40 CFR 721.6560 - Acrylic acid, polymer with substituted ethene.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Acrylic acid, polymer with substituted... Specific Chemical Substances § 721.6560 Acrylic acid, polymer with substituted ethene. (a) Chemical... as acrylic acid, polymer with substituted ethene (PMN P-91-521) is subject to reporting under this...

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzenesulfonic acid, amino... Specific Chemical Substances § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. (a) Chemical... as a benzenesulfonic acid, amino substituted phenylazo- (PMN P-95-86) is subject to reporting under...

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenesulfonic acid, amino... Specific Chemical Substances § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. (a) Chemical... as a benzenesulfonic acid, amino substituted phenylazo- (PMN P-95-86) is subject to reporting under...

Computational Design of Thermostabilizing d-Amino Acid Substitutions

PubMed Central

Rodriguez-Granillo, Agustina; Annavarapu, Srinivas; Zhang, Lei; Koder, Ronald L.; Nanda, Vikas

2012-01-01

Judicious incorporation of d-amino acids in engineered proteins confer many advantages such as preventing degradation by endogenous proteases, and designing novel structures and functions not accessible to homochiral polypeptides. Glycine to d-alanine substitutions at the carboxy-termini can stabilize α-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by d-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using d-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection of stabilizing d-amino acid mutations. Substituting a key glycine in the Trp-Cage mini-protein with d-Gln dramatically stabilizes the fold without altering the protein backbone. Stabilities of individual substitutions can be understood in terms of the balance of intramolecular forces at both the α-helix C-terminus and throughout the protein. PMID:21978298

40 CFR 721.2900 - Substituted aminobenzoic acid ester (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted aminobenzoic acid ester... Specific Chemical Substances § 721.2900 Substituted aminobenzoic acid ester (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance substituted aminobenzoic...

40 CFR 721.10032 - Acrylic acid, polymer with substituted acrylamides (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Acrylic acid, polymer with substituted... Specific Chemical Substances § 721.10032 Acrylic acid, polymer with substituted acrylamides (generic). (a... generically as acrylic acid, polymer with substituted acrylamides (PMN P-02-269) is subject to reporting under...

40 CFR 721.10032 - Acrylic acid, polymer with substituted acrylamides (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Acrylic acid, polymer with substituted... Specific Chemical Substances § 721.10032 Acrylic acid, polymer with substituted acrylamides (generic). (a... generically as acrylic acid, polymer with substituted acrylamides (PMN P-02-269) is subject to reporting under...

40 CFR 721.10032 - Acrylic acid, polymer with substituted acrylamides (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Acrylic acid, polymer with substituted... Specific Chemical Substances § 721.10032 Acrylic acid, polymer with substituted acrylamides (generic). (a... generically as acrylic acid, polymer with substituted acrylamides (PMN P-02-269) is subject to reporting under...

40 CFR 721.10032 - Acrylic acid, polymer with substituted acrylamides (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Acrylic acid, polymer with substituted... Specific Chemical Substances § 721.10032 Acrylic acid, polymer with substituted acrylamides (generic). (a... generically as acrylic acid, polymer with substituted acrylamides (PMN P-02-269) is subject to reporting under...

40 CFR 721.10032 - Acrylic acid, polymer with substituted acrylamides (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Acrylic acid, polymer with substituted... Specific Chemical Substances § 721.10032 Acrylic acid, polymer with substituted acrylamides (generic). (a... generically as acrylic acid, polymer with substituted acrylamides (PMN P-02-269) is subject to reporting under...

The tangled bank of amino acids

PubMed Central

Pollock, David D.

2016-01-01

Abstract The use of amino acid substitution matrices to model protein evolution has yielded important insights into both the evolutionary process and the properties of specific protein families. In order to make these models tractable, standard substitution matrices represent the average results of the evolutionary process rather than the underlying molecular biophysics and population genetics, treating proteins as a set of independently evolving sites rather than as an integrated biomolecular entity. With advances in computing and the increasing availability of sequence data, we now have an opportunity to move beyond current substitution matrices to more interpretable mechanistic models with greater fidelity to the evolutionary process of mutation and selection and the holistic nature of the selective constraints. As part of this endeavour, we consider how epistatic interactions induce spatial and temporal rate heterogeneity, and demonstrate how these generally ignored factors can reconcile standard substitution rate matrices and the underlying biology, allowing us to better understand the meaning of these substitution rates. Using computational simulations of protein evolution, we can demonstrate the importance of both spatial and temporal heterogeneity in modelling protein evolution. PMID:27028523

The tangled bank of amino acids.

PubMed

Goldstein, Richard A; Pollock, David D

2016-07-01

The use of amino acid substitution matrices to model protein evolution has yielded important insights into both the evolutionary process and the properties of specific protein families. In order to make these models tractable, standard substitution matrices represent the average results of the evolutionary process rather than the underlying molecular biophysics and population genetics, treating proteins as a set of independently evolving sites rather than as an integrated biomolecular entity. With advances in computing and the increasing availability of sequence data, we now have an opportunity to move beyond current substitution matrices to more interpretable mechanistic models with greater fidelity to the evolutionary process of mutation and selection and the holistic nature of the selective constraints. As part of this endeavour, we consider how epistatic interactions induce spatial and temporal rate heterogeneity, and demonstrate how these generally ignored factors can reconcile standard substitution rate matrices and the underlying biology, allowing us to better understand the meaning of these substitution rates. Using computational simulations of protein evolution, we can demonstrate the importance of both spatial and temporal heterogeneity in modelling protein evolution. © 2016 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

Amino acid substitutions in random mutagenesis libraries: lessons from analyzing 3000 mutations.

PubMed

Zhao, Jing; Frauenkron-Machedjou, Victorine Josiane; Kardashliev, Tsvetan; Ruff, Anna Joëlle; Zhu, Leilei; Bocola, Marco; Schwaneberg, Ulrich

2017-04-01

The quality of amino acid substitution patterns in random mutagenesis libraries is decisive for the success in directed evolution campaigns. In this manuscript, we provide a detailed analysis of the amino acid substitutions by analyzing 3000 mutations of three random mutagenesis libraries (1000 mutations each; epPCR with a low-mutation and a high-mutation frequency and SeSaM-Tv P/P) employing lipase A from Bacillus subtilis (bsla). A comparison of the obtained numbers of beneficial variants in the mentioned three random mutagenesis libraries with a site saturation mutagenesis (SSM) (covering the natural diversity at each amino acid position of BSLA) concludes the diversity analysis. Seventy-six percent of the SeSaM-Tv P/P-generated substitutions yield chemically different amino acid substitutions compared to 64% (epPCR-low) and 69% (epPCR-high). Unique substitutions from one amino acid to others are termed distinct amino acid substitutions. In the SeSaM-Tv P/P library, 35% of all theoretical distinct amino acid substitutions were found in the 1000 mutation library compared to 25% (epPCR-low) and 26% (epPCR-high). Thirty-six percent of distinct amino acid substitutions found in SeSaM-Tv P/P were unobtainable by epPCR-low. Comparison with the SSM library showed that epPCR-low covers 15%, epPCR-high 18%, and SeSaM-Tv P/P 21% of obtainable beneficial amino acid positions. In essence, this study provides first insights on the quality of epPCR and SeSaM-Tv P/P libraries in terms of amino acid substitutions, their chemical differences, and the number of obtainable beneficial amino acid positions.

40 CFR 721.530 - Substituted aliphatic acid halide (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted aliphatic acid halide... Specific Chemical Substances § 721.530 Substituted aliphatic acid halide (generic name). (a) Chemical... acid halide (PMN P-84-491) is subject to reporting under this section for the significant new uses...

40 CFR 721.530 - Substituted aliphatic acid halide (generic name).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted aliphatic acid halide... Specific Chemical Substances § 721.530 Substituted aliphatic acid halide (generic name). (a) Chemical... acid halide (PMN P-84-491) is subject to reporting under this section for the significant new uses...

Functionalization of Carbon Nanotubes via Electrophilic Substitution Reaction in Polyphosphoric Acid

DTIC Science & Technology

2006-07-26

1 Title of proposed research: Functionalization of Carbon Nanotubes via Electrophilic Substitution Reaction in Polyphosphoric Acid Proposer: Jong...Choi, J.-Y.; Tan, L.-S.; Baek, J.-B. “Functionalization of carbon nanotubes via electrophilic substitution reaction in polyphosphoric acid” AFOSR...2006 4. TITLE AND SUBTITLE Functionalization of carbon nanotubes via electrophilic substitution reaction in polyphosphoric acid 5a. CONTRACT

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

Effect of substitution of low linolenic acid soybean oil for hydrogenated soybean oil on fatty acid intake.

PubMed

DiRienzo, Maureen A; Astwood, James D; Petersen, Barbara J; Smith, Kim M

2006-02-01

Low linolenic acid soybean oil (LLSO) has been developed as a substitute for hydrogenated soybean oil to reduce intake of trans FA while improving stability and functionality in processed foods. We assessed the dietary impact of substitution of LLSO for hydrogenated soybean oil (HSBO) used in several food categories. All substitutions were done using an assumption of 100% market penetration. The impact of this substitution on the intake of five FA and trans FA was assessed. Substitution of LLSO for current versions of HSBO resulted in a 45% decrease in intake of trans FA. Impacts on other FA intakes were within the realm of typical dietary intakes. No decrease in intake of alpha-linolenic acid was associated with the use of LLSO in place of HSBO because LLSO substitutes for HSBO that are already low in alpha-linolenic acid.

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs.

PubMed

Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara; Lüning, Ulrich

2016-01-01

New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO 2 , NH 2 , OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine "cores" ( 3a , 3b ) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO 2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19 . Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers.

Effects of polyurethane matrices on fungal tannase and gallic acid production under solid state culture*

PubMed Central

Treviňo, Lucia; Contreras-Esquivel, Juan C.; Rodríguez-Herrera, Raul; Aguilar, Cristóbal Noé

2007-01-01

The influence of the physical structure of polyurethane matrix as a support in a solid state culture in tannase production and gallic acid accumulation by Aspergillus niger Aa-20 was evaluated. Three different polyurethane matrices were used as the support: continuous, semi-discontinuous and discontinuous. The highest tannase production at 2479.59 U/L during the first 12 h of culture was obtained using the discontinuous matrix. The gallic acid was accumulated at 7.64 g/L at the discontinuous matrix. The results show that the discontinuous matrix of polyurethane is better for tannase production and gallic acid accumulation in a solid state culture bioprocess than the continuous and semi-discontinuous matrices. PMID:17910122

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

PubMed Central

Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara

2016-01-01

New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO2, NH2, OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine “cores” (3a,3b) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19. Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers. PMID:28144293

Natural derivatives of diphenolic acid as substitutes for bisphenol-A

NASA Astrophysics Data System (ADS)

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.

40 CFR 721.10690 - Benzenedicarboxylic acid, polymer with substituted alkanediol, dodecanedioic acid, 1,2-ethanediol...

Code of Federal Regulations, 2014 CFR

2014-07-01

..., alkanediol,.alpha.-hydro-.omega.-hydroxypoly[oxyalkanediyl], 1,3-isobenzofurandione, methylene diphenyl...-ethanediol, alkanedioic acid, alkanediol,.alpha.-hydro-.omega.-hydroxypoly[oxyalkanediyl], 1,3... substituted alkanediol, dodecanedioic acid, 1,2-ethanediol, alkanedioic acid, alkanediol,.alpha.-hydro-.omega...

The synthesis and characterization of fatty acid salts of chitosan as novel matrices for prolonged intragastric drug delivery.

PubMed

Bani-Jaber, Ahmad; Hamdan, Imad; Alkawareek, Mahmoud

2012-07-01

The aim of this study was to prepare fatty acid salts of chitosan (CS) and to evaluate the salts as matrices for sustained drug release and prolonged gastric retention. CS-laurate and CS-palmitate were formed by mixing saturated CS solution and aqueous solutions of sodium laurate and sodium palmitate, respectively, and collected by centrifugation. They were characterized using Fourier-transform infrared spectroscopy and differential scanning calorimetry. Different matrices as effervescent tablets were prepared using each of these CS-salts, CS and the corresponding physical mixtures of CS and the fatty acids. Sodium bicarbonate as an effervescent agent and ranitidine HCl as a model drug were incorporated into these matrices. In vitro buoyancy and drug dissolution were studied for the matrices in 0.1 M HCl. Tablets with fatty acid salts of CS showed both rapid and prolonged buoyancy (> 8 h). Comparatively, CS tablets exhibited a short floatation period (< 2 h) and tablets were completely disintegrated within 1 h of soaking. In addition, slow and prolonged drug release was achieved from tablets of fatty acid salts of CS with average drug release of 80.1 and 71.8% for CS-laurate and CS-palmitate, respectively. Rapid drug release (> 80% at 1 h) was exhibited by tablets with CS or the physical mixtures.

40 CFR 721.9798 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenesulfonic acid, 2,2â²-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl]amino]-, sodium salt (generic). 721.9798... Substances § 721.9798 Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5...

40 CFR 721.9798 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzenesulfonic acid, 2,2â²-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl]amino]-, sodium salt (generic). 721.9798... Substances § 721.9798 Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5...

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Naphthalenedisulfonic acid, [amino... Specific Chemical Substances § 721.10107 Naphthalenedisulfonic acid, [amino-hydroxy-[(substituted)azo-sulfo... naphthalenedisulfonic acid, [amino-hydroxy-[(substituted)azo-sulfo-naphthaleneyl]azo]-hydroxy-[(methoxy-sulfophenyl)azo...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Naphthalenedisulfonic acid, [amino... Specific Chemical Substances § 721.10107 Naphthalenedisulfonic acid, [amino-hydroxy-[(substituted)azo-sulfo... naphthalenedisulfonic acid, [amino-hydroxy-[(substituted)azo-sulfo-naphthaleneyl]azo]-hydroxy-[(methoxy-sulfophenyl)azo...

Quantitative characterization of short- and long-chain perfluorinated acids in solid matrices in Shanghai, China.

PubMed

Li, Fei; Zhang, Chaojie; Qu, Yan; Chen, Jing; Chen, Ling; Liu, Ying; Zhou, Qi

2010-01-01

Perfluorinated acids (PFAs) have been recognized as emerging environmental pollutants because of their widespread occurrences, persistence, and bioaccumulative and toxicological effects. PFAs have been detected in aquatic environment and biota in China, but the occurrences of these chemicals have not been reported in solid matrices in China. In the present study, short- and long-chain PFAs (C2-C14) have been quantitatively determined in solid matrices including sediments, soils and sludge collected in Shanghai, China. The results indicate that sludge contains more PFAs than sediments and soils, and the total PFAs concentrations in sediments, soil and sludge are 62.5-276 ng g(-1), 141-237 ng g(-1) and 413-755 ng g(-1), respectively. In most cases, trifluoroacetic acid was the major PFA and accounted for 22-90% of the total PFAs. Although the levels of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) were not only lower than trifluoroacetic acid, but also lower than some short-chain PFCAs (acid are mildly phytotoxic and their higher levels in solid matrices were collected in Shanghai, China, these chemicals should be included in future environmental monitoring efforts.

Effects of tempering (annealing), acid hydrolysis, low-citric acid substitution on chemical and physicochemical properties of starches of four yam (Dioscorea spp.) cultivars.

PubMed

Falade, Kolawole O; Ayetigbo, Oluwatoyin E

2017-05-01

The effects of tempering (annealing), acid hydrolysis and low-citric acid substitution on chemical and physicochemical properties of starches of four Nigerian yam cultivars were investigated. Crude fat and protein contents of the native starches decreased significantly after the modifications, while nitrogen-free extract increased significantly with acid hydrolysis and citric acid substitution. Acid hydrolysis and low-citric acid substitution reduced the least concentration for gel formation of the starches from 4 to 2% w/v, but tempering had no effect. Swelling power of the starches reduced significantly, and water solubility increased significantly at 75 and 85 °C, especially with acid hydrolysis and low-citric acid substitution. However, tempering significantly reduced starch solubility in the four cultivars. Paste clarity of starches of white (29.17%), water (18.90%), yellow (30.90%) and bitter (10.57%) yams reduced significantly with tempering to 14.43, 11.83, 16.93 and 7.27%, but increased significantly with acid hydrolysis to 41.40, 35.37, 28.77 and 32.33%, and low-citric acid substitution to 36.60, 44.17, 50.67 and 14.33%, respectively. Pasting properties such as peak, trough, breakdown, final, and setback viscosities and peak time of native starches reduced significantly with acid hydrolysis and low-citric acid substitution, however, tempering significantly increased their pasting temperature, peak time, setback and final viscosities.

An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute.

PubMed

Su, Wen-Yu; Chen, Ko-Hua; Chen, Yu-Chun; Lee, Yen-Hsien; Tseng, Ching-Li; Lin, Feng-Huei

2011-01-01

Vitrectomy is a common procedure for treating ocular-related diseases. The surgery involves removing the vitreous humor from the center of the eye, and vitreous substitutes are needed to replace the vitreous humor after vitrectomy. In the present study, we developed a colorless, transparent and injectable hydrogel with appropriate refractive index as a vitreous substitute. The hydrogel is formed by oxidated hyaluronic acid (oxi-HA) cross-linked with adipic acid dihydrazide (ADH). Hyaluronic acid (HA) was oxidized by sodium periodate to create aldehyde functional groups, which could be cross-linked by ADH. The refractive index of this hydrogel ranged between 1.3420 and 1.3442, which is quite similar to human vitreous humor (1.3345). The degradation tests demonstrated that the hydrogel could maintain the gel matrix over 35 days, depending on the ADH concentration. In addition, the cytotoxicity was evaluated on retina pigmented epithelium (RPE) cells cultivated following the ISO standard (tests for in vitro cytotoxicity), and the hydrogel was found to be non-toxic. In a preliminary animal study, the oxi-HA/ADH hydrogel was injected into the vitreous cavity of rabbit eyes. The evaluations of slit-lamp observation, intraocular pressure, cornea thickness and histological examination showed no significant abnormal biological reactions for 3 weeks. This study suggests that the injectable oxi-HA/ADH hydrogel should be a potential vitreous substitute. Koninklijke Brill NV, Leiden, 2011

Predicting the combinatorial effects of water activity, pH and organic acids on Listeria growth in media and complex food matrices.

PubMed

Nyhan, L; Begley, M; Mutel, A; Qu, Y; Johnson, N; Callanan, M

2018-09-01

The aim of this study was to develop a model to predict growth of Listeria in complex food matrices as a function of pH, water activity and undissociated acetic and propionic acid concentration i.e. common food hurdles. Experimental growth curves of Listeria in food products and broth media were collected from ComBase, the literature and industry sources from which a bespoke secondary gamma model was constructed. Model performance was evaluated by comparing predictions to measured growth rates in growth media (BHI broth) and two adjusted food matrices (zucchini purée and béarnaise sauce). In general, observed growth rates were higher in broth than in the food matrices which resulted in the model over-estimating growth in the adjusted food matrices. In addition, model outputs were more accurate for conditions without acids, indicating that the organic acid component of the model was a source of inaccuracy. In summary, a new predictive growth model for innovating or renovating food products that rely on multi-hurdle technology was created. This study is the first to report on modelling of propionic acid as an inhibitor of Listeria in combination with other hurdles. Our findings provide valuable insights into predictive model design and performance and highlight the importance of experimental validation of models in real food matrices rather than laboratory media alone. Copyright © 2018 Elsevier Ltd. All rights reserved.

40 CFR 721.1680 - Substituted benzoic acid (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

...). 721.1680 Section 721.1680 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1680 Substituted benzoic acid (generic). (a) Chemical substance and significant new uses...

Thermally and vibrationally induced conformational isomerizations, infrared spectra, and photochemistry of gallic acid in low-temperature matrices

NASA Astrophysics Data System (ADS)

Justino, Licínia L. G.; Reva, Igor; Fausto, Rui

2016-07-01

Near-infrared (near-IR) narrowband selective vibrational excitation and annealing of gallic acid (3,4,5-trihydroxybenzoic acid) isolated in cryogenic matrices were used to induce interconversions between its most stable conformers. The isomerizations were probed by infrared spectroscopy. An extensive set of quantum chemical calculations, carried out at the DFT(B3LYP)/6-311++G(d,p) level of approximation, was used to undertake a detailed analysis of the ground state potential energy surface of the molecule. This investigation of the molecule conformational space allowed extracting mechanistic insights into the observed annealing- or near-IR-induced isomerization processes. The infrared spectra of the two most stable conformers of gallic acid in N2, Xe, and Ar matrices were fully assigned. Finally, the UV-induced photochemistry of the matrix isolated compound was investigated.

A strategy for simultaneous determination of fatty acid composition, fatty acid position, and position-specific isotope contents in triacylglycerol matrices by 13C-NMR.

PubMed

Merchak, Noelle; Silvestre, Virginie; Loquet, Denis; Rizk, Toufic; Akoka, Serge; Bejjani, Joseph

2017-01-01

Triacylglycerols, which are quasi-universal components of food matrices, consist of complex mixtures of molecules. Their site-specific 13 C content, their fatty acid profile, and their position on the glycerol moiety may significantly vary with the geographical, botanical, or animal origin of the sample. Such variables are valuable tracers for food authentication issues. The main objective of this work was to develop a new method based on a rapid and precise 13 C-NMR spectroscopy (using a polarization transfer technique) coupled with multivariate linear regression analyses in order to quantify the whole set of individual fatty acids within triacylglycerols. In this respect, olive oil samples were analyzed by means of both adiabatic 13 C-INEPT sequence and gas chromatography (GC). For each fatty acid within the studied matrix and for squalene as well, a multivariate prediction model was constructed using the deconvoluted peak areas of 13 C-INEPT spectra as predictors, and the data obtained by GC as response variables. This 13 C-NMR-based strategy, tested on olive oil, could serve as an alternative to the gas chromatographic quantification of individual fatty acids in other matrices, while providing additional compositional and isotopic information. Graphical abstract A strategy based on the multivariate linear regression of variables obtained by a rapid 13 C-NMR technique was developed for the quantification of individual fatty acids within triacylglycerol matrices. The conceived strategy was tested on olive oil.

The effect of amino acid deletions and substitutions in the longest loop of GFP

PubMed Central

Flores-Ramírez, Gabriela; Rivera, Manuel; Morales-Pablos, Alfredo; Osuna, Joel; Soberón, Xavier; Gaytán, Paul

2007-01-01

Background The effect of single and multiple amino acid substitutions in the green fluorescent protein (GFP) from Aequorea victoria has been extensively explored, yielding several proteins of diverse spectral properties. However, the role of amino acid deletions in this protein -as with most proteins- is still unknown, due to the technical difficulties involved in generating combinatorial in-phase amino acid deletions on a target region. Results In this study, the region I129-L142 of superglo GFP (sgGFP), corresponding to the longest loop of the protein and located far away from the central chromophore, was subjected to a random amino acid deletion approach, employing an in-house recently developed mutagenesis method termed Codon-Based Random Deletion (COBARDE). Only two mutants out of 16384 possible variant proteins retained fluorescence: sgGFP-Δ I129 and sgGFP-Δ D130. Interestingly, both mutants were thermosensitive and at 30°C sgGFP-Δ D130 was more fluorescent than the parent protein. In contrast with deletions, substitutions of single amino acids from residues F131 to L142 were well tolerated. The substitution analysis revealed a particular importance of residues F131, G135, I137, L138, H140 and L142 for the stability of the protein. Conclusion The behavior of GFP variants with both amino acid deletions and substitutions demonstrate that this loop is playing an important structural role in GFP folding. Some of the amino acids which tolerated any substitution but no deletion are simply acting as "spacers" to localize important residues in the protein structure. PMID:17594481

Thermally and vibrationally induced conformational isomerizations, infrared spectra, and photochemistry of gallic acid in low-temperature matrices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Justino, Licínia L. G., E-mail: liciniaj@ci.uc.pt; Reva, Igor; Fausto, Rui

2016-07-07

Near-infrared (near-IR) narrowband selective vibrational excitation and annealing of gallic acid (3,4,5-trihydroxybenzoic acid) isolated in cryogenic matrices were used to induce interconversions between its most stable conformers. The isomerizations were probed by infrared spectroscopy. An extensive set of quantum chemical calculations, carried out at the DFT(B3LYP)/6-311++G(d,p) level of approximation, was used to undertake a detailed analysis of the ground state potential energy surface of the molecule. This investigation of the molecule conformational space allowed extracting mechanistic insights into the observed annealing- or near-IR-induced isomerization processes. The infrared spectra of the two most stable conformers of gallic acid in N{sub 2},more » Xe, and Ar matrices were fully assigned. Finally, the UV-induced photochemistry of the matrix isolated compound was investigated.« less

40 CFR 721.6181 - Fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty acid, reaction product with... Specific Chemical Substances § 721.6181 Fatty acid, reaction product with substituted oxirane, formaldehyde... as fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...

40 CFR 721.6181 - Fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Fatty acid, reaction product with... Specific Chemical Substances § 721.6181 Fatty acid, reaction product with substituted oxirane, formaldehyde... as fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...

Dense tissue-like collagen matrices formed in cell-free conditions.

PubMed

Mosser, Gervaise; Anglo, Anny; Helary, Christophe; Bouligand, Yves; Giraud-Guille, Marie-Madeleine

2006-01-01

A new protocol was developed to produce dense organized collagen matrices hierarchically ordered on a large scale. It consists of a two stage process: (1) the organization of a collagen solution and (2) the stabilization of the organizations by a sol-gel transition that leads to the formation of collagen fibrils. This new protocol relies on the continuous injection of an acid-soluble collagen solution into glass microchambers. It leads to extended concentration gradients of collagen, ranging from 5 to 1000 mg/ml. The self-organization of collagen solutions into a wide array of spatial organizations was investigated. The final matrices obtained by this procedure varied in concentration, structure and density. Changes in the liquid state of the samples were followed by polarized light microscopy, and the final stabilized gel states obtained after fibrillogenesis were analyzed by both light and electron microscopy. Typical organizations extended homogeneously by up to three centimetres in one direction and several hundreds of micrometers in other directions. Fibrillogenesis of collagen solutions of high and low concentrations led to fibrils spatially arranged as has been described in bone and derm, respectively. Moreover, a relationship was revealed between the collagen concentration and the aggregation of and rotational angles between lateral fibrils. These results constitute a strong base from which to further develop highly enriched collagen matrices that could lead to substitutes that mimic connective tissues. The matrices thus obtained may also be good candidates for the study of the three-dimensional migration of cells.

ReplacementMatrix: a web server for maximum-likelihood estimation of amino acid replacement rate matrices.

PubMed

Dang, Cuong Cao; Lefort, Vincent; Le, Vinh Sy; Le, Quang Si; Gascuel, Olivier

2011-10-01

Amino acid replacement rate matrices are an essential basis of protein studies (e.g. in phylogenetics and alignment). A number of general purpose matrices have been proposed (e.g. JTT, WAG, LG) since the seminal work of Margaret Dayhoff and co-workers. However, it has been shown that matrices specific to certain protein groups (e.g. mitochondrial) or life domains (e.g. viruses) differ significantly from general average matrices, and thus perform better when applied to the data to which they are dedicated. This Web server implements the maximum-likelihood estimation procedure that was used to estimate LG, and provides a number of tools and facilities. Users upload a set of multiple protein alignments from their domain of interest and receive the resulting matrix by email, along with statistics and comparisons with other matrices. A non-parametric bootstrap is performed optionally to assess the variability of replacement rate estimates. Maximum-likelihood trees, inferred using the estimated rate matrix, are also computed optionally for each input alignment. Finely tuned procedures and up-to-date ML software (PhyML 3.0, XRATE) are combined to perform all these heavy calculations on our clusters. http://www.atgc-montpellier.fr/ReplacementMatrix/ olivier.gascuel@lirmm.fr Supplementary data are available at http://www.atgc-montpellier.fr/ReplacementMatrix/

Wide Tolerance to Amino Acids Substitutions In The OCTN1 Ergothioneine Transporter

PubMed Central

Frigeni, Marta; Iacobazzi, Francesco; Yin, Xue; Longo, Nicola

2016-01-01

Background Organic cation transporters transfer solutes with a positive charge across the plasma membrane. The novel organic cation transporter 1 (OCTN1) and 2 (OCTN2) transport ergothioneine and carnitine, respectively. Mutations in the SLC22A5 gene encoding OCTN2 cause primary carnitine deficiency, a recessive disorders resulting in low carnitine levels and defective fatty acid oxidation. Variations in the SLC22A4 gene encoding OCTN1 are associated with rheumatoid arthritis and Crohn disease. Methods Here we evaluate the functional properties of the OCTN1 transporter using chimeric transporters constructed by fusing different portion of the OCTN1 and OCTN2 cDNAs. Their relative abundance and subcellular distribution was evaluated through western blot analysis and confocal microscopy. Results Substitutions of the C-terminal portion of OCTN1 with the correspondent residues of OCTN2 generated chimeric OCTN transporters more active than wild-type OCTN1 in transporting ergothioneine. Additional single amino acid substitutions introduced in chimeric OCTN transporters further increased ergothioneine transport activity. Kinetic analysis indicated that increased transport activity was due to an increased Vmax, with modest changes in Km toward ergothioneine. Conclusions Our results indicate that the OCTN1 transporter is tolerant to extensive amino acid substitutions. This is in sharp contrast to the OCTN2 carnitine transporter that has been selected for high functional activity through evolution, with almost all substitutions reducing carnitine transport activity. General significance The widespread tolerance of OCTN1 to amino acid substitutions suggests that the corresponding SLC22A4 gene may have derived from a recent duplication of the SLC22A5 gene and might not yet have a defined physiological role. PMID:26994919

Synthesis, characterization, and subcellular localization studies of amino acid-substituted porphyrinic pigments

NASA Astrophysics Data System (ADS)

van Diggelen, Lisa; Khin, Hnin; Conner, Kip; Shao, Jenny; Sweezy, Margaretta; Jung, Anna H.; Isaac, Meden; Simonis, Ursula

2009-06-01

Stopping cancer in its path occurs when photosensitizers (PSs) induce apoptotic cell death after their exposure to light and the subsequent formation of reactive oxygen species. In pursuit of our hypothesis that mitochondrial localizing PSs will enhance the efficacy of the photosensitizing process in photodynamic therapy, since they provoke cell death by inducing apoptosis, we synthesized and characterized tetraphenylporphyrins (TPPs) that are substituted at the paraphenyl positions by two amino acids and two fluoro or hydroxyl groups, respectively. They were prepared according to the Lindsey-modified Adler-Longo methodology using trifluoromethanesulfonylchloride (CF3SO2Cl) as a catalyst instead of trifluoroacetic acid. The use of CF3SO2Cl yielded cleaner products in significantly higher yields. During the synthesis, not only the yields and work-up procedure of the TPPs were improved by using CF3SO2Cl as a catalyst, but also a better means of synthesizing the precursor dipyrromethanes was tested by using indium(III) chloride. Column chromatography, HPLC, and NMR spectroscopy were used to separate and characterize the di-amino acid-dihydroxy, or difluoro-substituted porphyrins and to ascertain their purity before subcellular localization studies were carried out. Studies using androgen-sensitive human prostate adenocarcinoma cells LNCaP revealed that certain amino acid substituted porphyrins that are positively charged in the slightly acidic medium of cancer cells are very useful in shedding light on the targets of TPPs in subcellular organelles of cancer cells. Although some of these compounds have properties of promising photosensitizers by revealing increased water solubility, acidic properties, and innate ability to provoke cell death by apoptosis, the cell killing efficacy of these TPPs is low. This correlates with their subcellular localization. The di-amino acid, di-hydroxy substituted TPPs localize mainly to the lysosomes, whereas the di-fluoro-substituted

40 CFR 721.1648 - Substituted benzenesulfonic acid salt (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1648 Substituted benzenesulfonic acid salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically...

Anaerobic biotransformation of roxarsone and related N-substituted phenylarsonic acids

USGS Publications Warehouse

Cortinas, I.; Field, J.A.; Kopplin, M.; Garbarino, J.R.; Gandolfi, A.J.; Sierra-Alvarez, R.

2006-01-01

Large quantities of arsenic are introduced into the environment through land application of poultry litter containing the organoarsenical feed additive roxarsone (3-nitro-4-hydroxyphenylarsonic acid). The objective of this study was to evaluate the bioconversion of roxarsone and related N-substituted phenylarsonic acid derivatives under anaerobic conditions. The results demonstrate that roxarsone is rapidly transformed in the absence of oxygen to the corresponding aromatic amine, 4-hydroxy-3-aminophenylarsonic acid (HAPA). The formation of HAPA is attributable to the facile reduction of the nitro group. Electron-donating substrates, such as hydrogen gas, glucose, and lactate, stimulated the rate of nitro group reduction, indicating a microbial role. During long-term incubations, HAPA and the closely related 4-aminophenylarsonic acid (4-APA) were slowly biologically eliminated by up to 99% under methanogenic and sulfate-reducing conditions, whereas little or no removal occurred in heat-killed inoculum controls. Arsenite and, to a lesser extent, arsenate were observed as products of the degradation. Freely soluble forms of the inorganic arsenical species accounted for 19-28% of the amino-substituted phenylarsonic acids removed. This constitutes the first report of a biologically catalyzed rupture of the phenylarsonic group under anaerobic conditions. ?? 2006 American Chemical Society.

Feature-based classification of amino acid substitutions outside conserved functional protein domains.

PubMed

Gemovic, Branislava; Perovic, Vladimir; Glisic, Sanja; Veljkovic, Nevena

2013-01-01

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.

40 CFR 721.5278 - Substituted naphthalenesulfonic acid, alkali salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted naphthalenesulfonic acid, alkali salt. 721.5278 Section 721.5278 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.5278...

Antimicrobial activity and stability of protonectin with D-amino acid substitutions.

PubMed

Qiu, Shuai; Zhu, Ranran; Zhao, Yanyan; An, Xiaoping; Jia, Fengjing; Peng, Jinxiu; Ma, Zelin; Zhu, Yuanyuan; Wang, Jiayi; Su, Jinhuan; Wang, Qingjun; Wang, Hailin; Li, Yuan; Wang, Kairong; Yan, Wenjin; Wang, Rui

2017-05-01

The misuse and overuse of antibiotics result in the emergence of resistant bacteria and fungi, which make an urgent need of the new antimicrobial agents. Nowadays, antimicrobial peptides have attracted great attention of researchers. However, the low physiological stability in biological system limits the application of naturally occurring antimicrobial peptides as novel therapeutics. In the present study, we synthesized derivatives of protonectin by substituting all the amino acid residues or the cationic lysine residue with the corresponding D-amino acids. Both the D-enantiomer of protonectin (D-prt) and D-Lys-protonectin (D-Lys-prt) exhibited strong antimicrobial activity against bacteria and fungi. Moreover, D-prt showed strong stability against trypsin, chymotrypsin and the human serum, while D-Lys-prt only showed strong stability against trypsin. Circular dichroism analysis revealed that D-Lys-prt still kept typical α-helical structure in the membrane mimicking environment, while D-prt showed left hand α-helical structure. In addition, propidium iodide uptake assay and bacteria and fungi killing experiments indicated that all D-amino acid substitution or partially D-amino acid substitution analogs could disrupt the integrity of membrane and lead the cell death. In summary, these findings suggested that D-prt and D-Lys-prt might be promising candidate antibiotic agents for therapeutic application against resistant bacteria and fungi infection. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Combining bar adsorptive microextraction with capillary electrophoresis--application for the determination of phenolic acids in food matrices.

PubMed

da Rosa Neng, Nuno; Sequeiros, Rute C P; Florêncio Nogueira, José Manuel

2014-09-01

In this contribution, bar adsorptive microextraction coated with a mixed-mode anion exchange/RP followed by liquid desorption was combined for the first time with a capillary electrophoresis-diode array detection system (BAμE(MAX)-LD/CE-DAD), for the determination of phenolic acids in food matrices, using chlorogenic, ferulic, cumaric, and caffeic acids as model compounds. Assays performed in aqueous media spiked at the 0.8 mg/L level yielded average recoveries up to 40% for all four phenolic acids, under optimized experimental conditions. The analytical performance showed also good precision (RSD < 15%), convenient LODs (18.0-85.0 μg/L) and linear dynamic ranges (0.8-8.0 mg/L) with convenient determination coefficients (r(2) > 0.9900). By using the standard addition method, the application to food matrices such as green tea, red fruit juice, and honey allowed very good performances for the determination of minor amounts of phenolic acids. The proposed methodology proved to be a suitable alternative for the analysis of polar to ionic compounds, showing to be easy to implement, reliable, sensitive, and requiring a low sample volume to determine phenolic acids in food samples. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

From N-triisopropylsilylpyrrole to an optically active C-4 substituted pyroglutamic acid: total synthesis of penmacric acid.

PubMed

Berini, Christophe; Pelloux-Léon, Nadia; Minassian, Frédéric; Denis, Jean-Noël

2009-11-07

The stereoselective synthesis of penmacric acid, an optically active C-4 substituted pyroglutamic acid, has been efficiently achieved through an unusual 11-step sequence starting from simple N-triisopropylsilylpyrrole. The key-steps are the initial addition of the pyrrole nucleus onto a chiral nitrone and the obtention of the pyroglutamic acid moiety by reductive hydrogenation of the pyrrole followed by oxidation of the corresponding pyrrolidine into pyrrolidinone.

Isolated glyoxylic acid-water 1:1 complexes in low temperature argon matrices.

PubMed

Lundell, Jan; Olbert-Majkut, Adriana

2015-02-05

The 1:1 hydrogen bonded complexes between glyoxylic acid (GA) and water are studied in low temperature argon matrices. Four different complex structures were found in deposited matrices. The lowest energy conformer (T1) of GA was found to form complex, where the water molecule was attached to the opposite side of the intramolecular hydrogen bond in the molecule (T1B). Interestingly, this complex was estimated to be+8.0 kJ mol(-1) higher in energy than the most stable structure (T1A), where the water is inserted into the internal hydrogen bond, and also found in solid argon but in smaller abundance. For the second-lowest energy conformer of GA (T2), the two lowest-energy complex structures were identified, with the most stable complex structure (T2A) also being the most abundant in the matrices. The difference between experiment and computational energetic order of the two complex structures of the same GA conformer is explained by contributions of deformation energy upon complexation and the effect of the environment. The computed BSSE-corrected interaction energies are for the two most stable complexes of the two GA conformers for T1A and T2A -42.11 and -45.03 kJ mol(-1), respectively, at the CCSD(T)/aug-cc-pVTZ//B3LYP/aug-cc-pVTZ level of theory. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reaction products of secondary alkyl... Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric acid... substances identified generically as reaction products of secondary alkyl amines with a substituted...

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reaction products of secondary alkyl... Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric acid... substances identified generically as reaction products of secondary alkyl amines with a substituted...

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

PubMed

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.

Combining Correlation Matrices: Simulation Analysis of Improved Fixed-Effects Methods

ERIC Educational Resources Information Center

Hafdahl, Adam R.

2007-01-01

The originally proposed multivariate meta-analysis approach for correlation matrices--analyze Pearson correlations, with each study's observed correlations replacing their population counterparts in its conditional-covariance matrix--performs poorly. Two refinements are considered: Analyze Fisher Z-transformed correlations, and substitute better…

FTIRI Parameters describing Acid Phosphate Substitution in Biologic Hydroxyapatite

PubMed Central

Spevak, Lyudmila; Flach, Carol R.; Hunter, Tracey; Mendelsohn, Richard; Boskey, Adele

2013-01-01

Acid phosphate substitution into mineralized tissue is an important determinant of their mechanical properties and their response to treatment. This study identifies and validates Fourier Transform Infrared Spectroscopic Imaging (FTIRI) spectral parameters that provide information on the acid phosphate (HPO4) substitution into hydroxyapatite in developing mineralized tissues. Curve fitting and Fourier self-deconvolution were used to identify subband positions in model compounds (with and without HPO4). The intensity of subbands at 1127 cm−1 and 1110 cm−1 correlated with the acid phosphate content in these models. Peak height ratios of these subbands to the ν3 vibration at 1096 cm−1 found in stoichiometric apatite, were evaluated in the model compounds and mixtures thereof. FTIRI spectra of bones and teeth at different developmental ages were analyzed using these spectral parameters. Factor analysis (a chemometric technique) was also conducted on the tissue samples and resulted in factor loadings with spectral features corresponding to the HPO4 vibrations described above. Images of both factor correlation coefficients and the peak height ratios 1127cm−1/1096cm−1 and 1112cm−1/1096cm−1 demonstrated higher acid phosphate content in younger vs. more mature regions in the same specimen. Maps of the distribution of acid phosphate content will be useful for characterizing the extent of new bone formation, areas of potential decreased strength, and the effects of therapies such as those used in metabolic bone diseases (osteoporosis, chronic kidney disease) on mineral composition. Because of the wider range of values obtained with the 1127 cm−1/1096 cm−1 parameter compared to the 1110 cm−1/1096 cm−1 parameter, and the smaller scatter in the slope, it is suggested that this ratio should be the parameter of choice. PMID:23380987

Evaluation of Commercially Available Cyanide Test Kits against Various Matrices

DTIC Science & Technology

2016-08-01

further evaluation in a second phase of testing. Cyantesmo paper was tested against 15 matrices, including baking soda, boric acid, brewer’s yeast...matrices were baking soda, boric acid, brewer’s yeast, chalk dust, chitin, coffee powder (instant coffee), cornstarch, drywall dust, flour, kaolin...TN);  DG powdered sugar;  DG talcum powder (Lot 14312THW);  DG Clover Valley baking soda (Lot PMHB51);  Boric acid (Lot 766965; Fisher

Advances in stir bar sorptive extraction for the determination of acidic pharmaceuticals in environmental water matrices Comparison between polyurethane and polydimethylsiloxane polymeric phases.

PubMed

Silva, Ana Rita M; Portugal, Fátima C M; Nogueira, J M F

2008-10-31

Stir bar sorptive extraction with polyurethane (PU) and polydimethylsiloxane (PDMS) polymeric phases followed by high-performance liquid chromatography with diode array detection [SBSE(PU or PDMS)/HPLC-DAD] was studied for the determination of six acidic pharmaceuticals [o-acetylsalicylic acid (ACA), ibuprofen (IBU), diclofenac sodium (DIC), naproxen (NAP), mefenamic acid (MEF) and gemfibrozil (GEM)], selected as non-steroidal acidic anti-inflammatory drugs and lipid regulators model compounds in environmental water matrices. The main parameters affecting the efficiency of the proposed methodology are fully discussed. Assays performed on 25 mL of water samples spiked at the 10 microg L(-1) level under optimized experimental conditions, yielded recoveries ranging from 45.3+/-9.0% (ACA) to 90.6+/-7.2% (IBU) by SBSE(PU) and 9.8+/-1.6% (NAP) to 73.4+/-5.0% (GEM) by SBSE(PDMS), where the former polymeric phase presented a better affinity to extract these target analytes from water matrices at the trace level. The methodology showed also excellent linear dynamic ranges for the six acidic pharmaceuticals studied, with correlation coefficients higher than 0.9976, limits of detection and quantification between 0.40-1.7 microg L(-1) and 1.5-5.8 microg L(-1), respectively, and suitable precision (RSD <15%). Moreover, the developed methodology was applied for the determination of these target analytes in several environmental matrices, including river, sea and wastewater samples, having achieved good performance and moderate matrix effects. In short, the PU foams demonstrated to be an excellent alternative for the enrichment of the more polar metabolites from water matrices by SBSE, overcoming the limitations of the conventional PDMS phase.

40 CFR 721.321 - Substituted acrylamides and acrylic acid copolymer (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.321 Substituted acrylamides and acrylic acid copolymer (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance...

Amino acid-substituted gemini surfactant-based nanoparticles as safe and versatile gene delivery agents.

PubMed

Singh, Jagbir; Yang, Peng; Michel, Deborah; Verrall, Ronald E; Foldvari, Marianna; Badea, Ildiko

2011-05-01

Gene based therapy represents an important advance in the treatment of diseases that heretofore have had either no treatment or cure. To capitalize on the true potential of gene therapy, there is a need to develop better delivery systems that can protect these therapeutic biomolecules and deliver them safely to the target sites. Recently, we have designed and developed a series of novel amino acid-substituted gemini surfactants with the general chemical formula C(12)H(25) (CH(3))(2)N(+)-(CH(2))(3)-N(AA)-(CH(2))(3)-N(+) (CH(3))(2)-C(12)H(25) (AA= glycine, lysine, glycyl-lysine and, lysyl-lysine). These compounds were synthesized and tested in rabbit epithelial cells using a model plasmid and a helper lipid. Plasmid/gemini/lipid (P/G/L) nanoparticles formulated using these novel compounds achieved higher gene expression than the nanoparticles containing the parent unsubstituted compound. In this study, we evaluated the cytotoxicity of P/G/L nanoparticles and explored the relationship between transfection efficiency/toxicity and their physicochemical characteristics (such as size, binding properties, etc.). An overall low toxicity is observed for all complexes with no significant difference among substituted and unsubstituted compounds. An interesting result revealed by the dye exclusion assay suggests a more balanced protection of the DNA by the glycine and glycyl-lysine substituted compounds. Thus, the higher transfection efficiency is attributed to the greater biocompatibility and flexibility of the amino acid/peptide-substituted gemini surfactants and demonstrates the feasibility of using amino acid-substituted gemini surfactants as gene carriers for the treatment of diseases affecting epithelial tissue.

N-Substituted carbazolyloxyacetic acids modulate Alzheimer associated gamma-secretase.

PubMed

Narlawar, Rajeshwar; Pérez Revuelta, Blanca I; Baumann, Karlheinz; Schubenel, Robert; Haass, Christian; Steiner, Harald; Schmidt, Boris

2007-01-01

N-Sulfonylated and N-alkylated carbazolyloxyacetic acids were investigated for the inhibition and modulation of the Alzheimer's disease associated gamma-secretase. The introduction of a lipophilic substituent, which may vary from arylsulfone to alkyl, turned 2-carbazolyloxyacetic acids into potent gamma-secretase modulators. This resulted in the selective reduction of Abeta(42) and an increase of the less aggregatory Abeta(38) fragment by several compounds (e.g., 7d and 8c). Introduction of an electron donating group at position 6 and 8 of N-substituted carbazolyloxyacetic acids either decreased the activity or inversed modulation. The most active compounds displayed activity on amyloid precursor protein (APP) overexpressing cell lines in the low micromolar range and little or no effect on the gamma-secretase cleavage at the epsilon-site.

Substitution of the methionine residues of calmodulin with the unnatural amino acid analogs ethionine and norleucine: biochemical and spectroscopic studies.

PubMed Central

Yuan, T.; Vogel, H. J.

