestic money and goods (and real assets. The paper demonstrates that once the effects of currency substitution, so common in developing countries, are taken into account, the inflation rate that maximizes the proceeds of the inflation tax can be quite lower than would be the case when currency substitution is ignored.

  3. Itaconic acid production from glycerol using Escherichia coli harboring a random synonymous codon-substituted 5'-coding region variant of the cadA gene.

    Jeon, Ho-Geun; Cheong, Dae-Eun; Han, Yunjon; Song, Jae Jun; Choi, Jong Hyun

    2016-07-01

    Aspergillus terreus cadA, encoding cis-aconitate decarboxylase, is an essential gene for itaconic acid (IA) biosynthesis, but it is primarily expressed as insoluble aggregates in most industrial hosts. This has been a hurdle for the development of recombinant strategies for IA production. Here, we created a library of synonymous codon variants (scv) of the cadA gene containing synonymous codons in the first 10 codons (except ATG) and screened it in Escherichia coli. Among positive clones, E. coli scvCadA_No8 showed more than 95% of expressed CadA in the soluble fraction, and in production runs, produced threefold more IA than wild-type E. coli in Luria-Bertani broth supplemented with 0.5% glucose. In M9 minimal media containing 0.85 g/L citrate and 1% glycerol, E. coli scvCadA_No8 produced 985.6 ± 33.4 mg/L IA during a 72-h culture after induction with isopropyl β-D-1-thiogalactopyranoside. In a 2-L fed-batch fermentation consisting of two stages (growth and nitrogen limitation conditions), we obtained 7.2 g/L IA by using E. coli by introducing only the scv_cadA gene and optimizing culture conditions for IA production. These results could be combined with metabolic engineering and generate an E. coli strain as an industrial IA producer. Biotechnol. Bioeng. 2016;113: 1504-1510. © 2015 Wiley Periodicals, Inc. PMID:26704570

  4. Research of three-dimensional model for acid fracturing and optimum design for the treatments

    Guo, J.; Li, Y.; Zhao, J. [Southwest Petroleum Inst., Nanchong, Sichuan (China); Luo, J. [Hade District of Tarim Oilfield (China)

    2004-07-01

    Natural fractures and cavities are prevalent in carbonate reservoirs which are primary mediums for storage or flowing hydrocarbons. The critical factors controlling well stimulation include the fracture length and conductivity. Several field practices have confirmed the feasibility of acid fracturing as a well stimulation method. Acid fracturing improves communication between natural fractures and cavities. This study accurately simulated the acid-etched fracture length and in-situ conductivity. A model for acid transport in fractures was developed based on the following assumptions: (1) acid flows along fractures in 3D stable laminar flow, (2) acid cannot be compressed, (3) fractures are filled with acid during acid flow, and (4) fracture boundaries are impermeable. The design technique was applied to a gas well in a dolomite gas field in a calcareous reservoir of the Tahe oilfield in China. The productivity of the acid fractured wells was significantly improved. 7 refs., 4 tabs., 13 figs.

  5. Diverse models for the prediction of CDK4 inhibitory activity of substituted 4-aminomethylene isoquinoline-1, 3-diones

    Monika Gupta; A K Madan

    2013-05-01

    In the present study, both classification and correlation approaches have been successfully employed for development of models for the prediction of CDK4 inhibitory activity using a dataset comprising of 52 analogues of 4-aminomethylene isoquinoline-1,3-(2,4)-dione. Decision tree, random forest, moving average analysis (MAA), multiple linear regression (MLR), partial least square regression (PLSR) and principal component regression (PCR) were used to develop models for prediction of CDK4 inhibitory activity. The statistical significance of models was assessed through specificity, sensitivity, overall accuracy, Mathew’s correlation coefficient (MCC), cross validated correlation coefficient, test, 2 for external test set (pred_r2), coefficient of correlation of predicted dataset (pred_r2Se) and intercorrelation analysis. High accuracy of prediction offers proposed models a vast potential for providing lead structures for the development of potent therapeutic agents for CDK4 inhibition.

  6. Antitrypanosomal Activities of Fluoroquinolones with Pyrrolidinyl Substitutions

    Nenortas, Elizabeth; Kulikowicz, Tomasz; Burri, Christian; Shapiro, Theresa A.

    2003-01-01

    Fluoroquinolones with pyrrolidinyl substitutions were tested against Trypanosoma brucei and mammalian cells. Bulky substituents at C-7 or a 1-2-bridging thiazolidine ring increased antitrypanosomal activity and selective toxicity. These compounds trap protein-DNA complexes and inhibit nucleic acid biosynthesis in trypanosomes, characteristics of topoisomerase II inhibition.

  7. Complexation of metal ions with humic acid: metal ion charge neutralization model

    The humic acid complexation reaction presented in this work is based on the concept of metal ion charge neutralization upon complexation to humic acid functional groups. Experimental results from the complexation of UO22+, Am3+, and Cm3+ with humic acids of different origin are presented to demonstrate and validate the proposed model. By introducing the operational humic acid concentration and the loading capacity, the complexation constants are derived, which are independent of the metal ion concentration, pH, and origin of humic acid. The loading capacity is an operational term needed for the intercomparison of stability constants and is the mole fraction of the maximum available complexing sites of humic acid under a given set of experimental conditions. The metal ion charge neutralization model adequately describes the thermodynamic equilibrium reaction of metal ions with humic acid and allows a direct application of the resulting stability constants for geochemical modeling of actinide migration at an environmentally relevant pH. (orig.)

  8. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    2010-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  9. Substitution of glutamine for lysine at the pyridoxal phosphate binding site of bacterial D-amino acid transaminase. Effects of exogenous amines on the slow formation of intermediates.

    Futaki, S; Ueno, H; Martinez del Pozo, A; Pospischil, M A; Manning, J M; Ringe, D; Stoddard, B; Tanizawa, K; Yoshimura, T; Soda, K