1999-01-01

Calmodulin (CaM) is a 148-residue regulatory calcium-binding protein that activates a wide range of target proteins and enzymes. Calcium-saturated CaM has a bilobal structure, and each domain has an exposed hydrophobic surface region where target proteins are bound. These two "active sites" of calmodulin are remarkably rich in Met residues. Here we have biosynthetically substituted (up to 90% incorporation) the unnatural amino acids ethionine (Eth) and norleucine (Nle) for the nine Met residues of CaM. The substituted proteins bind in a calcium-dependent manner to hydrophobic matrices and a synthetic peptide, encompassing the CaM-binding domain of myosin light-chain kinase (MLCK). Infrared and circular dichroism spectroscopy show that there are essentially no changes in the secondary structure of these proteins compared to wild-type CaM (WT-CaM). One- and two-dimensional NMR studies of the Eth-CaM and Nle-CaM proteins reveal that, while the core of the proteins is relatively unaffected by the substitutions, the two hydrophobic interaction surfaces adjust to accommodate the Eth and Nle residues. Enzyme activation studies with MLCK show that Eth-CaM and Nle-CaM activate the enzyme to 90% of its maximal activity, with little changes in dissociation constant. For calcineurin only 50% activation was obtained, and the K(D) for Nle-CaM also increased 3.5-fold compared with WT-CaM. These data show that the "active site" Met residues of CaM play a distinct role in the activation of different target enzymes, in agreement with site-directed mutagenesis studies of the Met residues of CaM. PMID:10210190

A Note on Parameters of Random Substitutions by γ-Diagonal Matrices

NASA Astrophysics Data System (ADS)

Kang, Ju-Sung

Random substitutions are very useful and practical method for privacy-preserving schemes. In this paper we obtain the exact relationship between the estimation errors and three parameters used in the random substitutions, namely the privacy assurance metric γ, the total number n of data records, and the size N of transition matrix. We also demonstrate some simulations concerning the theoretical result.

Inhibition kinetics and molecular simulation of p-substituted cinnamic acid derivatives on tyrosinase.

PubMed

Cui, Yi; Hu, Yong-Hua; Yu, Feng; Zheng, Jing; Chen, Lin-Shan; Chen, Qing-Xi; Wang, Qin

2017-02-01

This study was to investigate the inhibition effects of para-substituted cinnamic acid derivatives (4-chlorocinnamic acid, 4-ethoxycinnamic acid and 4-nitrocinnamic acid) on tyrosinase catalyzing the substrates, with the purpose of elucidating the inhibition mechanism of the tested derivatives on tyrosinase by the UV-vis spectrum, fluorescence spectroscopy, copper interacting and molecular docking, respectively. The native-PAGE results showed that 4-chlorocinnamic acid (4-CCA), 4-ethoxycinnamic acid (4-ECA) and 4-nitrocinnamic acid (4-NCA) had inhibitory effects on tyrosinase. Spectrophotometric analysis used to determine the inhibition capabilities of these compounds on tyrosinase catalyzing L-tyrosine (L-Tyr) and L-3,4-Dihydroxyphenylalanine (L-DOPA) as well. The IC 50 values and inhibition constants were further determined. Moreover, quenching mechanisms of tested compounds to tyrosinase belonged to static type and a red shift on fluorescence emission peak occurred when 4-NCA added. Copper interacting and molecular docking demonstrated that 4-CCA could not bind directly to the copper, but it could interact with residues in the active center of tyrosinase. Meanwhile, 4-ECA and 4-NCA could chelate a copper ion of tyrosinase. Anti-tyrosinase activities of para-substituted cinnamic acid derivatives would lay scientific foundation for their utilization in designing of novel tyrosinase inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.

Electron-Transfer Secondary Reaction Matrices for MALDI MS Analysis of Bacteriochlorophyll a in Rhodobacter sphaeroides and Its Zinc and Copper Analogue Pigments

NASA Astrophysics Data System (ADS)

Calvano, Cosima Damiana; Ventura, Giovanni; Trotta, Massimo; Bianco, Giuliana; Cataldi, Tommaso R. I.; Palmisano, Francesco

2017-01-01

Bacteriochlorophyll a ( BChl a), a photosynthetic pigment performing the same functions of chlorophylls in plants, features a bacteriochlorin macrocycle ring (18 π electrons) with two reduced pyrrole rings along with a hydrophobic terpenoid side chain (i.e., the phytol residue). Chlorophylls analysis by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) is not so straightforward since pheophytinization (i.e., release of the central metal ion) and cleavage of the phytol-ester linkage are invariably observed by employing protonating matrices such as 2,5-dihydroxybenzoic acid, sinapinic acid, and α-cyano-4-hydroxycinnamic acid. Using BChl a from Rhodobacter sphaeroides R26 strain as a model system, different electron-transfer (ET) secondary reaction matrices, leading to the formation of almost stable radical ions in both positive ([M]+•) and negative ([M]-•) ionization modes at m/z 910.55, were evaluated. Compared with ET matrices such as trans-2-[3-(4-t-butyl-phenyl)-2-methyl-2-propenylidene]malononitrile (DCTB), 2,2':5',2''-terthiophene (TER), anthracene (ANT), and 9,10-diphenylanthracene (DP-ANT), 1,5-diaminonaphthalene (DAN) was found to provide the highest ionization yield with a negligible fragmentation. DAN also displayed excellent ionization properties for two metal ion-substituted bacteriochlorophylls, (i.e., Zn- and Cu-BChl a at m/z 950.49 and 949.49), respectively. MALDI MS/MS of both radical charged molecular species provide complementary information, thus making analyte identification more straightforward.

Thermodynamics of axial substitution and kinetics of reactions with amino acids for the paddlewheel complex tetrakis(acetato)chloridodiruthenium(II,III).

PubMed

Santos, Rodrigo L S R; van Eldik, Rudi; de Oliveira Silva, Denise

2012-06-18

The known paddlewheel, tetrakis(acetato)chloridodiruthenium(II,III), offers a versatile synthetic route to a novel class of antitumor diruthenium(II,III) metallo drugs, where the equatorial ligands are nonsteroidal anti-inflammatory carboxylates. This complex was studied here as a soluble starting prototype model for antitumor analogues to elucidate the reactivity of the [Ru(2)(CH(3)COO)(4)](+) framework. Thermodynamic studies on equilibration reactions for axial substitution of water by chloride and kinetic studies on reactions of the diaqua complexes with the amino acids glycine, cysteine, histidine, and tryptophan were performed. The standard thermodynamic reaction parameters ΔH°, ΔS°, and ΔV° were determined and showed that both of the sequential axial substitution reactions are enthalpy driven. Kinetic rate laws and rate constants were determined for the axial substitution reactions of coordinated water by the amino acids that gave the corresponding aqua(amino acid)-Ru(2) substituted species. The results revealed that the [Ru(2)(CH(3)COO)(4)](+) paddlewheel framework remained stable during the axial ligand substitution reactions and was also mostly preserved in the presence of the amino acids.

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

PubMed

Sattath, Shmuel; Elyashiv, Eyal; Kolodny, Oren; Rinott, Yosef; Sella, Guy

2011-02-10

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 of adaptation.

40 CFR 747.195 - Triethanolamine salt of a substituted organic acid.

Code of Federal Regulations, 2011 CFR

2011-07-01

... subject to this section: P-84-310, triethanolamine salt of a substituted organic acid. (b) Definitions... used in or as a metalworking fluid, which includes as one of its components P-84-310, is prohibited... metalworking fluid a product containing P-84-310 is prohibited from adding any nitrosating agent to the product...

D-amino acid substitution enhances the stability of antimicrobial peptide polybia-CP.

PubMed

Jia, Fengjing; Wang, Jiayi; Peng, Jinxiu; Zhao, Ping; Kong, Ziqing; Wang, Kairong; Yan, Wenjin; Wang, Rui

2017-10-01

With the increasing emergence of resistant microbes toward conventional antimicrobial agents, there is an urgent need for the development of antimicrobial agents with novel action mode. Antimicrobial peptides (AMPs) are believed to be one kind of ideal alternatives. However, AMPs can be easily degraded by protease, which limited their therapeutic use. In the present study, D-amino acid substitution strategy was employed to enhance the stability of polybia-CP. We investigated the stability of peptides against the degradation of trypsin and chymotrypsin by determining the antimicrobial activity or determining the HPLC profile of peptides after incubation with proteases. Our results showed that both the all D-amino acid derivative (D-CP) and partial D-lysine substitution derivative (D-lys-CP) have an improved stability against trypsin and chymotrypsin. Although D-CP takes left-hand α-helical conformation and D-lys-CP loses some α-helical content, both of the D-amino acid-substituted derivatives maintain their parental peptides' membrane active action mode. In addition, D-lys-CP showed a slight weaker antimicrobial activity than polybia-CP, but the hemolytic activity decreased greatly. These results suggest that D-CP and D-lys-CP can offer strategy to improve the property of AMPs and may be leading compounds for the development of novel antimicrobial agents. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Amino Acid Substitutions in PB1 of Avian Influenza Viruses Influence Pathogenicity and Transmissibility in Chickens

PubMed Central

Suzuki, Yasushi; Uchida, Yuko; Tanikawa, Taichiro; Maeda, Naohiro; Takemae, Nobuhiro

2014-01-01

ABSTRACT Amino acid substitutions were introduced into avian influenza virus PB1 in order to characterize the interaction between polymerase activity and pathogenicity. Previously, we used recombinant viruses containing the hemagglutinin (HA) and neuraminidase (NA) genes from the highly pathogenic avian influenza virus (HPAIV) H5N1 strain and other internal genes from two low-pathogenicity avian influenza viruses isolated from chicken and wild-bird hosts (LP and WB, respectively) to demonstrate that the pathogenicity of highly pathogenic avian influenza viruses (HPAIVs) of subtype H5N1 in chickens is regulated by the PB1 gene (Y. Uchida et al., J. Virol. 86:2686–2695, 2012, doi:http://dx.doi.org/10.1128/JVI.06374-11). In the present study, we introduced a C38Y substitution into WB PB1 and demonstrated that this substitution increased both polymerase activity in DF-1 cells in vitro and the pathogenicity of the recombinant viruses in chickens. The V14A substitution in LP PB1 reduced polymerase activity but did not affect pathogenicity in chickens. Interestingly, the V14A substitution reduced viral shedding and transmissibility. These studies demonstrate that increased polymerase activity correlates directly with enhanced pathogenicity, while decreased polymerase activity does not always correlate with pathogenicity and requires further analysis. IMPORTANCE We identified 2 novel amino acid substitutions in the avian influenza virus PB1 gene that affect the characteristics of highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype, such as viral replication and polymerase activity in vitro and pathogenicity and transmissibly in chickens. An amino acid substitution at residue 38 in PB1 directly affected pathogenicity in chickens and was associated with changes in polymerase activity in vitro. A substitution at residue 14 reduced polymerase activity in vitro, while its effects on pathogenicity and transmissibility depended on the constellation of

Classification of group B streptococci with reduced β-lactam susceptibility (GBS-RBS) based on the amino acid substitutions in PBPs.

PubMed

Kimura, Kouji; Nagano, Noriyuki; Arakawa, Yoshichika

2015-01-01

All clinical isolates of group B Streptococcus (GBS; Streptococcus agalactiae) are considered uniformly susceptible to β-lactams, including penicillins. However, GBS with reduced penicillin susceptibility (PRGBS) were first identified by our group in Japan and have also been reported from North America. PRGBS are non-susceptible to penicillin because of acquisition of amino acid substitutions near the conserved active-site motifs in PBP2X. In particular, V405A and Q557E are considered the key amino acid substitutions responsible for penicillin non-susceptibility. We revealed that in addition to the substitutions in PBP2X, an amino acid substitution in PBP1A confers high-level cephalosporin resistance in GBS. As the number of publications on GBS with reduced β-lactam susceptibility (GBS-RBS), especially PRGBS, and concomitantly the need for a systematic classification of GBS-RBS is increasing, we propose here a classification of GBS-RBS based on the amino acid substitutions in their PBPs. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluation as potential enteric delivery system with folic acid as model drug.

PubMed

Taha, M O; Aiedeh, K M; Al-Hiari, Y; Al-Khatib, H

2005-10-01

The aim of this study is to explore the potential of synthetic modifications of alginic acid as a method to enhance the stability of its complexes with divalent cations under physiological conditions. A fraction of algin's carboxylic acid moieties was substituted with thiol groups to different substitution degrees through conjugating alginate to cysteine to produce alginate-cysteine (AC) conjugates. Infrared spectrophotometry and iodometry were used to characterize the resulting polymeric conjugates in terms of structure and degree of substitution. Moreover, zinc ions were used to crosslink the resulting AC polymers. Folic acid loaded beads were prepared from Zinc-crosslinked AC polymers (AC-Zn) of different cysteine substitution degrees. The generated beads were then investigated in vitro for their capacity to modify folic acid release. AC-Zn polymeric beads resisted drug release under acidic conditions (pH 1.0). However, upon transfer to a phosphate buffer solution (pH 7.0) they released most of their contents almost immediately. This change in drug release behavior is most probably due to the sequestering of zinc cations by phosphate ions within the buffer solution to form insoluble chelates and, to a lesser extent, the ionization of the carboxylic acid and thiol moieties. Removal of zinc ions from the polymeric matrix seems to promote polymeric disintegration and subsequent drug release. A similar behavior is expected in vivo due to the presence of natural zinc sequestering agents in the intestinal fluids. AC-Zn polymers provided a novel approach for enteric drug delivery as drug release from these matrices complied with the USP specifications for enteric dosage forms.

Dermal Matrices and Bioengineered Skin Substitutes: A Critical Review of Current Options

PubMed Central

Hamdi, Moustapha; Abberton, Keren; Morrison, Wayne

2015-01-01

Background: Over recent decades, scientists and surgeons have collaborated to develop various bioengineered and synthetic products as an alternative to skin grafts. Despite the numerous articles and reviews written about dermal skin substitutes, there is no general consensus. Methods: This article reviews dermal skin scaffolds used in clinical applications and experimental settings. For scaffold evaluation, we focused on clinical and/or histological results, and conclusions are listed. Explanations for general trends were sought based on existing knowledge about tissue engineering principles and wound healing mechanisms. Results: Decellularized dermis seems to remain the best option with no other acellular scaffold being clinically proven to gain better results yet. In general, chemically cross-linked products were seen to be less effective in skin tissue engineering. Biocompatibility could be enhanced by preseeding substitutes with fibroblasts to allow some natural scaffold remodeling before product application. Conclusions: Skin substitutes are a useful tool in plastic and reconstructive surgery practices as an alternative to skin grafts. In the choice of substitute, the general plastic surgery principle of replacing like tissue with like tissue seems to be still standing, and products most resembling the natural dermal extracellular matrix should be preferred. PMID:25674365

Evaluating EDTA as a substitute for phosphoric acid-etching of enamel and dentin.

PubMed

Imbery, Terence A; Kennedy, Matthew; Janus, Charles; Moon, Peter C

2012-01-01

Matrix metalloproteinases (MMPs) are proteolytic enzymes released when dentin is acid-etched. The enzymes are capable of destroying unprotected collagen fibrils that are not encapsulated by the dentin adhesive. Chlorhexidine applied after etching inhibits the activation of released MMPs, whereas neutral ethylenediamine tetra-acetic acid (EDTA) prevents the release of MMPs. The purpose of this study was to determine if conditioning enamel and dentin with EDTA can be a substitute for treating acid-etching enamel and dentin with chlorhexidine. A column of composite resin was bonded to enamel and dentin after conditioning. Shear bond strengths were evaluated after 48 hours and after accelerated aging for three hours in 12% sodium hypochlorite. Shear bond strengths ranged from 15.6 MP a for accelerated aged EDTA enamel specimens to 26.8 MPa for dentin conditioned with EDTA and tested after 48 hours. A three-way ANOVA and a Tukey HSD test found statistically significant differences among the eight groups and the three independent variables (P < 0.05). EDTA was successfully substituted for phosphoric acid-etched enamel and dentin treated with chlorhexidine. Interactions of conditioning agent and aging were significant for dentin but not for enamel. In an effort to reduce the detrimental effects of MMPs, conditioning enamel and dentin with EDTA is an alternative to treating acid-etched dentin and enamel with chlorhexidine.

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

PubMed Central

Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

2015-01-01

ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus

Fluorescence spectroscopy of UV-MALDI matrices and implications of ionization mechanisms

NASA Astrophysics Data System (ADS)

Lin, Hou-Yu; Hsu, Hsu Chen; Lu, I.-Chung; Hsu, Kuo-Tung; Liao, Chih-Yu; Lee, Yin-Yu; Tseng, Chien-Ming; Lee, Yuan-Tseh; Ni, Chi-Kung

2014-10-01

Matrix-assisted laser desorption ionization (MALDI) has been widely used in the mass analysis of biomolecules; however, there are a lot of debates about the ionization mechanisms. Previous studies have indicated that S1-S1 annihilation might be a key process in the generation of primary ions. This study investigates S1-S1 annihilation by examining the time-resolved fluorescence spectra of 12 matrices. No S1-S1 annihilation was observed in six of these matrices (3-hydroxy-picolinic acid, 6-aza-2-thiothymine, 2,4-dihydroxy-acetophenone, 2,6-dihydroxy-acetophenone, 2,4,6-trihydroxy-acetophenone, and ferulic acid). We observed two matrix molecules reacting in an electronically excited state (S1) in five of these matrices (2,5-dihydroxybenzoic acid, α-cyano-4-hydroxycinnamic acid, 2,5-dihydroxy-acetophenone, 2,3-dihydroxybenzoic acid, and 2,6-dihydroxybenzoic acid), and S1-S1 annihilation was a possible reaction. Among these five matrices, no S1-S1 annihilation was observed for 2,3-dihydroxybenzoic acid in typical peak power region of nanosecond laser pulses in MALDI, but a very small value of reaction rate constant was observed only in the high peak power region. The excited-state lifetime of sinapinic acid was too short to determine whether the molecules reacted in an electronically excited state. No correlation was observed between the ion generation efficiency of MALDI and S1-S1 annihilation. The results indicate that the proposal of S1-S1 annihilation is unnecessary in MALDI and energy pooling model for MALDI ionization mechanism has to be modified.

Efficient synthesis of hydroxystyrenes via biocatalytic decarboxylation/deacetylation of substituted cinnamic acids by newly isolated Pantoea agglomerans strains.

PubMed

Sharma, Upendra K; Sharma, Nandini; Salwan, Richa; Kumar, Rakesh; Kasana, Ramesh C; Sinha, Arun K

2012-02-01

Decarboxylation of substituted cinnamic acids is a predominantly followed pathway for obtaining hydroxystyrenes-one of the most extensively explored bioactive compounds in the food and flavor industry (e.g. FEMA GRAS approved 4-vinylguaiacol). For this, mild and green strategies providing good yields with high product selectivity are needed. Two newly isolated bacterial strains, i.e. Pantoea agglomerans KJLPB4 and P. agglomerans KJPB2, are reported for mild and effective decarboxylation of substituted cinnamic acids into corresponding hydroxystyrenes. Key operational parameters for the process, such as incubation temperature, incubation time, substrate concentration and effect of co-solvent, were optimized using ferulic acid as a model substrate. With strain KJLPB4, 1.51 g L⁻¹ 4-vinyl guaiacol (98% yield) was selectively obtained from 2 g L⁻¹ ferulic acid at 28 °C after 48 h incubation. However, KJPB2 provided vanillic acid in 85% yield after 72 h following the oxidative decarboxylation pathway. In addition, KJLPB4 was effectively exploited for the deacetylation of acetylated α-phenylcinnamic acids, providing corresponding compounds in 65-95% yields. Two newly isolated microbial strains are reported for the mild and selective decarboxylation of substituted cinnamic acids into hydroxystyrenes. Preparative-scale synthesis of vinyl guaiacol and utilization of renewable feedstock (ferulic acid extracted from maize bran) have been demonstrated to enhance the practical utility of the process. Copyright © 2011 Society of Chemical Industry.

Cell-Adhesive Matrices Composed of RGD Peptide-Displaying M13 Bacteriophage/Poly(lactic-co-glycolic acid) Nanofibers Beneficial to Myoblast Differentiation.

PubMed

Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Kim, Chuntae; Hong, Suck Won; Oh, Jin Woo; Han, Dong-Wook

2015-10-01

Recently, there has been considerable effort to develop suitable scaffolds for tissue engineering applications. Cell adhesion is a prerequisite for cells to survive. In nature, the extracellular matrix (ECM) plays this role. Therefore, an ideal scaffold should be structurally similar to the natural ECM and have biocompatibility and biodegradability. In addition, the scaffold should have biofunctionality, which provides the potent ability to enhance the cellular behaviors, such as adhesion, proliferation and differentiation. This study concentrates on fabricating cell-adhesive matrices composed of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) nanofibers. Long rod-shaped M13 bacteriophages are non-toxic and can express many desired proteins on their surface. A genetically engineered M13 phage was constructed to display RGD peptides on its surface. PLGA is a biodegradable polymer with excellent biocompatibility and suitable physicochemical property for adhesive matrices. In this study, RGD-M13 phage/PLGA hybrid nanofiber matrices were fabricated by electrospinning. The physicochemical properties of these matrices were characterized by scanning electron microscopy, atomic force microscopy, Raman spectroscopy, and contact angle measurement. In addition, the cellular behaviors, such as the initial attachment, proliferation and differentiation, were analyzed by a CCK-8 assay and immunofluorescence staining to evaluate the potential application of these matrices to tissue engineering scaffolds. The RGD-M13 phage/PLGA nanofiber matrices could enhance the cellular behaviors and promote the differentiation of C2C12 myoblasts. These results suggest that the RGD-M13 phage/PLGA nanofiber matrices are beneficial to myoblast differentiation and can serve as effective tissue engineering scaffolds.

Synthesis and stereochemical analysis of β-nitromethane substituted γ-amino acids and peptides.

PubMed

Ganesh Kumar, Mothukuri; Mali, Sachitanand M; Gopi, Hosahudya N

2013-02-07

The high diastereoselectivity in the Michael addition of nitromethane to α,β-unsaturated γ-amino esters, crystal conformations of β-nitromethane substituted γ-amino acids and peptides are studied. Results suggest that the N-Boc protected amide NH, conformations of α,β-unsaturated γ-amino esters and alkyl side chains play a crucial role in dictating the high diastereoselectivity of nitromethane addition to E-vinylogous amino esters. Investigation of the crystal conformations of both α,β-unsaturated γ-amino esters and the Michael addition products suggests that an H-C(γ)-C(β)=C(α) eclipsed conformer of the unsaturated amino ester leads to the major (anti) product compared to that of an N-C(γ)-C(β)=C(α) eclipsed conformer. The major diastereomers were separated and subjected to the peptide synthesis. The single crystal analysis of the dipeptide containing β-nitromethane substituted γ-amino acids reveals a helical type of folded conformation with an isolated H-bond involving a nine-atom pseudocycle.

Synthesis of ω-Oxo Amino Acids and trans-5-Substituted Proline Derivatives Using Cross-Metathesis of Unsaturated Amino Acids.

PubMed

Salih, Nabaz; Adams, Harry; Jackson, Richard F W

2016-09-16

A range of 7-oxo, 8-oxo, and 9-oxo amino acids, analogues of 8-oxo-2-aminodecanoic acid, one of the key components of the cyclic tetrapeptide apicidin, have been prepared by a three-step process involving copper-catalyzed allylation of serine-, aspartic acid-, and glutamic acid-derived organozinc reagents, followed by cross-metathesis of the resulting terminal alkenes with unsaturated ketones and hydrogenation. The intermediate 7-oxo-5-enones underwent a highly diastereoselective (dr ≥96:4) acid-catalyzed aza-Michael reaction to give trans-2,5-disubstituted pyrrolidines, 5-substituted proline derivatives. The aza-Michael reaction was first observed when the starting enones were allowed to stand in solution in deuterochloroform but can be efficiently promoted by catalytic amounts of dry HCl.

Fluorescence spectroscopy of UV-MALDI matrices and implications of ionization mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Hou-Yu; Hsu, Hsu Chen; Lu, I-Chung

2014-10-28

Matrix-assisted laser desorption ionization (MALDI) has been widely used in the mass analysis of biomolecules; however, there are a lot of debates about the ionization mechanisms. Previous studies have indicated that S{sub 1}-S{sub 1} annihilation might be a key process in the generation of primary ions. This study investigates S{sub 1}-S{sub 1} annihilation by examining the time-resolved fluorescence spectra of 12 matrices. No S{sub 1}-S{sub 1} annihilation was observed in six of these matrices (3-hydroxy-picolinic acid, 6-aza-2-thiothymine, 2,4-dihydroxy-acetophenone, 2,6-dihydroxy-acetophenone, 2,4,6-trihydroxy-acetophenone, and ferulic acid). We observed two matrix molecules reacting in an electronically excited state (S{sub 1}) in five of thesemore » matrices (2,5-dihydroxybenzoic acid, α-cyano-4-hydroxycinnamic acid, 2,5-dihydroxy-acetophenone, 2,3-dihydroxybenzoic acid, and 2,6-dihydroxybenzoic acid), and S{sub 1}-S{sub 1} annihilation was a possible reaction. Among these five matrices, no S{sub 1}-S{sub 1} annihilation was observed for 2,3-dihydroxybenzoic acid in typical peak power region of nanosecond laser pulses in MALDI, but a very small value of reaction rate constant was observed only in the high peak power region. The excited-state lifetime of sinapinic acid was too short to determine whether the molecules reacted in an electronically excited state. No correlation was observed between the ion generation efficiency of MALDI and S{sub 1}-S{sub 1} annihilation. The results indicate that the proposal of S{sub 1}-S{sub 1} annihilation is unnecessary in MALDI and energy pooling model for MALDI ionization mechanism has to be modified.« less

Determination of gamma-aminobutyric acid in food matrices by isotope dilution hydrophilic interaction chromatography coupled to mass spectrometry.

PubMed

Zazzeroni, Raniero; Homan, Andrew; Thain, Emma

2009-08-01

The estimation of the dietary intake of gamma-aminobutyric acid (GABA) is dependent upon the knowledge of its concentration values in food matrices. To this end, an isotope dilution liquid chromatography-mass spectrometry method has been developed employing the hydrophilic interaction chromatography technique for analyte separation. This approach enabled accurate quantification of GABA in apple, potato, soybeans, and orange juice without the need of a pre- or post-column derivatization reaction. A selective and precise analytical measurement has been obtained with a triple quadrupole mass spectrometer operating in multiple reaction monitoring using the method of standard additions and GABA-d(6) as an internal standard. The concentrations of GABA found in the matrices tested are 7 microg/g of apple, 342 microg/g of potatoes, 211 microg/g of soybeans, and 344 microg/mL of orange juice.

Nucleophilic Aromatic Substitution.

ERIC Educational Resources Information Center

Avila, Walter B.; And Others

1990-01-01

Described is a microscale organic chemistry experiment which demonstrates one feasible route in preparing ortho-substituted benzoic acids and provides an example of nucleophilic aromatic substitution chemistry. Experimental procedures and instructor notes for this activity are provided. (CW)

2-Aminobenzamide and 2-Aminobenzoic Acid as New MALDI Matrices Inducing Radical Mediated In-Source Decay of Peptides and Proteins

NASA Astrophysics Data System (ADS)

Smargiasso, Nicolas; Quinton, Loic; de Pauw, Edwin

2012-03-01

One of the mechanisms leading to MALDI in-source decay (MALDI ISD) is the transfer of hydrogen radicals to analytes upon laser irradiation. Analytes such as peptides or proteins may undergo ISD and this method can therefore be exploited for top-down sequencing. When performed on peptides, radical-induced ISD results in production of c- and z-ions, as also found in ETD and ECD activation. Here, we describe two new compounds which, when used as MALDI matrices, are able to efficiently induce ISD of peptides and proteins: 2-aminobenzamide and 2-aminobenzoic acid. In-source reduction of the disulfide bridge containing peptide Calcitonin further confirmed the radicalar mechanism of the ISD process. ISD of peptides led, in addition to c- and z-ions, to the generation of a-, x-, and y-ions both in positive and in negative ion modes. Finally, good sequence coverage was obtained for the sequencing of myoglobin (17 kDa protein), confirming the effectiveness of both 2-aminobenzamide and 2-aminobenzoic acid as MALDI ISD matrices.

2-Aminobenzamide and 2-aminobenzoic acid as new MALDI matrices inducing radical mediated in-source decay of peptides and proteins.

PubMed

Smargiasso, Nicolas; Quinton, Loic; De Pauw, Edwin

2012-03-01

One of the mechanisms leading to MALDI in-source decay (MALDI ISD) is the transfer of hydrogen radicals to analytes upon laser irradiation. Analytes such as peptides or proteins may undergo ISD and this method can therefore be exploited for top-down sequencing. When performed on peptides, radical-induced ISD results in production of c- and z-ions, as also found in ETD and ECD activation. Here, we describe two new compounds which, when used as MALDI matrices, are able to efficiently induce ISD of peptides and proteins: 2-aminobenzamide and 2-aminobenzoic acid. In-source reduction of the disulfide bridge containing peptide Calcitonin further confirmed the radicalar mechanism of the ISD process. ISD of peptides led, in addition to c- and z-ions, to the generation of a-, x-, and y-ions both in positive and in negative ion modes. Finally, good sequence coverage was obtained for the sequencing of myoglobin (17 kDa protein), confirming the effectiveness of both 2-aminobenzamide and 2-aminobenzoic acid as MALDI ISD matrices.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 themore » 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.« less

40 CFR 721.5262 - 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[substituted] amino]-1,3,5-triazin-2-yl]amino]-4...

Code of Federal Regulations, 2011 CFR

2011-07-01

... identified generically as 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[substituted] amino]-1,3,5-triazin-2... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[substituted] amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(1-sulfo-2-naphthalenyl)azo...

40 CFR 721.5262 - 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[substituted] amino]-1,3,5-triazin-2-yl]amino]-4...

Code of Federal Regulations, 2010 CFR

2010-07-01

... identified generically as 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[substituted] amino]-1,3,5-triazin-2... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[substituted] amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(1-sulfo-2-naphthalenyl)azo...

Identification by random forest method of HLA class I amino acid substitutions associated with lower survival at day 100 in unrelated donor hematopoietic cell transplantation.

PubMed

Marino, S R; Lin, S; Maiers, M; Haagenson, M; Spellman, S; Klein, J P; Binkowski, T A; Lee, S J; van Besien, K

2012-02-01

The identification of important amino acid substitutions associated with low survival in hematopoietic cell transplantation (HCT) is hampered by the large number of observed substitutions compared with the small number of patients available for analysis. Random forest analysis is designed to address these limitations. We studied 2107 HCT recipients with good or intermediate risk hematological malignancies to identify HLA class I amino acid substitutions associated with reduced survival at day 100 post transplant. Random forest analysis and traditional univariate and multivariate analyses were used. Random forest analysis identified amino acid substitutions in 33 positions that were associated with reduced 100 day survival, including HLA-A 9, 43, 62, 63, 76, 77, 95, 97, 114, 116, 152, 156, 166 and 167; HLA-B 97, 109, 116 and 156; and HLA-C 6, 9, 11, 14, 21, 66, 77, 80, 95, 97, 99, 116, 156, 163 and 173. In all 13 had been previously reported by other investigators using classical biostatistical approaches. Using the same data set, traditional multivariate logistic regression identified only five amino acid substitutions associated with lower day 100 survival. Random forest analysis is a novel statistical methodology for analysis of HLA mismatching and outcome studies, capable of identifying important amino acid substitutions missed by other methods.

Amino Acid Substitution in Trichophyton rubrum Squalene Epoxidase Associated with Resistance to Terbinafine

PubMed Central

Osborne, Colin S.; Leitner, Ingrid; Favre, Bertrand; Ryder, Neil S.

2005-01-01

There has only been one clinically confirmed case of terbinafine resistance in dermatophytes, where six sequential Trichophyton rubrum isolates from the same patient were found to be resistant to terbinafine and cross-resistant to other squalene epoxidase (SE) inhibitors. Microsomal SE activity from these resistant isolates was insensitive to terbinafine, suggesting a target-based mechanism of resistance (B. Favre, M. Ghannoum, and N. S. Ryder, Med. Mycol. 42:525-529, 2004). In this study, we have characterized at the molecular level the cause of the resistant phenotype of these clinical isolates. Cloning and sequencing of the SE gene and cDNA from T. rubrum revealed the presence of an intron in the gene and an open reading frame encoding a protein of 489 residues, with an equivalent similarity (57%) to both yeast and mammalian SEs. The nucleotide sequences of SE from two terbinafine-susceptible strains were identical whereas those of terbinafine-resistant strains, serially isolated from the same patient, each contained the same single missense introducing the amino acid substitution L393F. Introduction of the corresponding substitution in the Candida albicans SE gene (L398F) and expression of this gene in Saccharomyces cerevisiae conferred a resistant phenotype to the transformants when compared to those expressing the wild-type sequence. Terbinafine resistance in these T. rubrum clinical isolates appears to be due to a single amino acid substitution in SE. PMID:15980358

Cork-based activated carbons as supported adsorbent materials for trace level analysis of ibuprofen and clofibric acid in environmental and biological matrices.

PubMed

Neng, N R; Mestre, A S; Carvalho, A P; Nogueira, J M F

2011-09-16

In this contribution, powdered activated carbons (ACs) from cork waste were supported for bar adsorptive micro-extraction (BAμE), as novel adsorbent phases for the analysis of polar compounds. By combining this approach with liquid desorption followed by high performance liquid chromatography with diode array detection (BAμE(AC)-LD/HPLC-DAD), good analytical performance was achieved using clofibric acid (CLOF) and ibuprofen (IBU) model compounds in environmental and biological matrices. Assays performed on 30 mL water samples spiked at the 25.0 μg L(-1) level yielded recoveries around 80% for CLOF and 95% for IBU, under optimized experimental conditions. The ACs textural and surface chemistry properties were correlated with the results obtained. The analytical performance showed good precision (<15%), suitable detection limits (0.24 and 0.78 μg L(-1) for CLOF and IBU, respectively) and good linear dynamic ranges (r(2)>0.9922) from 1.0 to 600.0 μg L(-1). By using the standard addition methodology, the application of the present approach to environmental water and urine matrices allowed remarkable performance at the trace level. The proposed methodology proved to be a viable alternative for acidic pharmaceuticals analysis, showing to be easy to implement, reliable, sensitive and requiring low sample volume to monitor these priority compounds in environmental and biological matrices. Copyright © 2011 Elsevier B.V. All rights reserved.

Fourier transform infrared spectroscopic imaging parameters describing acid phosphate substitution in biologic hydroxyapatite.

PubMed

Spevak, Lyudmila; Flach, Carol R; Hunter, Tracey; Mendelsohn, Richard; Boskey, Adele

2013-05-01

Acid phosphate substitution into mineralized tissues is an important determinant of their mechanical properties and their response to treatment. This study identifies and validates Fourier transform infrared spectroscopic imaging (FTIRI) spectral parameters that provide information on the acid phosphate (HPO4) substitution into hydroxyapatite in developing mineralized tissues. Curve fitting and Fourier self-deconvolution were used to identify subband positions in model compounds (with and without HPO4). The intensity of subbands at 1127 and 1110 cm(-1) correlated with the acid phosphate content in these models. Peak height ratios of these subbands to the ν3 vibration at 1096 cm(-1) found in stoichiometric apatite were evaluated in the model compounds and mixtures thereof. FTIRI spectra of bones and teeth at different developmental ages were analyzed using these spectral parameters. Factor analysis (a chemometric technique) was also conducted on the tissue samples and resulted in factor loadings with spectral features corresponding to the HPO4 vibrations described above. Images of both factor correlation coefficients and the peak height ratios 1127/1096 and 1112/1096 cm(-1) demonstrated higher acid phosphate content in younger vs. more mature regions in the same specimen. Maps of the distribution of acid phosphate content will be useful for characterizing the extent of new bone formation, the areas of potential decreased strength, and the effects of therapies such as those used in metabolic bone diseases (osteoporosis, chronic kidney disease) on mineral composition. Because of the wider range of values obtained with the 1127/1096 cm(-1) parameter compared to the 1110/1096 cm(-1) parameter and the smaller scatter in the slope, it is suggested that this ratio should be the parameter of choice.

The thermal stability of photoacid generators in phenolic matrices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barclay, G.G.; Medeiros, D.R.; Sinta, R.F.

1993-12-31

The thermal stability of various photolabile sulfonate esters in phenolic matrices have been investigated by differential scanning calorimetry and thermogravimetric analysis. It was observed that the thermal stability of these photoacid generators is lowered in the presence of phenolic groups. As a result acid can be thermally generated, thereby reducing the selectivity of photoacid generation. The sulfonate esters investigated in phenolic matrices included nitrobenzyl tosylates, imino sulfonates, benzoin tosylate and 1,2,3-tris(methanesulfonyloxy)benzene. Also the effect of the thermal generation of acid from these photoacid generators on the temperature and rate of deprotection of partially t-butoxycarbonate blocked poly (vinylphenol) was studied bymore » thermogravimetric analysis and FTIR.« less

Lewis acid tuned facial stereodivergent HDA reactions using beta-substituted N-vinyloxazolidinones.

PubMed

Gohier, Frédéric; Bouhadjera, Keltoum; Faye, Djibril; Gaulon, Catherine; Maisonneuve, Vincent; Dujardin, Gilles; Dhal, Robert

2007-01-18

The [4 + 2] acido-catalyzed heterocycloaddition between new beta-substituted N-vinyl-1,3-oxazolidin-2-ones (with R' = Me, Ar, CH2 Ar) and beta,gamma-unsaturated alpha-ketoesters (R = Ar) afforded heteroadducts with high levels of endo and facial selectivities. A complete reversal of facial differentiation was achieved by varying the Lewis acid, leading to the stereoselective formation of either endo-alpha or endo-beta adducts. [reaction: see text].

Improved Synthesis of 5-Substituted 1H-Tetrazoles via the [3+2] Cycloaddition of Nitriles and Sodium Azide Catalyzed by Silica Sulfuric Acid

PubMed Central

Du, Zhenting; Si, Changmei; Li, Youqiang; Wang, Yin; Lu, Jing

2012-01-01

A silica supported sulfuric acid catalyzed [3+2] cycloaddition of nitriles and sodium azide to form 5-substituted 1H-tetrazoles is described. The protocol can provide a series of 5-substituted 1H-tetrazoles using silica sulfuric acid from nitriles and sodium azide in DMF in 72%–95% yield. PMID:22606004

Periodic GMP Matrices

NASA Astrophysics Data System (ADS)

Eichinger, Benjamin

2016-07-01

We recall criteria on the spectrum of Jacobi matrices such that the corresponding isospectral torus consists of periodic operators. Motivated by those known results for Jacobi matrices, we define a new class of operators called GMP matrices. They form a certain Generalization of matrices related to the strong Moment Problem. This class allows us to give a parametrization of almost periodic finite gap Jacobi matrices by periodic GMP matrices. Moreover, due to their structural similarity we can carry over numerous results from the direct and inverse spectral theory of periodic Jacobi matrices to the class of periodic GMP matrices. In particular, we prove an analogue of the remarkable ''magic formula'' for this new class.

Electronic Effects of 11β Substituted 17β-Estradiol Derivatives and Instrumental Effects on the Relative Gas Phase Acidity

NASA Astrophysics Data System (ADS)

Bourgoin-Voillard, Sandrine; Fournier, Françoise; Afonso, Carlos; Zins, Emilie-Laure; Jacquot, Yves; Pèpe, Claude; Leclercq, Guy; Tabet, Jean-Claude

2012-12-01

Numerous studies have highlighted the role of the proton donor characteristics of the phenol group of 17β-estradiol (E2) in its association with the estrogen receptor alpha (ERα). Since the substitutions at position C(11) have been reported to modulate this association, we hypothesized that such substitutions may modify the phenol acidity. Hence, phenol gas-phase acidity of nine C(11)-substituted E2-derivatives were evaluated using the extended Cooks' kinetic method, which is a method widely used to determine thermochemical properties by mass spectrometry. To enhance accuracy in data collection we recorded data from several instruments, including quadrupole ion trap, triple quadrupole, and hybrid QqTOF. Indeed, we report for the first time the use of the QqTOF instrument to provide a novel means to improve data accuracy by giving access to an intermediate effective temperature range. All experimental gas-phase acidity values were supported by theoretical calculations. Our results confirmed the ability of distant substituents at C(11) to modulate the phenol acidity through electrostatic interactions, electron withdrawing inductive effects, and mesomeric effects. However, no relationship was found between the phenol gas-phase acidity of investigated steroids and their binding affinity for ERα assessed in solution. Thus, our results highlight that the intrinsic properties of the hormone do not influence sufficiently the stabilization of the hormone/ERα complex. It is more likely that such stabilization would be more related to factors depending on the environment within the binding pocket such as hydrophobic, steric as well as direct intermolecular electrostatic effects between ERα residues and the substituted steroidal estrogens.

Contribution of single amino acid and codon substitutions to the production and secretion of a lipase by Bacillus subtilis.

PubMed

Skoczinski, Pia; Volkenborn, Kristina; Fulton, Alexander; Bhadauriya, Anuseema; Nutschel, Christina; Gohlke, Holger; Knapp, Andreas; Jaeger, Karl-Erich

2017-09-25

Bacillus subtilis produces and secretes proteins in amounts of up to 20 g/l under optimal conditions. However, protein production can be challenging if transcription and cotranslational secretion are negatively affected, or the target protein is degraded by extracellular proteases. This study aims at elucidating the influence of a target protein on its own production by a systematic mutational analysis of the homologous B. subtilis model protein lipase A (LipA). We have covered the full natural diversity of single amino acid substitutions at 155 positions of LipA by site saturation mutagenesis excluding only highly conserved residues and qualitatively and quantitatively screened about 30,000 clones for extracellular LipA production. Identified variants with beneficial effects on production were sequenced and analyzed regarding B. subtilis growth behavior, extracellular lipase activity and amount as well as changes in lipase transcript levels. In total, 26 LipA variants were identified showing an up to twofold increase in either amount or activity of extracellular lipase. These variants harbor single amino acid or codon substitutions that did not substantially affect B. subtilis growth. Subsequent exemplary combination of beneficial single amino acid substitutions revealed an additive effect solely at the level of extracellular lipase amount; however, lipase amount and activity could not be increased simultaneously. Single amino acid and codon substitutions can affect LipA secretion and production by B. subtilis. Several codon-related effects were observed that either enhance lipA transcription or promote a more efficient folding of LipA. Single amino acid substitutions could improve LipA production by increasing its secretion or stability in the culture supernatant. Our findings indicate that optimization of the expression system is not sufficient for efficient protein production in B. subtilis. The sequence of the target protein should also be considered as an

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

PubMed

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.

Kinetic resolution and stereoselective synthesis of 3-substituted aspartic acids by using engineered methylaspartate ammonia lyases.

PubMed

Raj, Hans; Szymanski, Wiktor; de Villiers, Jandré; Puthan Veetil, Vinod; Quax, Wim J; Shimamoto, Keiko; Janssen, Dick B; Feringa, Ben L; Poelarends, Gerrit J

2013-08-19

Enzymatic amino acid synthesis: Kinetic resolution and asymmetric synthesis of various valuable 3-substituted aspartic acids, which were obtained in fair to good yields with diastereomeric ratio values of up to >98:2 and enantiomeric excess values of up to >99 %, by using engineered methylaspartate ammonia lyases are described. These biocatalytic methodologies for the selective preparation of aspartic acid derivatives appear to be attractive alternatives for existing chemical methods. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of imputation on correlation: implications for analysis of mass spectrometry data from multiple biological matrices.

PubMed

Taylor, Sandra L; Ruhaak, L Renee; Kelly, Karen; Weiss, Robert H; Kim, Kyoungmi

2017-03-01

With expanded access to, and decreased costs of, mass spectrometry, investigators are collecting and analyzing multiple biological matrices from the same subject such as serum, plasma, tissue and urine to enhance biomarker discoveries, understanding of disease processes and identification of therapeutic targets. Commonly, each biological matrix is analyzed separately, but multivariate methods such as MANOVAs that combine information from multiple biological matrices are potentially more powerful. However, mass spectrometric data typically contain large amounts of missing values, and imputation is often used to create complete data sets for analysis. The effects of imputation on multiple biological matrix analyses have not been studied. We investigated the effects of seven imputation methods (half minimum substitution, mean substitution, k-nearest neighbors, local least squares regression, Bayesian principal components analysis, singular value decomposition and random forest), on the within-subject correlation of compounds between biological matrices and its consequences on MANOVA results. Through analysis of three real omics data sets and simulation studies, we found the amount of missing data and imputation method to substantially change the between-matrix correlation structure. The magnitude of the correlations was generally reduced in imputed data sets, and this effect increased with the amount of missing data. Significant results from MANOVA testing also were substantially affected. In particular, the number of false positives increased with the level of missing data for all imputation methods. No one imputation method was universally the best, but the simple substitution methods (Half Minimum and Mean) consistently performed poorly. © The Author 2016. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Substituent and solvent effects on electronic spectra of some substituted phenoxyacetic acids.

PubMed

Shanthi, M; Kabilan, S

2007-06-01

The effects of substituents and solvents have been studied through the absorption spectra of nearly 19 para- and ortho-substituted phenoxyacetic acids in the range of 200-400 nm. The effects of substituent on the absorption spectra of compounds under present investigation are interpreted by correlation of absorption frequencies with simple and extended Hammett equations. Effect of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by means of Kamlet equation and the results are discussed.

Substituent and solvent effects on electronic spectra of some substituted phenoxyacetic acids

NASA Astrophysics Data System (ADS)

Shanthi, M.; Kabilan, S.

2007-06-01

The effects of substituents and solvents have been studied through the absorption spectra of nearly 19 para- and ortho-substituted phenoxyacetic acids in the range of 200-400 nm. The effects of substituent on the absorption spectra of compounds under present investigation are interpreted by correlation of absorption frequencies with simple and extended Hammett equations. Effect of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by means of Kamlet equation and the results are discussed.

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry.

PubMed

Blincoe, William D; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A; Joyce, Leo A; Mangion, Ian; Sheng, Huaming

2018-04-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS 1 ). Significant water/alcohol loss (>30% abundance in MS 1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. Graphical Abstract ᅟ.

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry

NASA Astrophysics Data System (ADS)

Blincoe, William D.; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A.; Joyce, Leo A.; Mangion, Ian; Sheng, Huaming

2018-02-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS1). Significant water/alcohol loss (>30% abundance in MS1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. [Figure not available: see fulltext.

Substitution and addition reactions of •OH with p-substituted-phenols

NASA Astrophysics Data System (ADS)

Albarrán, Guadalupe; Galicia-Jiménez, Eduardo; Mendoza, Edith; Schuler, Robert H.

2017-04-01

The directing effect of a hydroxyl group on the substitution and addition reactions of •OH to the substituted and free positions in aromatic rings of p-substituted-phenols were studied in aqueous solutions containing either K3Fe(CN)6 as an oxidant of the substituted hydroxycyclohexadienyl radical initially formed or using ascorbic acid. The results showed that the attack of the •OH to the substituted position (ipso position) was followed by elimination of the substituent producing hydroquinone. The addition reaction of the •OH to the free position on the ring produced 4-substituent-catechol and 4-substituent-resorcinol derivatives. Identification and quantification of the radiolytic products were carried out using high performance liquid chromatography. The results of the yields are given for the p-halogen-phenols (p-X-Ph) p-F-Ph, p-Cl-Ph, p-Br-Ph and p-I-Ph. Other compounds, p-nitro-Ph, p-OH-benzoic acid, p-OH-benzonitrile, p-OH-benzaldehyde, p-OH-anisole and p-OH-benzyl alcohol (represented as p-Z-Ph), were only studied using K3Fe(CN)6 as the oxidant. The results show that the p-X-Ph are attacked by the •OH at the ipso position to the halogen in the proportion 1:0.53:0.46:0.11 for F>Cl>Br>I. The •OH attacked at the ipso position to the p-Z-Phs through a substitution reaction, which depended on the substituent group. Thus, the strongly deactivating groups produced less hydroquinone, indicating less substitution reaction than the strongly activating groups.

40 CFR 72.41 - Phase I substitution plans.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.41 Phase I substitution... section 410 of the Act. (b)(1) The designated representative may include, in the Acid Rain permit... an Acid Rain permit containing the plan, except that if the substitution plan is conditionally...

40 CFR 72.41 - Phase I substitution plans.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.41 Phase I substitution... section 410 of the Act. (b)(1) The designated representative may include, in the Acid Rain permit... an Acid Rain permit containing the plan, except that if the substitution plan is conditionally...

40 CFR 72.41 - Phase I substitution plans.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.41 Phase I substitution... section 410 of the Act. (b)(1) The designated representative may include, in the Acid Rain permit... an Acid Rain permit containing the plan, except that if the substitution plan is conditionally...

40 CFR 72.41 - Phase I substitution plans.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.41 Phase I substitution... section 410 of the Act. (b)(1) The designated representative may include, in the Acid Rain permit... an Acid Rain permit containing the plan, except that if the substitution plan is conditionally...

40 CFR 72.41 - Phase I substitution plans.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.41 Phase I substitution... section 410 of the Act. (b)(1) The designated representative may include, in the Acid Rain permit... an Acid Rain permit containing the plan, except that if the substitution plan is conditionally...

WEB-server for search of a periodicity in amino acid and nucleotide sequences

NASA Astrophysics Data System (ADS)

E Frenkel, F.; Skryabin, K. G.; Korotkov, E. V.

2017-12-01

A new web server (http://victoria.biengi.ac.ru/splinter/login.php) was designed and developed to search for periodicity in nucleotide and amino acid sequences. The web server operation is based upon a new mathematical method of searching for multiple alignments, which is founded on the position weight matrices optimization, as well as on implementation of the two-dimensional dynamic programming. This approach allows the construction of multiple alignments of the indistinctly similar amino acid and nucleotide sequences that accumulated more than 1.5 substitutions per a single amino acid or a nucleotide without performing the sequences paired comparisons. The article examines the principles of the web server operation and two examples of studying amino acid and nucleotide sequences, as well as information that could be obtained using the web server.

High temperature dissolution of chromium substituted nickel ferrite in nitrilotriacetic acid medium

NASA Astrophysics Data System (ADS)

Sathyaseelan, V. S.; Chandramohan, P.; Velmurugan, S.

2016-12-01

High temperature (HT) dissolution of chromium substituted nickel ferrite was carried out with relevance to the decontamination of nuclear reactors by way of chemical dissolution of contaminated corrosion product oxides present on stainless steel coolant circuit surfaces. Chromium substituted nickel ferrites of composition, NiFe(2-x)CrxO4 (x ≤ 1), was synthetically prepared and characterized. HT dissolution of these oxides was carried out in nitrilotriacetic acid medium at 160 °C. Dissolution was remarkably increased at 160 °C when compared to at 85 °C in a reducing decontamination formulation. Complete dissolution could be achieved for the oxides with chromium content 0 and 0.2. Increasing the chromium content brought about a marked reduction in the dissolution rate. About 40 fold decrease in rate of dissolution was observed when chromium was increased from 0 to 1. The rate of dissolution was not very significantly reduced in the presence of N2H4. Dissolution of oxide was found to be stoichiometric.

Equilibrium Acidities and Homolytic Bond Dissociation Enthalpies of the Acidic C-H Bonds in P-(Para-substituted benzyl)triphenylphosphonium Cations and Related Cations.

PubMed

Zhang, Xian-Man; Fry, Albert J.; Bordwell, Frederick G.

1996-06-14

Equilibrium acidities (pK(HA)) of six P-(para-substituted benzyl)triphenylphosphonium (p-GC(6)H(4)CH(2)PPh(3)(+)) cations, P-allyltriphenylphosphonium cation, P-cinnamyltriphenylphosphonium cation, and As-(p-cyanobenzyl)triphenylarsonium cation, together with the oxidation potentials [E(ox)(A(-))] of their conjugate anions (ylides) have been measured in dimethyl sulfoxide (DMSO) solution. The acidifying effects of the alpha-triphenylphosphonium groups on the acidic C-H bonds in toluene and propene were found to be ca 25 pK(HA) units (34 kcal/mol). Introduction of an electron-withdrawing group such as 4-NO(2), 4-CN, or 4-Br into the para position of the benzyl ring in p-GC(6)H(4)CH(2)PPh(3)(+) cations resulted in an additional acidity increase, but introduction of the 4-OEt electron-donating group decreases the acidity. The equilibrium acidities of p-GC(6)H(4)CH(2)PPh(3)(+) cations were nicely linearly correlated with the Hammett sigma(-) constants of the substituents (G) with a slope of 4.78 pK(HA) units (R(2) = 0.992) (Figure 1). Reversible oxidation potentials of the P-(para-substituted benzyl)triphenylphosphonium ylides were obtained by fast scan cyclic voltammetry. The homolytic bond dissociation enthalpies (BDEs) of the acidic C-H bonds in these cations, estimated by combining their equilibrium acidities with the oxidation potentials of their corresponding conjugate anions, showed that the alpha-Ph(3)P(+) groups have negligible stabilizing or destabilizing effects on the adjacent radicals. The equilibrium acidity of As-(p-cyanobenzyl)triphenylarsonium cation is 4 pK(HA) units weaker than that of P-(p-cyanobenzyl)triphenylphosphonium cation, but the BDE of the acidic C-H bond in As-(p-cyanobenzyl)triphenylarsonium cation is ca 2 kcal/mol higher than that in P-(p-cyanobenzyl)triphenylphosphonium cation.

Amino Acid Properties Conserved in Molecular Evolution

PubMed Central

Rudnicki, Witold R.; Mroczek, Teresa; Cudek, Paweł

2014-01-01

That amino acid properties are responsible for the way protein molecules evolve is natural and is also reasonably well supported both by the structure of the genetic code and, to a large extent, by the experimental measures of the amino acid similarity. Nevertheless, there remains a significant gap between observed similarity matrices and their reconstructions from amino acid properties. Therefore, we introduce a simple theoretical model of amino acid similarity matrices, which allows splitting the matrix into two parts – one that depends only on mutabilities of amino acids and another that depends on pairwise similarities between them. Then the new synthetic amino acid properties are derived from the pairwise similarities and used to reconstruct similarity matrices covering a wide range of information entropies. Our model allows us to explain up to 94% of the variability in the BLOSUM family of the amino acids similarity matrices in terms of amino acid properties. The new properties derived from amino acid similarity matrices correlate highly with properties known to be important for molecular evolution such as hydrophobicity, size, shape and charge of amino acids. This result closes the gap in our understanding of the influence of amino acids on evolution at the molecular level. The methods were applied to the single family of similarity matrices used often in general sequence homology searches, but it is general and can be used also for more specific matrices. The new synthetic properties can be used in analyzes of protein sequences in various biological applications. PMID:24967708

Dipole moment and solvatochromism of benzoic acid liquid crystals: Tuning the dipole moment and molecular orbital energies by substituted Au under external electric field

NASA Astrophysics Data System (ADS)

Sıdır, Yadigar Gülseven; Sıdır, İsa; Demiray, Ferhat

2017-06-01

The optical absorption and steady-state fluorescence spectra of 4-heptyloxybenzoic acid (4hoba), 4-octyloxybenzoic acid (4ooba) and 4-nonyloxybenzoic acid (4noba) liquid crystals have been measured in a series of different polarity organic solvents. The ground state (μg) and excited state (μe) dipole moments of the monomeric and dimeric 4-alkyloxybenzoic acid liquid crystals have been obtained by means of different solvatochromic shift methods. HOMO-LUMO gaps (HLG) and dipole moments have been tuned by applying external electric (EF) field on monomer, dimer and Au substituted monomer and dimer liquid crystal structures. By applying external electric field, Au substituted monomer liquid crystals display semiconductor character, while Au substituted dimer liquid crystals gain metallic character under E = 0.04 V/Å. Eventuated specific and non-specific interactions between solvent and solute in solvent medium have been expounded by using LSER (Linear Solvation Energy Relationships).

Analytical Applications Of High-Resolution Molecular Fluorescence Spectroscopy In Low Temperature Solid Matrices

NASA Astrophysics Data System (ADS)

Hofstraat, Johannes W.; van Zeijl, W. J.; Smedes, F.; Ariese, Freek; Gooijer, Cees; Velthorst, Nel H.; Locher, R.; Renn, Alois; Wild, Urs P.

1989-05-01

High-resolution fluorescence spectroscopy may be used to obtain highly specific, vibrationally resolved spectral signatures of molecules. Two techniques are presented that both make use of low temperature, solid matrices. In Shpol'skii spectroscopy highly resolved spectra are obtained by employing n-alkanes as solvents that form neat crystalline matrices at low temperatures in which the guest molecules occupy well defined substitutional sites. Fluorescence line-narrowing spectroscopy is based on the application of selective (mostly laser-) excitation of the guest molecules. Principles and analytical applications of both techniques will be discussed. Specific attention will be paid to the determination of pyrene in bird meat by means of Shpol'skii spectroscopy and to the possibilities of applying two-dimensional fluorescence line-narrowing spectroscopy.

Alternative CHCA-based matrices for the analysis of low molecular weight compounds by UV-MALDI-tandem mass spectrometry.

PubMed

Porta, Tiffany; Grivet, Chantal; Knochenmuss, Richard; Varesio, Emmanuel; Hopfgartner, Gérard

2011-02-01

Analysis of low molecular weight compounds (LMWC) in complex matrices by vacuum matrix-assisted laser desorption/ionization (MALDI) often suffers from matrix interferences, which can severely degrade limits of quantitation. It is, therefore, useful to have available a range of suitable matrices, which exhibit complementary regions of interference. Two newly synthesized α-cyanocinnamic acid derivatives are reported here; (E)-2-cyano-3-(naphthalen-2-yl)acrylic acid (NpCCA) and (2E)-3-(anthracen-9-yl)-2-cyanoprop-2enoic acid (AnCCA). Along with the commonly used α-cyano-4-hydroxycinnamic acid (CHCA), and the recently developed 4-chloro-α-cyanocinnamic acid (Cl-CCA) matrices, these constitute a chemically similar series of matrices covering a range of molecular weights, and with correspondingly differing ranges of spectral interference. Their performance was compared by measuring the signal-to-noise ratios (S/N) of 47 analytes, mostly pharmaceuticals, with the different matrices using the selected reaction monitoring (SRM) mode on a triple quadrupole instrument equipped with a vacuum MALDI source. AnCCA, NpCCA and Cl-CCA were found to offer better signal-to-noise ratios in SRM mode than CHCA, but Cl-CCA yielded the best results for 60% of the compounds tested. To better understand the relative performance of this matrix series, the proton affinities (PAs) were measured using the kinetic method. Their relative values were: AnCCA > CHCA > NpCCA > Cl-CCA. This ordering is consistent with the performance data. The synthesis of the new matrices is straightforward and they provide (1) tunability of matrix background interfering ions and (2) enhanced analyte response for certain classes of compounds. Copyright © 2011 John Wiley & Sons, Ltd.

Soluble organic matrices of aragonitic skeletons of Merulinidae (Cnidaria, Anthozoa).

PubMed

Dauphin, Yannicke; Cuif, Jean-Pierre; Williams, C Terry

2008-05-01

Our interpretation of the overall taxonomy and evolution of the Scleractinia, the most important reef builders in tropical areas, has long depended exclusively on morphology of the calcareous skeletons. The reported series of physical and biochemical characterizations of skeletons and the mineralizing matrices extracted from the skeletons allow, for the first time, the level of biochemical diversity among corallites of the same family to be estimated. Similarities and differences observed in the micro- and nanostructures of the skeletons reflect those of the soluble organic matrices. Sulphur is mainly associated with sulphated acidic sugars. The role of sulphated sugars on the biomineralization processes is still underestimated. The resulting data suggest that environmental conditions may act on the mineralization process through the detailed compositions of the mineralizing matrices.

Conformational properties of a pyridyl-substituted cinnamic acid studied by NMR measurements and computations

NASA Astrophysics Data System (ADS)

Csankó, K.; Forgo, P.; Boros, K.; Hohmann, J.; Sipos, P.; Pálinkó, I.

2013-07-01

Following a preliminary exploration of the conformational space by the PM3 and HF/6-31 G*ab initio methods the conformational characteristics of the scarcely available Z isomer of an α-pyridyl-substituted cinnamic acid dimer [Z-2(3‧-pyridyl)-3-phenylpropanoic acid] was studied by NMR spectroscopy (NOESY measurements) in DMSO(d6), methanol(d4) and chloroform(d1). Calculations predicted that full conjugation was overruled by steric interactions and the rotation of the pyridyl ring was not restricted. NOESY measurements verified indeed that in all three solvents the pyridyl group was virtually freely rotating, while some restriction applied for that of the phenyl group.

The computational analysis and modelling of substitution effects on hydrolysis of formanilides in acidic aqueous solutions

NASA Astrophysics Data System (ADS)

Lukeš, Vladimír; Škorňa, Peter; Michalík, Martin; Klein, Erik

2017-11-01

Various para, meta and ortho substituted formanilides have been theoretically studied. For trans and cis-isomers of non-substituted formanilide, the calculated B3LYP vibration normal modes were analyzed. Substituent effect on the selected normal modes was described and the comparison with the available experimental data is presented. The calculated B3LYP proton affinities were correlated with Hammett constants, Fujita-Nishioka equation and the rate constants of the hydrolysis in 1 M HCl. Found linear dependences allow predictions of dissociation constants (pKBH+) and hydrolysis rate constants. Obtained results indicate that protonation of amide group may represent the rate determining step of acid catalyzed hydrolysis.

Development of amino acid substituted gemini surfactant-based mucoadhesive gene delivery systems for potential use as noninvasive vaginal genetic vaccination.

PubMed

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

2015-02-01

Recently, we synthesized amino acid- and peptide-substituted gemini surfactants, 'biolipids' that exhibited high transfection efficiency in vitro. In this study, we developed these plasmid DNA and gemini surfactant lipid particles for noninvasive administration in vaginal cavity. Novel formulations of these gene delivery systems were prepared with poloxamer 407 to induce in situ gelling of the formulation and diethylene glycol monoethyl ether to improve their penetration across mucosal tissue. Poloxamer at 16% w/v concentration in diethylene glycol monoethyl ether aqueous solution produced dispersions that gelled near body temperature and had a high yield value, preventing leakage of the formulation from the vaginal cavity. Intravaginal administration in rabbits showed that the glycyl-lysine-substituted gemini surfactant led to a higher gene expression compared with the parent unsubstituted gemini surfactant. This provides a proof-of-concept that amino acid substituted gemini surfactants can be used as noninvasive mucosal (vaginal) gene delivery systems to treat diseases associated with mucosal epithelia.

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

NASA Astrophysics Data System (ADS)

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.

A Review of Analytical Methods for p-Coumaric Acid in Plant-Based Products, Beverages, and Biological Matrices.

PubMed

Ferreira, Paula Scanavez; Victorelli, Francesca Damiani; Fonseca-Santos, Bruno; Chorilli, Marlus

2018-05-14

p-Coumaric acid (p-CA), also known as 4-hydroxycinnamic acid, is a phenolic acid, which has been widely studied due to its beneficial effects against several diseases and its wide distribution in the plant kingdom. This phenolic compound can be found in the free form or conjugated with other molecules; therefore, its bioavailability and the pathways via which it is metabolized change according to its chemical structure. p-CA has potential pharmacological effects because it has high free radical scavenging, anti-inflammatory, antineoplastic, and antimicrobial activities, among other biological properties. It is therefore essential to choose the most appropriate and effective analytical method for qualitative and quantitative determination of p-CA in different matrices, such as plasma, urine, plant extracts, and drug delivery systems. The most-reported analytical method for this purpose is high-performance liquid chromatography, which is mostly coupled with some type of detectors, such as UV/Vis detector. However, other analytical techniques are also used to evaluate this compound. This review presents a summary of p-CA in terms of its chemical and pharmacokinetic properties, pharmacological effects, drug delivery systems, and the analytical methods described in the literature that are suitable for its quantification.

In Situ β-Glucan Fortification of Cereal-Based Matrices by Pediococcus parvulus 2.6: Technological Aspects and Prebiotic Potential

PubMed Central

Mohedano, María Luz; Spano, Giuseppe; Fiocco, Daniela; Russo, Pasquale; Capozzi, Vittorio

2017-01-01

Bacterial exopolysaccharides produced by lactic acid bacteria are of increasing interest in the food industry, since they might enhance the technological and functional properties of some edible matrices. In this work, Pediococcus parvulus 2.6, which produces an O2-substituted (1,3)-β-d-glucan exopolysaccharide only synthesised by bacteria, was proposed as a starter culture for the production of three cereal-based fermented foods. The obtained fermented matrices were naturally bio-fortified in microbial β-glucans, and used to investigate the prebiotic potential of the bacterial exopolysaccharide by analysing the impact on the survival of a probiotic Lactobacillus plantarum strain under starvation and gastrointestinal simulated conditions. All of the assays were performed by using as control of the P. parvulus 2.6’s performance, the isogenic β-glucan non-producing 2.6NR strain. Our results showed a differential capability of P. parvulus to ferment the cereal flours. During the fermentation step, the β-glucans produced were specifically quantified and their concentration correlated with an increased viscosity of the products. The survival of the model probiotic L. plantarum WCFS1 was improved by the presence of the bacterial β-glucans in oat and rice fermented foods under starvation conditions. The probiotic bacteria showed a significantly higher viability when submitted to a simulated intestinal stress in the oat matrix fermented by the 2.6 strain. Therefore, the cereal flours were a suitable substrate for in situ bio-fortification with the bacterial β-glucan, and these matrices could be used as carriers to enhance the beneficial properties of probiotic bacteria. PMID:28754020

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

PubMed Central

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

Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid.

PubMed

Wester, Anita; Devocelle, Marc; Tallant, E Ann; Chappell, Mark C; Gallagher, Patricia E; Paradisi, Francesca

2017-10-01

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide's therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP 3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer.

Exploiting genes and functional diversity of chlorogenic acid and luteolin biosyntheses in Lonicera japonica and their substitutes.

PubMed

Yuan, Yuan; Wang, Zhouyong; Jiang, Chao; Wang, Xumin; Huang, Luqi

2014-01-25

Chlorogenic acids (CGAs) and luteolin are active compounds in Lonicera japonica, a plant of high medicinal value in traditional Chinese medicine. This study provides a comprehensive overview of gene families involved in chlorogenic acid and luteolin biosynthesis in L. japonica, as well as its substitutes Lonicera hypoglauca and Lonicera macranthoides. The gene sequence feature and gene expression patterns in various tissues and buds of the species were characterized. Bioinformatics analysis revealed that 14 chlorogenic acid and luteolin biosynthesis-related genes were identified from the L. japonica transcriptome assembly. Phylogenetic analyses suggested that the function of individual gene could be differentiation and induce active compound diversity. Their orthologous genes were also recognized in L. hypoglauca and L. macranthoides genomic datasets, except for LHCHS1 and LMC4H2. The expression patterns of these genes are different in the tissues of L. japonica, L. hypoglauca and L. macranthoides. Results also showed that CGAs were controlled in the first step of biosynthesis, whereas both steps controlled luteolin in the bud of L. japonica. The expression of LJFNS2 exhibited positive correlation with luteolin levels in L. japonica. This study provides significant information for understanding the functional diversity of gene families involved in chlorogenic acid and the luteolin biosynthesis, active compound diversity of L. japonica and its substitutes, and the different usages of the three species. Copyright © 2012. Published by Elsevier B.V.

Conserved G-matrices of morphological and life-history traits among continental and island blue tit populations.

PubMed

Delahaie, B; Charmantier, A; Chantepie, S; Garant, D; Porlier, M; Teplitsky, C

2017-08-01

The genetic variance-covariance matrix (G-matrix) summarizes the genetic architecture of multiple traits. It has a central role in the understanding of phenotypic divergence and the quantification of the evolutionary potential of populations. Laboratory experiments have shown that G-matrices can vary rapidly under divergent selective pressures. However, because of the demanding nature of G-matrix estimation and comparison in wild populations, the extent of its spatial variability remains largely unknown. In this study, we investigate spatial variation in G-matrices for morphological and life-history traits using long-term data sets from one continental and three island populations of blue tit (Cyanistes caeruleus) that have experienced contrasting population history and selective environment. We found no evidence for differences in G-matrices among populations. Interestingly, the phenotypic variance-covariance matrices (P) were divergent across populations, suggesting that using P as a substitute for G may be inadequate. These analyses also provide the first evidence in wild populations for additive genetic variation in the incubation period (that is, the period between last egg laid and hatching) in all four populations. Altogether, our results suggest that G-matrices may be stable across populations inhabiting contrasted environments, therefore challenging the results of previous simulation studies and laboratory experiments.

Nicotinic Acid Adenine Dinucleotide Phosphate Analogs Substituted on the Nicotinic Acid and Adenine Ribosides. Effects on Receptor-Mediated Ca2+ release

PubMed Central

Trabbic, Christopher J.; Zhang, Fan; Walseth, Timothy F.; Slama, James T.

2015-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the nicotinic acid 5-position are recognized by the sea urchin receptor, albeit with a 20–500 fold loss in agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release Ca2+ with an EC50 of 31 µM and to compete with NAADP for receptor binding with an IC50 of 56 nM. Attachment of charged groups to the nicotinic acid of NAADP is associated with loss of activity, suggesting that the nicotinate riboside moiety is recognized as a neutral zwitterion. Substituents (Br- and N3-) can be introduced at the 8-adenosyl position of NAADP while preserving high potency and agonist efficacy and an NAADP derivative substituted at both the 5-position of the nicotinic acid and at the 8-adenosyl position was also recognized although the agonist potency was significantly reduced. PMID:25826221

The association of substituting carbohydrates with total fat and different types of fatty acids with mortality and weight change among diabetes patients.

PubMed

Campmans-Kuijpers, Marjo J; Sluijs, Ivonne; Nöthlings, Ute; Freisling, Heinz; Overvad, Kim; Boeing, Heiner; Masala, Giovanna; Panico, Salvatore; Tumino, Rosario; Sieri, Sabina; Johansson, Ingegerd; Winkvist, Anna; Katzke, Verena A; Kuehn, Tilman; Nilsson, Peter M; Halkjær, Jytte; Tjønneland, Anne; Spijkerman, Annemieke M; Arriola, Larraitz; Sacerdote, Carlotta; Barricarte, Aurelio; May, Anne M; Beulens, Joline W

2016-10-01

Substitution of carbohydrates with fat in a diet for type 2 diabetes patients is still debated. This study aimed to investigate the association between dietary carbohydrate intake and isocaloric substitution with (i) total fat, (ii) saturated fatty acids (SFA), (iii) mono-unsaturated fatty acids (MUFA) and (iv) poly-unsaturated fatty acids (PUFA) with all-cause and cardiovascular (CVD) mortality risk and 5-year weight change in patients with type 2 diabetes. The study included 6192 patients with type 2 diabetes from 15 cohorts of the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at recruitment with country-specific food-frequency questionnaires. Cox and linear regression were used to estimate the associations with (CVD) mortality and weight change, adjusting for confounders and using different methods to adjust for energy intake. After a mean follow-up of 9.2 y ± SD 2.3 y, 791 (13%) participants had died, of which 268 (4%) due to CVD. Substituting 10 g or 5 energy% of carbohydrates by total fat was associated with a higher all-cause mortality risk (HR 1.07 [1.02-1.13]), or SFAs (HR 1.25 [1.11-1.40]) and a lower risk when replaced by MUFAs (HR 0.89 [0.77-1.02]). When carbohydrates were substituted with SFAs (HR 1.22 [1.00-1.49]) or PUFAs (HR 1.29 [1.02-1.63]) CVD mortality risk increased. The 5-year weight was lower when carbohydrates were substituted with total fat or MUFAs. These results were consistent over different energy adjustment methods. In diabetes patients, substitution of carbohydrates with SFAs was associated with a higher (CVD) mortality risk and substitution by total fat was associated with a higher all-cause mortality risk. Substitution of carbohydrates with MUFAs may be associated with lower mortality risk and weight reduction. Instead of promoting replacement of carbohydrates by total fat, dietary guideline should continue focusing on replacement by fat-subtypes; especially SFAs by MUFAs

Invertible flexible matrices

NASA Astrophysics Data System (ADS)

Justino, Júlia

2017-06-01

Matrices with coefficients having uncertainties of type o (.) or O (.), called flexible matrices, are studied from the point of view of nonstandard analysis. The uncertainties of the afore-mentioned kind will be given in the form of the so-called neutrices, for instance the set of all infinitesimals. Since flexible matrices have uncertainties in their coefficients, it is not possible to define the identity matrix in an unique way and so the notion of spectral identity matrix arises. Not all nonsingular flexible matrices can be turned into a spectral identity matrix using Gauss-Jordan elimination method, implying that that not all nonsingular flexible matrices have the inverse matrix. Under certain conditions upon the size of the uncertainties appearing in a nonsingular flexible matrix, a general theorem concerning the boundaries of its minors is presented which guarantees the existence of the inverse matrix of a nonsingular flexible matrix.

Compound matrices

NASA Astrophysics Data System (ADS)

Kravvaritis, Christos; Mitrouli, Marilena

2009-02-01

This paper studies the possibility to calculate efficiently compounds of real matrices which have a special form or structure. The usefulness of such an effort lies in the fact that the computation of compound matrices, which is generally noneffective due to its high complexity, is encountered in several applications. A new approach for computing the Singular Value Decompositions (SVD's) of the compounds of a matrix is proposed by establishing the equality (up to a permutation) between the compounds of the SVD of a matrix and the SVD's of the compounds of the matrix. The superiority of the new idea over the standard method is demonstrated. Similar approaches with some limitations can be adopted for other matrix factorizations, too. Furthermore, formulas for the n - 1 compounds of Hadamard matrices are derived, which dodge the strenuous computations of the respective numerous large determinants. Finally, a combinatorial counting technique for finding the compounds of diagonal matrices is illustrated.

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

PubMed

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of hyperthermia on the repair of sublethal radiation damage in normal and membrane fatty acid substituted fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolters, H.; Kelholt, D.; Konings, A.W.

1987-02-01

The interaction of heat and X irradiation was studied in normal and polyunsaturated fatty acid (PUFA) substituted mouse fibroblast LM cells. As a result of the substitution the membranes of the PUFA cells were more fluid than the membranes of the normal cells. Three different heat doses were applied (60 min 42 degrees C, 20 min 43 degrees C, and 10 min 44 degrees C) in combination with single or split doses of X rays. Heat radiosensitization was the largest for the 60 min 42 degrees C treatment. Heat radiosensitization and the heat-induced inhibition of the rate of sublethal damagemore » repair were the same for the normal and the PUFA cells. It is concluded from the experiments reported that the processes of hyperthermic inhibition of SLD repair and hyperthermic radiosensitization are independent of membrane fluidity and membrane fatty acid composition.« less

Speciation of nanoscale objects by nanoparticle imprinted matrices

NASA Astrophysics Data System (ADS)

Hitrik, Maria; Pisman, Yamit; Wittstock, Gunther; Mandler, Daniel

2016-07-01

The toxicity of nanoparticles is not only a function of the constituting material but depends largely on their size, shape and stabilizing shell. Hence, the speciation of nanoscale objects, namely, their detection and separation based on the different species, similarly to heavy metals, is of outmost importance. Here we demonstrate the speciation of gold nanoparticles (AuNPs) and their electrochemical detection using the concept of ``nanoparticles imprinted matrices'' (NAIM). Negatively charged AuNPs are adsorbed as templates on a conducting surface previously modified with polyethylenimine (PEI). The selective matrix is formed by the adsorption of either oleic acid (OA) or poly(acrylic acid) (PAA) on the non-occupied areas. The AuNPs are removed by electrooxidation to form complementary voids. These voids are able to recognize the AuNPs selectively based on their size. Furthermore, the selectivity could be improved by adsorbing an additional layer of 1-hexadecylamine, which deepened the voids. Interestingly, silver nanoparticles (AgNPs) were also recognized if their size matched those of the template AuNPs. The steps in assembling the NAIMs and the reuptake of the nanoparticles were characterized carefully. The prospects for the analytical use of NAIMs, which are simple, of small dimension, cost-efficient and portable, are in the sensing and separation of nanoobjects.The toxicity of nanoparticles is not only a function of the constituting material but depends largely on their size, shape and stabilizing shell. Hence, the speciation of nanoscale objects, namely, their detection and separation based on the different species, similarly to heavy metals, is of outmost importance. Here we demonstrate the speciation of gold nanoparticles (AuNPs) and their electrochemical detection using the concept of ``nanoparticles imprinted matrices'' (NAIM). Negatively charged AuNPs are adsorbed as templates on a conducting surface previously modified with polyethylenimine (PEI). The

Multiple Genetic Pathways Involving Amino Acid Position 143 of HIV-1 Integrase Are Preferentially Associated with Specific Secondary Amino Acid Substitutions and Confer Resistance to Raltegravir and Cross-Resistance to Elvitegravir

PubMed Central

Frantzell, Arne; Fransen, Signe; Petropoulos, Christos J.

2013-01-01

Y143C,R substitutions in HIV-1 integrase define one of three primary raltegravir (RAL) resistance pathways. Here we describe clinical isolates with alternative substitutions at position 143 (Y143A, Y143G, Y143H, and Y143S [Y143A,G,H,S]) that emerge less frequently, and we compare the genotypic and phenotypic profiles of these viruses to Y143C,R viruses to reconcile the preferential selection of Y143C,R variants during RAL treatment. Integrase amino acid sequences and RAL susceptibility were characterized in 117 patient isolates submitted for drug resistance testing and contained Y143 amino acid changes. The influence of specific Y143 substitutions on RAL susceptibility and their preferential association with particular secondary substitutions were further defined by evaluating the composition of patient virus populations along with a large panel of site-directed mutants. Our observations demonstrate that the RAL resistance profiles of Y143A,G,H,S viruses and their association with specific secondary substitutions are similar to the well-established Y143C profile but distinct from the Y143R profile. Y143R viruses differ from Y143A,C,G,H,S viruses in that Y143R confers a greater reduction in RAL susceptibility as a single substitution, consistent with a lower resistance barrier. Among Y143A,C,G,H,S viruses, the higher prevalence of Y143C viruses is the result of a lower genetic barrier than that of the Y143A,G,S viruses and a lower resistance barrier than that of the Y143H viruses. In addition, Y143A,C,G,H,S viruses require multiple secondary substitutions to develop large reductions in RAL susceptibility. Patient-derived viruses containing Y143 substitutions exhibit cross-resistance to elvitegravir. PMID:23733474

Binding of ring-substituted indole-3-acetic acids to human serum albumin.

PubMed

Soskić, Milan; Magnus, Volker

2007-07-01

The plant hormone, indole-3-acetic acid (IAA), and its ring-substituted derivatives have recently attracted attention as promising pro-drugs in cancer therapy. Here we present relative binding constants to human serum albumin for IAA and 34 of its derivatives, as obtained using the immobilized protein bound to a support suitable for high-performance liquid chromatography. We also report their octanol-water partition coefficients (logK(ow)) computed from retention data on a C(18) coated silica gel column. A four-parameter QSPR (quantitative structure-property relationships) model, based on physico-chemical properties, is put forward, which accounts for more than 96% of the variations in the binding affinities of these compounds. The model confirms the importance of lipophilicity as a global parameter governing interaction with serum albumin, but also assigns significant roles to parameters specifically related to the molecular topology of ring-substituted IAAs. Bulky substituents at ring-position 6 increase affinity, those at position 2 obstruct binding, while no steric effects were noted at other ring-positions. Electron-withdrawing substituents at position 5 enhance binding, but have no obvious effect at other ring positions.

Substitution of Linoleic Acid for Other Macronutrients and the Risk of Ischemic Stroke.

PubMed

Venø, Stine K; Schmidt, Erik B; Jakobsen, Marianne U; Lundbye-Christensen, Søren; Bach, Flemming W; Overvad, Kim

2017-12-01

Ischemic stroke is a major health problem worldwide, but the influence of dietary factors on stroke risk is not well known. This study aimed to investigate the risk of ischemic stroke and its subtypes with a higher intake from linoleic acid and a concomitant lower intake from saturated fatty acids, monounsaturated fatty acids, or glycemic carbohydrates. In the Danish prospective Diet, Cancer, and Health Study of 57 053 participants aged 50 to 64 years at baseline, information on diet was collected using a validated semiquantitative food frequency questionnaire. Information on ischemic stroke was obtained from the Danish National Patient Register, and cases were all validated and subclassified according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Substitution of linoleic acid for saturated fatty acid, monounsaturated fatty acid, or glycemic carbohydrates was investigated in relation to the risk of ischemic stroke and subtypes. Cox proportional hazards regression was used to estimate the associations with ischemic stroke adjusting for appropriate confounders. During 13.5 years of follow-up 1879 participants developed ischemic stroke. A slightly lower risk of ischemic stroke was found with a 5% higher intake of linoleic acid and a concomitant lower intake of saturated fatty acid (hazard ratio, 0.98; 95% confidence interval, 0.83-1.16), monounsaturated fatty acid (hazard ratio, 0.80; 95% confidence interval, 0.63-1.02), and glycemic carbohydrates (hazard ratio, 0.92; 95% confidence interval, 0.78-1.09), although not statistically significant. Similar patterns of association were found for large-artery atherosclerosis and small-vessel occlusions. This study suggests that replacing saturated fatty acid, glycemic carbohydrate, or monounsaturated fatty acid with linoleic acid may be associated with a lower risk of ischemic stroke. © 2017 American Heart Association, Inc.

A Diastereoselective Multicomponent Reaction for Construction of Alkynylamide-Substituted α,β-Diamino Acid Derivatives To Hunt Hits.

PubMed

Lei, Ruirui; Wu, Yong; Dong, Suzhen; Jia, Kaili; Liu, Shunying; Hu, Wenhao

2017-03-17

A highly diasetereoselective Mannich-type multicomponent reaction was developed to rapidly construct alkynylamide-substituted α,β-diamino acid derivatives from simple starting materials under mild conditions in moderate to good yields for hit hunting. Most of the resulting products 4 exhibited good anticancer activity in HCT116, BEL7402, and SMMC7721 cells.

Rapid acquisition adaptive amino acid substitutions involved in the virulence enhancement of an H1N2 avian influenza virus in mice.

PubMed

Yu, Zhijun; Sun, Weiyang; Zhang, Xinghai; Cheng, Kaihui; Zhao, Chuqi; Xia, Xianzhu; Gao, Yuwei

2017-08-01

Although H1N2 avian influenza virus (AIV) only infect birds, documented cases of swine infection with H1N2 influenza viruses suggest this subtype AIV may pose a potential threat to mammals. Here, we generated mouse-adapted variants of a H1N2 AIV to identify adaptive changes that increased virulence in mammals. MLD 50 of the variants were reduced >1000-fold compared to the parental virus. Variants displayed enhanced replication in vitro and in vivo, and replicate in extrapulmonary organs. These data show that enhanced replication capacity and expanded tissue tropism may increase the virulence of H1N2 AIV in mice. Sequence analysis revealed multiple amino acid substitutions in the PB2 (L134H, I647L, and D701N), HA (G228S), and M1 (D231N) proteins. These results indicate that H1N2 AIV can rapidly acquire adaptive amino acid substitutions in mammalian hosts, and these amino acid substitutions collaboratively enhance the ability of H1N2 AIV to replicate and cause severe disease in mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

Prediction of Ras-effector interactions using position energy matrices.

PubMed

Kiel, Christina; Serrano, Luis

2007-09-01

One of the more challenging problems in biology is to determine the cellular protein interaction network. Progress has been made to predict protein-protein interactions based on structural information, assuming that structural similar proteins interact in a similar way. In a previous publication, we have determined a genome-wide Ras-effector interaction network based on homology models, with a high accuracy of predicting binding and non-binding domains. However, for a prediction on a genome-wide scale, homology modelling is a time-consuming process. Therefore, we here successfully developed a faster method using position energy matrices, where based on different Ras-effector X-ray template structures, all amino acids in the effector binding domain are sequentially mutated to all other amino acid residues and the effect on binding energy is calculated. Those pre-calculated matrices can then be used to score for binding any Ras or effector sequences. Based on position energy matrices, the sequences of putative Ras-binding domains can be scanned quickly to calculate an energy sum value. By calibrating energy sum values using quantitative experimental binding data, thresholds can be defined and thus non-binding domains can be excluded quickly. Sequences which have energy sum values above this threshold are considered to be potential binding domains, and could be further analysed using homology modelling. This prediction method could be applied to other protein families sharing conserved interaction types, in order to determine in a fast way large scale cellular protein interaction networks. Thus, it could have an important impact on future in silico structural genomics approaches, in particular with regard to increasing structural proteomics efforts, aiming to determine all possible domain folds and interaction types. All matrices are deposited in the ADAN database (http://adan-embl.ibmc.umh.es/). Supplementary data are available at Bioinformatics online.

Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme.

PubMed

Daar, I O; Artymiuk, P J; Phillips, D C; Maquat, L E

1986-10-01

Triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1) deficiency is a recessive disorder that results in hemolytic anemia and neuromuscular dysfunction. To determine the molecular basis of this disorder, a TPI allele from two unrelated patients homozygous for TPI deficiency was compared with an allele from a normal individual. Each disease-associated sequence harbors a G X C----C X G transversion in the codon for amino acid-104 and specifies a structurally altered protein in which a glutamate residue is replaced by an aspartate residue. The importance of glutamate-104 to enzyme structure and function is implicated by its conservation in the TPI protein of all species that have been characterized to date. The glutamate-to-aspartate substitution results in a thermolabile enzyme as demonstrated by assays of TPI activity in cultured fibroblasts of each patient and cultured Chinese hamster ovary (CHO) cells that were stably transformed with the mutant alleles. Although this substitution conserves the overall charge of amino acid-104, the x-ray crystal structure of chicken TPI indicates that the loss of a side-chain methylene group (-CH2CH2COO- ---- -CH2COO-) is sufficient to disrupt the counterbalancing of charges that normally exists within a hydrophobic pocket of the native enzyme.

Crystal Structure of a Novel N-Substituted L-Amino Acid Dioxygenase from Burkholderia ambifaria AMMD

PubMed Central

Qin, Hui-Min; Miyakawa, Takuya; Jia, Min Ze; Nakamura, Akira; Ohtsuka, Jun; Xue, You-Lin; Kawashima, Takashi; Kasahara, Takuya; Hibi, Makoto; Ogawa, Jun; Tanokura, Masaru

2013-01-01

A novel dioxygenase from Burkholderia ambifaria AMMD (SadA) stereoselectively catalyzes the C3-hydroxylation of N-substituted branched-chain or aromatic L-amino acids, especially N-succinyl-L-leucine, coupled with the conversion of α-ketoglutarate to succinate and CO2. To elucidate the structural basis of the substrate specificity and stereoselective hydroxylation, we determined the crystal structures of the SadA.Zn(II) and SadA.Zn(II).α-KG complexes at 1.77 Å and 1.98 Å resolutions, respectively. SadA adopted a double-stranded β-helix fold at the core of the structure. In addition, an HXD/EXnH motif in the active site coordinated a Zn(II) as a substitute for Fe(II). The α-KG molecule also coordinated Zn(II) in a bidentate manner via its 1-carboxylate and 2-oxo groups. Based on the SadA.Zn(II).α-KG structure and mutation analyses, we constructed substrate-binding models with N-succinyl-L-leucine and N-succinyl-L-phenylalanine, which provided new insight into the substrate specificity. The results will be useful for the rational design of SadA variants aimed at the recognition of various N-succinyl L-amino acids. PMID:23724013

Functional Compensation of a Detrimental Amino Acid Substitution in a Cytotoxic-T-Lymphocyte Epitope of Influenza A Viruses by Comutations

PubMed Central

Rimmelzwaan, G. F.; Berkhoff, E. G. M.; Nieuwkoop, N. J.; Fouchier, R. A. M.; Osterhaus, A. D. M. E.

2004-01-01

Influenza A viruses accumulate amino acid substitutions in cytotoxic-T-lymphocyte (CTL) epitopes, allowing these viruses to escape from CTL immunity. The arginine-to-glycine substitution at position 384 of the viral nucleoprotein is associated with escape from CTLs. Introduction of the R384G substitution in the nucleoprotein gene segment of influenza virus A/Hong Kong/2/68 by site-directed mutagenesis was detrimental to viral fitness. Introduction of one of the comutations associated with R384G, E375G, partially restored viral fitness and nucleoprotein functionality. We hypothesized that influenza A viruses need to overcome functional constraints to accumulate mutations in CTL epitopes and escape from CTLs. PMID:15280506

Structure-activity relationship of daptomycin analogues with substitution at (2S, 3R) 3-methyl glutamic acid position.

PubMed

Lin, Du'an; Lam, Hiu Yung; Han, Wenbo; Cotroneo, Nicole; Pandya, Bhaumik A; Li, Xuechen

2017-02-01

Daptomycin is a highly effective lipopeptide antibiotic against Gram-positive pathogens. The presence of (2S, 3R) 3-methyl glutamic acid (mGlu) in daptomycin has been found to be important to the antibacterial activity. However the role of (2S, 3R) mGlu is yet to be revealed. Herein, we reported the syntheses of three daptomycin analogues with (2S, 3R) mGlu substituted by (2S, 3R) methyl glutamine (mGln), dimethyl glutamic acid and (2S, 3R) ethyl glutamic acid (eGlu), respectively, and their antibacterial activities. The detailed synthesis of dimethyl glutamic acid was also reported. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human elastin polypeptides improve the biomechanical properties of three-dimensional matrices through the regulation of elastogenesis.

PubMed

Boccafoschi, Francesca; Ramella, Martina; Sibillano, Teresa; De Caro, Liberato; Giannini, Cinzia; Comparelli, Roberto; Bandiera, Antonella; Cannas, Mario

2015-03-01

The replacement of diseased tissues with biological substitutes with suitable biomechanical properties is one of the most important goal in tissue engineering. Collagen represents a satisfactory choice for scaffolds. Unfortunately, the lack of elasticity represents a restriction to a wide use of collagen for several applications. In this work, we studied the effect of human elastin-like polypeptide (HELP) as hybrid collagen-elastin matrices. In particular, we studied the biomechanical properties of collagen/HELP scaffolds considering several components involved in ECM remodeling (elastin, collagen, fibrillin, lectin-like receptor, metalloproteinases) and cell phenotype (myogenin, myosin heavy chain) with particular awareness for vascular tissue engineering applications. Elastin and collagen content resulted upregulated in collagen-HELP matrices, even showing an improved structural remodeling through the involvement of proteins to a ECM remodeling activity. Moreover, the hybrid matrices enhanced the contractile activity of C2C12 cells concurring to improve the mechanical properties of the scaffold. Finally, small-angle X-ray scattering analyses were performed to enable a very detailed analysis of the matrices at the nanoscale, comparing the scaffolds with native blood vessels. In conclusion, our work shows the use of recombinant HELP, as a very promising complement able to significantly improve the biomechanical properties of three-dimensional collagen matrices in terms of tensile stress and elastic modulus. © 2014 Wiley Periodicals, Inc.

Technological optimization of manufacture of probiotic whey cheese matrices.

PubMed

Madureira, Ana R; Brandão, Teresa; Gomes, Ana M; Pintado, Manuela E; Malcata, F Xavier

2011-03-01

In attempts to optimize their manufacture, whey cheese matrices obtained via thermal processing of whey (leading to protein precipitation) and inoculated with probiotic cultures were tested. A central composite, face-centered design was followed, so a total of 16 experiments were run using fractional addition of bovine milk to feedstock whey, homogenization time, and storage time of whey cheese as processing parameters. Probiotic whey cheese matrices were inoculated with Lactobacillus casei LAFTIL26 at 10% (v/v), whereas control whey cheese matrices were added with skim milk previously acidified with lactic acid to the same level. All whey cheeses were stored at 7 °C up to 14 d. Chemical and sensory analyses were carried out for all samples, as well as rheological characterization by oscillatory viscometry and textural profiling. As expected, differences were found between control and probiotic matrices: fractional addition of milk and storage time were the factors accounting for the most important effects. Estimation of the best operating parameters was via response surface analysis: milk addition at a rate of 10% to 15% (v/v), and homogenization for 5 min led to the best probiotic whey cheeses in terms of texture and organoleptic properties, whereas the best time for consumption was found to be by 9 d of storage following manufacture.

Evaluation of support matrices for immobilization of anaerobic consortia for efficient carbon cycling in waste regeneration.

PubMed

Chauhan, Ashvini; Ogram, Andrew

2005-02-18

Efficient metabolism of fatty acids during anaerobic waste digestion requires development of consortia that include "fatty acid consuming H(2) producing bacteria" and methanogenic bacteria. The objective of this research was to optimize methanogenesis from fatty acids by evaluating a variety of support matrices for use in maintaining efficient syntrophic-methanogenic consortia. Tested matrices included clays (montmorillonite and bentonite), glass beads (106 and 425-600mum), microcarriers (cytopore, cytodex, cytoline, and cultispher; conventionally employed for cultivation of mammalian cell lines), BioSep beads (powdered activated carbon), and membranes (hydrophilic; nylon, polysulfone, and hydrophobic; teflon, polypropylene). Data obtained from headspace methane (CH(4)) analyses as an indicator of anaerobic carbon cycling efficiency indicated that material surface properties were important in maintenance and functioning of the anaerobic consortia. Cytoline yielded significantly higher CH(4) than other matrices as early as in the first week of incubation. 16S rRNA gene sequence analysis from crushed cytoline matrix showed the presence of Syntrophomonas spp. (butyrate oxidizing syntrophs) and Syntrophobacter spp. (propionate oxidizing syntrophs), with Methanosaeta spp. (acetate utilizing methanogen), and Methanospirillum spp. (hydrogen utilizing methanogen) cells. It is likely that the more hydrophobic surfaces provided a suitable surface for adherence of cells of syntrophic-methanogenic consortia. Cytoline also appeared to protect entrapped consortia from air, resulting in rapid methanogenesis after aerial exposure. Our study suggests that support matrices can be used in anaerobic digestors, pre-seeded with immobilized or entrapped consortia on support matrices, and may be of value as inoculant-adsorbents to rapidly initiate or recover proper system functioning following perturbation.