    1990-12-25

    In bacterial D-amino acid transaminase, Lys-145, which binds the coenzyme pyridoxal 5'-phosphate in Schiff base linkage, was changed to Gln-145 by site-directed mutagenesis (K145Q). The mutant enzyme had 0.015% the activity of the wild-type enzyme and was capable of forming a Schiff base with D-alanine; this external aldimine was formed over a period of minutes depending upon the D-alanine concentration. The transformation of the pyridoxal-5'-phosphate form of the enzyme to the pyridoxamine-5'-phosphate form (i.e. the half-reaction of transamination) occurred over a period of hours with this mutant enzyme. Thus, information on these two steps in the reaction and on the factors that influence them can readily be obtained with this mutant enzyme. In contrast, these reactions with the wild-type enzyme occur at much faster rates and are not easily studied separately. The mutant enzyme shows distinct preference for D- over L-alanine as substrates but it does so about 50-fold less effectively than the wild-type enzyme. Thus, Lys-145 probably acts in concert with the coenzyme and other functional side chain(s) to lead to efficient and stereochemically precise transamination in the wild-type enzyme. The addition of exogenous amines, ethanolamine or methyl amine, increased the rate of external aldimine formation with D-alanine and the mutant enzyme but the subsequent transformation to the pyridoxamine-5'-phosphate form of the enzyme was unaffected by exogenous amines. The wild-type enzyme displayed a large negative trough in the circular dichroic spectrum at 420 nm, which was practically absent in the mutant enzyme. However, addition of D-alanine to the mutant enzyme generated this negative Cotton effect (due to formation of the external aldimine with D-alanine). This circular dichroism band gradually collapsed in parallel with the transformation to the pyridoxamine-5'-phosphate enzyme. Further studies on this mutant enzyme, which displays the characteristics of the wild

  10. Control of Chemical Risks by Substitution of Harmful Substances

    Jacobsen, Thomas

    1997-01-01

    Substitution of volatile, organic solvents with non-volatile, low-toxic esters of fatty acids for cleaning purposes in offset printing has successfully been implemented in several European countries. Similar substitutions in other industrial cleaning processes seem possible, especially regarding ...

  11. An efficient synthesis of substituted benzene-1,2-dicarboxaldehydes

    ZHU Peter C; WANG Dei-Haw; LU Kaitao; MANI Neelakandha

    2007-01-01

    Substituted-benzene-1,2-dicarbaldehydes were synthesized by the reaction of substituted-1,2-bis (dibromomethyl) benzenes with fuming sulfuric acid, followed by hydrolysis, The yields were significantly improved by introducing solid sodium bicarbonate into the reaction mixture before hydrolysis and workup.

  12. An efficient synthesis of substituted benzene-1,2-dicarboxaldehydes

    ZHU; Peter; C; WANG; Der-Haw; MANI; Neelakandha

    2007-01-01

    Substituted-benzene-1,2-dicarbaldehydes were synthesized by the reaction of substituted-1,2-bis(dibromomethyl) benzenes with fuming sulfuric acid,followed by hydrolysis. The yields were signifi-cantly improved by introducing solid sodium bicarbonate into the reaction mixture before hydrolysis and workup.

  13. Cobham's theorem for substitutions

    Durand, Fabien

    2010-01-01

    The seminal theorem of Cobham has given rise during the last 40 years to a lot of works around non-standard numeration systems and has been extended to many contexts. In this paper, as a result of fifteen years of improvements, we obtain a complete and general version for the so-called substitutive sequences. Let $\\alpha$ and $\\beta$ be two multiplicatively independent Perron numbers. Then, a sequence $x\\in A^\\mathbb{N}$, where $A$ is a finite alphabet, is both $\\alpha$-substitutive and $\\beta$-substitutive if and only if $x$ is ultimately periodic.

  14. d-Amino Acid Substitution of Peptide-Mediated NF-κB Suppression in mdx Mice Preserves Therapeutic Benefit in Skeletal Muscle, but Causes Kidney Toxicity

    Reay, Daniel P.; Bastacky, Sheldon I; Wack, Kathryn E; Stolz, Donna B.; Paul D Robbins; Clemens, Paula R

    2015-01-01

    In Duchenne muscular dystrophy (DMD) patients and the mdx mouse model of DMD, chronic activation of the classical nuclear factor-κB (NF-κB) pathway contributes to the pathogenesis that causes degeneration of muscle fibers, inflammation and fibrosis. Prior studies demonstrate that inhibition of inhibitor of κB kinase (IKK)-mediated NF-κB activation using l-isomer NF-κB essential modulator (NEMO)-binding domain (NBD) peptide-based approaches reduce muscle pathology in the mdx mouse. For our stu...

  15. Modeling acidic sites in zeolites and aluminosilicates by aluminosilsesquioxanes

    Duchateau, R; Harmsen, RJ; Abbenhuis, HCL; van Santen, RA; Meetsma, A; Thiele, SKH; Kranenburg, M

    1999-01-01

    Protolysis of alkylaluminum compounds with silsesquioxanes is an efficient procedure to synthesize both Lewis and Bronsted acidic aluminosilsesquioxanes. Treatment of AlEt3 with (c-C5H9)(7)Si7O9(OH)(3) and (c-C5H9)(7)Si7O9(OSiMe3)(OH)(2) gives the corresponding Lewis acidic aluminosilsesquioxanes, {

  16. Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage

    Yang, Ziheng; Nielsen, Rasmus

    2008-01-01

    to affect the estimation of sequence distances (such as the synonymous rate d(S), the nonsynonymous rate d(N), and the rate at the 4-fold degenerate sites d(4)), as found in previous studies, but the new models produced very similar estimates to some old ones. We also develop a likelihood ratio test...

  17. Electricity/oil substitution

    The extent to which electricity could substitute for imported oil in Canada is assessed and it is concluded that the bulk of projected oil imports could be displaced. This substitution of electricity for oil could be largely completed within two decades, with existing technology, using Canadian resources. The substitution of electricity for imported oil would result in relatively low energy costs and would stimulate economic growth. Energy self-sufficiency through the substitution of electricity for oil is uniquely a Canadian option; it is not open to other industrial countries. The option exists because of Canada's resources of oil sands for essential liquid fuels, hydraulic and nuclear electrical potential, and natural gas as an interim source of energy. While other countries face an energy crisis due to declining supplies of oil, Canada faces opportunities. The policies of Federal and Provincial governments, as perceived by individual decision makers, will have a major influence on Canada's ability to realize opportunities. (auth)

  18. Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy

    The neoplasms incidence has increased significantly in recent years and continued population growth and aging will increase the statistics of this illness in the world's diseases. The cancer treatment usually consists in individual or combined use of chemotherapy, surgery and radiotherapy depending on the etiology of the tumor. In cases where radiotherapy is used in addition to the therapeutic effects of radiation, specific complications can occur, and in the skin, these complications can be present with a clinical expression ranging from erythema to radionecrosis, and this latter being the adverse effect with greater severity. The radionecrosis treatment consists in debridement necrotic areas and covering the surgical wounds. Autologous grafts are most commonly used for this covering, however when large areas are affected, allografts can be used for occlusive treatment and the keratinocytes and adipose derived stem cells (ADSC) addition becomes an alternative, due to the knowing for immunomodulatory and regenerative response. For that reason, aiming to simulate the radionecrosis adverse effects, an animal model of induced cutaneous radionecrosis was created, in athymic mouse Nude (Nu/Nu), for developing regenerative therapies based on human dermal-epidermal substitutes containing keratinocytes and ADSC, which proved occlusive as an efficient treatment, furthermore, having this radionecrosis animal model established, new possibilities for treatment of diseases involving dermal regeneration, can be tested. (author)

  19. Applicability of cranial models in urethane resin and foam as a substitute for bone: are synthetic materials reliable?

    Muccino, Enrico; Porta, Davide; Magli, Francesca; Cigada, Alfredo; Sala, Remo; Gibelli, Daniele; Cattaneo, Cristina

    2013-09-01

    As literature is poor in functional synthetic cranial models, in this study, synthetic handmade models of cranial vaults were produced in two different materials (a urethane resin and a self-hardening foam), from multiple bone specimens (eight original cranial vaults: four human and four swine), in order to test their resemblance to bone structure in behavior, during fracture formation. All the vaults were mechanically tested with a 2-kg impact weight and filmed with a high-speed camera. Fracture patterns were homogeneous in all swine vaults and heterogeneous in human vaults, with resin fractures more similar to bone fractures. Mean fracture latency time extrapolated by videos were of 0.75 msec (bone), 1.5 msec (resin), 5.12 msec (foam) for human vaults and of 0.625 msec (bone), 1.87 msec (resin), 3.75 msec (foam) for swine vaults. These data showed that resin models are more similar to bone than foam reproductions, but that synthetic material may behave quite differently from bone as concerns fracture latency times. PMID:23865474

  20. Force Field Modeling of Amino Acid Conformational Energies.

    Kaminský, Jakub; Jensen, Frank

    2007-09-01

    The conformational degrees of freedom for four amino acids in a model peptide environment have been sampled with density functional and second-order Møller-Plesset methods. Geometries have been optimized with an augmented double-ζ basis set and relative energies estimated by extrapolation of results using double, triple, and quadruple-ζ basis sets and including higher order correlation effects. In addition, the effects of vibrational zero point energies and solvation have been considered. The density functional method is unable to locate all the minima found at the MP2 level, which most likely is due to the inability for describing dispersion interactions. The use of basis sets smaller than augmented polarized double-ζ with the MP2 method may also in some cases lead to artifacts. The effects on relative energies by enlarging the basis set beyond an augmented triple-ζ and including higher order correlation beyond MP2 is small. The MP2/aug-cc-pVTZ level is recommended as a level of theory capable of an accuracy of ∼1 kJ/mol for relative conformational energies. Eight different force fields are tested for reproducing the electronic structure reference data. Force fields that represent the electrostatic energy by fixed partial charges typically only account for half of the conformations, while the AMOEBA force field, which includes multipole moments and polarizability, can reproduce ∼80% of the conformations in terms of geometry. This not only suggests that multipole moments and polarizability are important factors in designing new force fields but also indicates that there is still room for improvements. PMID:26627621

  1. Modeling gallic acid production rate by empirical and statistical analysis

    Bratati Kar

    2000-01-01

    Full Text Available For predicting the rate of enzymatic reaction empirical correlation based on the experimental results obtained under various operating conditions have been developed. Models represent both the activation as well as deactivation conditions of enzymatic hydrolysis and the results have been analyzed by analysis of variance (ANOVA. The tannase activity was found maximum at incubation time 5 min, reaction temperature 40ºC, pH 4.0, initial enzyme concentration 0.12 v/v, initial substrate concentration 0.42 mg/ml, ionic strength 0.2 M and under these optimal conditions, the maximum rate of gallic acid production was 33.49 mumoles/ml/min.Para predizer a taxa das reações enzimaticas uma correlação empírica baseada nos resultados experimentais foi desenvolvida. Os modelos representam a ativação e a desativativação da hydrolise enzimatica. Os resultados foram avaliados pela análise de variança (ANOVA. A atividade máxima da tannase foi obtida após 5 minutos de incubação, temperatura 40ºC, pH 4,0, concentração inicial da enzima de 0,12 v/v, concentração inicial do substrato 0,42 mg/ml, força iônica 0,2 M. Sob essas condições a taxa máxima de produção ácido galico foi de 33,49 µmoles/ml/min.

  2. D-Amino Acid Substitution of Peptide-Mediated NF-κB Suppression in mdx Mice Preserves Therapeutic Benefit in Skeletal Muscle, but Causes Kidney Toxicity.

    Reay, Daniel P; Bastacky, Sheldon I; Wack, Kathryn E; Stolz, Donna B; Robbins, Paul D; Clemens, Paula R

    2015-01-01

    In Duchenne muscular dystrophy (DMD) patients and the mdx mouse model of DMD, chronic activation of the classical nuclear factor-κB (NF-κB) pathway contributes to the pathogenesis that causes degeneration of muscle fibers, inflammation and fibrosis. Prior studies demonstrate that inhibition of inhibitor of κB kinase (IKK)-mediated NF-κB activation using L-isomer NF-κB essential modulator (NEMO)-binding domain (NBD) peptide-based approaches reduce muscle pathology in the mdx mouse. For our studies, the NBD peptide is synthesized as a fusion peptide with an eight-lysine (8K) protein transduction domain to facilitate intracellular delivery. We hypothesized that the d-isoform peptide could have a greater effect than the naturally occurring L-isoform peptide due to the longer persistence of the D-isoform peptide in vivo. In this study, we compared systemic treatment with low (1 mg/kg) and high (10 mg/kg) doses of L- and D-isomer 8K-wild-type-NBD peptide in mdx mice. Treatment with both L- or D-isoform 8K-wild-type-NBD peptide resulted in decreased activation of NF-κB and improved histology in skeletal muscle of the mdx mouse. However, we observed kidney toxicity (characterized by proteinuria), increased serum creatinine, activation of NF-κB and pathological changes in kidney cortex that were most severe with treatment with the D-isoform of 8K-wild-type-NBD peptide. The observed toxicity was also seen in normal mice. PMID:26018805

  3. Measuring and modeling aqueous electrolyte/amino-acid solutions with ePC-SAFT

    Highlights: • Amino-acid solubilities and osmotic coefficients in ternary solutions containing one amino acids and one salt measured. • Weak salt influence on amino-acid solubilities except for salts containing Mg[2+] or NO3[−] (salting-in behavior). • Osmotic coefficients dominated by the solute with the highest molality. • Amino-acid solubilities and osmotic coefficients predicted reasonably with ePC-SAFT with deviations of 3.7% and 9.3%. • Predictions based on pure-component parameters for ions and amino acids using no ion/amino-acid fitting parameters. -- Abstract: In this work thermodynamic properties of electrolyte/amino acid/water solutions were measured and modeled. Osmotic coefficients at 298.15 K were measured by means of vapor-pressure osmometry. Amino-acid solubility at 298.15 K was determined gravimetrically. Considered aqueous systems contained one of the four amino acids: glycine, L-/DL-alanine, L-/DL-valine, and L-proline up to the respective amino-acid solubility limit and one of 13 salts composed of the ions Li+, Na+, K+, NH4+, Cl−, Br−, I−, NO3−, and SO42− at salt molalities of 0.5, 1.0, and 3.0 mol · kg−1, respectively. The data show that the salt influence is more pronounced on osmotic coefficients than on amino-acid solubility. The electrolyte Perturbed-Chain Statistical Association Theory (ePC-SAFT) was applied to model thermodynamic properties in aqueous electrolyte/amino-acid solutions. In previous works, this model had been applied to binary salt/water and binary amino acid/water systems. Without fitting any additional parameters, osmotic coefficients and amino-acid solubility in the ternary electrolyte/amino acid/water systems could be predicted with overall deviations of 3.7% and 9.3%, respectively, compared to the experimental data

  4. Molecular Modeling of Nucleic Acid Structure: Energy and Sampling

    Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E.