Emergence of fluoroquinolone-resistant Propionibacterium acnes caused by amino acid substitutions of DNA gyrase but not DNA topoisomerase IV.

PubMed

Nakase, Keisuke; Sakuma, Yui; Nakaminami, Hidemasa; Noguchi, Norihisa

2016-12-01

With the aim of elucidating the mechanisms of fluoroquinolones resistance in Propionibacterium acnes, we determined the susceptibility of fluoroquinolones in 211 isolates from patients with acne vulgaris. We identified five isolates (2.4%) with reduced susceptibility to nadifloxacin (minimum inhibitory concentration ≥ 4 μg/ml). Determination of the sequences of the DNA gyrase (gyrA and gyrB) and DNA topoisomerase (parC and parE) genes showed the amino acid substitutions Ser101Leu and Asp105Gly of GyrA in four and one of the isolates, respectively. In vitro mutation experiments showed that low-level fluoroquinolone-resistant mutants with the Ser101Leu or Asp105Gly substitution in GyrA could be obtained from selection with ciprofloxacin and levofloxacin. The pattern of substitution (Ser101Trp in GyrA) caused by nadifloxacin selection was different from that induced by the other fluoroquinolones. In the isolation of further high-level resistant mutants, acquisition of another amino acid substitution of GyrB in addition to those of GyrA was detected, but there were no substitutions of ParC and ParE. In addition, the mutant prevention concentration and mutation frequency of nadifloxacin were lowest among the tested fluoroquinolones. The growth of the Ser101Trp mutant was lower than that of the other mutants. Our findings suggest that the Ser101Trp mutant of P. acnes emerges rarely and disappears immediately, and the risk for the prevalence of fluoroquinolones-resistant P. acnes differs according to the GyrA mutation type. To our knowledge, this study is the first to demonstrate the mechanisms of resistance to fluoroquinolones in P. acnes. Copyright © 2016 Elsevier Ltd. All rights reserved.

What makes lithium substituted polyacrylic acid a better binder than polyacrylic acid for silicon-graphite composite anodes?

DOE PAGES

Hays, Kevin A.; Ruther, Rose E.; Kukay, Alexander J.; ...

2018-03-04

Lithium substituted polyacrylic acid (LiPAA) has previously been demonstrated as a superior binder over polyacrylic acid (PAA) for Si anodes, but from where does this enhanced performance arise? In this paper, full cells are assembled with PAA and LiPAA based Si-graphite composite anodes that dried at temperatures from 100 °C to 200 °C. The performance of full cells containing PAA based Si-graphite anodes largely depend on the secondary drying temperature, as decomposition of the binder is correlated to increased electrode moisture and a rise in cell impedance. Full cells containing LiPAA based Si-graphite composite electrodes display better Coulombic efficiency thanmore » those with PAA, because of the electrochemical reduction of the PAA binder. This is identified by attenuated total reflectance Fourier transform infrared spectrometry and observed gassing during the electrochemical reaction. Finally, Coulombic losses from the PAA and Si SEI, along with depletion of the Si capacity in the anode results in progressive underutilization of the cathode and full cell capacity loss.« less

What makes lithium substituted polyacrylic acid a better binder than polyacrylic acid for silicon-graphite composite anodes?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hays, Kevin A.; Ruther, Rose E.; Kukay, Alexander J.

Lithium substituted polyacrylic acid (LiPAA) has previously been demonstrated as a superior binder over polyacrylic acid (PAA) for Si anodes, but from where does this enhanced performance arise? In this paper, full cells are assembled with PAA and LiPAA based Si-graphite composite anodes that dried at temperatures from 100 °C to 200 °C. The performance of full cells containing PAA based Si-graphite anodes largely depend on the secondary drying temperature, as decomposition of the binder is correlated to increased electrode moisture and a rise in cell impedance. Full cells containing LiPAA based Si-graphite composite electrodes display better Coulombic efficiency thanmore » those with PAA, because of the electrochemical reduction of the PAA binder. This is identified by attenuated total reflectance Fourier transform infrared spectrometry and observed gassing during the electrochemical reaction. Finally, Coulombic losses from the PAA and Si SEI, along with depletion of the Si capacity in the anode results in progressive underutilization of the cathode and full cell capacity loss.« less

What makes lithium substituted polyacrylic acid a better binder than polyacrylic acid for silicon-graphite composite anodes?

NASA Astrophysics Data System (ADS)

Hays, Kevin A.; Ruther, Rose E.; Kukay, Alexander J.; Cao, Pengfei; Saito, Tomonori; Wood, David L.; Li, Jianlin

2018-04-01

Lithium substituted polyacrylic acid (LiPAA) has previously been demonstrated as a superior binder over polyacrylic acid (PAA) for Si anodes, but from where does this enhanced performance arise? In this study, full cells are assembled with PAA and LiPAA based Si-graphite composite anodes that dried at temperatures from 100 °C to 200 °C. The performance of full cells containing PAA based Si-graphite anodes largely depend on the secondary drying temperature, as decomposition of the binder is correlated to increased electrode moisture and a rise in cell impedance. Full cells containing LiPAA based Si-graphite composite electrodes display better Coulombic efficiency than those with PAA, because of the electrochemical reduction of the PAA binder. This is identified by attenuated total reflectance Fourier transform infrared spectrometry and observed gassing during the electrochemical reaction. Coulombic losses from the PAA and Si SEI, along with depletion of the Si capacity in the anode results in progressive underutilization of the cathode and full cell capacity loss.

Waste-free synthesis of condensed heterocyclic compounds by rhodium-catalyzed oxidative coupling of substituted arene or heteroarene carboxylic acids with alkynes.

PubMed

Shimizu, Masaki; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro

2009-05-01

The direct oxidative coupling of 2-amino- and 2-hydroxybenzoic acids with internal alkynes proceeds efficiently in the presence of a rhodium/copper catalyst system under air to afford the corresponding 8-substituted isocoumarin derivatives, some of which exhibit solid-state fluorescence. Depending on conditions, 4-ethenylcarbazoles can be synthesized selectively from 2-(arylamino)benzoic acids. The oxidative coupling reactions of heteroarene carboxylic acids as well as aromatic diacids with an alkyne are also described.

Cell-adhesive RGD peptide-displaying M13 bacteriophage/PLGA nanofiber matrices for growth of fibroblasts.

PubMed

Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Oh, Jin-Woo; Kim, Tai Wan; Han, Dong-Wook

2014-01-01

M13 bacteriophages can be readily fabricated as nanofibers due to non-toxic bacterial virus with a nanofiber-like shape. In the present study, we prepared hybrid nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 bacteriophages which were genetically modified to display the RGD peptide on their surface (RGD-M13 phage). The surface morphology and chemical composition of hybrid nanofiber matrices were characterized by scanning electron microscopy (SEM) and Raman spectroscopy, respectively. Immunofluorescence staining was conducted to investigate the existence of M13 bacteriophages in RGD-M13 phage/PLGA hybrid nanofibers. In addition, the attachment and proliferation of three different types of fibroblasts on RGD-M13 phage/PLGA nanofiber matrices were evaluated to explore how fibroblasts interact with these matrices. SEM images showed that RGD-M13 phage/PLGA hybrid matrices had the non-woven porous structure, quite similar to that of natural extracellular matrices, having an average fiber diameter of about 190 nm. Immunofluorescence images and Raman spectra revealed that RGD-M13 phages were homogeneously distributed in entire matrices. Moreover, the attachment and proliferation of fibroblasts cultured on RGD-M13 phage/PLGA matrices were significantly enhanced due to enriched RGD moieties on hybrid matrices. These results suggest that RGD-M13 phage/PLGA matrices can be efficiently used as biomimetic scaffolds for tissue engineering applications.

Field matric potential sensor

DOEpatents

Hubbell, Joel M.; Sisson, James B.

2001-01-01

A method of determining matric potential of a sample, the method comprising placing the sample in a container, the container having an opening; and contacting the sample with a tensiometer via the opening. An apparatus for determining matric potential of a sample, the apparatus comprising a housing configured to receive a sample; a portable matric potential sensing device extending into the housing and having a porous member; and a wall closing the housing to insulate the sample and at least a portion of the matric potential sensing device including the porous member.

Structural and catalytic effects of an invariant purine substitution in the hammerhead ribozyme: implications for the mechanism of acid-base catalysis.

PubMed

Schultz, Eric P; Vasquez, Ernesto E; Scott, William G

2014-09-01

The hammerhead ribozyme catalyzes RNA cleavage via acid-base catalysis. Whether it does so by general acid-base catalysis, in which the RNA itself donates and abstracts protons in the transition state, as is typically assumed, or by specific acid-base catalysis, in which the RNA plays a structural role and proton transfer is mediated by active-site water molecules, is unknown. Previous biochemical and crystallographic experiments implicate an invariant purine in the active site, G12, as the general base. However, G12 may play a structural role consistent with specific base catalysis. To better understand the role of G12 in the mechanism of hammerhead catalysis, a 2.2 Å resolution crystal structure of a hammerhead ribozyme from Schistosoma mansoni with a purine substituted for G12 in the active site of the ribozyme was obtained. Comparison of this structure (PDB entry 3zd4), in which A12 is substituted for G, with three previously determined structures that now serve as important experimental controls, allows the identification of structural perturbations that are owing to the purine substitution itself. Kinetic measurements for G12 purine-substituted schistosomal hammerheads confirm a previously observed dependence of rate on the pK(a) of the substituted purine; in both cases inosine, which is similar to G in pK(a) and hydrogen-bonding properties, is unexpectedly inactive. Structural comparisons indicate that this may primarily be owing to the lack of the exocyclic 2-amino group in the G12A and G12I substitutions and its structural effect upon both the nucleotide base and phosphate of A9. The latter involves the perturbation of a previously identified and well characterized metal ion-binding site known to be catalytically important in both minimal and full-length hammerhead ribozyme sequences. The results permit it to be suggested that G12 plays an important role in stabilizing the active-site structure. This result, although not inconsistent with the potential

40 CFR 721.5286 - Benzenediazonium, [[[[(substituted) azo]phenyl]sulfonyl]amino]-, coupled with aminophenol...

Code of Federal Regulations, 2010 CFR

2010-07-01

...) azo]phenyl]sulfonyl]amino]-, coupled with aminophenol, diazotized aminobenzoic acid, diazotized..., [[[[(substituted) azo]phenyl]sulfonyl]amino]-, coupled with aminophenol, diazotized aminobenzoic acid, diazotized..., [[[[(substituted)azo]phenyl]sulfonyl]amino]-, coupled with aminophenol, diazotized aminobenzoic acid, diazotized...

40 CFR 721.5286 - Benzenediazonium, [[[[(substituted) azo]phenyl]sulfonyl]amino]-, coupled with aminophenol...

Code of Federal Regulations, 2011 CFR

2011-07-01

...) azo]phenyl]sulfonyl]amino]-, coupled with aminophenol, diazotized aminobenzoic acid, diazotized..., [[[[(substituted) azo]phenyl]sulfonyl]amino]-, coupled with aminophenol, diazotized aminobenzoic acid, diazotized..., [[[[(substituted)azo]phenyl]sulfonyl]amino]-, coupled with aminophenol, diazotized aminobenzoic acid, diazotized...

Background of the Hammett equation as observed for isolated molecules: meta- and para-substituted benzoic acids.

PubMed

Exner, Otto; Böhm, Stanislav

2002-09-06

Fundamental model compounds for the Hammett equation, meta- and para-substituted benzoic acids, were investigated by the density functional theory at the B3LYP/6-311+G(d,p) level. Energies of 25 acids and of their anions were calculated in all possible conformations and from them the energies of the assumed mixture of conformers. Relative acidities correlated with the experimental gas-phase acidities almost within the experimental uncertainty, much more precisely than in the case of previous calculations at lower levels. Dissection of the substituent effects into those operating in the acid molecule and in the anion was carried out by means of isodesmic reactions starting from monosubstituted benzenes. Both effects are cooperating in the resulting effect on the acidity; those in the acid molecule are smaller but not negligible. They are also responsible for some deviations from the Hammett equation (through-resonance of para donor substituents) and for the weaker resonance in the acid molecule in meta derivatives; in the anions the inductive and resonance effects are almost equal. On the other hand, the cooperation of effects in the acid and in the anion makes the relative acidity more sensitive to electron withdrawing and is probably one of the reasons why the Hammett equation is so generally valid.

A Single Amino Acid Substitution in the Core Protein of West Nile Virus Increases Resistance to Acidotropic Compounds

PubMed Central

Martín-Acebes, Miguel A.; Blázquez, Ana-Belén; de Oya, Nereida Jiménez; Escribano-Romero, Estela; Shi, Pei-Yong; Saiz, Juan-Carlos

2013-01-01

West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses. PMID:23874963

Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives.

PubMed

Takebayashi, Jun; Kaji, Hiroaki; Ichiyama, Kenji; Makino, Kazutaka; Gohda, Eiichi; Yamamoto, Itaru; Tai, Akihiro

2007-10-15

Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S> or =Trolox=uric acid> or =AA-2P> or =AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against AAPH-derived peroxyl radical (ROO(*)) was much lower than that of AA, the derivatives exerted equal or more potent protective effects on AAPH-induced hemolysis and membrane protein oxidation. In addition, the AA derivatives were found to react per se with ROO(*), not via AA as an intermediate. These findings suggest that secondary reactions between the AA derivative radical and ROO(*) play a part in hemolysis inhibition. Delayed addition of the AA derivatives after AAPH-induced oxidation of erythrocytes had already proceeded showed weaker inhibition of hemolysis compared to that of AA. These results suggest that the AA derivatives per se act as biologically effective antioxidants under moderate oxidative stress and that AA-2G and AA-2P may be able to act under severe oxidative stress after enzymatic conversion to AA in vivo.

PON-Sol: prediction of effects of amino acid substitutions on protein solubility.

PubMed

Yang, Yang; Niroula, Abhishek; Shen, Bairong; Vihinen, Mauno

2016-07-01

Solubility is one of the fundamental protein properties. It is of great interest because of its relevance to protein expression. Reduced solubility and protein aggregation are also associated with many diseases. We collected from literature the largest experimentally verified solubility affecting amino acid substitution (AAS) dataset and used it to train a predictor called PON-Sol. The predictor can distinguish both solubility decreasing and increasing variants from those not affecting solubility. PON-Sol has normalized correct prediction ratio of 0.491 on cross-validation and 0.432 for independent test set. The performance of the method was compared both to solubility and aggregation predictors and found to be superior. PON-Sol can be used for the prediction of effects of disease-related substitutions, effects on heterologous recombinant protein expression and enhanced crystallizability. One application is to investigate effects of all possible AASs in a protein to aid protein engineering. PON-Sol is freely available at http://structure.bmc.lu.se/PON-Sol The training and test data are available at http://structure.bmc.lu.se/VariBench/ponsol.php mauno.vihinen@med.lu.se Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Z-sinapinic acid: the change of the stereochemistry of cinnamic acids as rational synthesis of a new matrix for carbohydrate MALDI-MS analysis.

PubMed

Salum, María L; Itovich, Lucia M; Erra-Balsells, Rosa

2013-11-01

Successful application of matrix-assisted laser desorption/ionization (MALDI) MS started with the introduction of efficient matrices such as cinnamic acid derivatives (i.e. 3,5-dimethoxy-4-hydroxycinnamic acid, SA; α-cyano-4-hydroxycinnamic acid). Since the empirical founding of these matrices, other commercial available cinnamic acids with different nature and location of substituents at benzene ring were attempted. Rational design and synthesis of new cinnamic acids have been recently described too. Because the presence of a rigid double bond in its molecule structure, cinnamic acids can exist as two different geometric isomers, the E-form and Z-form. Commercial available cinnamic acids currently used as matrices are the geometric isomers trans or E (E-cinnamic and trans-cinnamic acids). As a new rational design of MALDI matrices, Z-cinnamic acids were synthesized, and their properties as matrices were studied. Their performance was compared with that of the corresponding E-isomer and classical crystalline matrices (3,5-dihydroxybenzoic acid; norharmane) in the analysis of neutral/sulfated carbohydrates. Herein, we demonstrate the outstanding performance for Z-SA. Sulfated oligosaccharides were detected in negative ion mode, and the dissociation of sulfate groups was almost suppressed. Additionally, to better understand the quite different performance of each geometric isomer as matrix, the physical and morphological properties as well as the photochemical stability in solid state were studied. The influence of the E/Z photoisomerization of the matrix during MALDI was evaluated. Finally, molecular modeling (density functional theory study) of the optimized geometry and stereochemistry of E-cinnamic and Z-cinnamic acids revealed some factors governing the analyte-matrix interaction. Copyright © 2013 John Wiley & Sons, Ltd.

The Effect of Two Amino acid Residue Substitutions via RNA Editing on Dark-operative Protochlorophyllide Oxidoreductase in the Black Pine Chloroplasts.

PubMed

Yamamoto, Haruki; Kusumi, Junko; Yamakawa, Hisanori; Fujita, Yuichi

2017-05-24

Dark-operative protochlorophyllide oxidoreductase (DPOR) is a key enzyme to produce chlorophyll in the dark. Among photosynthetic eukaryotes, all three subunits chlL, chlN, and chlB are encoded by plastid genomes. In some gymnosperms, two codons of chlB mRNA are changed by RNA editing to codons encoding evolutionarily conserved amino acid residues. However, the effect of these substitutions on DPOR activity remains unknown. We first prepared cyanobacterial ChlB variants with amino acid substitution(s) to mimic ChlB translated from pre-edited mRNA. Their activities were evaluated by measuring chlorophyll content of dark-grown transformants of a chlB-lacking mutant of the cyanobacterium Leptolyngbya boryana that was complemented with pre-edited mimic chlB variants. The chlorophyll content of the transformant cells expressing the ChlB variant from the fully pre-edited mRNA was only one-fourth of the control cells. Co-purification experiments of ChlB with Strep-ChlN suggested that a stable complex with ChlN is greatly impaired in the substituted ChlB variant. We then confirmed that RNA editing efficiency was markedly greater in the dark than in the light in cotyledons of the black pine Pinus thunbergii. These results indicate that RNA editing on chlB mRNA is important to maintain appropriate DPOR activity in black pine chloroplasts.

Crucial aspects of high performance thin layer chromatography quantitative validation. The case of determination of rosmarinic acid in different matrices.

PubMed

Coran, Silvia A; Mulas, Stefano; Mulinacci, Nadia

2012-01-13

A new HPTLC method was envisaged to determine rosmarinic acid (RA) in different matrices with the aim of testing the influence of optimizing the main HPTLC operative parameters in view of a more stringent validation process. HPTLC LiChrospher silica gel 60 F254s, 20 cm × 10 cm, plates with toluene:ethyl formate:formic acid (6:4:1, v/v) as the mobile phase were used. Densitometric determinations were performed in reflectance mode at 330 nm. The method was validated giving rise to a dependable and high throughput procedure well suited to routine applications. RA was quantified in the range of 132-660 ng with RSD of repeatability and intermediate precision not exceeding 2.0% and accuracy within the acceptance limits. The method was tested on several commercial preparations containing RA in different amounts. Copyright © 2011 Elsevier B.V. All rights reserved.

Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme.

PubMed Central

Daar, I O; Artymiuk, P J; Phillips, D C; Maquat, L E

1986-01-01

Triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1) deficiency is a recessive disorder that results in hemolytic anemia and neuromuscular dysfunction. To determine the molecular basis of this disorder, a TPI allele from two unrelated patients homozygous for TPI deficiency was compared with an allele from a normal individual. Each disease-associated sequence harbors a G X C----C X G transversion in the codon for amino acid-104 and specifies a structurally altered protein in which a glutamate residue is replaced by an aspartate residue. The importance of glutamate-104 to enzyme structure and function is implicated by its conservation in the TPI protein of all species that have been characterized to date. The glutamate-to-aspartate substitution results in a thermolabile enzyme as demonstrated by assays of TPI activity in cultured fibroblasts of each patient and cultured Chinese hamster ovary (CHO) cells that were stably transformed with the mutant alleles. Although this substitution conserves the overall charge of amino acid-104, the x-ray crystal structure of chicken TPI indicates that the loss of a side-chain methylene group (-CH2CH2COO- ---- -CH2COO-) is sufficient to disrupt the counterbalancing of charges that normally exists within a hydrophobic pocket of the native enzyme. Images PMID:2876430

Determination of arsenic species in solid matrices utilizing supercritical fluid extraction coupled with gas chromatography after derivatization with thioglycolic acid n-butyl ester.

PubMed

Wang, Zhifeng; Cui, Zhaojie

2016-12-01

A method using derivatization and supercritical fluid extraction coupled with gas chromatography was developed for the analysis of dimethylarsinate, monomethylarsonate and inorganic arsenic simultaneously in solid matrices. Thioglycolic acid n-butyl ester was used as a novel derivatizing reagent. A systematic discussion was made to investigate the effects of pressure, temperature, flow rate of the supercritical CO 2 , extraction time, concentration of the modifier, and microemulsion on extraction efficiency. The application for real environmental samples was also studied. Results showed that thioglycolic acid n-butyl ester was an effective derivatizing reagent that could be applied for arsenic speciation. Using methanol as modifier of the supercritical CO 2 can raise the extraction efficiency, which can be further enhanced by adding a microemulsion that contains Triton X-405. The optimum extraction conditions were: 25 MPa, 90°C, static extraction for 10 min, dynamic extraction for 25 min with a flow rate of 2.0 mL/min of supercritical CO 2 modified by 5% v/v methanol and microemulsion. The detection limits of dimethylarsinate, monomethylarsonate, and inorganic arsenic in solid matrices were 0.12, 0.26, and 1.1 mg/kg, respectively. The optimized method was sensitive, convenient, and reliable for the extraction and analysis of different arsenic species in solid samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Release and diffusional modeling of metronidazole lipid matrices.

PubMed

Ozyazici, Mine; Gökçe, Evren H; Ertan, Gökhan

2006-07-01

In this study, the first aim was to investigate the swelling and relaxation properties of lipid matrix on diffusional exponent (n). The second aim was to determine the desired release profile of metronidazole lipid matrix tablets. We prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic acid, Cutina HR, Precirol ATO 5, and Compritol ATO 888 by hot fusion method and pressed the tablets of these granules. In vitro release test was performed using a standard USP dissolution apparatus I (basket method) with a stirring rate of 100 rpm at 37 degrees C in 900 ml of 0.1 N hydrochloric acid, adjusted to pH 1.2, as medium for the formulations' screening. Hardness, diameter-height ratio, friability, and swelling ratio were determined. Target release profile of metronidazole was also drawn. Stearic acid showed the highest and Carnauba wax showed the lowest release rates in all formulations used. Swelling ratios were calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for Cutina HR, Beeswax, Precirol ATO 5, and Compritol ATO 888, respectively. There was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax, was detected. According to the power law analysis, the diffusion mechanism was expressed as pure Fickian for Stearic acid and Carnauba wax and the coupling of Fickian and relaxation contributions for other Cutina HR, Beeswax, Compritol ATO 888, and Precirol ATO 5 tablets. It was found that Beeswax (kd=2.13) has a very close drug release rate with the target profile (kt=1.95). Our results suggested that swelling and relaxation properties of lipid matrices should be examined together for a correct evaluation on drug diffusion mechanism of insoluble matrices.

Colonization of bone matrices by cellular components

NASA Astrophysics Data System (ADS)

Shchelkunova, E. I.; Voropaeva, A. A.; Korel, A. V.; Mayer, D. A.; Podorognaya, V. T.; Kirilova, I. A.

2017-09-01

Practical surgery, traumatology, orthopedics, and oncology require bioengineered constructs suitable for replacement of large-area bone defects. Only rigid/elastic matrix containing recipient's bone cells capable of mitosis, differentiation, and synthesizing extracellular matrix that supports cell viability can comply with these requirements. Therefore, the development of the techniques to produce structural and functional substitutes, whose three-dimensional structure corresponds to the recipient's damaged tissues, is the main objective of tissue engineering. This is achieved by developing tissue-engineering constructs represented by cells placed on the matrices. Low effectiveness of carrier matrix colonization with cells and their uneven distribution is one of the major problems in cell culture on various matrixes. In vitro studies of the interactions between cells and material, as well as the development of new techniques for scaffold colonization by cellular components are required to solve this problem.

Fabrication of calcium phosphate–calcium sulfate injectable bone substitute using hydroxy-propyl-methyl-cellulose and citric acid

PubMed Central

Thai, Van Viet

2010-01-01

In this study, an injectable bone substitute (IBS) consisting of citric acid, chitosan, and hydroxyl propyl methyl cellulose (HPMC) as the liquid phase and tetra calcium phosphate (TTCP), dicalcium phosphate dihydrate (DCPD) and calcium sulfate dehydrate (CSD, CaSO4·2H2O) powders as the solid phase, were fabricated. Two groups were classified based on the percent of citric acid in the liquid phase (20, 40 wt%). In each groups, the HPMC percentage was 0, 2, and 4 wt%. An increase in compressive strength due to changes in morphology was confirmed by scanning electron microscopy images. A good conversion rate of HAp at 20% citric acid was observed in the XRD profiles. In addition, HPMC was not obviously affected by apatite formation. However, both HPMC and citric acid increased the compressive strength of IBS. The maximum compressive strength for IBS was with 40% citric acid and 4% HPMC after 14 days of incubation in 100% humidity at 37°C. PMID:20333539

Antiproliferative activity and SARs of caffeic acid esters with mono-substituted phenylethanols moiety.

PubMed

Xie, Jin; Yang, Fengzhi; Zhang, Man; Lam, Celine; Qiao, Yixue; Xiao, Jia; Zhang, Dongdong; Ge, Yuxuan; Fu, Lei; Xie, Dongsheng

2017-01-15

A series of CAPE derivatives with mono-substituted phenylethanols moiety were synthesized and evaluated by MTT assay on growth of 4 human cancer cell lines (Hela, DU-145, MCF-7 and ECA-109). The substituent effects on the antiproliferative activity were systematically investigated for the first time. It was found that electron-donating and hydrophobic substituents at 2'-position of phenylethanol moiety could significantly enhance CAPE's antiproliferative activity. 2'-Propoxyl derivative, as a novel caffeic acid ester, exhibited exquisite potency (IC 50 =0.4±0.02 & 0.6±0.03μM against Hela and DU-145 respectively). Copyright © 2016 Elsevier Ltd. All rights reserved.

Fungible Correlation Matrices: A Method for Generating Nonsingular, Singular, and Improper Correlation Matrices for Monte Carlo Research.

PubMed

Waller, Niels G

2016-01-01

For a fixed set of standardized regression coefficients and a fixed coefficient of determination (R-squared), an infinite number of predictor correlation matrices will satisfy the implied quadratic form. I call such matrices fungible correlation matrices. In this article, I describe an algorithm for generating positive definite (PD), positive semidefinite (PSD), or indefinite (ID) fungible correlation matrices that have a random or fixed smallest eigenvalue. The underlying equations of this algorithm are reviewed from both algebraic and geometric perspectives. Two simulation studies illustrate that fungible correlation matrices can be profitably used in Monte Carlo research. The first study uses PD fungible correlation matrices to compare penalized regression algorithms. The second study uses ID fungible correlation matrices to compare matrix-smoothing algorithms. R code for generating fungible correlation matrices is presented in the supplemental materials.

Preparing composite materials from matrices of processable aromatic polyimide thermoplastic blends

NASA Technical Reports Server (NTRS)

Johnston, Norman J. (Inventor); St.clair, Terry L. (Inventor); Baucom, Robert M. (Inventor); Gleason, John R. (Inventor)

1991-01-01

Composite materials with matrices of tough, thermoplastic aromatic polyimides are obtained by blending semi-crystalline polyimide powders with polyamic acid solutions to form slurries, which are used in turn to prepare prepregs, the consolidation of which into finished composites is characterized by excellent melt flow during processing.

ArrayPitope: Automated Analysis of Amino Acid Substitutions for Peptide Microarray-Based Antibody Epitope Mapping.

PubMed

Hansen, Christian Skjødt; Østerbye, Thomas; Marcatili, Paolo; Lund, Ole; Buus, Søren; Nielsen, Morten

2017-01-01

Identification of epitopes targeted by antibodies (B cell epitopes) is of critical importance for the development of many diagnostic and therapeutic tools. For clinical usage, such epitopes must be extensively characterized in order to validate specificity and to document potential cross-reactivity. B cell epitopes are typically classified as either linear epitopes, i.e. short consecutive segments from the protein sequence or conformational epitopes adapted through native protein folding. Recent advances in high-density peptide microarrays enable high-throughput, high-resolution identification and characterization of linear B cell epitopes. Using exhaustive amino acid substitution analysis of peptides originating from target antigens, these microarrays can be used to address the specificity of polyclonal antibodies raised against such antigens containing hundreds of epitopes. However, the interpretation of the data provided in such large-scale screenings is far from trivial and in most cases it requires advanced computational and statistical skills. Here, we present an online application for automated identification of linear B cell epitopes, allowing the non-expert user to analyse peptide microarray data. The application takes as input quantitative peptide data of fully or partially substituted overlapping peptides from a given antigen sequence and identifies epitope residues (residues that are significantly affected by substitutions) and visualize the selectivity towards each residue by sequence logo plots. Demonstrating utility, the application was used to identify and address the antibody specificity of 18 linear epitope regions in Human Serum Albumin (HSA), using peptide microarray data consisting of fully substituted peptides spanning the entire sequence of HSA and incubated with polyclonal rabbit anti-HSA (and mouse anti-rabbit-Cy3). The application is made available at: www.cbs.dtu.dk/services/ArrayPitope.

Deterministic matrices matching the compressed sensing phase transitions of Gaussian random matrices

PubMed Central

Monajemi, Hatef; Jafarpour, Sina; Gavish, Matan; Donoho, David L.; Ambikasaran, Sivaram; Bacallado, Sergio; Bharadia, Dinesh; Chen, Yuxin; Choi, Young; Chowdhury, Mainak; Chowdhury, Soham; Damle, Anil; Fithian, Will; Goetz, Georges; Grosenick, Logan; Gross, Sam; Hills, Gage; Hornstein, Michael; Lakkam, Milinda; Lee, Jason; Li, Jian; Liu, Linxi; Sing-Long, Carlos; Marx, Mike; Mittal, Akshay; Monajemi, Hatef; No, Albert; Omrani, Reza; Pekelis, Leonid; Qin, Junjie; Raines, Kevin; Ryu, Ernest; Saxe, Andrew; Shi, Dai; Siilats, Keith; Strauss, David; Tang, Gary; Wang, Chaojun; Zhou, Zoey; Zhu, Zhen

2013-01-01

In compressed sensing, one takes samples of an N-dimensional vector using an matrix A, obtaining undersampled measurements . For random matrices with independent standard Gaussian entries, it is known that, when is k-sparse, there is a precisely determined phase transition: for a certain region in the (,)-phase diagram, convex optimization typically finds the sparsest solution, whereas outside that region, it typically fails. It has been shown empirically that the same property—with the same phase transition location—holds for a wide range of non-Gaussian random matrix ensembles. We report extensive experiments showing that the Gaussian phase transition also describes numerous deterministic matrices, including Spikes and Sines, Spikes and Noiselets, Paley Frames, Delsarte-Goethals Frames, Chirp Sensing Matrices, and Grassmannian Frames. Namely, for each of these deterministic matrices in turn, for a typical k-sparse object, we observe that convex optimization is successful over a region of the phase diagram that coincides with the region known for Gaussian random matrices. Our experiments considered coefficients constrained to for four different sets , and the results establish our finding for each of the four associated phase transitions. PMID:23277588

A stochastic evolution model for residue Insertion-Deletion Independent from Substitution.

PubMed

Lèbre, Sophie; Michel, Christian J

2010-12-01

We develop here a new class of stochastic models of gene evolution based on residue Insertion-Deletion Independent from Substitution (IDIS). Indeed, in contrast to all existing evolution models, insertions and deletions are modeled here by a concept in population dynamics. Therefore, they are not only independent from each other, but also independent from the substitution process. After a separate stochastic analysis of the substitution and the insertion-deletion processes, we obtain a matrix differential equation combining these two processes defining the IDIS model. By deriving a general solution, we give an analytical expression of the residue occurrence probability at evolution time t as a function of a substitution rate matrix, an insertion rate vector, a deletion rate and an initial residue probability vector. Various mathematical properties of the IDIS model in relation with time t are derived: time scale, time step, time inversion and sequence length. Particular expressions of the nucleotide occurrence probability at time t are given for classical substitution rate matrices in various biological contexts: equal insertion rate, insertion-deletion only and substitution only. All these expressions can be directly used for biological evolutionary applications. The IDIS model shows a strongly different stochastic behavior from the classical substitution only model when compared on a gene dataset. Indeed, by considering three processes of residue insertion, deletion and substitution independently from each other, it allows a more realistic representation of gene evolution and opens new directions and applications in this research field. Copyright © 2010 Elsevier Ltd. All rights reserved.

RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

NASA Astrophysics Data System (ADS)

Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang-Seok; Hong, Suck Won; Han, Dong-Wook; Kim, Chuntae; Oh, Jin-Woo

2015-01-01

Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic- co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

Comparative analysis of poly-glycolic acid-based hybrid polymer starter matrices for in vitro tissue engineering.

PubMed

Generali, Melanie; Kehl, Debora; Capulli, Andrew K; Parker, Kevin K; Hoerstrup, Simon P; Weber, Benedikt

2017-10-01

Biodegradable scaffold matrixes form the basis of any in vitro tissue engineering approach by acting as a temporary matrix for cell proliferation and extracellular matrix deposition until the scaffold is replaced by neo-tissue. In this context several synthetic polymers have been investigated, however a concise systematic comparative analyses is missing. Therefore, the present study systematically compares three frequently used polymers for the in vitro engineering of extracellular matrix based on poly-glycolic acid (PGA) under static as well as dynamic conditions. Ultra-structural analysis was used to examine the polymers structure. For tissue engineering (TE) three human fibroblast cell lines were seeded on either PGA-poly-4-hydroxybutyrate (P4HB), PGA-poly-lactic acid (PLA) or PGA-poly-caprolactone (PCL) patches. These patches were analyzed after 21days of culture qualitative by histology and quantitative by determining the amount of DNA, glycosaminoglycan and hydroxyproline. We found that PGA-P4HB and PGA-PLA scaffolds enhance tissue formation significantly higher than PGA-PCL scaffolds (p<0.05). Polymer remnants were visualized by polarization microscopy. In addition, biomechanical properties of the tissue engineered patches were determined in comparison to native tissue. This study may allow future studies to specifically select certain polymer starter matrices aiming at specific tissue properties of the bioengineered constructs in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

A Facile Semi-Synthetic Approach towards Halogen-Substituted Aminobenzoic Acid Analogues of Platensimycin.

PubMed

Qiu, Lin; Tian, Kai; Pan, Jian; Jiang, Lin; Yang, Hu; Zhu, Xiangcheng; Shen, Ben; Duan, Yanwen; Huang, Yong

2017-02-09

Platensimycin (PTM), produced by several strains of Streptomyces platensis, is a promising drug lead for infectious diseases and diabetes. The recent pilot-scale production of PTM from S. platensis SB12026 has set the stage for the facile semi-synthesis of a focused library of PTM analogues. In this study, gram-quantity of platensic acid (PTMA) was prepared by the sulfuric acid-catalyzed ethanolysis of PTM, followed by a mild hydrolysis in aqueous lithium hydroxide. Three PTMA esters were also obtained in near quantitative yields in a single step, suggesting a facile route to make PTMA aliphatic esters. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU)-catalyzed coupling of PTMA and 33 aminobenzoates resulted in the synthesis of 28 substituted aminobenzoate analogues of PTM, among which 26 of them were reported for the first time. Several of the PTM analogues showed weak antibacterial activity against methicillin-resistant Staphylococcus aureus. Our study supported the potential utility to integrate natural product biosynthetic and semi-synthetic approaches for structure diversification.

Overdispersion of the Molecular Clock: Temporal Variation of Gene-Specific Substitution Rates in Drosophila

PubMed Central

Hartl, Daniel L.

2008-01-01

Simple models of molecular evolution assume that sequences evolve by a Poisson process in which nucleotide or amino acid substitutions occur as rare independent events. In these models, the expected ratio of the variance to the mean of substitution counts equals 1, and substitution processes with a ratio greater than 1 are called overdispersed. Comparing the genomes of 10 closely related species of Drosophila, we extend earlier evidence for overdispersion in amino acid replacements as well as in four-fold synonymous substitutions. The observed deviation from the Poisson expectation can be described as a linear function of the rate at which substitutions occur on a phylogeny, which implies that deviations from the Poisson expectation arise from gene-specific temporal variation in substitution rates. Amino acid sequences show greater temporal variation in substitution rates than do four-fold synonymous sequences. Our findings provide a general phenomenological framework for understanding overdispersion in the molecular clock. Also, the presence of substantial variation in gene-specific substitution rates has broad implications for work in phylogeny reconstruction and evolutionary rate estimation. PMID:18480070

Substitution determination of Fmoc‐substituted resins at different wavelengths

PubMed Central

Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

2017-01-01

In solid‐phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc‐substituted resins, substitution determination is often performed by suspending the Fmoc‐protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene–piperidine adduct that is quantified by ultraviolet–visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene–piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert–Beer's law, together with the substance‐specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol−1 cm−1 and 8100 l mol−1 cm−1 have been reported for the dibenzofulvene–piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. PMID:28635051

Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2 -Amino Acids.

PubMed

Nascimento de Oliveira, Marllon; Arseniyadis, Stellios; Cossy, Janine

2018-04-03

We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β 2,2 -amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

ArrayPitope: Automated Analysis of Amino Acid Substitutions for Peptide Microarray-Based Antibody Epitope Mapping

PubMed Central

Hansen, Christian Skjødt; Østerbye, Thomas; Marcatili, Paolo; Lund, Ole; Buus, Søren

2017-01-01

Identification of epitopes targeted by antibodies (B cell epitopes) is of critical importance for the development of many diagnostic and therapeutic tools. For clinical usage, such epitopes must be extensively characterized in order to validate specificity and to document potential cross-reactivity. B cell epitopes are typically classified as either linear epitopes, i.e. short consecutive segments from the protein sequence or conformational epitopes adapted through native protein folding. Recent advances in high-density peptide microarrays enable high-throughput, high-resolution identification and characterization of linear B cell epitopes. Using exhaustive amino acid substitution analysis of peptides originating from target antigens, these microarrays can be used to address the specificity of polyclonal antibodies raised against such antigens containing hundreds of epitopes. However, the interpretation of the data provided in such large-scale screenings is far from trivial and in most cases it requires advanced computational and statistical skills. Here, we present an online application for automated identification of linear B cell epitopes, allowing the non-expert user to analyse peptide microarray data. The application takes as input quantitative peptide data of fully or partially substituted overlapping peptides from a given antigen sequence and identifies epitope residues (residues that are significantly affected by substitutions) and visualize the selectivity towards each residue by sequence logo plots. Demonstrating utility, the application was used to identify and address the antibody specificity of 18 linear epitope regions in Human Serum Albumin (HSA), using peptide microarray data consisting of fully substituted peptides spanning the entire sequence of HSA and incubated with polyclonal rabbit anti-HSA (and mouse anti-rabbit-Cy3). The application is made available at: www.cbs.dtu.dk/services/ArrayPitope. PMID:28095436

Intake of dietary saturated fatty acids and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort: associations by types, sources of fatty acids and substitution by macronutrients.

PubMed

Liu, Shengxin; van der Schouw, Yvonne T; Soedamah-Muthu, Sabita S; Spijkerman, Annemieke M W; Sluijs, Ivonne

2018-03-09

The association between dietary saturated fatty acids (SFA) intake and type 2 diabetes (T2D) remains unclear. This study aimed at investigating the association between SFA intake and T2D risk based on (1) individual SFA (differing in carbon chain length), (2) food sources of SFA and (3) the substituting macronutrients. 37,421 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included in this study. Baseline dietary intake was assessed by a validated food frequency questionnaire. T2D risks were estimated by Cox regression models adjusted for non-dietary and dietary covariates. 893 incident T2D cases were documented during 10.1-year follow-up. We observed no association between total SFA and T2D risk. Marginally inverse associations were found for lauric acid (HR per 1 SD of energy%, 95% CI 0.92, 0.85-0.99), myristic acid (0.89, 0.79-0.99), margaric acid (0.84, 0.73-0.97), odd-chain SFA (pentadecylic plus margaric acids; 0.88, 0.79-0.99), and cheese derived SFA (0.90, 0.83-0.98). Soft and liquid fats derived SFA was found related to higher T2D risk (1.08, 1.01-1.17). When substituting SFA by proteins, carbohydrates and polyunsaturated fatty acids, significantly higher risks of T2D were observed (HRs per 1 energy% ranging from 1.05 to 1.15). In this Dutch population, total SFA does not relate to T2D risk. Rather, the association may depend on the types and food sources of SFA. Cheese-derived SFA and individual SFA that are commonly found in cheese, were significantly related to lower T2D risks. We cannot exclude the higher T2D risks found for soft and liquid fats derived SFA and for substituting SFA with other macronutrients are influenced by residual confounding by trans fatty acids or limited intake variation in polyunsaturated fatty acids and vegetable protein.

Development of calcium phosphate cement using chitosan and citric acid for bone substitute materials.

PubMed

Yokoyama, Atsuro; Yamamoto, Satoru; Kawasaki, Takao; Kohgo, Takao; Nakasu, Masanori

2002-02-01

We developed a calcium phosphate cement that could be molded into any desired shape due to its chewing-gum-like consistency after mixing. The powder component of the cement consists of alpha-tricalcium phosphate and tetracalcium phosphate, which were made by decomposition of hydroxyapatite ceramic blocks. The liquid component consists of citric acid, chitosan and glucose solution. In this study, we used 20% citric acid (group 20) and 45% citric acid (group 45). The mechanical properties and biocompatibility of this new cement were investigated. The setting times of cements were 5.5 min, in group 20 and 6.4 min, in group 45. When incubated in physiological saline, the cements were transformed to hydroxyapatite at 3, and 6 weeks, the compressive strengths were 15.6 and 20.7 MPa, in group 45 and group 20, respectively. The inflammatory response around the cement implanted on the bone and in the subcutaneous tissue in rats was more prominent in group 45 than in group 20 at 1 week after surgery. After 4 weeks, the inflammation disappeared and the cement had bound to bone in both groups. These results indicate that this new calcium phosphate cement is a suitable bone substitute material and that the concentration of citric acid in the liquid component affects its mechanical properties and biocompatibility.

Amino acid substitution converts WEREWOLF function from an activator to a repressor of Arabidopsis non-hair cell development.

PubMed

Tominaga-Wada, Rumi; Nukumizu, Yuka; Wada, Takuji

2012-02-01

Root hair cell or non-hair cell fate determination in Arabidopsis thaliana root epidermis is model system for plant cell development. Two types of MYB transcription factors, the R2R3-type MYB, WEREWOLF (WER), and an R3-type MYB, CAPRICE (CPC), are involved in this cell fate determination process. To study the molecular basis of this process, we analyzed the functional relationship of WER and CPC. WER-CPC chimeric constructs were made from WER where all or parts of the MYB R3 region were replaced with the corresponding regions from CPC R3, and the constructs were introduced into the cpc-2 mutant. Although, the WER gene did not rescue the cpc-2 mutant 'small number of root hairs' phenotype, the WER-CPC chimera with two amino acids substitution (WC6) completely rescued the cpc-2 mutant phenotype. Furthermore, the WER-CPC chimera with 37 amino acids substitution (WC5) excessively rescued the cpc-2 mutant and induced 2.5 times more root hairs than wild-type. Consistent with this phenotype, GL2 gene expression was strongly reduced in WC5 in a cpc-2 background. Our results suggest that swapping at least two amino acids is sufficient to convert WER to CPC function. Therefore, these key residues may have strongly contributed to the selection of these important functions over evolution. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Intrinsic character of Stokes matrices

NASA Astrophysics Data System (ADS)

Gagnon, Jean-François; Rousseau, Christiane

2017-02-01

Two germs of linear analytic differential systems x k + 1Y‧ = A (x) Y with a non-resonant irregular singularity are analytically equivalent if and only if they have the same eigenvalues and equivalent collections of Stokes matrices. The Stokes matrices are the transition matrices between sectors on which the system is analytically equivalent to its formal normal form. Each sector contains exactly one separating ray for each pair of eigenvalues. A rotation in S allows supposing that R+ lies in the intersection of two sectors. Reordering of the coordinates of Y allows ordering the real parts of the eigenvalues, thus yielding triangular Stokes matrices. However, the choice of the rotation in x is not canonical. In this paper we establish how the collection of Stokes matrices depends on this rotation, and hence on a chosen order of the projection of the eigenvalues on a line through the origin.

Superbasic alkyl-substituted bisphosphazene proton sponges: a new class of deprotonating matrices for negative ion matrix-assisted ionization/laser desorption mass spectrometry of low molecular weight hardly ionizable analytes.

PubMed

Calvano, C D; Cataldi, T R I; Kögel, J F; Monopoli, A; Palmisano, F; Sundermeyer, J

2016-07-30

Here hardly ionizable and low molecular weight compounds are detected in negative ion mode by using novel superbasic proton sponges based on 1,8-bisphosphazenylnaphthalene (PN) as MALDI matrices. Among the selected proton sponges, 1,8-bis(trispyrrolidinophosphazenyl)naphthalene (TPPN) has shown the best behaviour as matrix since it allows the direct detection of intact cholesterol without derivatization also in real challenging samples. Very weakly acidic compounds such as sterols, steroids, fatty alcohols and saccharides were detected in reflectron negative ion mode by a MALDI TOF/TOF system equipped with a neodymium-doped yttrium lithium fluoride (Nd:YLF) laser (345 nm) with typical mass accuracy of 10 ppm. MS/MS experiments were performed by using ambient air as the collision gas. Contrary to traditional MALDI matrices, superbasic proton sponges allowed the easy deprotonation of an alcohol functional group without a previous chemical derivatization step. Experimental evidence indicates that analyte deprotonation is achieved in the condensed phase, i.e. PN superbasic proton sponges operate according to a recently proposed model named matrix assisted ionization/laser desorption (MAILD). A detection limit of 3 pmol/spot of cholesterol (model compound) with a signal-to-noise ratio ≥ 10 was typically obtained. For the first time, the usefulness of novel superbasic proton sponges is demonstrated for MALDI detection of hardly ionizable compounds such as sterols, steroids, fatty alcohols and saccharides. The leading candidate TPPN has been successfully applied for negative ion MAILD-MS analysis of cholesterol, fatty acids and phospholipids in egg yolk and brain tissue extracts. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Identification of single amino acid substitutions (SAAS) in neuraminidase from influenza a virus (H1N1) via mass spectrometry analysis coupled with de novo peptide sequencing.

PubMed

Peng, Qisheng; Wang, Zijian; Wu, Donglin; Li, Xiaoou; Liu, Xiaofeng; Sun, Wanchun; Liu, Ning

2016-08-01

Amino acid substitutions in the neuraminidase of the influenza virus are the main cause of the emergence of resistance to zanamivir or oseltamivir during seasonal influenza treatment; they are the result of non-synonymous mutations in the viral genome that can be successfully detected by polymer chain reaction (PCR)-based approaches. There is always an urgent need to detect variation in amino acid sequences directly at the protein level. Mass spectrometry coupled with de novo sequencing has been explored as an alternative and straightforward strategy for detecting amino acid substitutions, as well - this approach is the primary focus of the present study. Influenza virus (A/Puerto Rico/8/1934 H1N1) propagated in embryonated chicken eggs was purified by ultracentrifugation, followed by PNGase F treatment. The deglycosylated virion was lysed and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The gel band corresponding to neuraminidase was picked up and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. LC-MS/MS analyses, coupled with manual de novo sequencing, allowed the determination of three amino acid substitutions: R346K, S349 N, and S370I/L, in the neuraminidase from the influenza virus (A/Puerto Rico/8/1934 H1N1), which were located in three mutated peptides of the neuraminidase: YGNGVWIGK, TKNHSSR, and PNGWTETDI/LK, respectively. We found that the amino acid substitutions in the proteins of RNA viruses (including influenza A virus) resulting from non-synonymous gene mutations can indeed be directly analyzed via mass spectrometry, and that manual interpretation of the MS/MS data may be beneficial. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Kinetics of the substitution of dehydroacetic acid in tris (dehydroacetato) Fe(III) complex by 8-hydroxyquinoline, di- and tetra-hydroxyquinone

NASA Astrophysics Data System (ADS)

Fouad, D. M.; Ismail, N. M.; El-Gahami, M. A.; Ibrahim, S. A.

2007-06-01

The ligand substitution reactions of dehydroacetic acid (Hdha) in [Fe(dha) 3] with second ligand such as 8-hydroxyquinoline (Hquin), 1,4-dihydroxyanthraquinone (H 2dhaq) and 1,4,5,8-tetra-hydroxyanthraquinone (H 4thaq) were investigated spectrophotometrically by in low polarity solvents like benzene, chloroform and dichloromethane. It is deduced that the substitution reaction takes place through one successive step. The reaction was performed at four different temperatures (5-25) °C, and it exhibits a first order dependence on the concentration of the starting complex. The observed rate constant depends on the concentration of both leaving and entering ligands. The evaluation of the kinetic data gives activation parameters which support an associative mechanism in the transition states and the higher rate of substitution of the dha in Fe(dha) 3 complex is due to entropy effect. The solid complexes were synthesized and characterized by elemental analysis, IR and UV-vis spectral techniques.

A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on antigenic structural change.

PubMed

Ren, Fengrong; Tsubota, Asahito; Hirokawa, Takatsugu; Kumada, Hiromitsu; Yang, Ziheng; Tanaka, Hiroshi

2006-11-15

Amino acid substitutions in the S gene of hepatitis B virus (HBV), especially in the 'a' determinant region, have been suggested to affect the antigenicity of the virus and the clinical outcome of the infected patient. However, no convincing evidence has been presented for this hypothesis, partly because the 3D structure of the S protein has not been determined. Comparative analysis of viral genes offers an approach to testing this hypothesis, as it may reveal signals of natural selection and provide insights into the functional significance of the observed amino acid substitutions. In this study, we analyze HBV S gene sequences obtained from 24 patients infected with HBV genotypes B or C, together with 16 representative viral strains of HBV genotypes A-F retrieved from GenBank. We use phylogenetic methods to infer evolutionary changes among HBV genotypes and to identify amino acid residues potentially under positive selective pressure. Furthermore, we employ the fragment assembly method to predict structural changes in the S protein. The results showed that an amino acid substitution within the 'a' determinant, T126I, was unique to genotype C, may affect the antigenicity of the HBsAg, and may result in poorer clinical outcomes of patients infected with genotype C viral strains. We suggest that an integrated approach of evolutionary comparison and structural prediction is useful in generating hypotheses for further laboratory validation.

Substitution determination of Fmoc-substituted resins at different wavelengths.

PubMed

Eissler, Stefan; Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

2017-10-01

In solid-phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc-substituted resins, substitution determination is often performed by suspending the Fmoc-protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene-piperidine adduct that is quantified by ultraviolet-visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene-piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert-Beer's law, together with the substance-specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol -1  cm -1 and 8100 l mol -1  cm -1 have been reported for the dibenzofulvene-piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

Blocking of proteolytic processing and deletion of glycosaminoglycan side chain of mouse DMP1 by substituting critical amino acid residues.

PubMed

Peng, Tao; Huang, Bingzhen; Sun, Yao; Lu, Yongbo; Bonewald, Lynda; Chen, Shuo; Butler, William T; Feng, Jerry Q; D'Souza, Rena N; Qin, Chunlin

2009-01-01

Dentin matrix protein 1 (DMP1) is present in the extracellular matrix (ECM) of dentin and bone as processed NH(2)- and COOH-terminal fragments, resulting from proteolytic cleavage at the NH(2) termini of 4 aspartic acid residues during rat DMP1 processing. One cleavage site residue, Asp(181) (corresponding to Asp(197) of mouse DMP1), and its flanking region are highly conserved across species. We speculate that cleavage at the NH(2) terminus of Asp(197) of mouse DMP1 represents an initial, first-step scission in the whole cascade of proteolytic processing. To test if Asp(197) is critical for initiating the proteolytic processing of mouse DMP1, we substituted Asp(197) with Ala(197) by mutating the corresponding nucleotides of mouse cDNA that encode this amino acid residue. This mutant DMP1 cDNA was cloned into a pcDNA3.1 vector. Data from transfection experiments indicated that this single substitution blocked the proteolytic processing of mouse DMP1 in HEK-293 cells, indicating that cleavage at the NH(2) terminus of Asp(197) is essential for exposing other cleavage sites for the conversion of DMP1 to its fragments. The NH(2)-terminal fragment of DMP1 occurs as a proteoglycan form (DMP1-PG) that contains a glycosaminoglycan (GAG) chain. Previously, we showed that a GAG chain is linked to Ser(74) in rat DMP1 (Ser(89) in mouse DMP1). To confirm that mouse DMP1-PG possesses a single GAG chain attached to Ser(89), we substituted Ser(89) by Gly(89). Data from transfection analysis indicated that this substitution completely prevented formation of the GAG-containing form, confirming that DMP1-PG contains a single GAG chain attached to Ser(89) in mouse DMP1. Copyright 2008 S. Karger AG, Basel.

Pyridine radical cation and its fluorine substituted derivatives

USGS Publications Warehouse

Bondybey, V.E.; English, J.H.; Shiley, R.H.

1982-01-01

The spectra and relaxation of the pyridine cation and of several of its fluorinated derivatives are studied in low temperature Ne matrices. The ions are generated by direct photoionization of the parent compounds. Of the compounds studied, laser induced → and → fluorescence is observed only for the 2, 6‐difluoropyridine cation. The analysis of the spectrum indicates that the ion is planar both in the and states. The large variety in the spectroscopic and relaxation behavior of fluoropyridine radical cations is explained in terms of their electronic structure and of the differential shifts of the individual electronic states caused by the fluorine substitution.

Effects of Hypoxanthine Substitution in Peptide Nucleic Acids Targeting KRAS2 Oncogenic mRNA Molecules: Theory and Experiment

PubMed Central

Sanders, Jeffrey M.; Wampole, Matthew E.; Chen, Chang-Po; Sethi, Dalip; Singh, Amrita; Dupradeau, François-Yves; Wang, Fan; Gray, Brian D.; Thakur, Mathew L.; Wickstrom, Eric

2013-01-01

Genetic disorders can arise from single base substitutions in a single gene. A single base substitution for wild type guanine in the twelfth codon of KRAS2 mRNA occurs frequently to initiate lung, pancreatic, and colon cancer. We have observed single base mismatch specificity in radioimaging of mutant KRAS2 mRNA in tumors in mice by in vivo hybridization with radiolabeled peptide nucleic acid (PNA) dodecamers. We hypothesized that multi-mutant specificity could be achieved with a PNA dodecamer incorporating hypoxanthine, which can form Watson-Crick basepairs with adenine, cytosine, thymine, and uracil. Using molecular dynamics simulations and free energy calculations, we show that hypoxanthine substitutions in PNAs are tolerated in KRAS2 RNA-PNA duplexes where wild type guanine is replaced by mutant uracil or adenine in RNA. To validate our predictions, we synthesized PNA dodecamers with hypoxanthine, and then measured the thermal stability of RNA-PNA duplexes. Circular dichroism thermal melting results showed that hypoxanthine-containing PNAs are more stable in duplexes where hypoxanthine-adenine and hypoxanthine-uracil base pairs are formed than single mismatch duplexes or duplexes containing hypoxanthine-guanine opposition. PMID:23972113

Molecular characterization of amino acid deletion in VP1 (1D) protein and novel amino acid substitutions in 3D polymerase protein of foot and mouth disease virus subtype A/Iran87.

PubMed

Esmaelizad, Majid; Jelokhani-Niaraki, Saber; Hashemnejad, Khadije; Kamalzadeh, Morteza; Lotfi, Mohsen

2011-12-01

The nucleotide sequence of the VP1 (1D) and partial 3D polymerase (3D(pol)) coding regions of the foot and mouth disease virus (FMDV) vaccine strain A/Iran87, a highly passaged isolate (~150 passages), was determined and aligned with previously published FMDV serotype A sequences. Overall analysis of the amino acid substitutions revealed that the partial 3D(pol) coding region contained four amino acid alterations. Amino acid sequence comparison of the VP1 coding region of the field isolates revealed deletions in the highly passaged Iranian isolate (A/Iran87). The prominent G-H loop of the FMDV VP1 protein contains the conserved arginine-glycine-aspartic acid (RGD) tripeptide, which is a well-known ligand for a specific cell surface integrin. Despite losing the RGD sequence of the VP1 protein and an Asp(26)→Glu substitution in a beta sheet located within a small groove of the 3D(pol) protein, the virus grew in BHK 21 suspension cell cultures. Since this strain has been used as a vaccine strain, it may be inferred that the RGD deletion has no critical role in virus attachment to the cell during the initiation of infection. It is probable that this FMDV subtype can utilize other pathways for cell attachment.

Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted C(α) amino acids.

PubMed

Hicks, Rickey P

2016-09-15

Eleven antimicrobial peptides (AMP) based on the incorporation of cyclic tetra substituted C(α) amino acids, as well as other unnatural amino acids were designed, synthesized and screened for in vitro activity against 18 strains of bacteria as well as 12 cancer cell lines. The AMPs discussed herein are derived from the following peptide sequence: Ac-GF(X)G(X)B(X)G(X)F(X)G(X)GB(X)BBBB-amide, X=any one of the following residues, A5c, A6c, Tic or Oic and B=any one of the following residues, Arg, Lys, Orn, Dpr or Dab. A diversity of in vitro inhibitory activity was observed for these AMPs. Several analogs exhibited single digit μM activity against drug resistant bacteria including; multiple drug resistant Mycobacterium tuberculosis, extremely drug resistant Mycobacterium tuberculosis and MRSA. The physicochemical properties of the basic amino acid residues incorporated into these AMPs seem to play a major role in defining antibacterial activity. Overall hydrophobicity seems to play a limited role in defining antibacterial activity. The ESKAPE pathogens were used to compare the activity of these AMPs to another family of synthetic AMPs incorporating the unnatural amino acids Tic and Oic. In most cases similarly substituted members of both families exhibited similar inhibitory activity against the ESKAPE pathogens. In specific cases differences in activity as high as 15 fold were observed between analogs. In addition four of these AMPs exhibited promising IC50 (<7.5μM) values against 12 different and diverse cancer cell lines. Five other AMPs exhibited promising IC50 (<7.5μM) values against selected cancer cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular interaction between lipoteichoic acids and Lactobacillus delbrueckii phages depends on D-alanyl and alpha-glucose substitution of poly(glycerophosphate) backbones.

PubMed

Räisänen, Liisa; Draing, Christian; Pfitzenmaier, Markus; Schubert, Karin; Jaakonsaari, Tiina; von Aulock, Sonja; Hartung, Thomas; Alatossava, Tapani

2007-06-01

Lipoteichoic acids (LTAs) have been shown to act as bacterial counterparts to the receptor binding proteins of LL-H, LL-H host range mutant LL-H-a21, and JCL1032. Here we have used LTAs purified by hydrophobic interaction chromatography from different phage-resistant and -sensitive strains of Lactobacillus delbrueckii subsp. lactis. Nuclear magnetic resonance analyses revealed variation in the degree of alpha-glucosyl and D-alanyl substitution of the 1,3-linked poly(glycerophosphate) LTAs between the phage-sensitive and phage-resistant strains. Inactivation of phages was less effective if there was a high level of D-alanine residues in the LTA backbones. Prior incubation of the LTAs with alpha-glucose-specific lectin inhibited the LL-H phage inactivation. The overall level of decoration or the specific spatial combination of alpha-glucosyl-substituted, D-alanyl-substituted, and nonsubstituted glycerol residues may also affect phage adsorption.

Molecular Interaction between Lipoteichoic Acids and Lactobacillus delbrueckii Phages Depends on d-Alanyl and α-Glucose Substitution of Poly(Glycerophosphate) Backbones▿

PubMed Central

Räisänen, Liisa; Draing, Christian; Pfitzenmaier, Markus; Schubert, Karin; Jaakonsaari, Tiina; von Aulock, Sonja; Hartung, Thomas; Alatossava, Tapani

2007-01-01

Lipoteichoic acids (LTAs) have been shown to act as bacterial counterparts to the receptor binding proteins of LL-H, LL-H host range mutant LL-H-a21, and JCL1032. Here we have used LTAs purified by hydrophobic interaction chromatography from different phage-resistant and -sensitive strains of Lactobacillus delbrueckii subsp. lactis. Nuclear magnetic resonance analyses revealed variation in the degree of α-glucosyl and d-alanyl substitution of the 1,3-linked poly(glycerophosphate) LTAs between the phage-sensitive and phage-resistant strains. Inactivation of phages was less effective if there was a high level of d-alanine residues in the LTA backbones. Prior incubation of the LTAs with α-glucose-specific lectin inhibited the LL-H phage inactivation. The overall level of decoration or the specific spatial combination of α-glucosyl-substituted, d-alanyl-substituted, and nonsubstituted glycerol residues may also affect phage adsorption. PMID:17416656

Genetic code, hamming distance and stochastic matrices.

PubMed

He, Matthew X; Petoukhov, Sergei V; Ricci, Paolo E

2004-09-01

In this paper we use the Gray code representation of the genetic code C=00, U=10, G=11 and A=01 (C pairs with G, A pairs with U) to generate a sequence of genetic code-based matrices. In connection with these code-based matrices, we use the Hamming distance to generate a sequence of numerical matrices. We then further investigate the properties of the numerical matrices and show that they are doubly stochastic and symmetric. We determine the frequency distributions of the Hamming distances, building blocks of the matrices, decomposition and iterations of matrices. We present an explicit decomposition formula for the genetic code-based matrix in terms of permutation matrices, which provides a hypercube representation of the genetic code. It is also observed that there is a Hamiltonian cycle in a genetic code-based hypercube.

Halogeno-substituted 2-aminobenzoic acid derivatives for negative ion fragmentation studies of N-linked carbohydrates.

PubMed

Harvey, David J

2005-01-01

Negative ion electrospray mass spectra of high-mannose N-linked glycans derivatised with 2-aminobenzoic acids and ionised from solutions containing ammonium hydroxide gave prominent [M-H](-) ions accompanied by weaker [M-2H](2-) ions. Fragmentation of both types of ions gave prominent singly charged glycosidic cleavage ions containing the derivatised reducing terminus and ions from the non-reducing terminus that appeared to be products of cross-ring cleavages. Differentiation of these two groups of ions was conveniently achieved in a single spectrum by use of chloro- or bromo-substituted benzoic acids in order to label ions containing the derivative with an atom with a distinctive isotope pattern. Fragmentation of the doubly charged ions gave more abundant fragments, both singly and doubly charged, than did fragmentation of the singly charged ions, but information of chain branching was masked by the appearance of prominent ions produced by internal cleavages. Copyright (c) 2005 John Wiley & Sons, Ltd.

Affinity chromatography matrices for depletion and purification of casein glycomacropeptide from bovine whey.

PubMed

Baieli, María F; Urtasun, Nicolás; Martinez, María J; Hirsch, Daniela B; Pilosof, Ana M R; Miranda, María V; Cascone, Osvaldo; Wolman, Federico J

2017-01-01

Casein glycomacropeptide (CMP) is a 64- amino acid peptide found in cheese whey, which is released after κ-casein specific cleavage by chymosin. CMP lacks aromatic amino acids, a characteristic that makes it usable as a nutritional supplement for people with phenylketonuria. CMP consists of two nonglycosylated isoforms (aCMP A and aCMP B) and its different glycosylated forms (gCMP A and gCMP B). The most predominant carbohydrate of gCMP is N-acetylneuraminic acid (sialic acid). Here, we developed a CMP purification process based on the affinity of sialic acid for wheat germ agglutinin (WGA). After formation of chitosan beads and adsorption of WGA, the agglutinin was covalently attached with glutaraldehyde. Two matrices with different WGA density were assayed for CMP adsorption. Maximum adsorption capacities were calculated according to the Langmuir model from adsorption isotherms developed at pH 7.0, being 137.0 mg/g for the matrix with the best performance. In CMP reduction from whey, maximum removal percentage was 79% (specifically 33.7% of gCMP A and B, 75.8% of aCMP A, and 93.9% of aCMP B). The CMP was recovered as an aggregate with an overall yield of 64%. Therefore, the matrices developed are promising for CMP purification from cheese whey. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:171-180, 2017. © 2016 American Institute of Chemical Engineers.

Recent developments in polyfluoroalkyl compounds research: a focus on human/environmental health impact, suggested substitutes and removal strategies.

PubMed

Mudumbi, John Baptist Nzukizi; Ntwampe, Seteno Karabo Obed; Matsha, Tandi; Mekuto, Lukhanyo; Itoba-Tombo, Elie Fereche

2017-08-01

Between the late 1940s and early 1950s, humans manufactured polyfluoroalkyl compounds (PFCs) using electrochemical fluorination and telomerisation technologies, whereby hydrogen atoms are substituted by fluorine atoms, thus conferring unnatural and unique physicochemical properties to these compounds. Presently, there are wide ranges of PFCs, and owing to their bioaccumulative properties, they have been detected in various environmental matrices and in human sera. It has thus been suggested that they are hazardous. Hence, this review aims at highlighting the recent development in PFC research, with a particular focus on perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), the most studied and predominantly found PFCs in various environmental matrices, although recent reports have included perfluorobutane sulfonate (PFBS), which was previously regarded as innocuously harmless, when compared to its counterparts, PFOA and PFOS. As such, proper investigations are thus required for a better understanding of short-chain PFC substitutes, which have been suggested as suitable replacements to long-chained PFCs, although these substitutes have also been suggested to pose various health risks comparable to those associated with long-chain PFCs. Similarly, several novel technologies, such as PFC reduction using zero-valent iron, including removal at point of use, adsorption and coagulation, have been proposed. However, regardless of how efficient removers some of these techniques have proven to be, short-chain PFCs remain a challenge to overcome for scientists, in this regard.

Detection of the anaerobic dechlorinating microorganism Desulfomonile tiedjei in environmental matrices by its signature lipopolysacchride branched-long-chain hydroxy fatty acids

USGS Publications Warehouse

Ringleberg, D.B.; Townsend, G.T.; DeWeerd, K.A.; Suflita, J.M.; White, D.C.

1994-01-01

Desulfomonile tiedjei is a Gram-negative sulfate-reducing bacterium capable of catalyzing aryl reductive dehalogenation reactions. Since many toxic and persistent contaminants in the subsurface are halogenated aromatic compounds, the detection and enumeration of dehalogenating microorganisms in the environment may be a useful tool for planning and evaluating bioremediation efforts. In this study, we show that D. tiedjei contains unique lipopolysaccharide branched 3-hydroxy fatty acids, unknown as yet in other bacteria, and that it is possible to detect the bacterium in inoculated aquifer sediments based on these signature lipid biomarkers. The detection of D. tiedjeiand other dehalogenating microorganisms possessing similar cellular properties in environmental matrices may be possible by this technique. Additionally, the effect of such inoculation on dehalogenation activity is examined.

New gene cluster from the thermophile Bacillus fordii MH602 in the conversion of DL-5-substituted hydantoins to L-amino acids.

PubMed

Mei, Yan-Zhen; Wan, Yong-Min; He, Bing-Fang; Ying, Han-Jie; Ouyang, Ping-Kai

2009-12-01

The thermophile Bacillus fordii MH602 was screened for stereospecifically hydrolyzing DL-5-substituted hydantoins to L-alpha-amino acids. Since the reaction at higher temperature, the advantageous for enhancement of substrate solubility and for racemization of DL-5-substituted hydantoins during the conversion were achieved. The hydantoin metabolism gene cluster from thermophile was firstly reported in this paper. The genes involved in hydantoin utilization (hyu) were isolated on an 8.2 kb DNA fragment by Restriction Site-dependent PCR, and six ORFs were identified by DNA sequence analysis. The hyu gene cluster contained four genes with novel cluster organization characteristics: the hydantoinase gene hyuH, putative transport protein hyuP, hyperprotein hyuHP, and L-carbamoylase gene hyuC. The hyuH and hyuC genes were heterogeneously expressed in E. coli. The results indicated that hyuH and hyuC are involved in the conversion of DL-5-substituted hydantoins to an N-carbamyl intermediate that is subsequently converted to L-alpha-amino acids. Hydantoinase and carbamoylase from B. fordii MH602 comparing respectively with reported hydantoinase and carbamoylase showed the highest identities of 71% and 39%. The novel cluster organization characteristics and the difference of the key enzymes between thermopile B. fordii MH602 and other mesophiles were presumed to be related to the evolutionary origins of concerned metabolism.

Visualization of newt aragonitic otoconial matrices using transmission electron microscopy

NASA Technical Reports Server (NTRS)

Steyger, P. S.; Wiederhold, M. L.

1995-01-01

Otoconia are calcified protein matrices within the gravity-sensing organs of the vertebrate vestibular system. These protein matrices are thought to originate from the supporting or hair cells in the macula during development. Previous studies of mammalian calcitic, barrel-shaped otoconia revealed an organized protein matrix consisting of a thin peripheral layer, a well-defined organic core and a flocculent matrix inbetween. No studies have reported the microscopic organization of the aragonitic otoconial matrix, despite its protein characterization. Pote et al. (1993b) used densitometric methods and inferred that prismatic (aragonitic) otoconia have a peripheral protein distribution, compared to that described for the barrel-shaped, calcitic otoconia of birds, mammals, and the amphibian utricle. By using tannic acid as a negative stain, we observed three kinds of organic matrices in preparations of fixed, decalcified saccular otoconia from the adult newt: (1) fusiform shapes with a homogenous electron-dense matrix; (2) singular and multiple strands of matrix; and (3) more significantly, prismatic shapes outlined by a peripheral organic matrix. These prismatic shapes remain following removal of the gelatinous matrix, revealing an internal array of organic matter. We conclude that prismatic otoconia have a largely peripheral otoconial matrix, as inferred by densitometry.

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

NASA Astrophysics Data System (ADS)

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.

A single beta-amino acid substitution to angiotensin II confers AT2 receptor selectivity and vascular function.

PubMed

Jones, Emma S; Del Borgo, Mark P; Kirsch, Julian F; Clayton, Daniel; Bosnyak, Sanja; Welungoda, Iresha; Hausler, Nicholas; Unabia, Sharon; Perlmutter, Patrick; Thomas, Walter G; Aguilar, Marie-Isabel; Widdop, Robert E

2011-03-01

Novel AT(2)R ligands were designed by substituting individual β-amino acid in the sequence of the native ligand angiotensin II (Ang II). Relative ATR selectivity and functional vascular assays (in vitro AT(2)R-mediated vasorelaxation and in vivo vasodepressor action) were determined. In competition binding experiments using either AT(1)R- or AT(2)R- transfected HEK-293 cells, only β-Asp(1)-Ang II and Ang II fully displaced [(125)I]-Ang II from AT(1)R. In contrast, β-substitutions at each position of Ang II exhibited AT(2)R affinity, with β-Tyr(4)-Ang II and β-Ile(5)-Ang II exhibiting ≈ 1000-fold AT(2)R selectivity. In mouse aortic rings, β-Tyr(4)-Ang II and β-Ile(5)-Ang II evoked vasorelaxation that was sensitive to blockade by the AT(2)R antagonist PD123319 and the nitric oxide synthase inhibitor L-NAME. When tested with a low level of AT(1)R blockade, β-Ile(5)-Ang II (15 pmol/kg per minute IV for 4 hours) reduced blood pressure (BP) in conscious spontaneously hypertensive rats (β-Ile(5)-Ang II plus candesartan, -24 ± 4 mm Hg) to a greater extent than candesartan alone (-11 ± 3 mm Hg, n=7, P<0.05), an effect that was abolished by concomitant PD123319 infusion. However, in an identical experimental protocol, β-Tyr(4)-Ang II had no influence on BP (n=10), and it was less stable than β-Ile(5)-Ang II in plasma stability assays. Thus, this study demonstrated that a single β-amino acid substitution resulted in a compound that demonstrated both in vitro vasorelaxation and in vivo depressor activity via AT(2)R. This approach to the design and synthesis of novel AT(2)R-selective peptidomimetics shows great potential to provide insight into AT(2)R function.

Miscellaneous methods for measuring matric or water potential

USGS Publications Warehouse

Scanlon, Bridget R.; Andraski, Brian J.; Bilskie, Jim; Dane, Jacob H.; Topp, G. Clarke

2002-01-01

A variety of techniques to measure matric potential or water potential in the laboratory and in the field are described in this section. The techniques described herein require equilibration of some medium whose matric or water potential can be determined from previous calibration or can be measured directly. Under equilibrium conditions the matric or water potential of the medium is equal to that of the soil. The techniques can be divided into: (i) those that measure matric potential and (ii) those that measure water potential (sum of matric and osmotic potentials). Matric potential is determined when the sensor matrix is in direct contact with the soil, so salts are free to diffuse in or out of the sensor matrix, and the equilibrium measurement therefore reflects matric forces acting on the water. Water potential is determined when the sensor is separated from the soil by a vapor gap, so salts are not free to move in or out of the sensor, and the equilibrium measurement reflects the sum of the matric and osmotic forces acting on the water.Seven different techniques are described in this section. Those that measure matric potential include (i) heat dissipation sensors, (ii) electrical resistance sensors, (iii) frequency domain and time domain sensors, and (iv) electro-optical switches. A method that can be used to measure matric potential or water potential is the (v) filter paper method. Techniques that measure water potential include (vi) the Dew Point Potentiameter (Decagon Devices, Inc., Pullman, WA1) (water activity meter) and (vii) vapor equilibration.The first four techniques are electronically based methods for measuring matric potential. Heat dissipation sensors and electrical resistance sensors infer matric potential from previously determined calibration relations between sensor heat dissipation or electrical resistance and matric potential. Frequency-domain and timedomain matric potential sensors measure water content, which is related to matric

Complex symmetric matrices with strongly stable iterates

NASA Technical Reports Server (NTRS)

Tadmor, E.

1985-01-01

Complex-valued symmetric matrices are studied. A simple expression for the spectral norm of such matrices is obtained, by utilizing a unitarily congruent invariant form. A sharp criterion is provided for identifying those symmetric matrices whose spectral norm is not exceeding one: such strongly stable matrices are usually sought in connection with convergent difference approximations to partial differential equations. As an example, the derived criterion is applied to conclude the strong stability of a Lax-Wendroff scheme.

Chemiluminescence in cryogenic matrices

NASA Astrophysics Data System (ADS)

Lotnik, S. V.; Kazakov, Valeri P.

1989-04-01

The literature data on chemiluminescence (CL) in cryogenic matrices have been classified and correlated for the first time. The role of studies on phosphorescence and CL at low temperatures in the development of cryochemistry is shown. The features of low-temperature CL in matrices of nitrogen and inert gases (fine structure of spectra, matrix effects) and the data on the mobility and reactivity of atoms and radicals at very low temperatures are examined. The trends in the development of studies on CL in cryogenic matrices, such as the search for systems involving polyatomic molecules and extending the forms of CL reactions, are followed. The reactions of active nitrogen with hydrocarbons that are accompanied by light emission and CL in the oxidation of carbenes at T >= 77 K are examined. The bibliography includes 112 references.

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

PubMed

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 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 to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 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 to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 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 to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 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 to...

Effect of chemical substitutions on photo-switching properties of 3-hydroxy-picolinic acid studied by ab initio methods

NASA Astrophysics Data System (ADS)

Rode, Michał F.; Sobolewski, Andrzej L.

2014-02-01

Effect of chemical substitutions to the molecular structure of 3-hydroxy-picolinic acid on photo-switching properties of the system operating on excited-state intramolecular double proton transfer (d-ESIPT) process [M. F. Rode and A. L. Sobolewski, Chem. Phys. 409, 41 (2012)] was studied with the aid of electronic structure theory methods. It was shown that simultaneous application of electron-donating and electron-withdrawing substitutions at certain positions of the molecular frame increases the height of the S0-state tautomerization barrier (ensuring thermal stability of isomers) and facilitates a barrierless access to the S1/S0 conical intersection from the Franck-Condon region of the S1 potential-energy surface. Results of study point to the conclusion that the most challenging issue for practical design of a fast molecular photoswitch based on d-ESIPT phenomenon are to ensure a selectivity of optical excitation of a given tautomeric form of the system.

Establishment of an evaluation model for human milk fat substitutes.

PubMed

Wang, Yong-Hua; Mai, Qing-Yun; Qin, Xiao-Li; Yang, Bo; Wang, Zi-Lian; Chen, Hai-Tian

2010-01-13

Fatty acid composition and distribution of human milk fat (HMF), from mothers over different lactating periods in Guangzhou, China, were analyzed. The universal characteristics were consistent with previously reported results although the fatty acid content was within a different range and dependent on the local population (low saturated fatty acid and high oleic acid for Guangdong mothers' milk fat). Based on the composition of the total and sn-2 fatty acids of mature milk fat, an efficient evaluation model was innovatively established by adopting the "deducting score" principle. The model showed good agreement between the scores and the degree of similarity by assessing 15 samples from different sources including four samples of HMF, eight samples of human milk fat substitutes (HMFSs) and infant formulas, and three samples of fats and oils. This study would allow for the devolvement of individual human milk fat substitutes with different and specific fatty acid compositions for local infants.

A broad survey reveals substitution tolerance of residues ligating FeS clusters in [NiFe] hydrogenase

PubMed Central

2014-01-01

Background In order to understand the effects of FeS cluster attachment in [NiFe] hydrogenase, we undertook a study to substitute all 12 amino acid positions normally ligating the three FeS clusters in the hydrogenase small subunit. Using the hydrogenase from Alteromonas macleodii “deep ecotype” as a model, we substituted one of four amino acids (Asp, His, Asn, Gln) at each of the 12 ligating positions because these amino acids are alternative coordinating residues in otherwise conserved-cysteine positions found in a broad survey of NiFe hydrogenase sequences. We also hoped to discover an enzyme with elevated hydrogen evolution activity relative to a previously reported “G1” (H230C/P285C) improved enzyme in which the medial FeS cluster Pro and the distal FeS cluster His were each substituted for Cys. Results Among all the substitutions screened, aspartic acid substitutions were generally well-tolerated, and examination suggests that the observed deficiency in enzyme activity may be largely due to misprocessing of the small subunit of the enzyme. Alignment of hydrogenase sequences from sequence databases revealed many rare substitutions; the five substitutions present in databases that we tested all exhibited measurable hydrogen evolution activity. Select substitutions were purified and tested, supporting the results of the screening assay. Analysis of these results confirms the importance of small subunit processing. Normalizing activity to quantity of mature small subunit, indicative of total enzyme maturation, weakly suggests an improvement over the “G1” enzyme. Conclusions We have comprehensively screened 48 amino acid substitutions of the hydrogenase from A. macleodii “deep ecotype”, to understand non-canonical ligations of amino acids to FeS clusters and to improve hydrogen evolution activity of this class of hydrogenase. Our studies show that non-canonical ligations can be functional and also suggests a new limiting factor in the production of

Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases.

PubMed

Schaafsma, Gerard C P; Vihinen, Mauno

2017-07-01

Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitutions (AASs) in nine representative protein groups by using the PON-P2 method. The effects on 996 proteins were studied and vast differences were noticed. Proteins in the cancer group harbor the largest proportion of harmful variants (42.1%), whereas the non-disease group of proteins not known to have a disease association and not involved in the housekeeping functions had the lowest number of harmful variants (4.2%). Differences in the proportions of the harmful and benign variants are wide within each group, but they still show clear differences between the groups. Frequently appearing protein domains show a wide spectrum of variant frequencies, whereas no major protein structural class-specific differences were noticed. AAS types in the original and variant residues showed distinctive patterns, which are shared by all the protein groups. The observations are relevant for understanding genetic bases of diseases, variation interpretation, and for the development of methods for that purpose. © 2017 Wiley Periodicals, Inc.

Biodegradable organic acid-crosslinked alkali-treated gelatins with anti-thrombogenic and endothelialization properties

PubMed Central

Inoue, Motoki; Sasaki, Makoto; Taguchi, Tetsushi

2012-01-01

Gelatins were crosslinked with organic acids and treated with alkali to impart to them endothelialization and anti-thrombogenic properties. These matrices were characterized by biochemical and physicochemical techniques. The amounts of residual amino groups in the matrices decreased with increasing crosslinker concentration. The matrices with the highest crosslinking densities showed excellent endothelial cell adhesion and proliferation. In addition, the adhesion of platelets and formation of fibrin networks on the matrices were suppressed with increasing crosslinker concentration. The matrices also exhibited excellent biodegradability, and the degradation rate decreased with increasing crosslinking density. All the organic acid-crosslinked alkali-treated gelatins showed excellent anti-thrombogenic and endothelialization properties, superior to those of glutaraldehyde-crosslinked alkali-treated gelatins. PMID:27877542

Condition Number Estimation of Preconditioned Matrices

PubMed Central

Kushida, Noriyuki

2015-01-01

The present paper introduces a condition number estimation method for preconditioned matrices. The newly developed method provides reasonable results, while the conventional method which is based on the Lanczos connection gives meaningless results. The Lanczos connection based method provides the condition numbers of coefficient matrices of systems of linear equations with information obtained through the preconditioned conjugate gradient method. Estimating the condition number of preconditioned matrices is sometimes important when describing the effectiveness of new preconditionerers or selecting adequate preconditioners. Operating a preconditioner on a coefficient matrix is the simplest method of estimation. However, this is not possible for large-scale computing, especially if computation is performed on distributed memory parallel computers. This is because, the preconditioned matrices become dense, even if the original matrices are sparse. Although the Lanczos connection method can be used to calculate the condition number of preconditioned matrices, it is not considered to be applicable to large-scale problems because of its weakness with respect to numerical errors. Therefore, we have developed a robust and parallelizable method based on Hager’s method. The feasibility studies are curried out for the diagonal scaling preconditioner and the SSOR preconditioner with a diagonal matrix, a tri-daigonal matrix and Pei’s matrix. As a result, the Lanczos connection method contains around 10% error in the results even with a simple problem. On the other hand, the new method contains negligible errors. In addition, the newly developed method returns reasonable solutions when the Lanczos connection method fails with Pei’s matrix, and matrices generated with the finite element method. PMID:25816331

Condition number estimation of preconditioned matrices.

PubMed

Kushida, Noriyuki

2015-01-01

The present paper introduces a condition number estimation method for preconditioned matrices. The newly developed method provides reasonable results, while the conventional method which is based on the Lanczos connection gives meaningless results. The Lanczos connection based method provides the condition numbers of coefficient matrices of systems of linear equations with information obtained through the preconditioned conjugate gradient method. Estimating the condition number of preconditioned matrices is sometimes important when describing the effectiveness of new preconditionerers or selecting adequate preconditioners. Operating a preconditioner on a coefficient matrix is the simplest method of estimation. However, this is not possible for large-scale computing, especially if computation is performed on distributed memory parallel computers. This is because, the preconditioned matrices become dense, even if the original matrices are sparse. Although the Lanczos connection method can be used to calculate the condition number of preconditioned matrices, it is not considered to be applicable to large-scale problems because of its weakness with respect to numerical errors. Therefore, we have developed a robust and parallelizable method based on Hager's method. The feasibility studies are curried out for the diagonal scaling preconditioner and the SSOR preconditioner with a diagonal matrix, a tri-daigonal matrix and Pei's matrix. As a result, the Lanczos connection method contains around 10% error in the results even with a simple problem. On the other hand, the new method contains negligible errors. In addition, the newly developed method returns reasonable solutions when the Lanczos connection method fails with Pei's matrix, and matrices generated with the finite element method.

Amino acid substitutions of conserved residues in the carboxyl-terminal domain of the [alpha]I(X) chain of type X collagen occur in two unrelated families with metaphyseal chondrodysplasia type Schmid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallis, G.A.; Rash, B.; Sweetman, W.A.

1994-02-01

Type X collagen is a homotrimeric, short-chain, nonfibrillar extracellular-matrix component that is specifically and transiently synthesized by hypertrophic chondrocytes at the site of endochondral ossification. The precise function of type X collagen is not known, but its specific pattern of expression suggests that mutations within the encoding gene (COL10A1) that alter the structure or synthesis of the protein may cause heritable forms of chondrodysplasia. The authors used the PCR and the SSCP techniques to analyze the coding and upstream promoter regions of the COL10A1 gene in a number of individuals with forms of chondrodysplasia. Using this approach, they identified twomore » individuals with metaphyseal chondrodysplasia type Schmid (MCDS) with SSCP changes in the region of the gene encoding the carboxyl-terminal domain. Sequence analysis demonstrated that the individuals were heterozygous for two unique single-base-pair transitions that led to the substitution of the highly conserved amino acid residue tyrosine at position 598 by aspartic acid in one person and of leucine at position 614 by proline in the other. The substitution at residue 598 segregated with the phenotype in a family of eight (five affected and three unaffected) related persons. The substitutions at residue 614 occurred in a sporadically affected individual but not in her unaffected mother and brother. Additional members of this family were not available for further study. These results suggest that certain amino acid substitutions within the carboxyl-terminal domain of the chains of the type X collagen molecule cause MCDS. These amino acid substitutions are likely to alter either chain recognition or assembly of the type X collagen molecule, thereby depleting the amount of normal type X collagen deposited in the extracellular matrix, with consequent aberrations in bone growth and development. 36 refs., 5 figs.« less

Enhancing Understanding of Transformation Matrices

ERIC Educational Resources Information Center

Dick, Jonathan; Childrey, Maria

2012-01-01

With the Common Core State Standards' emphasis on transformations, teachers need a variety of approaches to increase student understanding. Teaching matrix transformations by focusing on row vectors gives students tools to create matrices to perform transformations. This empowerment opens many doors: Students are able to create the matrices for…

Arsenic scavenging by aluminum-substituted ferrihydrites in a circumneutral pH river impacted by acid mine drainage.

PubMed

Adra, Areej; Morin, Guillaume; Ona-Nguema, Georges; Menguy, Nicolas; Maillot, Fabien; Casiot, Corinne; Bruneel, Odile; Lebrun, Sophie; Juillot, Farid; Brest, Jessica

2013-11-19

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 of aluminum-rich Fh, and their role in arsenic scavenging in river-bed sediments from 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. TEM-EDXS elemental mapping and SEM-EDXS analyses combined with EXAFS analysis indicates that Al(3+) substitutes for Fe(3+) ions into the Fh structure in the natural sediment samples, with local aluminum concentration within the 25-30 ± 10 mol %Al range. Synthetic aluminous Fh prepared in the present study are found to be less Al-substituted (14-20 ± 5 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 evidence for the scavenging of arsenic by natural Al-Fh, which emphasize the possible implication of such material for scavenging pollutants in natural or engineered systems.

T-Reg Comparator: an analysis tool for the comparison of position weight matrices

PubMed Central

Roepcke, Stefan; Grossmann, Steffen; Rahmann, Sven; Vingron, Martin

2005-01-01

T-Reg Comparator is a novel software tool designed to support research into transcriptional regulation. Sequence motifs representing transcription factor binding sites are usually encoded as position weight matrices. The user inputs a set of such weight matrices or binding site sequences and our program matches them against the T-Reg database, which is presently built on data from the Transfac [E. Wingender (2004) In Silico Biol., 4, 55–61] and Jaspar [A. Sandelin, W. Alkema, P. Engstrom, W. W. Wasserman and B. Lenhard (2004) Nucleic Acids Res., 32, D91–D94]. Our tool delivers a detailed report on similarities between user-supplied motifs and motifs in the database. Apart from simple one-to-one relationships, T-Reg Comparator is also able to detect similarities between submatrices. In addition, we provide a user interface to a program for sequence scanning with weight matrices. Typical areas of application for T-Reg Comparator are motif and regulatory module finding and annotation of regulatory genomic regions. T-Reg Comparator is available at . PMID:15980506

T-Reg Comparator: an analysis tool for the comparison of position weight matrices.

PubMed

Roepcke, Stefan; Grossmann, Steffen; Rahmann, Sven; Vingron, Martin

2005-07-01

T-Reg Comparator is a novel software tool designed to support research into transcriptional regulation. Sequence motifs representing transcription factor binding sites are usually encoded as position weight matrices. The user inputs a set of such weight matrices or binding site sequences and our program matches them against the T-Reg database, which is presently built on data from the Transfac [E. Wingender (2004) In Silico Biol., 4, 55-61] and Jaspar [A. Sandelin, W. Alkema, P. Engstrom, W. W. Wasserman and B. Lenhard (2004) Nucleic Acids Res., 32, D91-D94]. Our tool delivers a detailed report on similarities between user-supplied motifs and motifs in the database. Apart from simple one-to-one relationships, T-Reg Comparator is also able to detect similarities between submatrices. In addition, we provide a user interface to a program for sequence scanning with weight matrices. Typical areas of application for T-Reg Comparator are motif and regulatory module finding and annotation of regulatory genomic regions. T-Reg Comparator is available at http://treg.molgen.mpg.de.

The underexposed role of food matrices in probiotic products: Reviewing the relationship between carrier matrices and product parameters.

PubMed

Flach, Joost; van der Waal, Mark B; van den Nieuwboer, Maurits; Claassen, Eric; Larsen, Olaf F A

2017-06-13

Probiotic microorganisms are increasingly incorporated into food matrices in order to confer proposed health benefits on the consumer. It is important that the health benefits, sensory properties, shelf-life and probiotic gastrointestinal tract (GIT) survival of these products are carefully balanced as they determine functionality and drive consumer acceptance. The strain-specific effects of probiotic species are imperative in this process but carrier matrices may play a pivotal role as well. This study therefore recapitulates the wealth of knowledge on carrier matrices and their interaction with probiotic strains. The most substantiated carrier matrices, factors that influence probiotic functionality and matrix effects on shelf-life, GIT survival and clinical efficacy are reviewed. Results indicate that carrier matrices have a significant impact on the quality of probiotic products. Matrix components, such as proteins, carbohydrates and flavoring agents are shown to alter probiotic efficacy and viability. In vivo studies furthermore revealed strain-dependent matrix effects on the GIT survival of probiotic bacteria. However, only a limited number of studies have specifically addressed the effects of carrier matrices on the aforementioned product-parameters; most studies seem to focus solely on the strain-specific effects of probiotic microorganisms. This hampers the innovation of probiotic products. More human studies, comparing not only different probiotic strains but different carrier matrices as well, are needed to drive the innovation cycle.

Structure and stability of genetic variance-covariance matrices: A Bayesian sparse factor analysis of transcriptional variation in the three-spined stickleback.

PubMed

Siren, J; Ovaskainen, O; Merilä, J

2017-10-01

The genetic variance-covariance matrix (G) is a quantity of central importance in evolutionary biology due to its influence on the rate and direction of multivariate evolution. However, the predictive power of empirically estimated G-matrices is limited for two reasons. First, phenotypes are high-dimensional, whereas traditional statistical methods are tuned to estimate and analyse low-dimensional matrices. Second, the stability of G to environmental effects and over time remains poorly understood. Using Bayesian sparse factor analysis (BSFG) designed to estimate high-dimensional G-matrices, we analysed levels variation and covariation in 10,527 expressed genes in a large (n = 563) half-sib breeding design of three-spined sticklebacks subject to two temperature treatments. We found significant differences in the structure of G between the treatments: heritabilities and evolvabilities were higher in the warm than in the low-temperature treatment, suggesting more and faster opportunity to evolve in warm (stressful) conditions. Furthermore, comparison of G and its phenotypic equivalent P revealed the latter is a poor substitute of the former. Most strikingly, the results suggest that the expected impact of G on evolvability-as well as the similarity among G-matrices-may depend strongly on the number of traits included into analyses. In our results, the inclusion of only few traits in the analyses leads to underestimation in the differences between the G-matrices and their predicted impacts on evolution. While the results highlight the challenges involved in estimating G, they also illustrate that by enabling the estimation of large G-matrices, the BSFG method can improve predicted evolutionary responses to selection. © 2017 John Wiley & Sons Ltd.

Amino acid substitutions in the hormone-binding domain of the human androgen receptor alter the stability of the hormone receptor complex.