    2001-01-01

    An overview of computer simulation techniques as applied to nucleic acid systems is presented. This unit discusses methods used to treat the energy and to sample representative configurations. Emphasis is placed on molecular mechanics and empirical force fields.

  5. SYNTHESIS AND ANTITUBERCULAR ACTIVITY OF SOME SUBSTITUTED 2, 3-SUBSTITUTED QUINAZOLINONE ANALOGS

    S. Rajasekaran*, Gopalkrishna Rao and H.S. Niranjan

    2012-01-01

    Full Text Available In recent years, there is a tremendous increase of drug resistant pathogens, leading to the design and development of newer antitubercular agents. A series of 2-(substituted-phenyl-1,3-benzoxazin-4-ones and 3-amino-2-(substituted-phenylquinazolin-4(3H-ones were synthesized by the reaction of substituted benzoyl chloride with anthranilic acid and 2- (substituted phenyl-1,3-benzoxazin-4-one with hydrazine hydrate in absolute alcohol respectively. The title compounds 2-substituted phenyl-3-(thiophen-2-ylmethyleneamino quinazolin-4(3H-ones and 2-(substituted phenyl-3-(1-(furan-2-ylethylideneamino quinazolin-4(3H-ones were obtained by reacting 3-amino-2-(substituted phenyl quinazolin-4(3H-one with thiophene-2-carboxaldehyde and 2-acetyl furan respectively. The title compounds have been characterized by UV, IR, 1H-NMR and Mass spectra. The synthesized compounds have been evaluated for their antitubercular activity. Few of the compounds exhibited significant antitubercular while other compounds showed moderate activity.

  6. ESR, electrochemical, molecular modeling and biological evaluation of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones as potential anti- Trypanosoma cruzi agents

    Aguilera-Venegas, Benjamín; Olea-Azar, Claudio; Norambuena, Ester; Arán, Vicente J.; Mendizábal, Fernando; Lapier, Michel; Maya, Juan Diego; Kemmerling, Ulrike; López-Muñoz, Rodrigo

    2011-03-01

    Electrochemical and ESR studies were carried out in this work with the aim of characterizing the reduction mechanisms of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones by means of cyclic voltammetry in DMSO as aprotic solvent. Two reduction mechanisms were found for these compounds: the first, for compounds bearing a labile hydrogen by following a self-protonation mechanism (ECE steps), and the second, for compounds without labile hydrogen, based on a purely electrochemical reduction mechanism (typical of nitroheterocycles). The electrochemical results were corroborated using ESR spectroscopy allowing us to propose the hyperfine splitting pattern of the nitro-radical, which was later corroborated by the ESR simulation spectra. All these compounds were assayed as growth inhibitors against Trypanosoma cruzi: first, on the non-proliferative (and infective) form of the parasite (trypomastigote stage), and then, the ones that displayed activity, were assayed on the non-infective form (epimastigote stage). Thus, we found four new compounds highly active against T. cruzi. Finally, molecular modeling studies suggest the inhibition of the trypanothione reductase like one of the possible mechanisms involved in the trypanocidal action.

  7. Bone Regeneration Using a Mixture of Silicon-Substituted Coral HA and β-TCP in a Rat Calvarial Bone Defect Model

    Jiyeon Roh

    2016-02-01

    Full Text Available The demand of bone graft materials has been increasing. Among various origins of bone graft materials, natural coral composed of up to 99% calcium carbonate was chosen and converted into hydroxyapatite (HA; silicon was then substituted into the HA. Then, the Si-HA was mixed with β-tricalcium phosphate (TCP in the ratios 100:0 (S100T0, 70:30 (S70T30, 60:40 (S60T40, and 50:50 (S50T50. The materials were implanted for four and eight weeks in a rat calvarial bone defect model (8 mm. The MBCPTM (HA:β-TCP = 60:40, Biomatalante, Vigneux de Bretagne, France was used as a control. After euthanasia, the bone tissue was analyzed by making histological slides. From the results, S60T40 showed the fastest bone regeneration in four weeks (p < 0.05. In addition, S60T40, S50T50, and MBCPTM showed significant new bone formation in eight weeks (p < 0.05. In conclusion, Si-HA/TCP showed potential as a bone graft material.

  8. Understanding E2 versus SN2 Competition under Acidic and Basic Conditions

    Wolters, Lando P.; Ren, Yi; Bickelhaupt, F. Matthias

    2014-01-01

    Our purpose is to understand the mechanism through which pH affects the competition between base-induced elimination and substitution. To this end, we have quantum chemically investigated the competition between elimination and substitution pathways in H2O+C2H5OH2 + and OH−+C2H5OH, that is, two related model systems that represent, in a generic manner, the same reaction under acidic and basic conditions, respectively. We find that substitution is favored in the acidic case while elimination p...

  9. Numerical modeling of Gondwana coal seams in India as coalbed methane reservoirs substituted for carbon dioxide sequestration

    India has recently witnessed the production of coalbed methane (CBM) on a commercial scale. The analysis of Garg and Shukla (2009) summarizes that initial carbon dioxide storage opportunities should be ventured in CBM sector where the effective cost of the process is partly lowered due to enhanced recovery of methane. This research work was carried out to understand and establish the technical feasibility of CO2 driven enhanced CBM recovery in Indian coals. A regional scale underground coal seam/block was modeled using a commercial reservoir simulator, COMET3. It was found that approximately 218 Mm3 of CO2 can be sequestered in place of 74 Mm3 of CH4 produced from the chosen dimensions of coal block. The changes in fracture gas saturation, matrix CO2 concentration and matrix CH4 concentration with space and time were monitored. Eventually, the numerical values for peak saturation at certain time intervals have been reported. This study is an initial technical estimate for CO2 driven ECBM (enhanced coalbed methane) at a regional scale in India. The results are expected to prove useful not only to reduce India's contribution to greenhouse gases emission into the atmosphere but also to partially meet with the growing energy demand by enhanced recovery of methane from deep, unminable coal seams. -- Highlights: ► Critical numerical simulation of storage of CO2 in coal vis-à-vis capture of natural gas. ► Approximately 218 Mm3 of CO2 can be sequestered in the chosen dimensions of Gondwana coal block. ► A total of 74 Mm3 of CH4 can be produced for the period of study (4000 days). ► Monitoring matrix gas saturation, fracture CO2-CBM saturation with space and time. ► A brief review on possible CO2 sinks in India.

  10. Effects of caffeic acid on learning deficits in a model of Alzheimer's disease.

    Wang, Yunliang; Wang, Yutong; Li, Jinfeng; Hua, Linlin; Han, Bing; Zhang, Yuzhen; Yang, Xiaopeng; Zeng, Zhilei; Bai, Hongying; Yin, Honglei; Lou, Jiyu

    2016-09-01

    Caffeic acid is a type of phenolic acid and organic acid. It is found in food (such as tomatoes, carrots, strawberries, blueberries and wheat), beverages (such as wine, tea, coffee and apple juice) as well as Chinese herbal medicines. In the present study, we examined the effects of caffeic acid on learning deficits in a rat model of Alzheimer's disease (AD). The rats were randomly divided into three groups: i) control group, ii) AD model group and iii) caffeic acid group. Caffeic acid significantly rescued learning deficits and increased cognitive function in the rats with AD as demonstrated by the Morris water maze task. Furthermore, caffeic acid administration resulted in a significant decrease in acetylcholinesterase activity and nitrite generation in the rats with AD compared with the AD model group. Furthermore, caffeic acid suppressed oxidative stress, inflammation, nuclear factor‑κB‑p65 protein expression and caspase‑3 activity as well as regulating the protein expression of p53 and phosphorylated (p-)p38 MAPK expression in the rats with AD. These experimental results indicate that the beneficial effects of caffeic acid on learning deficits in a model of AD were due to the suppression of oxidative stress and inflammation through the p38 MAPK signaling pathway. PMID:27430591

  11. Identification of Critical Amino Acids Conferring Lethality in VopK, a Type III Effector Protein of Vibrio cholerae: Lessons from Yeast Model System.

    Leela Krishna Bankapalli

    Full Text Available VopK, a type III effector protein, has been implicated in the pathogenesis of Vibrio cholerae strains belonging to diverse serogroups. Ectopic expression of this protein exhibits strong toxicity in yeast model system. In order to map critical residues in VopK, we scanned the primary sequence guided by available data on various toxins and effector proteins. Our in silico analysis of VopK indicated the presence of predicted MCF1-SHE (SHxxxE serine peptidase domain at the C-terminus region of the protein. Substitution of each of the predicted catalytic triad residues namely Ser314, His353 and Glu357 with alanine resulted in recombinant VopK proteins varying in lethality as evaluated in yeast model system. We observed that replacement of glutamate357 to alanine causes complete loss in toxicity while substitutions of serine314 and histidine353 with alanine exhibited partial loss in toxicity without affecting the stability of variants. In addition, replacement of another conserved serine residue at position 354 (S354 within predicted S314H353E357 did not affect toxicity of VopK. In essence, combined in silico and site directed mutagenesis, we have identified critical amino acids contributing to the lethal activity of VopK in yeast model system.

  12. Potential protein post-translational modifications and find potential single amino acid substitutions in hepatitis B large envelope protein Posibles modificaciones postranslacionales y sustituciones de un solo aminoácido en la proteína grande de la superficie del virus de la hepatitis B

    V Wiwanitkit

    2008-01-01

    Post-translational modifications of proteins control many biological processes. This is also important process in virus including hepatitis B. However, there is no in-depth study on the whole hepatitis B virus large envelope protein. In this work, potential protein post-translational modifications in hepatitis B virus large envelope protein were determined by a standard bioinformatics technique. Furthermore, potential single amino acid substitutions in hepatitis B large envelope protein were ...

  13. Ozonolysis mechanism of lignin model compounds and microbial treatment of organic acids produced.

    Nakamura, Y; Daidai, M; Kobayashi, F

    2004-01-01

    Treatment methods comprising ozonolysis and microbial treatment of lignin discharged from the pulp manufacture industries were investigated by using a sulfite pulp wastewater and a lignin model compound, i.e. sodium lignosulfonate. Dynamic behaviors for the formations of intermediate derivatives such as muconic acid, maleic acid, and oxalic acid produced from the ozonolysis of sulfite pulp wastewater were observed from data of UV absorption at 280 nm by a spectrophotometer and at 210 nm by high performance liquid chromatography. The microorganisms that were isolated by the enrichment culture method were used to degrade the organic acids such as oxalic acid and acetic acid. Time courses of biological degradation of these organic acids indicated diauxic growth, which was found in a culture with mixed substrates. In the treatment of sodium lignosulfonate, the ozonolysis and microbial treatment using activated sludge converted sodium lignosulfonate into carbon dioxide and water almost completely. PMID:15461411

  14. LAT-1 activity of meta-substituted phenylalanine and tyrosine analogs.

    Augustyn, Evan; Finke, Karissa; Zur, Arik A; Hansen, Logan; Heeren, Nathan; Chien, Huan-Chieh; Lin, Lawrence; Giacomini, Kathleen M; Colas, Claire; Schlessinger, Avner; Thomas, Allen A

    2016-06-01

    The transporter protein Large-neutral Amino Acid Transporter 1 (LAT-1, SLC7A5) is responsible for transporting amino acids such as tyrosine and phenylalanine as well as thyroid hormones, and it has been exploited as a drug delivery mechanism. Recently its role in cancer has become increasingly appreciated, as it has been found to be up-regulated in many different tumor types, and its expression levels have been correlated with prognosis. Substitution at the meta position of aromatic amino acids has been reported to increase affinity for LAT-1; however, the SAR for this position has not previously been explored. Guided by newly refined computational models of the binding site, we hypothesized that groups capable of filling a hydrophobic pocket would increase binding to LAT-1, resulting in improved substrates relative to parent amino acid. Tyrosine and phenylalanine analogs substituted at the meta position with halogens, alkyl and aryl groups were synthesized and tested in cis-inhibition and trans-stimulation cell assays to determine activity. Contrary to our initial hypothesis we found that lipophilicity was correlated with diminished substrate activity and increased inhibition of the transporter. The synthesis and SAR of meta-substituted phenylalanine and tyrosine analogs is described. PMID:27106710