PubMed Central

Marcelli, M; Zoppi, S; Wilson, C M; Griffin, J E; McPhaul, M J

1994-01-01

We have investigated the basis of androgen resistance in seven unrelated individuals with complete testicular feminization or Reifenstein syndrome caused by single amino acid substitutions in the hormone-binding domain of the androgen receptor. Monolayer-binding assays of cultured genital skin fibroblasts demonstrated absent ligand binding, qualitative abnormalities of androgen binding, or a decreased amount of qualitatively normal receptor. The consequences of these mutations were examined by introducing the mutations by site-directed mutagenesis into the androgen receptor cDNA sequence and expressing the mutant cDNAs in mammalian cells. The effects of the amino acid substitutions on the binding of different androgens and on the capacity of the ligand-bound receptors to activate a reporter gene were investigated. Substantial differences were found in the responses of the mutant androgen receptors to incubation with testosterone, 5 alpha-dihydrotestosterone, and mibolerone. In several instances, increased doses of hormone or increased frequency of hormone addition to the incubation medium resulted in normal or near normal activation of a reporter gene by cells expressing the mutant androgen receptors. These studies suggest that the stability of the hormone receptor complex is a major determinant of receptor function in vivo. Images PMID:7929841

Selection of anion exchangers for detoxification of dilute-acid hydrolysates from spruce.

PubMed

Horváth, Ilona Sárvári; Sjöde, Anders; Nilvebrant, Nils-Olof; Zagorodni, Andrei; Jönsson, Leif J

2004-01-01

Six anion-exchange resins with different properties were compared with respect to detoxification of a dilute-acid hydrolysate of spruce prior to ethanolic fermentation with Saccharomyces cerevisiae. The six resins encompassed strong and weak functional groups as well as styrene-, phenol-, and acrylic-based matrices. In an analytical experimental series, fractions from columns packed with the different resins were analyzed regarding pH, glucose, furfural, hydroxymethylfurfural, phenolic compounds, levulinic acid, acetic acid, formic acid, and sulfate. An initial adsorption of glucose occurred in the strong alkaline environment and led to glucose accumulation at a later stage. Acetic and levulinic acid passed through the column before formic acid, whereas sulfate had the strongest affinity. In a preparative experimental series, one fraction from each of six columns packed with the different resins was collected for assay of the fermentability and analysis of glucose, mannose, and fermentation inhibitors. The fractions collected from strong anion-exchange resins with styrene-based matrices displayed the best fermentability: a sevenfold enhancement of ethanol productivity compared with untreated hydrolysate. Fractions from a strong anion exchanger with acrylic-based matrix and a weak exchanger with phenol-based resin displayed an intermediate improvement in fermentability, a four- to fivefold increase in ethanol productivity. The fractions from two weak exchangers with styrene- and acrylic-based matrices displayed a twofold increase in ethanol productivity. Phenolic compounds were more efficiently removed by resins with styrene- and phenol-based matrices than by resins with acrylic-based matrices.

Matrices for Sensors from Inorganic, Organic, and Biological Nanocomposites

PubMed Central

Nicolini, Claudio; Sivozhelezov, Victor; Bavastrello, Valter; Bezzerra, Tercio; Scudieri, Dora; Spera, Rosanna; Pechkova, Eugenia

2011-01-01

Matrices and sensors resulting from inorganic, organic and biological nanocomposites are presented in this overview. The term nanocomposite designates a solid combination of a matrix and of nanodimensional phases differing in properties from the matrix due to dissimilarities in structure and chemistry. The nanoocomposites chosen for a wide variety of health and environment sensors consist of Anodic Porous Allumina and P450scc, Carbon nanotubes and Conductive Polymers, Langmuir Blodgett Films of Lipases, Laccases, Cytochromes and Rhodopsins, Three-dimensional Nanoporous Materials and Nucleic Acid Programmable Protein Arrays. PMID:28824154

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

PubMed Central

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

Inference for High-dimensional Differential Correlation Matrices *

PubMed Central

Cai, T. Tony; Zhang, Anru

2015-01-01

Motivated by differential co-expression analysis in genomics, we consider in this paper estimation and testing of high-dimensional differential correlation matrices. An adaptive thresholding procedure is introduced and theoretical guarantees are given. Minimax rate of convergence is established and the proposed estimator is shown to be adaptively rate-optimal over collections of paired correlation matrices with approximately sparse differences. Simulation results show that the procedure significantly outperforms two other natural methods that are based on separate estimation of the individual correlation matrices. The procedure is also illustrated through an analysis of a breast cancer dataset, which provides evidence at the gene co-expression level that several genes, of which a subset has been previously verified, are associated with the breast cancer. Hypothesis testing on the differential correlation matrices is also considered. A test, which is particularly well suited for testing against sparse alternatives, is introduced. In addition, other related problems, including estimation of a single sparse correlation matrix, estimation of the differential covariance matrices, and estimation of the differential cross-correlation matrices, are also discussed. PMID:26500380

Inference for High-dimensional Differential Correlation Matrices.

PubMed

Cai, T Tony; Zhang, Anru

2016-01-01

Motivated by differential co-expression analysis in genomics, we consider in this paper estimation and testing of high-dimensional differential correlation matrices. An adaptive thresholding procedure is introduced and theoretical guarantees are given. Minimax rate of convergence is established and the proposed estimator is shown to be adaptively rate-optimal over collections of paired correlation matrices with approximately sparse differences. Simulation results show that the procedure significantly outperforms two other natural methods that are based on separate estimation of the individual correlation matrices. The procedure is also illustrated through an analysis of a breast cancer dataset, which provides evidence at the gene co-expression level that several genes, of which a subset has been previously verified, are associated with the breast cancer. Hypothesis testing on the differential correlation matrices is also considered. A test, which is particularly well suited for testing against sparse alternatives, is introduced. In addition, other related problems, including estimation of a single sparse correlation matrix, estimation of the differential covariance matrices, and estimation of the differential cross-correlation matrices, are also discussed.

Association of Dietary Proportions of Macronutrients with Visceral Adiposity Index: Non-Substitution and Iso-Energetic Substitution Models in a Prospective Study.

PubMed

Moslehi, Nazanin; Ehsani, Behnaz; Mirmiran, Parvin; Hojjat, Parvane; Azizi, Fereidoun

2015-10-26

We aimed to investigate associations between dietary macronutrient proportions and prospective visceral adiposity index changes (ΔVAI). The study included 1254 adults (18-74 years), from the Tehran Lipid and Glucose Study (TLGS), who were followed for three years. Dietary intakes were assessed twice using food frequency questionnaires. Associations of dietary macronutrient with ΔVAI and risk of visceral adiposity dysfunction (VAD) after three years were investigated. The percentage of energy intake from protein in the total population, and from fat in women, were associated with higher increases in VAI. A 5% higher energy intake from protein substituted for carbohydrate, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) was associated with higher ΔVAI. Higher energy intake from animal protein substituted for PUFAs was positively associated with ΔVAI. Substituting protein and PUFAs with MUFAs were related to higher ΔVAI. The associations were similar in men and women, but reached significance mostly among women. Risk of VAD was increased when 1% of energy from protein was replaced with MUFAs. Substituting protein for carbohydrate and fat, and fat for carbohydrate, resulted in increased risk of VAD in women. Higher dietary proportions of protein and animal-derived MUFA may be positively associated with ΔVAI and risk of VAD.

Computer-Access-Code Matrices

NASA Technical Reports Server (NTRS)

Collins, Earl R., Jr.

1990-01-01

Authorized users respond to changing challenges with changing passwords. Scheme for controlling access to computers defeats eavesdroppers and "hackers". Based on password system of challenge and password or sign, challenge, and countersign correlated with random alphanumeric codes in matrices of two or more dimensions. Codes stored on floppy disk or plug-in card and changed frequently. For even higher security, matrices of four or more dimensions used, just as cubes compounded into hypercubes in concurrent processing.

Unraveling the effects of amino acid substitutions enhancing lipase resistance to an ionic liquid: a molecular dynamics study.

PubMed

Zhao, Jing; Frauenkron-Machedjou, Victorine Josiane; Fulton, Alexander; Zhu, Leilei; Davari, Mehdi D; Jaeger, Karl-Erich; Schwaneberg, Ulrich; Bocola, Marco

2018-04-04

Understanding of the structural and dynamic properties of enzymes in non-aqueous media (e.g., ionic liquids, ILs) is highly attractive for protein engineers and synthetic biochemists. Despite a growing number of molecular dynamics (MD) simulation studies on the influence of different ILs on wild-type enzymes, the effects of various amino acid substitutions on the stability and activity of enzymes in ILs remain to be unraveled at the molecular level. Herein, we selected fifty previously reported Bacillus subtilis lipase A (BSLA) variants with increased resistance towards an IL (15 vol% 1-butyl-3-methylimidazolium trifluoromethanesulfonate; [Bmim][TfO]), and also ten non-resistant BSLA variants for a MD simulation study to identify the underlying molecular principles. Some important properties differentiating resistant and non-resistant BSLA variants from wild-type were elucidated. Results show that, in 15 vol% [Bmim][TfO] aqueous solution, 40% and 60% of non-resistant variants have lower and equal probabilities to form a catalytically important hydrogen bond between S77 and H156 compared to wild-type, whereas 36% and 56% of resistant variants show increased and equal probabilities, respectively. Introducing positively charged amino acids close to the substrate-binding cleft for instance I12R is beneficial for the BSLA resistance towards 15 vol% [Bmim][TfO], likely due to the reduced probability of [Bmim]+ cations clustering near the cleft. In contrast, substitution with a large hydrophobic residue like I12F can block the cleft through hydrophobic interaction with a neighboring nonpolar loop 134-137 or/and an attractive π-π interaction with [Bmim]+ cations. In addition, the resistant variants having polar substitutions on the surface show higher ability to stabilize the surface water molecule network in comparison to non-resistant variants. This study can guide experimentalists to rationally design promising IL-resistant enzymes, and contribute to a deeper

Making almost commuting matrices commute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hastings, Matthew B

Suppose two Hermitian matrices A, B almost commute ({parallel}[A,B]{parallel} {<=} {delta}). Are they close to a commuting pair of Hermitian matrices, A', B', with {parallel}A-A'{parallel},{parallel}B-B'{parallel} {<=} {epsilon}? A theorem of H. Lin shows that this is uniformly true, in that for every {epsilon} > 0 there exists a {delta} > 0, independent of the size N of the matrices, for which almost commuting implies being close to a commuting pair. However, this theorem does not specifiy how {delta} depends on {epsilon}. We give uniform bounds relating {delta} and {epsilon}. The proof is constructive, giving an explicit algorithm to construct A'more » and B'. We provide tighter bounds in the case of block tridiagonal and tridiagnonal matrices. Within the context of quantum measurement, this implies an algorithm to construct a basis in which we can make a projective measurement that approximately measures two approximately commuting operators simultaneously. Finally, we comment briefly on the case of approximately measuring three or more approximately commuting operators using POVMs (positive operator-valued measures) instead of projective measurements.« less

Effects of a naturally occurring amino acid substitution in bovine PrP: a model for inherited prion disease in a natural host species

USDA-ARS?s Scientific Manuscript database

The most common hereditary prion disease is human Creutzfeldt-Jakob disease (CJD) associated with a mutation in the prion gene (PRNP) resulting in a glutamic acid to lysine substitution at position 200 (E200K) in the prion protein. Models of E200K CJD in transgenic mice have proven interesting but h...

Tandem SN2' nucleophilic substitution/oxidative radical cyclization of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds.

PubMed

Zhang, Zhen; Li, Cheng; Wang, Shao-Hua; Zhang, Fu-Min; Han, Xue; Tu, Yong-Qiang; Zhang, Xiao-Ming

2017-04-11

A novel and efficient tandem S N 2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc) 3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

High-throughput quantitation of amino acids in rat and mouse biological matrices using stable isotope labeling and UPLC-MS/MS analysis.

PubMed

Takach, Edward; O'Shea, Thomas; Liu, Hanlan

2014-08-01

Quantifying amino acids in biological matrices is typically performed using liquid chromatography (LC) coupled with fluorescent detection (FLD), requiring both derivatization and complete baseline separation of all amino acids. Due to its high specificity and sensitivity, the use of UPLC-MS/MS eliminates the derivatization step and allows for overlapping amino acid retention times thereby shortening the analysis time. Furthermore, combining UPLC-MS/MS with stable isotope labeling (e.g., isobaric tag for relative and absolute quantitation, i.e., iTRAQ) of amino acids enables quantitation while maintaining sensitivity, selectivity and speed of analysis. In this study, we report combining UPLC-MS/MS analysis with iTRAQ labeling of amino acids resulting in the elution and quantitation of 44 amino acids within 5 min demonstrating the speed and convenience of this assay over established approaches. This chromatographic analysis time represented a 5-fold improvement over the conventional HPLC-MS/MS method developed in our laboratory. In addition, the UPLC-MS/MS method demonstrated improvements in both specificity and sensitivity without loss of precision. In comparing UPLC-MS/MS and HPLC-MS/MS results of 32 detected amino acids, only 2 amino acids exhibited imprecision (RSD) >15% using UPLC-MS/MS, while 9 amino acids exhibited RSD >15% using HPLC-MS/MS. Evaluating intra- and inter-assay precision over 3 days, the quantitation range for 32 detected amino acids in rat plasma was 0.90-497 μM, with overall mean intra-day precision of less than 15% and mean inter-day precision of 12%. This UPLC-MS/MS assay was successfully implemented for the quantitative analysis of amino acids in rat and mouse plasma, along with mouse urine and tissue samples, resulting in the following concentration ranges: 0.98-431 μM in mouse plasma for 32 detected amino acids; 0.62-443 μM in rat plasma for 32 detected amino acids; 0.44-8590μM in mouse liver for 33 detected amino acids; 0.61-1241 �

Nonsynonymous substitution rate heterogeneity in the peptide-binding region among different HLA-DRB1 lineages in humans.

PubMed

Yasukochi, Yoshiki; Satta, Yoko

2014-05-02

An extraordinary diversity of amino acid sequences in the peptide-binding region (PBR) of human leukocyte antigen [HLA; human major histocompatibility complex (MHC)] molecules has been maintained by balancing selection. The process of accumulation of amino acid diversity in the PBR for six HLA genes (HLA-A, B, C, DRB1, DQB1, and DPB1) shows that the number of amino acid substitutions in the PBR among alleles does not linearly correlate with the divergence time of alleles at the six HLA loci. At these loci, some pairs of alleles show significantly less nonsynonymous substitutions at the PBR than expected from the divergence time. The same phenomenon was observed not only in the HLA but also in the rat MHC. To identify the cause for this, DRB1 sequences, a representative case of a typical nonlinear pattern of substitutions, were examined. When the amino acid substitutions in the PBR were placed with maximum parsimony on a maximum likelihood tree based on the non-PBR substitutions, heterogeneous rates of nonsynonymous substitutions in the PBR were observed on several branches. A computer simulation supported the hypothesis that allelic pairs with low PBR substitution rates were responsible for the stagnation of accumulation of PBR nonsynonymous substitutions. From these observations, we conclude that the nonsynonymous substitution rate at the PBR sites is not constant among the allelic lineages. The deceleration of the rate may be caused by the coexistence of certain pathogens for a substantially long time during HLA evolution. Copyright © 2014 Yasukochi and Satta.

A fluorescent colorimetric pH sensor and the influences of matrices on sensing performances.

PubMed

Tian, Yanqing; Fuller, Emily; Klug, Summer; Lee, Fred; Su, Fengyu; Zhang, Liqiang; Chao, Shih-Hui; Meldrum, Deirdre R

2013-10-01

A fluorescent colorimetric pH sensor was developed by a polymerization of a monomeric fluorescein based green emitter ( SM1 ) with a monomeric 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran derived red emitter ( SM2 ) in poly(2-hydroxyethyl methacrylate)- co -polyacrylamide (PHEMA-co-PAM) matrices. Polymerized SM1 ( PSM1 ) in the polymer matrices showed bright emissions at basic conditions and weak emissions at acidic conditions. Polymerized SM2 ( PSM2 ) in the polymer matrices exhibited a vastly different response when compared to PSM1 . The emissions of PSM2 are stronger under acidic conditions than those under basic conditions. When SM1 and SM2 were polymerized in the same polymer matrix, a dual emission sensor acting as a ratiometric pH sensor ( PSM1,2 ) was successfully developed. Because the PSM1 and PSM2 exhibited different pH responses and separated emission windows, the changes in the emission colors were clearly observed in their dual color sensor of PSM1,2 , which changed emission colors dramatically from green at pH 7 to red at pH 4, which was detected visually and/or by using a color camera under an excitation of 488 nm. In addition to the development of the dual color ratiometric pH sensor, we also studied the effects of different matrix compositions, crosslinkers, and charges on the reporting capabilities of the sensors (sensitivity and p K a ).

A fluorescent colorimetric pH sensor and the influences of matrices on sensing performances

PubMed Central

Tian, Yanqing; Fuller, Emily; Klug, Summer; Lee, Fred; Su, Fengyu; Zhang, Liqiang; Chao, Shih-hui; Meldrum, Deirdre R.

2013-01-01

A fluorescent colorimetric pH sensor was developed by a polymerization of a monomeric fluorescein based green emitter (SM1) with a monomeric 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran derived red emitter (SM2) in poly(2-hydroxyethyl methacrylate)-co-polyacrylamide (PHEMA-co-PAM) matrices. Polymerized SM1 (PSM1) in the polymer matrices showed bright emissions at basic conditions and weak emissions at acidic conditions. Polymerized SM2 (PSM2) in the polymer matrices exhibited a vastly different response when compared to PSM1. The emissions of PSM2 are stronger under acidic conditions than those under basic conditions. When SM1 and SM2 were polymerized in the same polymer matrix, a dual emission sensor acting as a ratiometric pH sensor (PSM1,2) was successfully developed. Because the PSM1 and PSM2 exhibited different pH responses and separated emission windows, the changes in the emission colors were clearly observed in their dual color sensor of PSM1,2, which changed emission colors dramatically from green at pH 7 to red at pH 4, which was detected visually and/or by using a color camera under an excitation of 488 nm. In addition to the development of the dual color ratiometric pH sensor, we also studied the effects of different matrix compositions, crosslinkers, and charges on the reporting capabilities of the sensors (sensitivity and pKa). PMID:24078772

Morphological effects of porous poly-d,l-lactic acid/hydroxyapatite scaffolds produced by supercritical CO2 foaming on their mechanical performance.

PubMed

Rouholamin, Davood; van Grunsven, William; Reilly, Gwendolen C; Smith, Patrick J

2016-08-01

A novel supercritical CO2 foaming technique was used to fabricate scaffolds of controllable morphology and mechanical properties, with the potential to tailor the scaffolds to specific tissue engineering applications. Biodegradable scaffolds are widely used as temporary supportive structures for bone regeneration. The scaffolds must provide a sufficient mechanical support while allowing cell attachment and growth as well as metabolic activities. In this study, supercritical CO2 foaming was used to prepare fully interconnected porous scaffolds of poly-d,l-lactic acid and poly-d,l-lactic acid/hydroxyapatite. The morphological, mechanical and cell behaviours of the scaffolds were measured to examine the effect of hydroxyapatite on these properties. These scaffolds showed an average porosity in the range of 86%-95%, an average pore diameter of 229-347 µm and an average pore interconnection of 103-207 µm. The measured porosity, pore diameter, and interconnection size are suitable for cancellous bone regeneration. Compressive strength and modulus of up to 36.03 ± 5.90 and 37.97 ± 6.84 MPa were measured for the produced porous scaffolds of various compositions. The mechanical properties presented an improvement with the addition of hydroxyapatite to the structure. The relationship between morphological and mechanical properties was investigated. The matrices with different compositions were seeded with bone cells, and all the matrices showed a high cell viability and biocompatibility. The number of cells attached on the matrices slightly increased with the addition of hydroxyapatite indicating that hydroxyapatite improves the biocompatibility and proliferation of the scaffolds. The produced poly-d,l-lactic acid/hydroxyapatite scaffolds in this study showed a potential to be used as bone graft substitutes. © IMechE 2016.

Active Sites of Reduced Epidermal Fluorescence1 (REF1) Isoforms Contain Amino Acid Substitutions That Are Different between Monocots and Dicots

PubMed Central

Missihoun, Tagnon D.; Kotchoni, Simeon O.; Bartels, Dorothea

2016-01-01

Plant aldehyde dehydrogenases (ALDHs) play important roles in cell wall biosynthesis, growth, development, and tolerance to biotic and abiotic stresses. The Reduced Epidermal Fluorescence1 is encoded by the subfamily 2C of ALDHs and was shown to oxidise coniferaldehyde and sinapaldehyde to ferulic acid and sinapic acid in the phenylpropanoid pathway, respectively. This knowledge has been gained from works in the dicotyledon model species Arabidopsis thaliana then used to functionally annotate ALDH2C isoforms in other species, based on the orthology principle. However, the extent to which the ALDH isoforms differ between monocotyledons and dicotyledons has rarely been accessed side-by-side. In this study, we used a phylogenetic approach to address this question. We have analysed the ALDH genes in Brachypodium distachyon, alongside those of other sequenced monocotyledon and dicotyledon species to examine traits supporting either a convergent or divergent evolution of the ALDH2C/REF1-type proteins. We found that B. distachyon, like other grasses, contains more ALDH2C/REF1 isoforms than A. thaliana and other dicotyledon species. Some amino acid residues in ALDH2C/REF1 isoforms were found as being conserved in dicotyledons but substituted by non-equivalent residues in monocotyledons. One example of those substitutions concerns a conserved phenylalanine and a conserved tyrosine in monocotyledons and dicotyledons, respectively. Protein structure modelling suggests that the presence of tyrosine would widen the substrate-binding pocket in the dicotyledons, and thereby influence substrate specificity. We discussed the importance of these findings as new hints to investigate why ferulic acid contents and cell wall digestibility differ between the dicotyledon and monocotyledon species. PMID:27798665

Active Sites of Reduced Epidermal Fluorescence1 (REF1) Isoforms Contain Amino Acid Substitutions That Are Different between Monocots and Dicots.

PubMed

Missihoun, Tagnon D; Kotchoni, Simeon O; Bartels, Dorothea

2016-01-01

Plant aldehyde dehydrogenases (ALDHs) play important roles in cell wall biosynthesis, growth, development, and tolerance to biotic and abiotic stresses. The Reduced Epidermal Fluorescence1 is encoded by the subfamily 2C of ALDHs and was shown to oxidise coniferaldehyde and sinapaldehyde to ferulic acid and sinapic acid in the phenylpropanoid pathway, respectively. This knowledge has been gained from works in the dicotyledon model species Arabidopsis thaliana then used to functionally annotate ALDH2C isoforms in other species, based on the orthology principle. However, the extent to which the ALDH isoforms differ between monocotyledons and dicotyledons has rarely been accessed side-by-side. In this study, we used a phylogenetic approach to address this question. We have analysed the ALDH genes in Brachypodium distachyon, alongside those of other sequenced monocotyledon and dicotyledon species to examine traits supporting either a convergent or divergent evolution of the ALDH2C/REF1-type proteins. We found that B. distachyon, like other grasses, contains more ALDH2C/REF1 isoforms than A. thaliana and other dicotyledon species. Some amino acid residues in ALDH2C/REF1 isoforms were found as being conserved in dicotyledons but substituted by non-equivalent residues in monocotyledons. One example of those substitutions concerns a conserved phenylalanine and a conserved tyrosine in monocotyledons and dicotyledons, respectively. Protein structure modelling suggests that the presence of tyrosine would widen the substrate-binding pocket in the dicotyledons, and thereby influence substrate specificity. We discussed the importance of these findings as new hints to investigate why ferulic acid contents and cell wall digestibility differ between the dicotyledon and monocotyledon species.

Two-Center Evaluation of Disinfectant Efficacy against Ebola Virus in Clinical and Laboratory Matrices.

PubMed

Smither, Sophie J; Eastaugh, Lin; Filone, Claire Marie; Freeburger, Denise; Herzog, Artemas; Lever, M Stephen; Miller, David M; Mitzel, Dana; Noah, James W; Reddick-Elick, Mary S; Reese, Amy; Schuit, Michael; Wlazlowski, Carly B; Hevey, Michael; Wahl-Jensen, Victoria

2018-01-01

Ebola virus (EBOV) in body fluids poses risk for virus transmission. However, there are limited experimental data for such matrices on the disinfectant efficacy against EBOV. We evaluated the effectiveness of disinfectants against EBOV in blood on surfaces. Only 5% peracetic acid consistently reduced EBOV titers in dried blood to the assay limit of quantification.

A novel amino acid substitution in a voltage-gated sodium channel is associated with knockdown resistance to permethrin in Aedes aegypti.

PubMed

Chang, Cheng; Shen, Wen-Kai; Wang, Tzu-Ting; Lin, Ying-Hsi; Hsu, Err-Lieh; Dai, Shu-Mei

2009-04-01

To identify pertinent mutations associated with knockdown resistance to permethrin, the entire coding sequence of the voltage-gated sodium channel gene Aa-para was sequenced and analyzed from a Per-R strain with 190-fold resistance to permethrin and two susceptible strains of Aedes aegypti. The longest transcript, a 6441bp open reading frame, encodes 2147 amino acid residues with an estimated molecular mass of 241kDa. A total of 33 exons were found in the Aa-para gene over 293kb of genomic DNA. Three previously unreported optional exons were identified. The first two exons, m and n, were located within the intracellular domain I/II, and the third, f', was found within the II/III linkers. The two mutually exclusive exons, d and l, were the only alternative exons in all the cDNA clones sequenced in this study. The most distinct finding was a novel amino acid substitution mutation, D1794Y, located within the extracellular linker between IVS5 and IVS6, which is concurrent with the known V1023G mutation in Aa-para of the Per-R strain. The high frequency and coexistence of the two mutations in the Per-R strain suggest that they might exert a synergistic effect to provide the knockdown resistance to permethrin. Furthermore, both cDNA and genomic DNA data from the same individual mosquitoes have demonstrated that RNA editing was not involved in amino acid substitutions of the Per-R strain.

The Effects of Mineral Matrices and Extraction Method on Quantification of Bacterial Phospholipid Fatty Acids.

NASA Astrophysics Data System (ADS)

Ford, S. E.; McKelvie, J. R. M.; Sherwood Lollar, B.; Slater, G. F.

2017-12-01

Understanding the distribution, abundances and metabolic activities of microbial life in the subsurface is fundamental to our understanding of biogeochemical cycling on Earth. Given that the most likely environments for life to still exist, or be preserved, on other planets and moons in the solar system are in the subsurface, a better understanding of subsurface life on Earth is also a key factor in our ability to search for life beyond the Earth. While we have made progress in investigating life in the continental subsurface in recent years, significant challenges remain. In particular, the low biomass abundance, heterogeneous distribution of biomass, and the potential for matrix effects during sampling and analysis mean that further development and optimization of methods to study subsurface life are needed. Phospholipid fatty acids (PLFA) are a useful biosignature of extant, viable microbial communities that are applied in a wide range of environments. Here we test the sensitivity of two methods of PLFA analysis (modified Bligh and Dyer, Microwave Assisted Extraction) to detect known numbers of cells doped into two distinct matrices (bentonite, crushed granite). Samples were prepared by adding known cellular concentrations of Basciullus subtilis subtilis (ATCC 6051) to crushed bentonite, or to granite, respectively, to create dilution series. Samples were extracted for PLFA using a dichloromethane-methanol modified Bligh & Dyer (mBD) or Microwave Assisted Extraction (MAE) and then quantified using GC - MS and GC - FID. Pure culture extractions yielded a linearly decreasing trend to the level of the process blank. The ratio of cells to PLFA for this trend was 2.4x104 +/- 1.9x104 cells/pmol at the lower end of the generic range of 2 to 6 x105 cells/pmol. For bentonite the PLFA results were lower than for the pure culture. PLFA results for bentonite followed a linear trend at higher concentrations, but departed from this at low concentrations indicating the

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudwaleit, M.; Bowness, P.; Wordsworth, P.

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.

Graphene oxide-stimulated myogenic differentiation of C2C12 cells on PLGA/RGD peptide nanofiber matrices

NASA Astrophysics Data System (ADS)

Shin, Y. C.; Lee, J. H.; Kim, M. J.; Hong, S. W.; Oh, J.-W.; Kim, C.-S.; Kim, B.; Hyun, J. K.; Kim, Y.-J.; Han, D.-W.

2015-07-01

During the last decade, much attention has been paid to graphene-based nanomaterials because they are considered as potential candidates for biomedical applications such as scaffolds for tissue engineering and substrates for the differentiation of stem cells. Until now, electrospun matrices composed of various biodegradable copolymers have been extensively developed for tissue engineering and regeneration; however, their use in combination with graphene oxide (GO) is novel and challenging. In this study, nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 phage with RGD peptide displayed on its surface (RGD peptide-M13 phage) were prepared as extracellular matrix (ECM)-mimicking substrates. RGD peptide is a tripeptide (Arg-Gly-Asp) found on ECM proteins that promotes various cellular behaviors. The physicochemical properties of PLGA and RGD peptide-M13 phage (PLGA/RGD peptide) nanofiber matrices were characterized by atomic force microscopy, Fourier-transform infrared spectroscopy and thermogravimetric analysis. In addition, the growth of C2C12 mouse myoblasts on the PLGA/RGD peptide matrices was examined by measuring the metabolic activity. Moreover, the differentiation of C2C12 mouse myoblasts on the matrices when treated with GO was evaluated. The cellular behaviors, including growth and differentiation of C2C12 mouse myoblasts, were substantially enhanced on the PLGA/RGD peptide nanofiber matrices when treated with GO. Overall, these findings suggest that the PLGA/RGD peptide nanofiber matrices can be used in combination with GO as a novel strategy for skeletal tissue regeneration.

Natural variation in a single amino acid substitution underlies physiological responses to topoisomerase II poisons.

PubMed

Zdraljevic, Stefan; Strand, Christine; Seidel, Hannah S; Cook, Daniel E; Doench, John G; Andersen, Erik C

2017-07-01

Many chemotherapeutic drugs are differentially effective from one patient to the next. Understanding the causes of this variability is a critical step towards the development of personalized treatments and improvements to existing medications. Here, we investigate sensitivity to a group of anti-neoplastic drugs that target topoisomerase II using the model organism Caenorhabditis elegans. We show that wild strains of C. elegans vary in their sensitivity to these drugs, and we use an unbiased genetic approach to demonstrate that this natural variation is explained by a methionine-to-glutamine substitution in topoisomerase II (TOP-2). The presence of a non-polar methionine at this residue increases hydrophobic interactions between TOP-2 and its poison etoposide, as compared to a polar glutamine. We hypothesize that this stabilizing interaction results in increased genomic instability in strains that contain a methionine residue. The residue affected by this substitution is conserved from yeast to humans and is one of the few differences between the two human topoisomerase II isoforms (methionine in hTOPIIα and glutamine in hTOPIIβ). We go on to show that this amino acid difference between the two human topoisomerase isoforms influences cytotoxicity of topoisomerase II poisons in human cell lines. These results explain why hTOPIIα and hTOPIIβ are differentially affected by various poisons and demonstrate the utility of C. elegans in understanding the genetics of drug responses.

Multiple adaptive amino acid substitutions increase the virulence of a wild waterfowl-origin reassortant H5N8 avian influenza virus in mice.

PubMed

Yu, Zhijun; Cheng, Kaihui; Sun, Weiyang; Zhang, Xinghai; Xia, Xianzhu; Gao, Yuwei

2018-01-15

A novel H5N8 highly pathogenic avian influenza virus (HPAIV) caused poultry outbreaks in the Republic of Korea in 2014. The novel H5N8 HPAIV has spread to Asia, Europe, and North America and caused great public concern from then on. Here, we generated mouse-adapted variants of a wild waterfowl-origin H5N8 HPAIV to identify adaptive mutants that confer enhanced pathogenicity in mammals. The mouse lethal doses (MLD 50 ) of the mouse-adapted variants were reduced 31623-fold compared to the wild-type (WT) virus. Mouse-adapted variants displayed enhanced replication in vitro and in vivo, and expanded tissue tropism in mice. Sequence analysis revealed four amino acid substitutions in the PB2 (E627K), PA (F35S), HA (R227H), and NA (I462V) proteins. These data suggest that multiple amino acid substitutions collaboratively increase the virulence of a wild bird-origin reassortant H5N8 HPAIV and cause severe disease in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Emergence of Avian Influenza Viruses with Enhanced Transcription Activity by a Single Amino Acid Substitution in the Nucleoprotein during Replication in Chicken Brains ▿

PubMed Central

Tada, Tatsuya; Suzuki, Koutaro; Sakurai, Yu; Kubo, Masanori; Okada, Hironao; Itoh, Toshihiro; Tsukamoto, Kenji

2011-01-01

To explore the genetic basis of the pathogenesis and adaptation of avian influenza viruses (AIVs) to chickens, the A/duck/Yokohama/aq10/2003 (H5N1) (DkYK10) virus was passaged five times in the brains of chickens. The brain-passaged DkYK10-B5 caused quick death of chickens through rapid and efficient replication in tissues, accompanied by severe apoptosis. Genome sequence comparison of two viruses identified a single amino acid substitution at position 109 in NP from isoleucine to threonine (NP I109T). By analyzing viruses constructed by the reverse-genetic method, we established that the NP I109T substitution also contributed to increased viral replication and polymerase activity in chicken embryo fibroblasts, but not in duck embryo fibroblasts. Real-time RT-PCR analysis demonstrated that the NP I109T substitution enhances mRNA synthesis quickly and then cRNA and viral RNA (vRNA) synthesis slowly. Next, to determine the mechanism underlying the appearance of the NP I109T substitution during passages, four H5N1 highly pathogenic AIVs (HPAIVs) were passaged in the lungs and brains of chicken embryos. Single-nucleotide polymorphism analysis, together with a database search, suggests that the NP I109T mutation would be induced frequently during replication of HPAIVs in brains, but not in lungs. These results demonstrate that the amino acid at position 109 in NP enhances viral RNA synthesis and the pathogenicity of highly pathogenic avian influenza viruses in chickens and that the NP mutation emerges quickly during replication of the viruses in chicken brains. PMID:21795332

Two-Center Evaluation of Disinfectant Efficacy against Ebola Virus in Clinical and Laboratory Matrices

PubMed Central

Smither, Sophie J.; Eastaugh, Lin; Filone, Claire Marie; Freeburger, Denise; Herzog, Artemas; Lever, M. Stephen; Miller, David M.; Mitzel, Dana; Noah, James W.; Reddick-Elick, Mary S.; Reese, Amy; Schuit, Michael; Wlazlowski, Carly B.; Hevey, Michael

2018-01-01

Ebola virus (EBOV) in body fluids poses risk for virus transmission. However, there are limited experimental data for such matrices on the disinfectant efficacy against EBOV. We evaluated the effectiveness of disinfectants against EBOV in blood on surfaces. Only 5% peracetic acid consistently reduced EBOV titers in dried blood to the assay limit of quantification. PMID:29261093

A rapid and sensitive assay of perfluorocarboxylic acids in aqueous matrices by headspace solid phase microextraction-gas chromatography-triple quadrupole mass spectrometry.

PubMed

Monteleone, Marcello; Naccarato, Attilio; Sindona, Giovanni; Tagarelli, Antonio

2012-08-17

The work aims at developing a rapid and sensitive method for the quantification of perfluorocarboxylic acids in aqueous matrices. The proposed analytical approach is based on the use of solid phase microextraction in headspace mode after a fast derivatization of the carboxylate function by propylchloroformate/propanol mixture. Several fibers were evaluated and the optimization of the parameters affecting the SPME process was carried out using a central composite design. The optimum working conditions in terms of response values were achieved by performing analysis with CAR/PDMS fiber at room temperature, without addition of NaCl, with a sample volume of 6 ml and an extraction time of 10 min. Assay of PFCAs was performed by using a gas chromatography-triple quadrupole mass spectrometry (GC-QqQ MS) system in negative chemical ionization mode with ammonia as reagent gas. An overall evaluation of all analytical parameters shows that the proposed method provides satisfactory results. In particular, the observed accuracies, ranging from 84.4% to 116.8%, and the RSD values in the range 0.4% and 14.5% confirm the effectiveness of the developed protocol in the assay of PFCAs content in aqueous matrices. Moreover, LOD and LOQ values ranging from 0.08 to 6.6 ng l(-1) and from 0.17 to 14.3 ng l(-1), respectively, can be considered very satisfactory. None of the compounds were detected in six samples of river collected in Calabria. Copyright © 2012 Elsevier B.V. All rights reserved.

A Brief Historical Introduction to Matrices and Their Applications

ERIC Educational Resources Information Center

Debnath, L.

2014-01-01

This paper deals with the ancient origin of matrices, and the system of linear equations. Included are algebraic properties of matrices, determinants, linear transformations, and Cramer's Rule for solving the system of algebraic equations. Special attention is given to some special matrices, including matrices in graph theory and electrical…

Amino acid substitutions in low pathogenic avian influenza virus strains isolated from wild birds in Korea.

PubMed

Oh, Kwang-Hyun; Mo, Jong-Suk; Bae, Yeon-Ji; Lee, Seung-Baek; Lai, Van Dam; Wang, Seung-Jun; Mo, In-Pil

2018-06-01

Wild birds are natural hosts and reservoirs for influenza A viruses. However, many species, such as many waterfowl, are asymptomatic when infected and so facilitate the generation of viral genetic diversity. Mutations of key genes affect the replicability, pathogenicity, transmissibility, and antiviral resistance of influenza A viruses. In this study, we isolated avian influenza (AI) viruses from wild bird fecal samples and analyzed changes in amino acids over time and geographic region to monitor the biological change of the AI virus. Between 2014 and 2016, we collected 38,921 fresh fecal samples from major wild bird habitats located throughout Korea and isolated 123 AI viruses. We subsequently selected 22 amino acid sites to analyze for changes. These sites included ten sites associated with replication, ten sites associated with pathogenicity, three sites associated with transmission, and seven sites associated with antiviral resistance. We found substitution rates of 71.7% at the C38Y amino acid site within the polymerase basic protein 1 (PB1) gene, 66.7% at the D222G site within the hemagglutinin (HA) 1 gene, and 75.6% at the A184 site within the nucleoprotein (NP) gene. Alterations of the PB1, HA1, and NP genes are closely associated with increased pathogenicity in chickens and mammals. The remaining sites of interest exhibited few modifications. In this study, we confirmed that AI viruses circulating among wild birds in Korea consistently exhibit modifications at amino acid sites linked with replication and pathogenicity.

Arrowheaded enhanced multivariance products representation for matrices (AEMPRM): Specifically focusing on infinite matrices and converting arrowheadedness to tridiagonality

NASA Astrophysics Data System (ADS)

Özdemir, Gizem; Demiralp, Metin

2015-12-01

In this work, Enhanced Multivariance Products Representation (EMPR) approach which is a Demiralp-and-his- group extension to the Sobol's High Dimensional Model Representation (HDMR) has been used as the basic tool. Their discrete form have also been developed and used in practice by Demiralp and his group in addition to some other authors for the decomposition of the arrays like vectors, matrices, or multiway arrays. This work specifically focuses on the decomposition of infinite matrices involving denumerable infinitely many rows and columns. To this end the target matrix is first decomposed to the sum of certain outer products and then each outer product is treated by Tridiagonal Matrix Enhanced Multivariance Products Representation (TMEMPR) which has been developed by Demiralp and his group. The result is a three-matrix- factor-product whose kernel (the middle factor) is an arrowheaded matrix while the pre and post factors are invertable matrices decomposed of the support vectors of TMEMPR. This new method is called as Arrowheaded Enhanced Multivariance Products Representation for Matrices. The general purpose is approximation of denumerably infinite matrices with the new method.

HS-SPME determination of volatile carbonyl and carboxylic compounds in different matrices.

PubMed

Stashenko, Elena E; Mora, Amanda L; Cervantes, Martha E; Martínez, Jairo R

2006-07-01

Specific chromatographic methodologies are developed for the analysis of carboxylic acids (C(2)-C(6), benzoic) and aldehydes (C(2)-C(10)) of low molecular weight in diverse matrices, such as air, automotive exhaust gases, human breath, and aqueous matrices. For carboxylic acids, the method is based on their reaction with pentafluorobenzyl bromide in aqueous solution, followed by the separation and identification of the resultant pentafluorobenzyl esters by means of headspace (HS)-solid-phase microextraction (SPME) combined with gas chromatography (GC) and electron capture detection (ECD). Detection limits in the microg/m(3) range are reached, with relative standard deviation (RSD) less than 10% and linear response (R(2) > 0.99) over two orders of magnitude. The analytical methodology for aldehydes is based on SPME with simultaneous derivatization of the analytes on the fiber, by reaction with pentafluorophenylhydrazine. The derivatization reagent is previously deposited on the SPME fiber, which is then exposed to the gaseous matrix or the HS of the sample solution. The pentafluorophenyl hydrazones formed on the fiber are analyzed selectively by means of GC-ECD, with detection limits in the ng/m(3) range, RSD less than 10%, and linear response (R(2) > 0.99) over two orders of magnitude.

ESTIMATION OF FUNCTIONALS OF SPARSE COVARIANCE MATRICES.

PubMed

Fan, Jianqing; Rigollet, Philippe; Wang, Weichen

High-dimensional statistical tests often ignore correlations to gain simplicity and stability leading to null distributions that depend on functionals of correlation matrices such as their Frobenius norm and other ℓ r norms. Motivated by the computation of critical values of such tests, we investigate the difficulty of estimation the functionals of sparse correlation matrices. Specifically, we show that simple plug-in procedures based on thresholded estimators of correlation matrices are sparsity-adaptive and minimax optimal over a large class of correlation matrices. Akin to previous results on functional estimation, the minimax rates exhibit an elbow phenomenon. Our results are further illustrated in simulated data as well as an empirical study of data arising in financial econometrics.

ESTIMATION OF FUNCTIONALS OF SPARSE COVARIANCE MATRICES

PubMed Central

Fan, Jianqing; Rigollet, Philippe; Wang, Weichen

2016-01-01

High-dimensional statistical tests often ignore correlations to gain simplicity and stability leading to null distributions that depend on functionals of correlation matrices such as their Frobenius norm and other ℓr norms. Motivated by the computation of critical values of such tests, we investigate the difficulty of estimation the functionals of sparse correlation matrices. Specifically, we show that simple plug-in procedures based on thresholded estimators of correlation matrices are sparsity-adaptive and minimax optimal over a large class of correlation matrices. Akin to previous results on functional estimation, the minimax rates exhibit an elbow phenomenon. Our results are further illustrated in simulated data as well as an empirical study of data arising in financial econometrics. PMID:26806986

On Fluctuations of Eigenvalues of Random Band Matrices

NASA Astrophysics Data System (ADS)

Shcherbina, M.

2015-10-01

We consider the fluctuations of linear eigenvalue statistics of random band matrices whose entries have the form with i.i.d. possessing the th moment, where the function u has a finite support , so that M has only nonzero diagonals. The parameter b (called the bandwidth) is assumed to grow with n in a way such that . Without any additional assumptions on the growth of b we prove CLT for linear eigenvalue statistics for a rather wide class of test functions. Thus we improve and generalize the results of the previous papers (Jana et al., arXiv:1412.2445; Li et al. Random Matrices 2:04, 2013), where CLT was proven under the assumption . Moreover, we develop a method which allows to prove automatically the CLT for linear eigenvalue statistics of the smooth test functions for almost all classical models of random matrix theory: deformed Wigner and sample covariance matrices, sparse matrices, diluted random matrices, matrices with heavy tales etc.

Stimulating effect of graphene oxide on myogenesis of C2C12 myoblasts on RGD peptide-decorated PLGA nanofiber matrices.

PubMed

Shin, Yong Cheol; Lee, Jong Ho; Kim, Min Jeong; Hong, Suck Won; Kim, Bongju; Hyun, Jung Keun; Choi, Yu Suk; Park, Jong-Chul; Han, Dong-Wook

2015-01-01

In the field of biomedical engineering, many studies have focused on the possible applications of graphene and related nanomaterials due to their potential for use as scaffolds, coating materials and delivery carriers. On the other hand, electrospun nanofiber matrices composed of diverse biocompatible polymers have attracted tremendous attention for tissue engineering and regenerative medicine. However, their combination is intriguing and still challenging. In the present study, we fabricated nanofiber matrices composed of M13 bacteriophage with RGD peptide displayed on its surface (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) and characterized their physicochemical properties. In addition, the effect of graphene oxide (GO) on the cellular behaviors of C2C12 myoblasts, which were cultured on PLGA decorated with RGD-M13 phage (RGD/PLGA) nanofiber matrices, was investigated. Our results revealed that the RGD/PLGA nanofiber matrices have suitable physicochemical properties as a tissue engineering scaffold and the growth of C2C12 myoblasts were significantly enhanced on the matrices. Moreover, the myogenic differentiation of C2C12 myoblasts was substantially stimulated when they were cultured on the RGD/PLGA matrices in the presence of GO. In conclusion, these findings propose that the combination of RGD/PLGA nanofiber matrices and GO can be used as a promising strategy for skeletal tissue engineering and regeneration.

Trifluoromethyl-substituted polymers

NASA Technical Reports Server (NTRS)

1993-01-01

Current work sponsored by the grant at Southwest Texas State University is directed toward the synthesis and characterization of: (1) N-alkylated polyamides derived from o-fluorinated diacids; (2) highly fluorinated polyethers; (3) polyesters derived from 2-hydroxy-2-propyl substituted arenes and/or 2,5-difluoroterephthalic acid; and (4) silicon-containing fluoropolymers. Work during the period from 1 July to 31 Dec. 1993 focused primarily on items 3 and 4 and on the development of a phosphorus containing modification of '12F-PEK.'

Matric potential

Treesearch

Melvin T. Tyree

2003-01-01

Matric potential, r, is a component of water potential, ?, but has different meanings in plant physiology vs. soil science. A rigorous definition of r requires a reference to principles of thermodynamics (both classical and irreversible thermodynamics). A rigorous treatment is beyond the scope of this brief overview. Readers...

Synthetic versatility of 2-substituted-6-methyl 2,3-dihydropyridinones in the synthesis of polyfunctional piperidine-based compounds and related β amino acid derivatives.

PubMed

Yang, Yang; Hardman, Clayton

2017-10-18

Chiral 2-substituted-6-methyl 2,3-dihydropyidinones 9, which can be facilely obtained from an asymmetric vinylogous Mannich reaction (VMR) with 1,3-bis-trimethysily enol ether, were used as versatile intermediates in constructing chiral polyfunctional piperidine-based compounds. The 6-methyl group of such compounds can be conveniently functionalized via alkylation and acylation reactions to provide efficient entries to the synthesis of a variety of chiral multi-substituted piperidine-based compounds. Further elaboration of the corresponding intermediates also provided access to polyfunctional indolizidine-based compounds. These methods were showcased in an asymmetric synthesis of 2,6-di-substituted piperidine compound 13, reported as the key intermediate in the synthesis of (+)-calvine and a natural alkaloid (-)-indolizidine 209D. Furthermore, selective C5 iodination of compound 9 enabled the installation of additional functional groups at this position. Finally, we demonstrated that the oxidative cleavage of 2-substituted-6-methyl-2,3-dihydropyidinones is a practical and efficient method for the enantioselective synthesis of β-amino acids, which can undergo further intra-molecular cyclization to give the corresponding chiral four-membered β-lactam derivatives.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernández-Sainz, I.J.; Largo, E.; Gladue, D.P.