  15. Site-specific time heterogeneity of the substitution process and its impact on phylogenetic inference

    Philippe Hervé

    2011-01-01

    Full Text Available Abstract Background Model violations constitute the major limitation in inferring accurate phylogenies. Characterizing properties of the data that are not being correctly handled by current models is therefore of prime importance. One of the properties of protein evolution is the variation of the relative rate of substitutions across sites and over time, the latter is the phenomenon called heterotachy. Its effect on phylogenetic inference has recently obtained considerable attention, which led to the development of new models of sequence evolution. However, thus far focus has been on the quantitative heterogeneity of the evolutionary process, thereby overlooking more qualitative variations. Results We studied the importance of variation of the site-specific amino-acid substitution process over time and its possible impact on phylogenetic inference. We used the CAT model to define an infinite mixture of substitution processes characterized by equilibrium frequencies over the twenty amino acids, a useful proxy for qualitatively estimating the evolutionary process. Using two large datasets, we show that qualitative changes in site-specific substitution properties over time occurred significantly. To test whether this unaccounted qualitative variation can lead to an erroneous phylogenetic tree, we analyzed a concatenation of mitochondrial proteins in which Cnidaria and Porifera were erroneously grouped. The progressive removal of the sites with the most heterogeneous CAT profiles across clades led to the recovery of the monophyly of Eumetazoa (Cnidaria+Bilateria, suggesting that this heterogeneity can negatively influence phylogenetic inference. Conclusion The time-heterogeneity of the amino-acid replacement process is therefore an important evolutionary aspect that should be incorporated in future models of sequence change.

  16. Geometric realizations of substitutive tilings

    Bedaride, Nicolas

    2011-01-01

    We define 2-dimensional topological substitutions. A tiling of the Euclidean plane, or of the hyperbolic plane, is substitutive if the underlying 2-complex can be obtained by iteration of a 2-dimensional topological substitution. We prove that there is no primitive substitutive tiling of the hyperbolic plane $\\mathbb{H}^2$. However, we give an example of substitutive tiling of $\\Hyp^2$ which is non-primitive.

  17. Study of a Model Humic Acid-type Polymer by Fluorescence Spectroscopy and Atomic Force Microscopy

    Marcos Antonio Piza; Nelson Consolin-Filho; Sérgio da Costa Saab; Daiana Kotra Deda; Fábio de Lima Leite; Marcilene Ferrari Barriquello; Ladislau Martin-Neto

    2012-01-01

    A model HA-type polymer of para-benzoquinone synthetic humic acid (SHA) and its complexes with copper, iron and manganese metal ions were studied using atomic force microscopy (AFM). Natural humic acids (HA) and synthetic humic acids (SHA) were examined by fluorescence spectroscopy, which indicated similarity of SHA and HA spectra. The AFM images of SHA and its complexes revealed variable morphologies, such as small spheres, aggregates and a sponge-like structure. The SHA complexes displayed ...

  18. [Delegation yes, substitution no!].

    Schroeder, A

    2014-08-01

    The aging of society leads on the one hand to increasing case numbers and on the other hand to a reduction in the number of physicians available for patient treatment. The delegation and substitution of medical duties as a tried and tested method is increasingly being recommended in order to compensate for the lack of physicians. The Berufsverband der Deutschen Urologen (BDU, Professional Association of German Urologists) supports the guiding principle of the Bundesärztekammer (Federal Medical Council) of "delegation yes, substitution no" and rejects a substitution of medical duties by non-medical academic health personnel. Against the background of the demographic changes, the increasing need for treatment and the current deficiency of junior physicians, a more extensive inclusion of well-qualified and experienced non-medical personnel by the delegation of medically responsible duties (medical scope of practice) can be an appropriate measure to maintain a good medical service in practices, hospitals and nursing homes. PMID:25047595

  19. Degradation modelling of concrete submitted to sulfuric acid attack

    Yuan, Haifeng; Dangla, Patrick; Chatellier, Patrice; Chaussadent, Thierry

    2013-01-01

    Bio-deterioration of concrete,which is very common in sewer system and waste water treatment plant, results in significant structure degradation. Normally, the process can be described by the two following steps: Biochemical reactions producing biogenic aggressive species (H2SO4 is one of the most significant biogenic acid in sewer pipes), and chemical reactions between biogenic aggressive species and cement hydration products which is responsible for concrete degradation. A reactive transpor...

  20. Saving Outweighs Substituting

    Sophia

    2007-01-01

    @@ Energy crisis has become great challenge to the whole world.As the vehicle population keeps soaring in China,effectie countermeasures should be taken timely to deal with global energy crisis.There are two ways out:one is to substitute and one is to save.

  1. A new theoretical model for the origin of amino acid homochirality

    2007-01-01

    Amino acid homochirality, as a unique behavior of life, could have originated synchronously with the genetic code. In this paper, phosphoryl amino-acid -5'-nucleosides with P-N bond are postulated to be a chiral origin model in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleotide base and the amino-acid side-chain determines the stability of the particular complex, resulting in a preferred conformation associated with the chirality of amino acids. Based on the theoretical model, our experiments and calculations show that the chiral selection of the earliest amino acids for L-enantiomers seems to be a strict stereochemical/physicochemical determinism. As other amino acids developed biosynthetically from the earliest amino acids, we infer that the chirality of the later amino acids was inherited from the precursor amino acids. This idea probably goes far back in history, but it is hoped that it will be a guide for further experiments in this area.

  2. Coarse-Grained Modeling of Nucleic Acids Using Anisotropic Gay-Berne and Electric Multipole Potentials.

    Li, Guohui; Shen, Hujun; Zhang, Dinglin; Li, Yan; Wang, Honglei

    2016-02-01

    In this work, we attempt to apply a coarse-grained (CG) model, which is based on anisotropic Gay-Berne and electric multipole (EMP) potentials, to the modeling of nucleic acids. First, a comparison has been made between the CG and atomistic models (AMBER point-charge model) in the modeling of DNA and RNA hairpin structures. The CG results have demonstrated a good quality in maintaining the nucleic acid hairpin structures, in reproducing the dynamics of backbone atoms of nucleic acids, and in describing the hydrogen-bonding interactions between nucleic acid base pairs. Second, the CG and atomistic AMBER models yield comparable results in modeling double-stranded DNA and RNA molecules. It is encouraging that our CG model is capable of reproducing many elastic features of nucleic acid base pairs in terms of the distributions of the interbase pair step parameters (such as shift, slide, tilt, and twist) and the intrabase pair parameters (such as buckle, propeller, shear, and stretch). Finally, The GBEMP model has shown a promising ability to predict the melting temperatures of DNA duplexes with different lengths. PMID:26717419

  3. Acidification of Forest Soils: A Model for Analyzing Impacts of Acidic Deposition in Europe - Version II

    Kauppi, P.; Kaemaeri, J.; Posch, M; Kauppi, L.; Matzner, E.