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 adoptedmore » 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.« less

Application of ChemDraw NMR Tool: Correlation of Program-Generated 13C Chemical Shifts and pKa Values of para-Substituted Benzoic Acids

NASA Astrophysics Data System (ADS)

Wang, Hongyi

2005-09-01

An application of ChemDraw NMR Tool was demonstrated by correlation of program-generated 13 C NMR chemical shifts and p K a values of para-substituted benzoic acids. Experimental 13 C NMR chemical shifts were analyzed in the same way for comparison. The project can be used as an assignment at the end of the first-year organic chemistry course to review topics or explore new techniques: Hammett equation, acid base equilibrium theory, electronic nature of functional groups, inductive and resonance effects, structure reactivity relationship, NMR spectroscopy, literature search, database search, and ChemDraw software.

Oxidation of Alkyl-substituted Cyclic Hydrocarbons by a Nocardia during Growth on n-Alkanes

PubMed Central

Davis, J. B.; Raymond, R. L.

1961-01-01

Nocardia 107-332, a soil isolate, oxidizes short-chain alkyl-substituted cyclic hydrocarbons to cyclic acids while growing on n-alkanes. Cyclic acids are produced also from relatively long-chain alkyl-substituted cyclics such as n-nonylbenzene or n-dodecylbenzene which alone support growth in a mineral-salts medium. ω-Oxidation of the alkyl substituents is followed by β-oxidation. It is of particular interest that cyclic acids such as cyclohexaneacetic and phenylacetic with C2 residual carboxylic acid substituents are resistant to further oxidation by the nocardia but cyclic acids with C1 or C3 substituents are readily oxidized and utilized for growth. The specificity of microbial oxidations is demonstrated by the conversion of p-isopropyltoluene (p-cymene) to p-isopropylbenzoic acid in n-alkane, growth-supported nocardia cultures. PMID:13720182

Synthesis of [.sup.13C] and [.sup.2H] substituted methacrylic acid, [.sup.13C] and [.sup.2H] substituted methyl methacrylate and/or related compounds

DOEpatents

Alvarez, Marc A [Santa Fe, NM; Martinez, Rodolfo A [Santa Fe, NM; Unkefer, Clifford J [Los Alamos, NM

2008-01-22

The present invention is directed to labeled compounds of the formulae ##STR00001## wherein Q is selected from the group consisting of --S--, --S(.dbd.O)--, and --S(.dbd.O).sub.2--, Z is selected from the group consisting of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure ##STR00002## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently selected from the group consisting of hydrogen, a C.sub.1-C.sub.4 lower alkyl, a halogen, and an amino group selected from the group consisting of NH.sub.2, NHR and NRR' where R and R' are each independently selected from the group consisting of a C.sub.1-C.sub.4 lower alkyl, an aryl, and an alkoxy group, and X is selected from the group consisting of hydrogen, a C.sub.1-C.sub.4 lower alkyl group, and a fully-deuterated C.sub.1-C.sub.4 lower alkyl group. The present invention is also directed to a process of preparing labeled compounds, e.g., process of preparing [.sup.13C]methacrylic acid by reacting a (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13CH.sub.2)-- aryl sulfone precursor with .sup.13CHI to form a (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13C(.sup.13CH.sub.3).sub.2)-- aryl sulfone intermediate, and, reacting the (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13C(.sup.13CH.sub.3).sub.2)-- aryl sulfone intermediate with sodium hydroxide, followed by acid to form [.sup.13C]methacrylic acid. The present invention is further directed to a process of preparing [.sup.2H.sub.8]methyl methacrylate by reacting a (HOOC--C(C.sup.2H.sub.3).sub.2-- aryl sulfinyl intermediate with CD.sub.3I to form a (.sup.2H.sub.3COOC--C(C.sup.2H.sub.3).sub.2)-- aryl sulfinyl intermediate, and heating the(.sup.2H.sub.3COOC--C(C.sup.2H.sub.3).sub.2)-- aryl sulfinyl intermediate at temperatures and for time sufficient to form [.sup.2H.sub.8]methyl methacrylate.

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.981 Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new...

Homology search with binary and trinary scoring matrices.

PubMed

Smith, Scott F

2006-01-01

Protein homology search can be accelerated with the use of bit-parallel algorithms in conjunction with constraints on the values contained in the scoring matrices. Trinary scoring matrices (containing only the values -1, 0, and 1) allow for significant acceleration without significant reduction in the receiver operating characteristic (ROC) score of a Smith-Waterman search. Binary scoring matrices (containing the values 0 and 1) result in some reduction in ROC score, but result in even more acceleration. Binary scoring matrices and five-bit saturating scores can be used for fast prefilters to the Smith-Waterman algorithm.

Structure-activity studies of lGnRH-III through rational amino acid substitution and NMR conformational studies.

PubMed

Pappa, Eleni V; Zompra, Aikaterini A; Diamantopoulou, Zoi; Spyranti, Zinovia; Pairas, George; Lamari, Fotini N; Katsoris, Panagiotis; Spyroulias, George A; Cordopatis, Paul

2012-01-01

Lamprey gonadotropin-releasing hormone type III (lGnRH-III) is an isoform of GnRH isolated from the sea lamprey (Petromyzon marinus) with negligible endocrine activity in mammalian systems. Data concerning the superior direct anticancer activity of lGnRH-III have been published, raising questions on the structure-activity relationship. We synthesized 21 lGnRH-III analogs with rational amino acid substitutions and studied their effect on PC3 and LNCaP prostate cancer cell proliferation. Our results question the importance of the acidic charge of Asp⁶ for the antiproliferative activity and indicate the significance of the stereochemistry of Trp in positions 3 and 7. Furthermore, conjugation of an acetyl-group to the side chain of Lys⁸ or side chain cyclization of amino acids 1-8 increased the antiproliferative activity of lGnRH-III demonstrating that the proposed salt bridge between Asp⁶ and Lys⁸ is not crucial. Conformational studies of lGnRH-III were performed through NMR spectroscopy, and the solution structure of GnRH-I was solved. In solution, lGnRH-III adopts an extended backbone conformation in contrast to the well-defined β-turn conformation of GnRH-I. Copyright © 2012 Wiley Periodicals, Inc.

Novel electrospun nanofibrous matrices prepared from poly(lactic acid)/poly(butylene adipate) blends for controlled release formulations of an anti-rheumatoid agent.

PubMed

Siafaka, Panoraia I; Barmbalexis, Panagiotis; Bikiaris, Dimitrios N

2016-06-10

In the present work, a series of novel formulations consisting of poly(lactic acid)/poly(butylene adipate) (PLA/PBAd) electrospun blends was examined as controlled release matrices for Leflunomide's active metabolite, Teriflunomide (TFL). The mixtures were prepared using different ratios of PLA and PBAd in order to produce nanofibrous matrices with different characteristics. Miscibility studies of the blended polymeric fibers were performed through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolytic degradation in the prepared fibers was evaluated at 37°C using a phosphate buffered saline solution. Different concentrations of (TFL) (5, 10, 15wt.%) were incorporated into nanofibers for examining the drug release behavior in simulated body fluids (SBF), at 37°C. The drug-loaded nanofibrous formulations were further characterized by Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, DSC and XRD. Gel permeation chromatography (GPC) analysis was used to evaluate the mechanism of TFL release. Artificial neural networks (ANN) and multi-linear-regression (MLR) models were used to evaluate the effect of % content of PBAd (X1) and TFL (X2) on an initial burst effect and a dissolution behavior. It was found that PLA/PBAd nanofibers have different diameters depending on the ratio of used polyesters and added drug. TFL was incorporated in an amorphous form inside the polymeric nanofibers. In vitro release studies reveal that a drug release behavior is correlated with the size of the nanofibers, drug loading and matrix degradation after a specific time. ANN dissolution modeling showed increased correlation efficacy compared to MLR. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural and functional interaction of fatty acids with human liver fatty acid-binding protein (L-FABP) T94A variant.

PubMed

Huang, Huan; McIntosh, Avery L; Martin, Gregory G; Landrock, Kerstin K; Landrock, Danilo; Gupta, Shipra; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

2014-05-01

The human liver fatty acid-binding protein (L-FABP) T94A variant, the most common in the FABP family, has been associated with elevated liver triglyceride levels. How this amino acid substitution elicits these effects is not known. This issue was addressed using human recombinant wild-type (WT) and T94A variant L-FABP proteins as well as cultured primary human hepatocytes expressing the respective proteins (genotyped as TT, TC and CC). The T94A substitution did not alter or only slightly altered L-FABP binding affinities for saturated, monounsaturated or polyunsaturated long chain fatty acids, nor did it change the affinity for intermediates of triglyceride synthesis. Nevertheless, the T94A substitution markedly altered the secondary structural response of L-FABP induced by binding long chain fatty acids or intermediates of triglyceride synthesis. Finally, the T94A substitution markedly decreased the levels of induction of peroxisome proliferator-activated receptor α-regulated proteins such as L-FABP, fatty acid transport protein 5 and peroxisome proliferator-activated receptor α itself meditated by the polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid in cultured primary human hepatocytes. Thus, although the T94A substitution did not alter the affinity of human L-FABP for long chain fatty acids, it significantly altered human L-FABP structure and stability, as well as the conformational and functional response to these ligands. © 2014 FEBS.

Virial expansion for almost diagonal random matrices

NASA Astrophysics Data System (ADS)

Yevtushenko, Oleg; Kravtsov, Vladimir E.

2003-08-01

Energy level statistics of Hermitian random matrices hat H with Gaussian independent random entries Higeqj is studied for a generic ensemble of almost diagonal random matrices with langle|Hii|2rangle ~ 1 and langle|Hi\

Amino acid substitutions affecting aspartic acid 605 and valine 606 decrease the interaction strength between the influenza virus RNA polymerase PB2 '627' domain and the viral nucleoprotein.

PubMed

Hsia, Ho-Pan; Yang, Yin-Hua; Szeto, Wun-Chung; Nilsson, Benjamin E; Lo, Chun-Yeung; Ng, Andy Ka-Leung; Fodor, Ervin; Shaw, Pang-Chui

2018-01-01

The influenza virus RNA genome is transcribed and replicated in the context of the viral ribonucleoprotein (vRNP) complex by the viral RNA polymerase. The nucleoprotein (NP) is the structural component of the vRNP providing a scaffold for the viral RNA. In the vRNP as well as during transcription and replication the viral polymerase interacts with NP but it is unclear which parts of the polymerase and NP mediate these interactions. Previously the C-terminal '627' domain (amino acids 538-693) of PB2 was shown to interact with NP. Here we report that a fragment encompassing amino acids 146-185 of NP is sufficient to mediate this interaction. Using NMR chemical shift perturbation assays we show that amino acid region 601 to 607 of the PB2 '627' domain interacts with this fragment of NP. Substitutions of these PB2 amino acids resulted in diminished RNP activity and surface plasmon resonance assays showed that amino acids D605 was essential for the interaction with NP and V606 may also play a partial role in the interaction. Collectively these results reveal a possible interaction surface between NP and the PB2 subunit of the RNA polymerase complex.

Quinolone resistance-associated amino acid substitutions affect enzymatic activity of Mycobacterium leprae DNA gyrase.

PubMed

Yamaguchi, Tomoyuki; Yokoyama, Kazumasa; Nakajima, Chie; Suzuki, Yasuhiko

2017-07-01

Quinolones are important antimicrobials for treatment of leprosy, a chronic infectious disease caused by Mycobacterium leprae. Although it is well known that mutations in DNA gyrase are responsible for quinolone resistance, the effect of those mutations on the enzymatic activity is yet to be studied in depth. Hence, we conducted in vitro assays to observe supercoiling reactions of wild type and mutated M. leprae DNA gyrases. DNA gyrase with amino acid substitution Ala91Val possessed the highest activity among the mutants. DNA gyrase with Gly89Cys showed the lowest level of activity despite being found in clinical strains, but it supercoiled DNA like the wild type does if applied at a sufficient concentration. In addition, patterns of time-dependent conversion from relaxed circular DNA into supercoiled DNA by DNA gyrases with clinically unreported Asp95Gly and Asp95Asn were observed to be distinct from those by the other DNA gyrases.

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

NASA Astrophysics Data System (ADS)

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).

Synchronous correlation matrices and Connes’ embedding conjecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dykema, Kenneth J., E-mail: kdykema@math.tamu.edu; Paulsen, Vern, E-mail: vern@math.uh.edu

In the work of Paulsen et al. [J. Funct. Anal. (in press); preprint arXiv:1407.6918], the concept of synchronous quantum correlation matrices was introduced and these were shown to correspond to traces on certain C*-algebras. In particular, synchronous correlation matrices arose in their study of various versions of quantum chromatic numbers of graphs and other quantum versions of graph theoretic parameters. In this paper, we develop these ideas further, focusing on the relations between synchronous correlation matrices and microstates. We prove that Connes’ embedding conjecture is equivalent to the equality of two families of synchronous quantum correlation matrices. We prove thatmore » if Connes’ embedding conjecture has a positive answer, then the tracial rank and projective rank are equal for every graph. We then apply these results to more general non-local games.« less

STRUCTURAL AND FUNCTIONAL INTERACTION OF FATTY ACIDS WITH HUMAN LIVER FATTY ACID BINDING PROTEIN (L-FABP) T94A VARIANT

PubMed Central

Huang, Huan; McIntosh, Avery L.; Martin, Gregory G.; Landrock, Kerstin K.; Landrock, Danilo; Gupta, Shipra; Atshaves, Barbara P.; Kier, Ann B.; Schroeder, Friedhelm

2014-01-01

The human liver fatty acid binding protein (L-FABP) T94A variant, the most common in the FABP family, has been associated with elevated liver triglyceride (TG) levels. How this amino acid substitution elicits these effects is not known. This issue was addressed with human recombinant wild-type (WT, T94T) and T94A variant L-FABP proteins as well as cultured primary human hepatocytes expressing the respective proteins (genotyped as TT, TC, and CC). T94A substitution did not or only slightly alter L-FABP binding affinities for saturated, monounsaturated, or polyunsaturated long chain fatty acids (LCFA), nor did it change the affinity for intermediates in TG synthesis. Nevertheless, T94A substitution markedly altered the secondary structural response of L-FABP induced by binding LCFA or intermediates of TG synthesis. Finally, T94A substitution markedly diminished polyunsaturated fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), induction of peroxisome proliferator-activated receptor alpha (PPARα) - regulated proteins such as L-FABP, fatty acid transport protein 5 (FATP5), and PPARα itself in cultured primary human hepatocytes. Thus, while T94A substitution did not alter the affinity of human L-FABP for LCFAs, it significantly altered human L-FABP structure and stability as well as conformational and functional response to these ligands. PMID:24628888

Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression.

PubMed

Avgerinos, Theodoros; Kantiranis, Nikolaos; Panagopoulou, Athanasia; Malamataris, Stavros; Kachrimanis, Kyriakos; Nikolakakis, Ioannis

2018-02-01

Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release. Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit ® RSPO the matrix former and citric acid or Lutrol ® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer's type and content on the extrusion pressure (P e ) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters. Resistance to extrusion and tablet ejection force were reduced by Lutrol ® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P e correlated with T and resistance to deformation of the corresponding pellets (r 2  = 0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r 2  = 0.990) and for HME the diffusion coefficient (D e ) and retreat rate constant (k b ) decreased linearly with T (r 2  = 0.934 and 0.972). Lutrol ® F127 and citric acid are efficient plasticizers and Lutrol ® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.

Imidazoline phosphonic acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redmore, D.

1972-07-04

Nitrogen-heterocyclic phosphonic acids and derivatives are characterized by aminomethyl (or substituted methyl) phosphonic acids or derivatives thereof bonded directly or indirectly, i.e., through a N-side chain to the nitrogen atom in the heterocyclic ring, for example those containing in the molecule at least one of the following units: ..pi..Equation/sup -/ where represents a heterocyclic ring having a nitrogen atom on the ring; -R'N- represents an amino- terminated side chain attached directly to the ring nitrogen (which side chain may or may not be present); and ..pi..Equation/sup -/ represents a methyl (or substituted methyl) phosphonic acid group where M is hydrogen,more » an alcohol or a salt moiety, and X and Y are hydrogen or a substituted group such as alkyl, aryl, etc., of which one or 2 units may be present depending on the available nitrogen bonded by hydrogens, and to uses for these compounds, for example, as scale inhibitors, corrosion inhibitors, etc. (5 claims)« less

Time series, correlation matrices and random matrix models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vinayak; Seligman, Thomas H.

2014-01-08

In this set of five lectures the authors have presented techniques to analyze open classical and quantum systems using correlation matrices. For diverse reasons we shall see that random matrices play an important role to describe a null hypothesis or a minimum information hypothesis for the description of a quantum system or subsystem. In the former case various forms of correlation matrices of time series associated with the classical observables of some system. The fact that such series are necessarily finite, inevitably introduces noise and this finite time influence lead to a random or stochastic component in these time series.more » By consequence random correlation matrices have a random component, and corresponding ensembles are used. In the latter we use random matrices to describe high temperature environment or uncontrolled perturbations, ensembles of differing chaotic systems etc. The common theme of the lectures is thus the importance of random matrix theory in a wide range of fields in and around physics.« less

Quantum Entanglement and Reduced Density Matrices

NASA Astrophysics Data System (ADS)

Purwanto, Agus; Sukamto, Heru; Yuwana, Lila

2018-05-01

We investigate entanglement and separability criteria of multipartite (n-partite) state by examining ranks of its reduced density matrices. Firstly, we construct the general formula to determine the criterion. A rank of origin density matrix always equals one, meanwhile ranks of reduced matrices have various ranks. Next, separability and entanglement criterion of multipartite is determined by calculating ranks of reduced density matrices. In this article we diversify multipartite state criteria into completely entangled state, completely separable state, and compound state, i.e. sub-entangled state and sub-entangledseparable state. Furthermore, we also shorten the calculation proposed by the previous research to determine separability of multipartite state and expand the methods to be able to differ multipartite state based on criteria above.

Estimating soil matric potential in Owens Valley, California

USGS Publications Warehouse

Sorenson, Stephen K.; Miller, R.F.; Welch, M.R.; Groeneveld, D.P.; Branson, F.A.

1988-01-01

Much of the floor of the Owens Valley, California, is covered with alkaline scrub and alkaline meadow plant communities, whose existence is dependent partly on precipitation and partly on water infiltrated into the rooting zone from the shallow water table. The extent to which these plant communities are capable of adapting to and surviving fluctuations in the water table depends on physiological adaptations of the plants and on the water content, matric potential characteristics of the soils. Two methods were used to estimate soil matric potential in test sites in Owens Valley. The first was the filter-paper method, which uses water content of filter papers equilibrated to water content of soil samples taken with a hand auger. The other method of estimating soil matric potential was a modeling approach based on data from this and previous investigations. These data indicate that the base 10 logarithm of soil matric potential is a linear function of gravimetric soil water content for a particular soil. Estimates of soil water characteristic curves were made at two sites by averaging the gravimetric soil water content and soil matric potential values from multiple samples at 0.1 m depths derived by using the hand auger and filter paper method and entering these values in the soil water model. The characteristic curves then were used to estimate soil matric potential from estimates of volumetric soil water content derived from neutron-probe readings. Evaluation of the modeling technique at two study sites indicated that estimates of soil matric potential within 0.5 pF units of the soil matric potential value derived by using the filter paper method could be obtained 90 to 95% of the time in soils where water content was less than field capacity. The greatest errors occurred at depths where there was a distinct transition between soils of different textures. (Lantz-PTT)

Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

PubMed

Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

2003-07-01

The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of

The construction of 3D-engineered tissues composed of cells and extracellular matrices by hydrogel template approach.

PubMed

Matsusaki, Michiya; Yoshida, Hiroaki; Akashi, Mitsuru

2007-06-01

The three-dimensional (3D)-engineered tissues composed of only cells and extracellular matrices (ECM) were constructed by the hydrogel template approach. The disulfide-crosslinked poly(gamma-glutamic acid) hydrogels were prepared as a template hydrogel. These template hydrogels were easily decomposed under physiological conditions using reductants such as cysteine, glutathione and dithiothreitol by cleavage of disulfide crosslinkage to thiol groups. The decomposed polymers are soluble in cell culture medium. The cleaving of disulfide bond was determined by UV-vis and FT-IR spectroscopies. We successfully prepared the 3D-engineered tissues (thickness/diameter, 2mm/1cm) composed of mouse L929 fibroblast cells and ECM by the decomposition of only the template hydrogel with cysteine after 10 days 3D-cell culture on/in the template hydrogel. The size and thickness of the 3D-engineered tissues was completely transferred from the template hydrogel. The cultured L929 cells viability in the obtained engineered tissues was confirmed by a culture test, WST-1 method and LIVE/DEAD staining assay. The engineered tissue was self-standing and highly dense composite of the cultured cells and collagen produced by the cells. This hydrogel template approach may be useful as a new class of soft-tissue engineering technology to substitute a synthetic polymer scaffold to the ECM scaffold produced from the cultured cells.

Tensor Sparse Coding for Positive Definite Matrices.

PubMed

Sivalingam, Ravishankar; Boley, Daniel; Morellas, Vassilios; Papanikolopoulos, Nikos

2013-08-02

In recent years, there has been extensive research on sparse representation of vector-valued signals. In the matrix case, the data points are merely vectorized and treated as vectors thereafter (for e.g., image patches). However, this approach cannot be used for all matrices, as it may destroy the inherent structure of the data. Symmetric positive definite (SPD) matrices constitute one such class of signals, where their implicit structure of positive eigenvalues is lost upon vectorization. This paper proposes a novel sparse coding technique for positive definite matrices, which respects the structure of the Riemannian manifold and preserves the positivity of their eigenvalues, without resorting to vectorization. Synthetic and real-world computer vision experiments with region covariance descriptors demonstrate the need for and the applicability of the new sparse coding model. This work serves to bridge the gap between the sparse modeling paradigm and the space of positive definite matrices.

Tensor sparse coding for positive definite matrices.

PubMed

Sivalingam, Ravishankar; Boley, Daniel; Morellas, Vassilios; Papanikolopoulos, Nikolaos

2014-03-01

In recent years, there has been extensive research on sparse representation of vector-valued signals. In the matrix case, the data points are merely vectorized and treated as vectors thereafter (for example, image patches). However, this approach cannot be used for all matrices, as it may destroy the inherent structure of the data. Symmetric positive definite (SPD) matrices constitute one such class of signals, where their implicit structure of positive eigenvalues is lost upon vectorization. This paper proposes a novel sparse coding technique for positive definite matrices, which respects the structure of the Riemannian manifold and preserves the positivity of their eigenvalues, without resorting to vectorization. Synthetic and real-world computer vision experiments with region covariance descriptors demonstrate the need for and the applicability of the new sparse coding model. This work serves to bridge the gap between the sparse modeling paradigm and the space of positive definite matrices.

Malware analysis using visualized image matrices.

PubMed

Han, KyoungSoo; Kang, BooJoong; Im, Eul Gyu

2014-01-01

This paper proposes a novel malware visual analysis method that contains not only a visualization method to convert binary files into images, but also a similarity calculation method between these images. The proposed method generates RGB-colored pixels on image matrices using the opcode sequences extracted from malware samples and calculates the similarities for the image matrices. Particularly, our proposed methods are available for packed malware samples by applying them to the execution traces extracted through dynamic analysis. When the images are generated, we can reduce the overheads by extracting the opcode sequences only from the blocks that include the instructions related to staple behaviors such as functions and application programming interface (API) calls. In addition, we propose a technique that generates a representative image for each malware family in order to reduce the number of comparisons for the classification of unknown samples and the colored pixel information in the image matrices is used to calculate the similarities between the images. Our experimental results show that the image matrices of malware can effectively be used to classify malware families both statically and dynamically with accuracy of 0.9896 and 0.9732, respectively.

Malware Analysis Using Visualized Image Matrices

PubMed Central

Im, Eul Gyu

2014-01-01

This paper proposes a novel malware visual analysis method that contains not only a visualization method to convert binary files into images, but also a similarity calculation method between these images. The proposed method generates RGB-colored pixels on image matrices using the opcode sequences extracted from malware samples and calculates the similarities for the image matrices. Particularly, our proposed methods are available for packed malware samples by applying them to the execution traces extracted through dynamic analysis. When the images are generated, we can reduce the overheads by extracting the opcode sequences only from the blocks that include the instructions related to staple behaviors such as functions and application programming interface (API) calls. In addition, we propose a technique that generates a representative image for each malware family in order to reduce the number of comparisons for the classification of unknown samples and the colored pixel information in the image matrices is used to calculate the similarities between the images. Our experimental results show that the image matrices of malware can effectively be used to classify malware families both statically and dynamically with accuracy of 0.9896 and 0.9732, respectively. PMID:25133202

Multiple Natural Substitutions in Avian Influenza A Virus PB2 Facilitate Efficient Replication in Human Cells.

PubMed

Mänz, Benjamin; de Graaf, Miranda; Mögling, Ramona; Richard, Mathilde; Bestebroer, Theo M; Rimmelzwaan, Guus F; Fouchier, Ron A M

2016-07-01

A strong restriction of the avian influenza A virus polymerase in mammalian cells generally limits viral host-range switching. Although substitutions like E627K in the PB2 polymerase subunit can facilitate polymerase activity to allow replication in mammals, many human H5N1 and H7N9 viruses lack this adaptive substitution. Here, several previously unknown, naturally occurring, adaptive substitutions in PB2 were identified by bioinformatics, and their enhancing activity was verified using in vitro assays. Adaptive substitutions enhanced polymerase activity and virus replication in mammalian cells for avian H5N1 and H7N9 viruses but not for a partially human-adapted H5N1 virus. Adaptive substitutions toward basic amino acids were frequent and were mostly clustered in a putative RNA exit channel in a polymerase crystal structure. Phylogenetic analysis demonstrated divergent dependency of influenza viruses on adaptive substitutions. The novel adaptive substitutions found in this study increase basic understanding of influenza virus host adaptation and will help in surveillance efforts. Influenza viruses from birds jump the species barrier into humans relatively frequently. Such influenza virus zoonoses may pose public health risks if the virus adapts to humans and becomes a pandemic threat. Relatively few amino acid substitutions-most notably in the receptor binding site of hemagglutinin and at positions 591 and 627 in the polymerase protein PB2-have been identified in pandemic influenza virus strains as determinants of host adaptation, to facilitate efficient virus replication and transmission in humans. Here, we show that substantial numbers of amino acid substitutions are functionally compensating for the lack of the above-mentioned mutations in PB2 and could facilitate influenza virus emergence in humans. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Infrared spectroscopy of water clusters isolated in methane matrices: Effects of isotope substitution and annealing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamakawa, Koichiro, E-mail: koichiro.yamakawa@gakushuin.ac.jp; Ehara, Namika; Ozawa, Nozomi

2016-07-15

Using infrared-active solvents of CH{sub 4} and CD{sub 4} for matrix isolation, we measured infrared spectra of H{sub 2}O and D{sub 2}O clusters at 7 K. The solute-concentration dependence of the spectrum of H{sub 2}O clusters in a CH{sub 4} matrix was investigated and was used for the peak assignment. Annealing procedures were found to promote the size growth of water clusters in methane matrices for all the combinations of (H{sub 2}O, CH{sub 4}), (H{sub 2}O, CD{sub 4}), (D{sub 2}O, CH{sub 4}), and (D{sub 2}O, CD{sub 4}). We also monitored the ν{sub 3} absorption due to methane to find themore » annealing-induced structural change only of solid CH{sub 4}. The matrix effects on the vibrations of the clusters are discussed on the basis of “T{sub c} plots”, where their frequencies are plotted as a function of the square root of the matrix critical temperature, T{sub c}. The obtained plots assure the validity of the assignment of the cluster peaks.« less

Comparison of Antioxidant Evaluation Assays for Investigating Antioxidative Activity of Gallic Acid and Its Alkyl Esters in Different Food Matrices.

PubMed

Phonsatta, Natthaporn; Deetae, Pawinee; Luangpituksa, Pairoj; Grajeda-Iglesias, Claudia; Figueroa-Espinoza, Maria Cruz; Le Comte, Jérôme; Villeneuve, Pierre; Decker, Eric A; Visessanguan, Wonnop; Panya, Atikorn

2017-08-30

The addition of antioxidants is one of the strategies to inhibit lipid oxidation, a major cause of lipid deterioration in foods leading to rancidity development and nutritional losses. However, several studies have been reported that conventional antioxidant assays, e.g., TPC, ABTS, FRAP, and ORAC could not predict antioxidant performance in several foods. This study aimed to investigate the performance of two recently developed assays, e.g., the conjugated autoxidizable triene (CAT) and the apolar radical-initiated conjugated autoxidizable triene (ApoCAT) assays to predict the antioxidant effectiveness of gallic acid and its esters in selected food models in comparison with the conventional antioxidant assays. The results indicated that the polarities of the antioxidants have a strong impact on antioxidant activities. In addition, different oxidant locations demonstrated by the CAT and ApoCAT assays influenced the overall antioxidant performances of the antioxidants with different polarities. To validate the predictability of the assays, the antioxidative performance of gallic acid and its alkyl esters was investigated in oil-in-water (O/W) emulsions, bulk soybean oils, and roasted peanuts as the lipid food models. The results showed that only the ApoCAT assay could be able to predict the antioxidative performances in O/W emulsions regardless of the antioxidant polarities. This study demonstrated that the relevance of antioxidant assays to food models was strongly dependent on physical similarities between the tested assays and the food structure matrices.

Computation of transform domain covariance matrices

NASA Technical Reports Server (NTRS)

Fino, B. J.; Algazi, V. R.

1975-01-01

It is often of interest in applications to compute the covariance matrix of a random process transformed by a fast unitary transform. Here, the recursive definition of fast unitary transforms is used to derive recursive relations for the covariance matrices of the transformed process. These relations lead to fast methods of computation of covariance matrices and to substantial reductions of the number of arithmetic operations required.

[Effect of triester glycerol type of plasticizers on release of albumin from biodegradable polymer matrices].

PubMed

Kladnícková, I; Klein, T; Dittrich, M

2004-01-01

Bovine serum albumin was heterogeneously dispersed in the terpolymer of DL-lactic acid, glycolic acid, and mannitol. The terpolymeric carrier was plasticized by triacetin, tributyrin, or a mixture of triacetin with tricaprylin. Matrices were prepared by mixing a melt of the carrier with the plasticizer and albumin. Liberation was tested in 1/15 mol.l-1 phosphate buffer pH 7.4 and took place in two stages--the burst and the stage of the continual process. The burst represented 30% to 90% of liberated albumin. The second, continual stage began on day 4 of liberation and within ten days maximally 10% of the total amount of albumin was released. The course of liberation was most markedly influenced by the parameters of the oligoester carrier, its molecular weight, and the degree of branching. The total extent of albumin liberation was influenced partly by its irreversible adsorption on the carrier, partly by its polymerization. The extent of adsorption and polymerization of albumin was increased with the molecular weight of the carrier and decreased with the increasing degree of its branching. Albumin liberation was positively influenced by the presence of plasticizers in matrices, triacetin being demonstrated as the best one.

Rh(III)-Catalyzed Decarboxylative Coupling of Acrylic Acids with Unsaturated Oxime Esters: Carboxylic Acids Serve as Traceless Activators

PubMed Central

2015-01-01

α,β-Unsaturated carboxylic acids undergo Rh(III)-catalyzed decarboxylative coupling with α,β-unsaturated O-pivaloyl oximes to provide substituted pyridines in good yield. The carboxylic acid, which is removed by decarboxylation, serves as a traceless activating group, giving 5-substituted pyridines with very high levels of regioselectivity. Mechanistic studies rule out a picolinic acid intermediate, and an isolable rhodium complex sheds further light on the reaction mechanism. PMID:24512241

Lipozyme RM IM-catalyzed acidolysis of Cinnamomum camphora seed oil with oleic acid to produce human milk fat substitutes enriched in medium-chain fatty acids.

PubMed

Zou, Xian-Guo; Hu, Jiang-Ning; Zhao, Man-Li; Zhu, Xue-Mei; Li, Hong-Yan; Liu, Xiao-Ru; Liu, Rong; Deng, Ze-Yuan

2014-10-29

In the present study, a human milk fat substitute (HMFS) enriched in medium-chain fatty acids (MCFAs) was synthesized through acidolysis reaction from Cinnamomum camphora seed oil (CCSO) with oleic acid in a solvent-free system. A commercial immobilized lipase, Lipozyme RM IM, from Rhizomucor miehei, was facilitated as a biocatalyst. Effects of different reaction conditions, including substrate molar ratio, enzyme concentration, reaction temperature, and reaction time were investigated using response surface methodology (RSM) to obtain the optimal oleic acid incorporation. After optimization, results showed that the maximal incorporation of oleic acid into HMFS was 59.68%. Compared with CCSO, medium-chain fatty acids at the sn-2 position of HMFS accounted for >70%, whereas oleic acid was occupied predominantly at the sn-1,3 position (78.69%). Meanwhile, triacylglycerol (TAG) components of OCO (23.93%), CCO (14.94%), LaCO (13.58%), OLaO (12.66%), and OOO (11.13%) were determined as the major TAG species in HMFS. The final optimal reaction conditions were carried out as follows: substrate molar ratio (oleic acid/CCSO), 5:1; enzyme concentration, 12.5% (w/w total reactants); reaction temperature, 60 °C; and reaction time, 28 h. The reusability of Lipozyme RM IM in the acidolysis reaction was also evaluated, and it was found that it could be reused up to 9 times without significant loss of activities. Urea inclusion method was used to separate and purify the synthetic product. As the ratio of HMFS/urea increased to 1:2, the acid value lowered to the minimum. In a scale-up experiment, the contents of TAG and total tocopherols in HMFS (modified CCSO) were 77.28% and 12.27 mg/100 g, respectively. All of the physicochemical indices of purified product were within food standards. Therefore, such a MCFA-enriched HMFS produced by using the acidolysis method might have potential application in the infant formula industry.

Decision Matrices: Tools to Enhance Middle School Engineering Instruction

ERIC Educational Resources Information Center

Gonczi, Amanda L.; Bergman, Brenda G.; Huntoon, Jackie; Allen, Robin; McIntyre, Barb; Turner, Sheri; Davis, Jen; Handler, Rob

2017-01-01

Decision matrices are valuable engineering tools. They allow engineers to objectively examine solution options. Decision matrices can be incorporated in K-12 classrooms to support authentic engineering instruction. In this article we provide examples of how decision matrices have been incorporated into 6th and 7th grade classrooms as part of an…

19 CFR 10.90 - Master records and metal matrices.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301, containing...

19 CFR 10.90 - Master records and metal matrices.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301, containing...

19 CFR 10.90 - Master records and metal matrices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301, containing...

19 CFR 10.90 - Master records and metal matrices.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301, containing...

19 CFR 10.90 - Master records and metal matrices.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301, containing...

Laminin active peptide/agarose matrices as multifunctional biomaterials for tissue engineering.

PubMed

Yamada, Yuji; Hozumi, Kentaro; Aso, Akihiro; Hotta, Atsushi; Toma, Kazunori; Katagiri, Fumihiko; Kikkawa, Yamato; Nomizu, Motoyoshi

2012-06-01

Cell adhesive peptides derived from extracellular matrix components are potential candidates to afford bio-adhesiveness to cell culture scaffolds for tissue engineering. Previously, we covalently conjugated bioactive laminin peptides to polysaccharides, such as chitosan and alginate, and demonstrated their advantages as biomaterials. Here, we prepared functional polysaccharide matrices by mixing laminin active peptides and agarose gel. Several laminin peptide/agarose matrices showed cell attachment activity. In particular, peptide AG73 (RKRLQVQLSIRT)/agarose matrices promoted strong cell attachment and the cell behavior depended on the stiffness of agarose matrices. Fibroblasts formed spheroid structures on the soft AG73/agarose matrices while the cells formed a monolayer with elongated morphologies on the stiff matrices. On the stiff AG73/agarose matrices, neuronal cells extended neuritic processes and endothelial cells formed capillary-like networks. In addition, salivary gland cells formed acini-like structures on the soft matrices. These results suggest that the peptide/agarose matrices are useful for both two- and three-dimensional cell culture systems as a multifunctional biomaterial for tissue engineering. Copyright © 2012 Elsevier Ltd. All rights reserved.

PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion.

PubMed

Li, Yongcheng; Lu, Ming; Wu, Chuanbin

2017-11-10

The purpose of this study was to explore poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) as a novel release-modifier to tailor the drug release from ethylcellulose (EC)-based mini-matrices prepared via hot melt extrusion (HME). Quetiapine fumarate (QF) was selected as model drug. QF/EC/PVP VA64 mini-matrices were extruded with 30% drug loading. The physical state of QF in extruded mini-matrices was characterized using differential scanning calorimetry, X-ray powder diffraction, and confocal Raman microscopy. The release-controlled ability of PVP VA64 was investigated and compared with that of xanthan gum, crospovidone, and low-substituted hydroxypropylcellulose. The influences of PVP VA64 content and processing temperature on QF release behavior and mechanism were also studied. The results indicated QF dispersed as the crystalline state in all mini-matrices. The release of QF from EC was very slow as only 4% QF was released in 24 h. PVP VA64 exhibited the best ability to enhance the drug release as compared with other three release-modifiers. The drug release increased to 50-100% in 24 h with the addition of 20-40% PVP VA64. Increasing processing temperature slightly slowed down the drug release by decreasing free volume and pore size. The release kinetics showed good fit with the Ritger-Peppas model. The values of release exponent (n) increased as PVP VA64 is added (0.14 for pure EC, 0.41 for 20% PVP VA64, and 0.61 for 40% PVP VA64), revealing that the addition of PVP VA64 enhanced the erosion mechanism. This work presented a new polymer blend system of EC with PVP VA64 for sustained-release prepared via HME.

Effect of acyl donor chain length and substitutions pattern on the enzymatic acylation of flavonoids.

PubMed

Ardhaoui, M; Falcimaigne, A; Ognier, S; Engasser, J M; Moussou, P; Pauly, G; Ghoul, M

2004-06-10

Rutin and esculin were enzymatically acylated with different aliphatic acids as acyl donors (fatty acids, dicarboxylic acids and omega-substituted fatty acids) by an immobilized lipase from Candida antarctica. The effect of the water content and the acyl donors pattern on the flavonoid initial acylation rate and conversion yield were investigated. The obtained results indicated that the water content of the medium has a strong effect on the performance of these reactions. The best conversion yields were reached when the water content was kept lower than 200 ppm. At low water content of the medium, these syntheses are influenced by carbon chain length and substitution pattern of the acyl donors. Higher conversion yields of esculin and rutin (>70%) were obtained with aliphatic acids having high carbon chain length (>12). Moreover, it has been found that the amine and thiol groups on omega-substituted fatty acid chain were unfavourable to these reactions. The 1H NMR and 13C NMR analyses of some synthesized esters (esculin and rutin palmitate) show that only monoesters were produced and that the esterification takes place on the primary OH of glucose moiety of the esculin and on the secondary 4"'-OH of the rhamnose residue of rutin. Copyright 2004 Elsevier B.V.

Estimating soil matric potential in Owens Valley, California

USGS Publications Warehouse

Sorenson, Stephen K.; Miller, Reuben F.; Welch, Michael R.; Groeneveld, David P.; Branson, Farrel A.

1989-01-01

Much of the floor of Owens Valley, California, is covered with alkaline scrub and alkaline meadow plant communities, whose existence is dependent partly on precipitation and partly on water infiltrated into the rooting zone from the shallow water table. The extent to which these plant communities are capable of adapting to and surviving fluctuations in the water table depends on physiological adaptations of the plants and on the water content, matric potential characteristics of the soils. Two methods were used to estimate soil matric potential in test sites in Owens Valley. The first, the filter-paper method, uses water content of filter papers equilibrated to water content of soil samples taken with a hand auger. The previously published calibration relations used to estimate soil matric potential from the water content of the filter papers were modified on the basis of current laboratory data. The other method of estimating soil matric potential was a modeling approach based on data from this and previous investigations. These data indicate that the base-10 logarithm of soil matric potential is a linear function of gravimetric soil water content for a particular soil. The slope and intercepts of this function vary with the texture and saturation capacity of the soil. Estimates of soil water characteristic curves were made at two sites by averaging the gravimetric soil water content and soil matric potential values from multiple samples at 0.1-m depth intervals derived by using the hand auger and filter-paper method and entering these values in the soil water model. The characteristic curves then were used to estimate soil matric potential from estimates of volumetric soil water content derived from neutron-probe readings. Evaluation of the modeling technique at two study sites indicated that estimates of soil matric potential within 0.5 pF units of the soil matric potential value derived by using the filter-paper method could be obtained 90 to 95 percent of the

Towards the Rational Design of Ionic Liquid Matrices for Secondary Ion Mass Spectrometry: Role of the Anion

NASA Astrophysics Data System (ADS)

Dertinger, Jennifer J.; Walker, Amy V.

2013-08-01

The role of the ionic liquid (IL) anion structure on analyte signal enhancements has been systematically investigated in secondary ion mass spectrometry (SIMS) using a variety of samples, including lipids, sterols, polymers, and peptides. Twenty-four ILs were synthesized. The 12 matrix acids were cinnamic acid derivatives. Two bases were employed: 1-methylimidazole and tripropylamine. Three matrices, methylimmidazolium o-coumarate, tripropylammonium o-coumarate, and tripropylammonium 3,4,5-trimethoxycinnamate, were "universal" matrices enhancing all analytes tested. The pKa of the matrix acid does not appear to have a strong effect on analyte ion intensities. Rather, it is observed that a single hydroxyl group on the anion aromatic ring leads to significantly increased molecular ion intensities. No analyte signal enhancements were observed for -CH3, -CF3 and -OCH3 groups present on the aromatic ring. The position of the -OH group on the aromatic ring also alters molecular ion intensity enhancements. As well as the chemical identity and position of substituents, the number of moieties on the aromatic ring may affect the analyte signal enhancements observed. These observations suggest that the activation of the IL anion aromatic ring is important for optimizing analyte signal intensities. The implications for SIMS imaging of complex structures, such as biological samples, are discussed.

Immobilization of long-lived radionuclides in carbon matrices produced with the use of polyimide binders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdulakhatov, Murat; Bartenev, Sergey; Firsin, Nikolai

Available in abstract form only. Full text of publication follows: Conditions for immobilization of long-lived radionuclides {sup 99}Tc, {sup 129}I and {sup 241}Am in carbon matrices were investigated by using their chemical analogs. Stable isotopes of rhenium, iodine and europium were used as chemical analogs of {sup 99}Tc, {sup 129}I and {sup 241}Am, respectively. It is shown that the carbon matrices incorporating the above elements can be produced by carbonization of composites with ITA-31 polyimide binder of the following composition: equal molar ratio between dianhydride of 3,3/,4,4/-benzophenone-tetracarboxylic acid and tetraacetyl derivative of 4,4/-diaminodiphenyl ester, radionuclide being investigated or its chemicalmore » analog and carbon fabric as reinforcing component. The elements under investigation were used both in the form of salts or oxides and in the form of their complexes with ion-exchange resins. The produced composites were carbonized in inert gas (argon) or in vacuum. The physical-chemical properties of the samples were studied. It was revealed that the resultant matrices meet the requirements imposed on waste storage and final disposal. (authors)« less

Enhanced osteoconductivity of sodium-substituted hydroxyapatite by system instability.

PubMed

Sang Cho, Jung; Um, Seung-Hoon; Su Yoo, Dong; Chung, Yong-Chae; Hye Chung, Shin; Lee, Jeong-Cheol; Rhee, Sang-Hoon

2014-07-01

The effect of substituting sodium for calcium on enhanced osteoconductivity of hydroxyapatite was newly investigated. Sodium-substituted hydroxyapatite was synthesized by reacting calcium hydroxide and phosphoric acid with sodium nitrate followed by sintering. As a control, pure hydroxyapatite was prepared under identical conditions, but without the addition of sodium nitrate. Substitution of calcium with sodium in hydroxyapatite produced the structural vacancies for carbonate ion from phosphate site and hydrogen ion from hydroxide site of hydroxyapatite after sintering. The total system energy of sodium-substituted hydroxyapatite with structural defects calculated by ab initio methods based on quantum mechanics was much higher than that of hydroxyapatite, suggesting that the sodium-substituted hydroxyapatite was energetically less stable compared with hydroxyapatite. Indeed, sodium-substituted hydroxyapatite exhibited higher dissolution behavior of constituent elements of hydroxyapatite in simulated body fluid (SBF) and Tris-buffered deionized water compared with hydroxyapatite, which directly affected low-crystalline hydroxyl-carbonate apatite forming capacity by increasing the degree of apatite supersaturation in SBF. Actually, sodium-substituted hydroxyapatite exhibited markedly improved low-crystalline hydroxyl-carbonate apatite forming capacity in SBF and noticeably higher osteoconductivity 4 weeks after implantation in calvarial defects of New Zealand white rabbits compared with hydroxyapatite. In addition, there were no statistically significant differences between hydroxyapatite and sodium-substituted hydroxyapatite on cytotoxicity as determined by BCA assay. Taken together, these results indicate that sodium-substituted hydroxyapatite with structural defects has promising potential for use as a bone grafting material due to its enhanced osteoconductivity compared with hydroxyapatite. © 2013 Wiley Periodicals, Inc.

Vibrational spectra for uric acid and its D- and 15N-substituted analogues. Assignments for its normal modes from ab initio 3-21G force field.

NASA Astrophysics Data System (ADS)

Majoube, M.; Vergoten, G.

1993-03-01

FTR, Raman, FTIR spectra are obtained for polycrystalline uric acid and seven of its D-and 15N-substituted analogues. Assignments are given from a normal coordinate analysis carried out using a 3-21G ab initio force field. These are discussed by considering observed and calculated frequencies and D- and 15N-isotopic shifts.

CMV matrices in random matrix theory and integrable systems: a survey

NASA Astrophysics Data System (ADS)

Nenciu, Irina

2006-07-01

We present a survey of recent results concerning a remarkable class of unitary matrices, the CMV matrices. We are particularly interested in the role they play in the theory of random matrices and integrable systems. Throughout the paper we also emphasize the analogies and connections to Jacobi matrices.

A new molecular evolution model for limited insertion independent of substitution.