    1985-01-01

    Acidification is an unfavorable process in forest soils. Timber logging, natural accumulation of biomass in the ecosystem, and acidic deposition are sources of acidification. Acidification causes a risk of damage to plant roots and a subsequent risk of a decline in ecosystem productivity. A dynamic model is introduced for describing the acidification of forest soils. In one-year time steps the model calculates the soil pH as function of acid stress and the buffer mechanisms of the soil. ...

  4. Acidification of Forest Soils: Model Development and Application for Analyzing Impacts of Acidic Deposition in Europe

    P. E. Kauppi; KÀmÀri, J.; Posch, M; Kauppi, L.; Matzner, E.

    1984-01-01

    Acidification is considered as an unfavorable process in forest soils. Timber logging, natural accumulation of biomass in the ecosystem, and acidic deposition are known as sources of acidification. Acidification causes the risk of damage to plant roots and subsequent risk of a decline in ecosystem productivity. A dynamic model is introduced for describing the acidification of forest soils. In one-year time steps the model calculates the soil pH as function of the acid stress and the buff...

  5. MODELING THE FERMENTATIVE PRODUCTION OF L-GLUTAMIC ACID BY CORYNEBACTERIUM GLUTAMICUM IN A BATCH BIOREACTOR

    N. S. Khan

    2013-01-01

    Full Text Available The fermentation kinetics of L-glutamic acid by Corynebacterium glutamicum was studied in a batch bioreactor. Mathematical model using the logistic equation for growth, Leudeking-Piret kinetic equation for product formation and Leudeking-Piret like equation for substrate consumption was proposed. Based on the analysis of experimental data followed by computer simulation, the model seemed to provide a reasonable description for L-glutamic acid fermentation.

  6. A dynamic mechanistic model of lactic acid metabolism in the rumen

    Mills, J.A.N.; Crompton, L.A.; Ellis, J.L.; Dijkstra, J.; Bannink, A.; Hook, S.E.; Benchaar, C.; France, J.

    2014-01-01

    Current feed evaluation systems for ruminants are too imprecise to describe diets in terms of their acidosis risk. The dynamic mechanistic model described herein arises from the integration of a lactic acid (La) metabolism module into an extant model of whole-rumen function. The model was evaluated

  7. Towards metagenome-scale models for industrial applications-the case of Lactic Acid Bacteria

    Branco Dos Santos, F.; Vos, de W.M.; Teusink, B.

    2013-01-01

    We review the uses and limitations of modelling approaches that are in use in the field of Lactic Acid Bacteria (LAB). We describe recent developments in model construction and computational methods, starting from application of such models to monocultures. However, since most applications in food b

  8. An Electron Spin Resonance Study of Stearic Acid Interactions in Model Wheat Starch and Gluten Systems

    Pearce, L. E.; Davis, E. A.; Gordon, J.; Miller, W. G.

    1987-01-01

    Electron spin resonance (ESR) was used to examine interactions of 16- Doxyl stearic acid in wheat starch-water (starch:water "'1: 1), vital wheat gluten-water and glut en-starch-water model systems, Immobilization of the 16-Doxyl stearic acid, shown by broadIine ESR powder patterns , occurred in wheat starch model systems. In contrast to the starch systems, 16-Doxylstearic acid in gluten-water systems did not display broad line powder patterns. Broadened 3- line ESR spectra were recorded for ...

  9. The geochemical model of neutral and acidic thermal water in the Tatun Volcano Group, Taiwan

    Tsai, Y.; Kuo, C.; Liu, C.

    2013-12-01

    The geochemical model can provide a quantitative method for water-rock interaction and understand the processes of neutralization of initially acidic water. The Tatun Volcano Group (TVG) is one of the Quaternary volcanoes of northern Taiwan. In the Southern Sulfur River of the TVG, it has neutral and acidic thermal water that can provide good materials for modeling the flow path of acidic and neutral thermal water. This study collects 7 thermal springs and identifies into two types, which are neutral and acidic thermal water. The host rock of neutral thermal water has fresh andesitic rock and is weak fumaroles, and the field observations of acidic thermal waters have been alternated andesitic rock and strong degassing fumaroles. The Geochemist's Workbench software (GWB) can model the processes of neutralization of initially acidic water. Furthermore, this study will collect the meteoric water, thermal springs, and country rock along the Southern Sulfur River and use the GWB software to model the processes of neutralization of initially acidic water in the Southern Sulfur River in the future.

  10. Capacity of DNA Data Embedding Under Substitution Mutations

    Balado, Félix

    2011-01-01

    A number of methods have been proposed over the last decade for encoding information using deoxyribonucleic acid (DNA), giving rise to the emerging area of DNA data embedding. Since a DNA sequence is conceptually equivalent to a sequence of quaternary symbols (bases), DNA data embedding (diversely called DNA watermarking or DNA steganography) can be seen as a digital communications problem where channel errors are tantamount to mutations of DNA bases. Depending on the use of coding or noncoding DNA hosts, which, respectively, denote DNA segments that can or cannot be translated into proteins, DNA data embedding is essentially a problem of communications with or without side information at the encoder. In this paper the Shannon capacity of DNA data embedding is obtained for the case in which DNA sequences are subject to substitution mutations modelled using the Kimura model from molecular evolution studies. Inferences are also drawn with respect to the biological implications of some of the results presented.

  11. Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids

    Conti, Paola; De Amici, Marco; Grazioso, Giovanni;

    2005-01-01

    The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis of two pairs of enantiomers, which were subsequently resolved by enzymatic procedures. These four stereoisomers and the four...... stereoisomers of the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, and (-)-3 were tested at ionotropic and metabotropic glutamate receptor subtypes. The most potent NMDA receptor antagonists [(+)-2, (-)-4, and (+)-5] showed a significant...... derivatives showed high antagonist potency with preference for the NR2A and NR2B subtypes, with derivative (-)-4 behaving as the most potent antagonist. The biological data are discussed on the basis of homology models reported in the literature for NMDA receptors and mGluRs....

  12. Some studies on the radiation-induced strand break of deoxyribonucleic acid (DNA) systems. I. polyinosinic acid model system

    In this study the model system polyinosinic acid(poly I) was investigated. A successful attempt was made to change the multi-stranded nature of this compound to single-stranded molecules. For this purpose the thermal treatment at 75 degree C for about ten minutes at PH between 7 and 8 was found to be the nest method for achieving this goal. Furthermore, it was possible to change to single-stranded molecules in absence of salt (KCl). The gamma-irradiation of poly I resulted in a non-significant change in the molecular weight, however,post-irradiation re denaturation gave rise to a marked change. The G-values were calculated for the single strand breaks of polyinosinic acid (G(ssb))

  13. A single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein renders simian-human immunodeficiency virus (SHIVKU-1bMC33) susceptible to rimantadine

    Previous studies from our laboratory have shown that the transmembrane domain (TM) of the Vpu protein of human immunodeficiency virus type 1 (HIV-1) contributes to the pathogenesis of SHIVKU-1bMC33 in macaques and that the TM domain of Vpu could be replaced with the M2 protein viroporin from influenza A virus. Recently, we showed that the replacement of the TM domain of Vpu with that of the M2 protein of influenza A virus resulted in a virus (SHIVM2) that was sensitive to rimantadine [Hout, D.R., Gomez, M.L., Pacyniak, E., Gomez, L.M., Inbody, S.H., Mulcahy, E.R., Culley, N., Pinson, D.M., Powers, M.F., Wong, S.W., Stephens, E.B., 2006. Substitution of the transmembrane domain of Vpu in simian human immunodeficiency virus (SHIVKU-1bMC33) with that of M2 of influenza A results in a virus that is sensitive to inhibitors of the M2 ion channel and is pathogenic for pig-tailed macaques. Virology 344, 541-558]. Based on previous studies of the M2 protein which have shown that the His-X-X-X-Trp motif within the M2 is essential to the function of the M2 proton channel, we have constructed a novel SHIV in which the alanine at position 19 of the TM domain was replaced with a histidine residue resulting in the motif His-Ile-Leu-Val-Trp. The SHIVVpuA19H replicated with similar kinetics as the parental SHIVKU-1bMC33 and pulse-chase analysis revealed that the processing of viral proteins was similar to SHIVKU-1bMC33. This SHIVVpuA19H virus was found to be more sensitive to the M2 ion channel blocker rimantadine than SHIVM2. Electron microscopic examination of SHIVVpuA19H-infected cells treated with rimantadine revealed an accumulation of viral particles at the cell surface and within intracellular vesicles, which was similar to that previously observed to SHIVM2-infected cells treated with rimantadine. These data indicate that the Vpu protein of HIV-1 can be converted into a rimantadine-sensitive ion channel with the alteration of one amino acid and provide additional evidence

  14. Parallel substitution algorithm theory and application

    Achasova, S; Markova, V; Piskunov, S

    1994-01-01

    Parallel Substitution Algorithm (PSA) is a new model for distributed (cellular) computations. It provides a concise mapping of distributed computation processes into cellular arrays. A PSA is specified by a set of parallel substitutions operating over a cellular array.Two concepts make PSA a powerful tool for modelling cellular computations: 1) naming functions which allow the specification of any type of interactions in the computation space, 2) a context which serves to represent control of a computational process in time.The foundation of PSA theory comprises validity conditions of computat

  15. Evaluation, in an animal model study, of the effect of diet composition change and diet supplementation with b-group vitamins on the liver fatty acid profile

    Zuzanna Goluch-Koniuszy

    2012-12-01

    Full Text Available Introduction. Contemporary diet of men is characterised by a significant contribution of processed and puri- fied products impoverished by technological processing in, e.g., B-group vitamins taking part in the synthesis of fatty acids. One of the means to prevent their insufficient intake is supplementation of food products with those components. Hence, an animal model study was undertaken in order to determine whether modification of diet composition in which whole-grain components (whole grains of wheat and maize are isocalorically substituted with white flour and saccharose, and its complementary supplementation with B-group vitamins may trigger changes in the profile of fatty acids synthesized in liver of rats. Material and methods. The study was conducted on 30 male rats aged 5 months. Group I was receiving the basal feed mixture (Labofed B, which contained among other things whole grains of wheat and maize. Groups II-III, in free access, were administered modified feed mixture in which 83.5% of wheat present in the basal diet was substituted with wheat flour, and 50% of maize – with saccharose. Contents of vitamin B1 , B2 ,B6  and PP and basic chemical composition in the feed mixture are determined by HPLC method and the fatty acid profile with the modified Folch method using gas chromatography. Groups I and II were receiving water to drink, whereas the animals from group III were administered 25 ml of an aqueous solution of vitamins in the following doses: B1 – 0.94 mg, B2 – 0.48 mg, B6 – 0.5 mg, PP – 1.9 mg. In group III – to supplement differences in contents of those vitamins between feed mixtures resulting from the exchange of components, which to some extent simulated the mode of supplementation in humans. Concentration of glucose was determined in blood serum and the amount of fat was determined with Soxhlet method in the dissected animals liver and the fatty acid profile with the modified Folch method using gas

  16. Surface complexation modeling of uranium (Vi) retained onto zirconium diphosphate in presence of organic acids

    In the field of nuclear waste disposal, predictions regarding radionuclide migration through the geosphere, have to take account the effects of natural organic matter. This work presents an investigation of interaction mechanisms between U (Vi) and zirconium diphosphate (ZrP2O7) in presence of organic acids (citric acid and oxalic acid). The retention reactions were previously examined using a batch equilibrium method. Previous results showed that U (Vi) retention was more efficient when citric acid or oxalic acid was present in solid surface at lower ph values. In order to determine the retention equilibria for both systems studied, a phosphorescence spectroscopy study was carried out. The experimental data were then fitted using the Constant Capacitance Model included in the FITEQL4.0 code. Previous results concerning surface characterization of ZrP2O7 (surface sites density and surface acidity constants) were used to constraint the modeling. The best fit for U (Vi)/citric acid/ZrP2O7 and U (Vi)/oxalic acid/ZrP2O7 systems considered the formation of a ternary surface complex. (Author)

  17. Modeling and optimizing the design of matrix treatments in carbonate reservoirs with self-diverting acid systems

    Application of a self-diverting-acid based on viscoelastic surfactant (SDVA) is a promising technology for improving the efficacy of acid treatment in oil and gas-bearing carbonate reservoirs. In this study, we present a mathematical model for assessing SDVA flow and reaction with carbonate rock using the SDVA rheological characteristics. The model calculates the technological parameters for acidizing operations and the prediction of well productivity after acid treatment, in addition to technical and economic optimization of the acidizing process by modeling different acid treatment options with varying volumes, injection rates, process fluids stages and initial economic scenarios

  18. Developmental nephrotoxicity of aristolochic acid in a zebrafish model

    Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ± 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.

  19. Developmental nephrotoxicity of aristolochic acid in a zebrafish model

    Ding, Yu-Ju; Chen, Yau-Hung, E-mail: yauhung@mail.tku.edu.tw

    2012-05-15

    Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ± 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.

  20. Selfdual Substitutions in Dimension One

    Berthé, Valérie; Sirvent, Victor

    2011-01-01

    There are several notions of the 'dual' of a word/tile substitution. We show that the most common ones are equivalent for substitutions in dimension one, where we restrict ourselves to the case of two letters/tiles. Furthermore, we obtain necessary and sufficient arithmetic conditions for substitutions being selfdual in this case.