PubMed

Lèbre, Sophie; Michel, Christian J

2013-10-01

We recently introduced a new molecular evolution model called the IDIS model for Insertion Deletion Independent of Substitution [13,14]. In the IDIS model, the three independent processes of substitution, insertion and deletion of residues have constant rates. In order to control the genome expansion during evolution, we generalize here the IDIS model by introducing an insertion rate which decreases when the sequence grows and tends to 0 for a maximum sequence length nmax. This new model, called LIIS for Limited Insertion Independent of Substitution, defines a matrix differential equation satisfied by a vector P(t) describing the sequence content in each residue at evolution time t. An analytical solution is obtained for any diagonalizable substitution matrix M. Thus, the LIIS model gives an expression of the sequence content vector P(t) in each residue under evolution time t as a function of the eigenvalues and the eigenvectors of matrix M, the residue insertion rate vector R, the total insertion rate r, the initial and maximum sequence lengths n0 and nmax, respectively, and the sequence content vector P(t0) at initial time t0. The derivation of the analytical solution is much more technical, compared to the IDIS model, as it involves Gauss hypergeometric functions. Several propositions of the LIIS model are derived: proof that the IDIS model is a particular case of the LIIS model when the maximum sequence length nmax tends to infinity, fixed point, time scale, time step and time inversion. Using a relation between the sequence length l and the evolution time t, an expression of the LIIS model as a function of the sequence length l=n(t) is obtained. Formulas for 'insertion only', i.e. when the substitution rates are all equal to 0, are derived at evolution time t and sequence length l. Analytical solutions of the LIIS model are explicitly derived, as a function of either evolution time t or sequence length l, for two classical substitution matrices: the 3

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xinsheng, E-mail: xzhang@iavi.org; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY; Wallace, Olivia L.

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,more » 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.« less

Aspartic acid substitutions in monoamine oxidase-A reveal both catalytic-dependent and -independent influences on cell viability and proliferation.

PubMed

Wei, Zelan; Satram-Maharaj, Tamara; Chaharyn, Bradley; Kuski, Kelly; Pennington, Paul R; Cao, Xia; Chlan, Jennifer; Mousseau, Darrell D

2012-11-01

Post-translational influences could underlie the ambiguous roles of monoamine oxidase-A (MAO-A) in pathologies such as depression, cancer and Alzheimer disease. In support of this, we recently demonstrated that the Ca²⁺-sensitive component of MAO-A catalytic activity is inhibited by a pro-survival p38 (MAPK)-dependent mechanism. We substituted three aspartic acid (D) residues in human MAO-A that reside in putative Ca²⁺-binding motifs and overexpressed the individual proteins in the human HEK293 cell line. We assayed the overexpressed proteins for catalytic activity and for their influence on cell viability (using MTT conversion and trypan blue exclusion) and proliferation/DNA synthesis [using bromodeoxyuridine (BrdU) incorporation]. Innate MAO-A catalytic activity (and the capacity for generating hydrogen peroxide) was unaffected by the D61A substitution, but inhibited moderately or completely by the D248A and D328G substitutions, respectively. The Ca²⁺-sensitive activities of wild-type and D248A MAO-A proteins were enhanced by treatment with the selective p38(MAPK) inhibitor, SB203580, but was completely abrogated by the D61A substitution. Monoamine oxidase-A(D61A) was toxic to cells and exerted no effect on cell proliferation, while MAO-A(D248A) was generally comparable to wild-type MAO-A. As expected, the catalytic-dead MAO-A(D328G) was not cytotoxic, but unexpectedly enhanced both MTT conversion and BrdU staining. Variant-dependent changes in Bax and Bcl-2/Bcl-XL protein expression were observed. A different pattern of effects in N2-a cells suggests cell line-dependent roles for MAO-A. A catalytic-dependent mechanism influences MAO-A-mediated cytotoxicity, whereas a catalytic-independent mechanism contributes to proliferation. Context-dependent inputs by either mechanism could underlie the ambiguous pathological contributions of MAO-A.

Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein.

PubMed

Tsai, Ting-Yueh; Yeh, Teng-Kuang; Chen, Xin; Hsu, Tsu; Jao, Yu-Chen; Huang, Chih-Hsiang; Song, Jen-Shin; Huang, Yu-Chen; Chien, Chia-Hui; Chiu, Jing-Huai; Yen, Shih-Chieh; Tang, Hung-Kuan; Chao, Yu-Sheng; Jiaang, Weir-Torn

2010-09-23

Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAP inhibitor is needed in evaluating that FAP as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation. To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SAR studies resulted in a number of FAP inhibitors having IC(50) of <100 nM with excellent selectivity over DPP-IV, DPP-II, DPP8, and DPP9 (IC(50) > 100 μM). Compounds 18a, 18b, and 19 are the only known potent and selective FAP inhibitors, which prompts us to further study the physiological role of FAP.

Comparative studies on the interaction of caffeic acid, chlorogenic acid and ferulic acid with bovine serum albumin

NASA Astrophysics Data System (ADS)

Li, Shuang; Huang, Kelong; Zhong, Ming; Guo, Jun; Wang, Wei-zheng; Zhu, Ronghua

2010-10-01

The substitution of the hydrogen on aromatic and esterification of carboxyl group of the phenol compounds plays an important role in their bio-activities. In this paper, caffeic acid (CaA), chlorogenic acid (ChA) and ferulic acid (FA) were selected to investigate the binding to bovine serum albumin (BSA) using UV absorption spectroscopy, fluorescence spectroscopy and synchronous fluorescence spectroscopy. It was found that the methoxyl group substituting for the 3-hydroxyl group of CaA decreased the affinity for BSA and the esterification of carboxyl group of CaA with quinic acid increased the affinities. The affinities of ChA and FA with BSA were more sensitive to the temperature than that of CaA with BSA. Synchronous fluorescence spectroscopy and time-resolved fluorescence indicated that the Stern-Volmer plots largely deviated from linearity at high concentrations and were caused by complete quenching of the tyrosine fluorescence of BSA.

Comparing HPLC-ESI-ITMS and UPLC-ESI-OA-TOF-MS in Characterizing Macrolide Antibiotics and Illicit Drugs in Complex Environmental Matrices

EPA Science Inventory

Among the challenges of characterizing emerging contaminants in complex environmental matrices (e.g., biosolids, sewage, or wastewater) are the co-eluting interferences. For example, surfactants, fats, and humic acids, can be preferentially ionized instead of the analyte(s) of in...

Introduction to the QIAT Self-Evaluation Matrices

ERIC Educational Resources Information Center

Zabala, Joy Smiley; Carl, Diana F.

2004-01-01

The QIAT Self-Evaluation Matrices (QILT, 2001) were developed in response to formative evaluation data indicating a need for a model that could assist in the application of the Quality Indicators for Assistive Technology Services in Schools (Zabala, et al, 2000). The QIAT Matrices are based on the idea that change does not happen immediately, but…

"G.P.S Matrices" programme: A method to improve the mastery level of social science students in matrices operations

NASA Astrophysics Data System (ADS)

Lee, Ken Voon

2013-04-01

The purpose of this action research was to increase the mastery level of Form Five Social Science students in Tawau II National Secondary School in the operations of addition, subtraction and multiplication of matrices in Mathematics. A total of 30 students were involved. Preliminary findings through the analysis of pre-test results and questionnaire had identified the main problem faced in which the students felt confused with the application of principles of the operations of matrices when performing these operations. Therefore, an action research was conducted using an intervention programme called "G.P.S Matrices" to overcome the problem. This programme was divided into three phases. 'Gift of Matrices' phase aimed at forming matrix teaching aids. The second and third phases were 'Positioning the Elements of Matrices' and 'Strenghtening the Concept of Matrices'. These two phases were aimed at increasing the level of understanding and memory of the students towards the principles of matrix operations. Besides, this third phase was also aimed at creating an interesting learning environment. A comparison between the results of pre-test and post-test had shown a remarkable improvement in students' performances after implementing the programme. In addition, the analysis of interview findings also indicated a positive feedback on the changes in students' attitude, particularly in the aspect of students' understanding level. Moreover, the level of students' memory also increased following the use of the concrete matrix teaching aids created in phase one. Besides, teachers felt encouraging when conducive learning environment was created through students' presentation activity held in third phase. Furthermore, students were voluntarily involved in these student-centred activities. In conclusion, this research findings showed an increase in the mastery level of students in these three matrix operations and thus the objective of the research had been achieved.

Effect of leucine-to-methionine substitutions on the diffraction quality of histone chaperone SET/TAF-Ibeta/INHAT crystals.

PubMed

Senda, Miki; Muto, Shinsuke; Horikoshi, Masami; Senda, Toshiya

2008-10-01

One of the most frequent problems in crystallization is poor quality of the crystals. In order to overcome this obstacle several methods have been utilized, including amino-acid substitutions of the target protein. Here, an example is presented of crystal-quality improvement by leucine-to-methionine substitutions. A variant protein with three amino-acid substitutions enabled improvement of the crystal quality of the histone chaperone SET/TAF-Ibeta/INHAT when combined with optimization of the cryoconditions. This procedure improved the resolution of the SET/TAF-Ibeta/INHAT crystals from around 5.5 to 2.3 A without changing the crystallization conditions.

An amino acid depleted cell-free protein synthesis system for the incorporation of non-canonical amino acid analogs into proteins.

PubMed

Singh-Blom, Amrita; Hughes, Randall A; Ellington, Andrew D

2014-05-20

Residue-specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an efficient amino acid depleted cell-free protein synthesis system that can be used to study residue-specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines a simple methodology and high protein expression titers with a high-efficiency analog substitution into a target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein-wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo methodologies. Copyright © 2014 Elsevier B.V. All rights reserved.

Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

PubMed Central

Kumar, Amit; Tripathi, Amit Kumar; Kathuria, Manoj; Shree, Sonal; Tripathi, Jitendra Kumar; Purshottam, R. K.; Ramachandran, Ravishankar; Mitra, Kalyan

2016-01-01

Piscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue. Two more analogs, namely, I5F,F6A-piscidin-1 and V12I-piscidin-1, were designed for investigating the effect of interchanging an alanine residue at a d position with an adjacent phenylalanine residue and replacing a valine residue with an isoleucine residue at another d position of the heptad repeat of piscidin-1, respectively. Single alanine-substituted analogs exhibited significantly reduced cytotoxicity against mammalian cells compared with that of piscidin-1 but appreciably retained the antibacterial and antiendotoxin activities of piscidin-1. All the single valine-substituted piscidin-1 analogs and I5F,F6A-piscidin-1 showed cytotoxicity greater than that of the corresponding alanine-substituted analogs, antibacterial activity marginally greater than or similar to that of the corresponding alanine-substituted analogs, and also antiendotoxin activity superior to that of the corresponding alanine-substituted analogs. Interestingly, among these peptides, V12I-piscidin-1 showed the highest cytotoxicity and antibacterial and antiendotoxin activities. Lipopolysaccharide (12 mg/kg of body weight)-treated mice, further treated with I16A-piscidin-1, the piscidin-1 analog with the highest therapeutic index, at a single dose of 1 or 2 mg/kg of body weight, showed 80 and 100% survival, respectively. Structural and functional characterization of these peptides revealed the basis of their biological activity and demonstrated that nontoxic piscidin-1 analogs with

Sugar Substitutes

MedlinePlus

... Substitutes Share Print Sugar substitutes are chemical or plant-based substances used to sweeten or enhance the ... made with saccharin. Stevia sweeteners Stevia is a plant-based sugar substitute that has no calories. The ...

X-ray photoelectron spectroscopy study of para-substituted benzoic acids chemisorbed to aluminum oxide thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreil, Justin; Ellingsworth, Edward; Szulczewski, Greg

A series of para-substituted, halogenated (F, Cl, Br, and I) benzoic acid monolayers were prepared on the native oxide of aluminum surfaces by solution self-assembly and spin-coating techniques. The monolayers were characterized by x-ray photoelectron spectroscopy (XPS) and water contact angles. Several general trends are apparent. First, the polarity of the solvent is critical to monolayer formation. Protic polar solvents produced low coverage monolayers; in contrast, nonpolar solvents produced higher coverage monolayers. Second, solution deposition yields a higher surface coverage than spin coating. Third, the thickness of the monolayers determined from XPS suggests the plane of the aromatic ring ismore » perpendicular to the surface with the carboxylate functional group most likely binding in a bidentate chelating geometry. Fourth, the saturation coverage (∼2.7 × 10{sup 14} molecules cm{sup −2}) is independent of the para-substituent.« less

Novel sustained-release dosage forms of proteins using polyglycerol esters of fatty acids.

PubMed

Yamagata, Y; Iga, K; Ogawa, Y

2000-02-03

In order to develop a novel delivery system for proteins based on polyglycerol esters of fatty acids (PGEFs), we studied a model system using interferon-alpha (IFN-alpha) as the test protein. A cylindrical matrix was prepared by a heat extrusion technique using a lyophilized powder of the protein and 11 different types of synthetic PGEFs, which varied in degree of glycerol polymerization (di- and tetra-), chain length of fatty acids (myristate, palmitate and stearate) and degree of fatty acid esterification (mono-, di- and tri-). In an in-vitro release study using an enzyme-linked immunosorbent assay (ELISA) as a detection method, the matrices prepared from a monoglyceride (used for comparison) and from diglycerol esters exhibited a biphasic release pattern with a large initial burst followed by slow release. In contrast, the matrices prepared from tetraglycerol esters showed a steady rate of release without a large initial burst. In an in vivo release study, initial bursts of IFN-alpha release were, also, dramatically reduced when the matrices were prepared from the tetraglycerol esters of palmitate and stearate, and the mean residence time (MRT) of IFN-alpha was prolonged, whereas the matrices prepared from monoglyceride and from diglycerol esters showed large initial bursts of IFN-alpha release. Since the release rates from the matrices prepared from the tetraglycerol esters of palmitate and stearate were governed by Jander's equation modified for a cylindrical matrix, the release from those matrices was concluded to be a diffusion-controlled process. The bioavailability of IFN-alpha after implantation of the matrix formulation prepared using all types of PGEFs, except for tetraglycerol triesters, was almost equivalent to that after injection of IFN-alpha solution; consequently, IFN-alpha in these matrices appears to remain stable during the release period.

Amino acid substitutions and intron polymorphism of acetylcholinesterase1 associated with mevinphos resistance in diamondback moth, Plutella xylostella (L.).

PubMed

Yeh, Shih-Chia; Lin, Chia-Li; Chang, Cheng; Feng, Hai-Tung; Dai, Shu-Mei

2014-06-01

The diamondback moth, Plutella xylostella L., is the most destructive insect pest of Brassica crops in the world. It has developed resistance rapidly to almost every insecticide used for its control. Mevinphos, a fast degrading and slow resistance evocating organophosphorus insecticide, has been recommended for controlling P. xylostella in Taiwan for more than 40years. SHM strain of P. xylostella, with ca. 22-fold resistance to this chemical, has been established from a field SH strain by selecting with mevinphos since 1997. Three mutations, i.e., G892T, G971C, and T1156T/G leading to A298S, G324A, and F386F/V amino acid substitutions in acetylcholinesterase1 (AChE1), were identified in these two strains; along with three haplotype pairs and a polymorphic intron in AChE1 gene (ace1). Two genetically pure lines, i.e., an SHggt wild type with intron AS and an SHMTCN mutant carrying G892T, G971C, T1156T/G mutations and intron AR in ace1, were established by single pair mating and haplotype determination. The F1 of SHMTCN strain had 52-fold resistance to mevinphos in comparison with the F1 of SHggt strain. In addition, AChE1 of this SHMTCN population, which exhibited lower maximum velocity (Vmax) and affinity (Km), was less susceptible to the inhibition of mevinphos, with an I50 32-fold higher than that of the SHggt F1 population. These results imply that amino acid substitutions in AChE1 of SHMTCN strain are associated with mevinphos resistance in this insect pest, and this finding is important for insecticide resistance management of P. xylostella in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Immunohistochemical detection of a substituted 1,N(2)-ethenodeoxyguanosine adduct by omega-6 polyunsaturated fatty acid hydroperoxides in the liver of rats fed a choline-deficient, L-amino acid-defined diet.

PubMed

Kawai, Yoshichika; Kato, Yoji; Nakae, Dai; Kusuoka, Osamu; Konishi, Yoichi; Uchida, Koji; Osawa, Toshihiko

2002-03-01

Endogenous lipid peroxidation products react with DNA and form exocyclic DNA adducts. The purpose of this study was to investigate the in vivo formation of 7-(2-oxo-heptyl)-substituted 1,N(2)-etheno-2'-deoxyguanosine adduct (Oxo-heptyl-varepsilondG), one of the major products from the reaction of 13-hydroperoxyoctadecadienoic acid (13-HPODE) with dG. The monoclonal antibody specific to Oxo-heptyl-varepsilondG was prepared using a chemically synthesized conjugate of Oxo-heptyl-varepsilondG and carrier protein as immunogen. The characterization showed that the obtained antibody (mAb6A3) is specific to the Oxo-heptyl-varepsilondG moiety. Using the novel antibody, the presence of the Oxo-heptyl-varepsilondG adduct in vivo was immunohistochemically revealed in the liver of rats fed a choline-deficient, L-amino acid-defined diet, an endogenous carcinogenesis model, for 3 days. In addition, the Oxo-heptyl-varepsilondG formation was confirmed in DNAs treated with peroxidized linoleic acid, arachidonic acid and gamma-linolenic acid, respectively, suggesting that the hydroperoxides of omega-6 polyunsaturated fatty acids could be the potential sources of Oxo-heptyl-varepsilondG formation in vivo. Collectively, the results in this study suggest the first evidence that the formation of Oxo-heptyl-varepsilondG, the omega-6 lipid hydroperoxide-mediated DNA adduct, may be a potential biomarker for the early phase of carcinogenesis.

M-matrices with prescribed elementary divisors

NASA Astrophysics Data System (ADS)

Soto, Ricardo L.; Díaz, Roberto C.; Salas, Mario; Rojo, Oscar

2017-09-01

A real matrix A is said to be an M-matrix if it is of the form A=α I-B, where B is a nonnegative matrix with Perron eigenvalue ρ (B), and α ≥slant ρ (B) . This paper provides sufficient conditions for the existence and construction of an M-matrix A with prescribed elementary divisors, which are the characteristic polynomials of the Jordan blocks of the Jordan canonical form of A. This inverse problem on M-matrices has not been treated until now. We solve the inverse elementary divisors problem for diagonalizable M-matrices and the symmetric generalized doubly stochastic inverse M-matrix problem for lists of real numbers and for lists of complex numbers of the form Λ =\\{λ 1, a+/- bi, \\ldots, a+/- bi\\} . The constructive nature of our results allows for the computation of a solution matrix. The paper also discusses an application of M-matrices to a capacity problem in wireless communications.

Transition metal-substituted cobalt ferrite nanoparticles for biomedical applications.

PubMed

Sanpo, Noppakun; Berndt, Christopher C; Wen, Cuie; Wang, James

2013-03-01

Transition metals of copper, zinc, chromium and nickel were substituted into cobalt ferrite nanoparticles via a sol-gel route using citric acid as a chelating agent. The microstructure and elemental composition were characterized using scanning electron microscopy combined with energy-dispersive X-ray spectroscopy. Phase analysis of transition metal-substituted cobalt ferrite nanoparticles was performed via X-ray diffraction. Surface wettability was measured using the water contact angle technique. The surface roughness of all nanoparticles was measured using profilometry. Moreover, thermogravimetric analysis and differential scanning calorimetry were performed to determine the temperature at which the decomposition and oxidation of the chelating agents took place. Results indicated that the substitution of transition metals influences strongly the microstructure, crystal structure and antibacterial property of the cobalt ferrite nanoparticles. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Carbocation Rearrangement in An Electrophilic Aromatic Substitution Discovery Laboratory

ERIC Educational Resources Information Center

Polito, Victoria; Hamann, Christian S.; Rhile, Ian J.

2010-01-01

In this discovery laboratory, students performed electrophilic aromatic substitution reactions between 1,4-dimethoxybenzene and either 2-methyl-2-butanol or 3-methyl-2-butanol with sulfuric acid as a catalyst. The carbocation from 3-methyl-2-butanol undergoes a hydride shift, and hence, both reactions afford…

The Modern Origin of Matrices and Their Applications

ERIC Educational Resources Information Center

Debnath, L.

2014-01-01

This paper deals with the modern development of matrices, linear transformations, quadratic forms and their applications to geometry and mechanics, eigenvalues, eigenvectors and characteristic equations with applications. Included are the representations of real and complex numbers, and quaternions by matrices, and isomorphism in order to show…

Frequency of Interferon-Resistance Conferring Substitutions in Amino Acid Positions 70 and 91 of Core Protein of the Russian HCV 1b Isolates Analyzed in the T-Cell Epitopic Context

PubMed Central

Soboleva, N. V.; Karlsen, A. A.; Isaeva, O. V.; Isaguliants, M. G.; Mikhailov, M. I.

2018-01-01

Amino acid substitutions R70Q/H and L91M in HCV subtype 1b core protein can affect the response to interferon and are associated with the development of hepatocellular carcinoma. We found that the rate of R70Q/H in HCV 1b from Russia was 31.2%, similar to that in HCV strains from Asia (34.0%), higher than that in the European (18.0%, p = 0.0010), but lower than that in the US HCV 1b strains (62.8%, p < 0.0001). Substitution L91M was found in 80.4% of the Russian HCV 1b isolates, higher than in Asian isolates (43.8%, p < 0.0001). Thus, a significant proportion of Russian HCV 1b isolates carry the unfavorable R70Q/H and/or L91M substitution. In silico analysis of the epitopic structure of the regions of substitutions revealed that both harbor clusters of T-cell epitopes. Peptides encompassing these regions were predicted to bind to a panel of HLA class I molecules, with substitutions impairing peptide recognition by HLA I molecules of the alleles prevalent in Russia. This indicates that HCV 1b with R70Q/H and L91M substitutions may have evolved as the immune escape variants. Impairment of T-cell recognition may play a part in the negative effect of these substitutions on the response to IFN treatment. PMID:29577052

Flux Jacobian Matrices For Equilibrium Real Gases

NASA Technical Reports Server (NTRS)

Vinokur, Marcel

1990-01-01

Improved formulation includes generalized Roe average and extension to three dimensions. Flux Jacobian matrices derived for use in numerical solutions of conservation-law differential equations of inviscid flows of ideal gases extended to real gases. Real-gas formulation of these matrices retains simplifying assumptions of thermodynamic and chemical equilibrium, but adds effects of vibrational excitation, dissociation, and ionization of gas molecules via general equation of state.

Controlled growth factor release from synthetic extracellular matrices

NASA Astrophysics Data System (ADS)

Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

2000-12-01

Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

Matrices. New Topics for Secondary School Mathematics: Materials and Software.

ERIC Educational Resources Information Center

North Carolina School of Science and Mathematics. Dept. of Mathematics and Computer Science.

This material on matrices is part of "Introduction to College Mathematics" (ICM), designed to prepare high school students who have students who have completed algebra II for the variety of mathematics they will encounter in college and beyond. The concept goals of this unit are to use matrices to model real-world phenomena, to use matrices as…

[Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids improves body composition and lipid profile in a patient with human immunodeficiency virus lipodystrophy].

PubMed

Vázquez, C; Reyes, R; Alcaraz, F; Balsa, J A; Botella-Carretero, J I

2006-01-01

Lipodystrophy is a frequent disorder among patients with human immunodeficiency virus (HIV) infection, characterized by a loss of adipose tissue from the extremities, gluteal region and face, with excess fat in the neck and abdominal region. Metabolic abnormalities such as hyperlipidaemia and diabetes mellitus frequently coexist, posing these patients to an increased cardiovascular risk. Drug therapy may improve some of these metabolic disturbances, but to date there are no treatments for lipodystrophy with proven benefit. A 42-year-old man with HIV lipodystrophy was started on a standard low caloric diet with <30% of total fat and <10% of saturated fat, together with rosiglitazone 8 mg daily. After five months of treatment, given that lipodystrophic features and dyslipidaemia were still present in our patient, we tried to further improve therapeutic results by eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids. Three months later, a dramatic change in body composition was shown with an increase in lean mass and a decrease in fat mass, together with an improvement in lipid profile. Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids may produce therapeutic benefits in HIV lipodystrophy.

Almost commuting self-adjoint matrices: The real and self-dual cases

NASA Astrophysics Data System (ADS)

Loring, Terry A.; Sørensen, Adam P. W.

2016-08-01

We show that a pair of almost commuting self-adjoint, symmetric matrices is close to a pair of commuting self-adjoint, symmetric matrices (in a uniform way). Moreover, we prove that the same holds with self-dual in place of symmetric and also for paths of self-adjoint matrices. Since a symmetric, self-adjoint matrix is real, we get a real version of Huaxin Lin’s famous theorem on almost commuting matrices. Similarly, the self-dual case gives a version for matrices over the quaternions. To prove these results, we develop a theory of semiprojectivity for real C*-algebras and also examine various definitions of low-rank for real C*-algebras.

Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors.

PubMed

Ning, Chengqing; Bi, Yanjing; He, Yujun; Huang, WenYuan; Liu, Lifei; Li, Yi; Zhang, Sihan; Liu, Xiaoyu; Yu, Niefang

2013-12-01

A novel class of di-substituted cinnamic hydroxamic acid derivatives containing urea or thiourea unit was designed, synthesized and evaluated as HDAC inhibitors. All tested compounds demonstrated significant HDAC inhibitory activities and anti-proliferative effects against diverse human tumor cell lines. Among them, 7l exhibited most potent pan-HDAC inhibitory activity, with an IC50 value of 130 nM. It also showed strong cellular inhibition against diverse cell lines including HCT-116, MCF-7, MDB-MB-435 and NCI-460, with GI50 values of 0.35, 0.22, 0.51 and 0.48 μM, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hydrazide and hydrazine reagents as reactive matrices for MALDI-MS to detect gaseous aldehydes.

PubMed

Shigeri, Yasushi; Ikeda, Shinya; Yasuda, Akikazu; Ando, Masanori; Sato, Hiroaki; Kinumi, Tomoya

2014-08-01

The reagents 19 hydrazide and 14 hydrazine were examined to function as reactive matrices for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to detect gaseous aldehydes. Among them, two hydrazide (2-hydroxybenzohydrazide and 3-hydroxy-2-naphthoic acid hydrazide) and two hydrazine reagents [2-hydrazinoquinoline and 2,4-dinitrophenylhydrazine (DNPH)] were found to react efficiently with carbonyl groups of gaseous aldehydes (formaldehyde, acetaldehyde and propionaldehyde); these are the main factors for sick building syndrome and operate as reactive matrices for MALDI-MS. Results from accurate mass measurements by JMS-S3000 Spiral-TOF suggested that protonated ion peaks corresponding to [M + H](+) from the resulting derivatives were observed in all cases with the gaseous aldehydes in an incubation, time-dependent manner. The two hydrazide and two hydrazine reagents all possessed absorbances at 337 nm (wavelength of MALDI nitrogen laser), with, significant electrical conductivity of the matrix crystal and functional groups, such as hydroxy group and amino group, being important for desorption/ionization efficiency in MALDI-MS. To our knowledge, this is the first report that gaseous molecules could be derivatized and detected directly in a single step by MALDI-MS using novel reactive matrices that were derivatizing agents with the ability to enhance desorption/ionization efficiency. Copyright © 2014 John Wiley & Sons, Ltd.

Kinetic and thermodynamic acidities of substituted 1-benzyl-1-methoxy-2-nitroethylenes. Strong reduction of the transition state imbalance compared to other nitroalkanes.

PubMed

Bernasconi, Claude F; Ali, Mahammad; Gunter, Janette C

2003-01-08

Acidity constants of six substituted 1-benzyl-1-methoxy-2-nitroethylenes (2-Z with Z = m-NO(2), m-CF(3), m-Cl, H, p-Me, p-MeO) and their respective nitronic acids were determined in 50% DMSO-50% water (v/v) at 20 degrees C. Kinetic data were obtained on the reversible deprotonation of all six 2-Z by OH(-) and piperidine and on the reversible deprotonation of 2-NO(2)() by piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine in the same solvent. These data allowed a determination of the Brønsted coefficients alpha (dependence on acidity of 2-Z) and beta (dependence on amine basicity). The fact that alpha > beta indicates the presence of a transition state imbalance which, however, is much smaller than that for the deprotonation of arylnitromethanes. The reasons for this reduction in the imbalance and their relevance to a recent study of the deprotonation of Fischer carbene complexes are discussed.

Enantioselectivity of anteiso-fatty acids in hitherto uninspected sample matrices.

PubMed

Eibler, Dorothee; Seyfried, Carolin; Vetter, Walter

2017-09-01

Anteiso-fatty acids (aFAs) are chiral molecules due to a methyl substituent on the antepenultimate carbon of the otherwise straight acyl chain. 12-Methyltetradecanoic acid (a15:0) and 14-methylhexadecanoic acid (a17:0) are the predominant aFAs in nature but their individual contributions e.g. to food lipids are usually low. Enantioselective data has been collected in fish, bovine milk/cheese, and Brussels sprouts. In this study, we determined the enantioselectivity of a15:0 and a17:0 in shea butter, moose and camel milk, two soil samples and mold (collected from contaminated cheese). For this purpose, sample lipids were extracted and containing fatty acids were converted into methyl esters. Methyl esters of aFAs were selectively enriched by hydrogenation, urea complexation and/or RP-HPLC-fractionation. Enantioselective gas chromatography with mass spectrometry operated in the selected ion monitoring mode using a chiral stationary phase consisting of 66% tert.-butyldimethylsilylated β-cyclodextrin in OV-1701. While a15:0 and a17:0 in moose milk were (S)-enantiopure, all other determined samples contained up to 10% (R)-aFAs. The highest proportions of (R)-enantiomers were detected in the soil samples (ee=80%). Copyright © 2017 Elsevier B.V. All rights reserved.

Interaction of green tea polyphenols with dairy matrices in a simulated gastrointestinal environment.

PubMed

Lamothe, Sophie; Azimy, Naheed; Bazinet, Laurent; Couillard, Charles; Britten, Michel

2014-10-01

The consumption of polyphenols in green tea has been associated with beneficial health effects. Although polyphenols are unstable in the intestinal environment, they may be protected by interactions with dairy proteins during digestion. The objectives of this study were to evaluate the effect of a green tea extract on the digestibility of different dairy matrices and to monitor the antioxidant activity of these matrices with or without the green tea extract during digestion in a simulated gastrointestinal environment. Milk, yogurt and cheese with similar fat-to-protein ratios were subjected to simulated digestion. Matrix degradation, protein and fat hydrolysis, polyphenol concentration and radical scavenging activity were analyzed during gastric and intestinal digestion phases. Cheese was the matrix most resistant to protein and fat digestion. The addition of the green tea extract significantly decreased proteolysis in the gastric phase but had no effect in the intestinal phase. The kinetics of fatty acid release was reduced by the presence of the green tea extract. Transition from the gastric phase to the intestinal phase induced a 50% decrease in the antioxidant activity of the control (tea extract dispersed in water) due to the degradation of polyphenols. The presence of dairy matrices significantly improved polyphenol stability in the intestinal phase and increased the antioxidant activity by 29% (cheese) to 42% (milk) compared to the control. These results suggest that simultaneous consumption of green tea and dairy products helps to maintain the integrity and antioxidant activity of polyphenols during digestion.

ANAEROBIC BIODEGRADATION OF NITROGEN-SUBSTITUTED AND SULFONATED BENZENE AQUIFER CONTAMINANTS (JOURNAL)

EPA Science Inventory

A literature survey of ground water contaminants indicated that aquifers are repositories for hazardous wastes, including N- and 5-substituted benzene derivatives. We therefore examined the susceptibility of several anilines, benzamides, benenesulfonic acids and benenesulfonamide...

Bunch-Kaufman factorization for real symmetric indefinite banded matrices

NASA Technical Reports Server (NTRS)

Jones, Mark T.; Patrick, Merrell L.

1989-01-01

The Bunch-Kaufman algorithm for factoring symmetric indefinite matrices was rejected for banded matrices because it destroys the banded structure of the matrix. Herein, it is shown that for a subclass of real symmetric matrices which arise in solving the generalized eigenvalue problem using Lanczos's method, the Bunch-Kaufman algorithm does not result in major destruction of the bandwidth. Space time complexities of the algorithm are given and used to show that the Bunch-Kaufman algorithm is a significant improvement over LU factorization.

WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4

PubMed Central

Liu, Qian; Chen, Haoqian; Ojode, Teresa; Gao, Xiangxi; Anaya-O'Brien, Sandra; Turner, Nicholas A.; Ulrick, Jean; DeCastro, Rosamma; Kelly, Corin; Cardones, Adela R.; Gold, Stuart H.; Hwang, Eugene I.; Wechsler, Daniel S.; Malech, Harry L.; Murphy, Philip M.

2012-01-01

WHIM syndrome is a rare, autosomal dominant, immunodeficiency disorder so-named because it is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (defective neutrophil egress from the BM). Gain-of-function mutations that truncate the C-terminus of the chemokine receptor CXCR4 by 10-19 amino acids cause WHIM syndrome. We have identified a family with autosomal dominant inheritance of WHIM syndrome that is caused by a missense mutation in CXCR4, E343K (1027G → A). This mutation is also located in the C-terminal domain, a region responsible for negative regulation of the receptor. Accordingly, like CXCR4R334X, the most common truncation mutation in WHIM syndrome, CXCR4E343K mediated approximately 2-fold increased signaling in calcium flux and chemotaxis assays relative to wild-type CXCR4; however, CXCR4E343K had a reduced effect on blocking normal receptor down-regulation from the cell surface. Therefore, in addition to truncating mutations in the C-terminal domain of CXCR4, WHIM syndrome may be caused by a single charge-changing amino acid substitution in this domain, E343K, that results in increased receptor signaling. PMID:22596258

A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig-tailed macaques has a limited number of amino acid substitutions in both SIVmac and HIV-1 regions of the genome and has offered cytotropism.

PubMed

Stephens, E B; Mukherjee, S; Sahni, M; Zhuge, W; Raghavan, R; Singh, D K; Leung, K; Atkinson, B; Li, Z; Joag, S V; Liu, Z Q; Narayan, O

1997-05-12

We have examined both the sequence changes in the LTR, gag, vif, vpr, vpx, tat, rev, vpu, env, and nef genes and the cell tropism of a cell-free stock of chimeric simian-human immunodeficiency virus (SHIV) isolated from the cerebrospinal fluid of a pig-tailed macaque (PNb) that developed AIDS. This virus (SHIVKU-1) is highly pathogenic when inoculated into other macaques. DNA sequence analysis of PCR-amplified products revealed a total of 5 nucleotide changes in the LTR while vif had 2 consensus amino acid changes. The gag, vif, and vpx had no consensus amino acid substitutions, whereas vpr had 1 consensus substitution. The tat and rev genes of the HXB2 region of SHIVKU-1 had 2 and 1 consensus amino acid changes, respectively. The vpu gene of the HXB2 region of SHIV, which originally had an ACG at the beginning of the gene, reverted to an initiation ATG codon and in addition contained a consensus amino acid substitution at position 69 of this protein. As expected, the majority of the nucleotide substitutions were found in the env and nef genes. Thirteen and 5 amino acid changes were predicted for the corresponding Env and Nef proteins, respectively. In addition, one-third of the env gene clones isolated from the SHIVKU-1 stock had a 5-amino-acid deletion in the V4 region. Using three independent assays, we determined that the changes in the SHIVKU-1 were associated with an increase in the efficiency of replication in macrophages. The strikingly few consensus changes in the virus suggest that conversion of this virus to one capable of causing AIDS in pig-tailed macaques was associated with relatively few changes in the viral envelope and/or accessory genes. These results will provide the basis for the development of a pathogenic, molecular clone of SHIV capable of causing AIDS in pig-tailed macaques.

40 CFR 747.195 - Triethanolamine salt of a substituted organic acid.

Code of Federal Regulations, 2013 CFR

2013-07-01

... solely for research and development, have the same meaning as in § 720.3 of this chapter. (2... processor or distributor may not use the substance except in small quantities solely for research and... of a substance known to cause cancer in laboratory animals. The triethanolamine salt of a substituted...

40 CFR 747.195 - Triethanolamine salt of a substituted organic acid.

Code of Federal Regulations, 2014 CFR

2014-07-01

... solely for research and development, have the same meaning as in § 720.3 of this chapter. (2... processor or distributor may not use the substance except in small quantities solely for research and... of a substance known to cause cancer in laboratory animals. The triethanolamine salt of a substituted...

40 CFR 747.195 - Triethanolamine salt of a substituted organic acid.

Code of Federal Regulations, 2012 CFR

2012-07-01

... solely for research and development, have the same meaning as in § 720.3 of this chapter. (2... processor or distributor may not use the substance except in small quantities solely for research and... of a substance known to cause cancer in laboratory animals. The triethanolamine salt of a substituted...

Analysis of the breast milk of giant pandas (Ailuropoda melanoleuca) and the preparation of substitutes

PubMed Central

ZHANG, Zhihe; HOU, Rong; LAN, Jingchao; WANG, Hairui; KUROKAWA, Hiroyuki; TAKATSU, Zenta; KOBAYASHI, Toyokazu; KOIE, Hiroshi; KAMATA, Hiroshi; KANAYAMA, Kiichi; WATANABE, Toshi

2016-01-01

The first milk substitute for giant panda cubs was developed in 1988 based on limited data about giant panda breast milk and that of certain types of bear. Mixtures of other formulas have also been fed to cubs at some facilities. However, they are not of sufficient nutritional quality for promoting growth in panda cubs. Here, we report analysis of giant panda breast milk and propose new milk substitutes for cubs, which were developed based on the results of our analysis. The Chengdu Research Base of Giant Panda Breeding obtained breast milk samples from three giant pandas. Up to 30 ml of breast milk were collected from each mother by hand. Then, the milk samples were frozen and sent to Nihon University. The levels of protein, fat, carbohydrates, ash, moisture, vitamins, minerals, total amino acids, fatty acids, lactose and other carbohydrates in the milk were analyzed. The breast milk samples exhibited the following nutritional values: protein: 6.6–8.5%, fat: 6.9–16.4%, carbohydrates: 2.5–9.1%, ash: 0.9–1.0% and moisture: 67–83%. We designed two kinds of milk substitutes based on the data obtained and the nutritional requirements of dogs, cats and rodents. The nutritional composition of the milk substitutes for the first and second stages was as follows: protein: 38 and 26%, fat: 40 and 40%, carbohydrates: 13 and 25%, ash: 6 and 6% and moisture: 3 and 3%, respectively. In addition, the substitutes contained vitamins, minerals, taurine, docosahexaenoic acid, lactoferrin, nucleotides and other nutrients. PMID:26781707

Designing Inhibitors of Cytochrome c/Cardiolipin Peroxidase Complexes: Mitochondria-Targeted Imidazole-Substituted Fatty Acids

PubMed Central

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.

2014-01-01

Mitochondria have emerged as the major regulatory platform responsible for 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 anti-apoptotic mechanism of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogues of stearic acid TPP-n-ISA with different 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-ISA indeed were able to potently suppress CL induced structural re-arrangements in cyt c paving the way to its peroxidase competence. TPP-n-ISA analogues 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 anti-apoptotic 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 computations predictions, we identified TPP-6-ISA as a candidate drug with optimized anti-apoptotic potency. PMID:24631490

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

PubMed

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA.

PubMed

Xiang, Kuan-Hui; Michailidis, Eleftherios; Ding, Hai; Peng, Ya-Qin; Su, Ming-Ze; Li, Yao; Liu, Xue-En; Dao Thi, Viet Loan; Wu, Xian-Fang; Schneider, William M; Rice, Charles M; Zhuang, Hui; Li, Tong

2017-02-01

As important virological markers, serum hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels show large fluctuations among chronic hepatitis B patients. The aim of this study was to reveal the potential impact and mechanisms of amino acid substitutions in small hepatitis B surface proteins (SHBs) on serum HBsAg and HBV DNA levels. Serum samples from 230 untreated chronic hepatitis B patients with genotype C HBV were analyzed in terms of HBV DNA levels, serological markers of HBV infection and SHBs sequences. In vitro functional analysis of the identified SHBs mutants was performed. Among 230 SHBs sequences, there were 39 (16.96%) sequences with no mutation detected (wild-type) and 191 (83.04%) with single or multiple mutations. SHBs consist of 226 amino acids, of which 104 (46.02%) had mutations in our study. Some mutations (e.g., sE2G, sL21S, sR24K, sT47A/K, sC69stop (sC69∗), sL95W, sL98V, and sG145R) negatively correlated with serum HBsAg levels. HBsAg and HBV DNA levels from this group of patients had a positive correlation (r=0.61, p<0.001). In vitro analysis showed that these mutations reduced extracellular HBsAg and HBV DNA levels by restricting virion secretion and antibody binding capacity. Virion secretion could be rescued for sE2G, sC69∗, and sG145R by co-expression of wild-type HBsAg. The serum HBsAg levels were lower in untreated CHB patients with novel SHBs mutations outside the major antigenic region than those without mutations. Underlying mechanisms include impairment of virion secretion and lower binding affinity to antibodies used for HBsAg measurements. The hepatitis B surface antigen (HBsAg) is a major viral protein of the hepatitis B virus (HBV) secreted into patient blood serum and its quantification value serves as an important marker for the evaluation of chronic HBV infection and antiviral response. We found a few new amino acid substitutions in HBsAg associated with lower serum HBsAg and HBV DNA levels. These

BindML/BindML+: Detecting Protein-Protein Interaction Interface Propensity from Amino Acid Substitution Patterns.

PubMed

Wei, Qing; La, David; Kihara, Daisuke

2017-01-01

Prediction of protein-protein interaction sites in a protein structure provides important information for elucidating the mechanism of protein function and can also be useful in guiding a modeling or design procedures of protein complex structures. Since prediction methods essentially assess the propensity of amino acids that are likely to be part of a protein docking interface, they can help in designing protein-protein interactions. Here, we introduce BindML and BindML+ protein-protein interaction sites prediction methods. BindML predicts protein-protein interaction sites by identifying mutation patterns found in known protein-protein complexes using phylogenetic substitution models. BindML+ is an extension of BindML for distinguishing permanent and transient types of protein-protein interaction sites. We developed an interactive web-server that provides a convenient interface to assist in structural visualization of protein-protein interactions site predictions. The input data for the web-server are a tertiary structure of interest. BindML and BindML+ are available at http://kiharalab.org/bindml/ and http://kiharalab.org/bindml/plus/ .

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

PubMed

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.

Optimal neighborhood indexing for protein similarity search.

PubMed

Peterlongo, Pierre; Noé, Laurent; Lavenier, Dominique; Nguyen, Van Hoa; Kucherov, Gregory; Giraud, Mathieu

2008-12-16

Similarity inference, one of the main bioinformatics tasks, has to face an exponential growth of the biological data. A classical approach used to cope with this data flow involves heuristics with large seed indexes. In order to speed up this technique, the index can be enhanced by storing additional information to limit the number of random memory accesses. However, this improvement leads to a larger index that may become a bottleneck. In the case of protein similarity search, we propose to decrease the index size by reducing the amino acid alphabet. The paper presents two main contributions. First, we show that an optimal neighborhood indexing combining an alphabet reduction and a longer neighborhood leads to a reduction of 35% of memory involved into the process, without sacrificing the quality of results nor the computational time. Second, our approach led us to develop a new kind of substitution score matrices and their associated e-value parameters. In contrast to usual matrices, these matrices are rectangular since they compare amino acid groups from different alphabets. We describe the method used for computing those matrices and we provide some typical examples that can be used in such comparisons. Supplementary data can be found on the website http://bioinfo.lifl.fr/reblosum. We propose a practical index size reduction of the neighborhood data, that does not negatively affect the performance of large-scale search in protein sequences. Such an index can be used in any study involving large protein data. Moreover, rectangular substitution score matrices and their associated statistical parameters can have applications in any study involving an alphabet reduction.

Optimal neighborhood indexing for protein similarity search

PubMed Central

Peterlongo, Pierre; Noé, Laurent; Lavenier, Dominique; Nguyen, Van Hoa; Kucherov, Gregory; Giraud, Mathieu

2008-01-01

Background Similarity inference, one of the main bioinformatics tasks, has to face an exponential growth of the biological data. A classical approach used to cope with this data flow involves heuristics with large seed indexes. In order to speed up this technique, the index can be enhanced by storing additional information to limit the number of random memory accesses. However, this improvement leads to a larger index that may become a bottleneck. In the case of protein similarity search, we propose to decrease the index size by reducing the amino acid alphabet. Results The paper presents two main contributions. First, we show that an optimal neighborhood indexing combining an alphabet reduction and a longer neighborhood leads to a reduction of 35% of memory involved into the process, without sacrificing the quality of results nor the computational time. Second, our approach led us to develop a new kind of substitution score matrices and their associated e-value parameters. In contrast to usual matrices, these matrices are rectangular since they compare amino acid groups from different alphabets. We describe the method used for computing those matrices and we provide some typical examples that can be used in such comparisons. Supplementary data can be found on the website . Conclusion We propose a practical index size reduction of the neighborhood data, that does not negatively affect the performance of large-scale search in protein sequences. Such an index can be used in any study involving large protein data. Moreover, rectangular substitution score matrices and their associated statistical parameters can have applications in any study involving an alphabet reduction. PMID:19087280

Effects of Xylan Side-Chain Substitutions on Xylan-Cellulose Interactions and Implications for Thermal Pretreatment of Cellulosic Biomass.

PubMed

Pereira, Caroline S; Silveira, Rodrigo L; Dupree, Paul; Skaf, Munir S

2017-04-10

Lignocellulosic biomass is mainly constituted by cellulose, hemicellulose, and lignin and represents an important resource for the sustainable production of biofuels and green chemistry materials. Xylans, a common hemicellulose, interact with cellulose and often exhibit various side chain substitutions including acetate, (4-O-methyl) glucuronic acid, and arabinose. Recent studies have shown that the distribution of xylan substitutions is not random, but follows patterns that are dependent on the plant taxonomic family and cell wall type. Here, we use molecular dynamics simulations to investigate the role of substitutions on xylan interactions with the hydrophilic cellulose face, using the recently discovered xylan decoration pattern of the conifer gymnosperms as a model. The results show that α-1,2-linked substitutions stabilize the binding of single xylan chains independently of the nature of the substitution and that Ca 2+ ions can mediate cross-links between glucuronic acid substitutions of two neighboring xylan chains, thus stabilizing binding. At high temperature, xylans move from the hydrophilic to the hydrophobic cellulose surface and are also stabilized by Ca 2+ cross-links. Our results help to explain the role of substitutions on xylan-cellulose interactions, and improve our understanding of the plant cell wall architecture and the fundamentals of biomass pretreatments.

Estimation for the Linear Model With Uncertain Covariance Matrices

NASA Astrophysics Data System (ADS)

Zachariah, Dave; Shariati, Nafiseh; Bengtsson, Mats; Jansson, Magnus; Chatterjee, Saikat

2014-03-01

We derive a maximum a posteriori estimator for the linear observation model, where the signal and noise covariance matrices are both uncertain. The uncertainties are treated probabilistically by modeling the covariance matrices with prior inverse-Wishart distributions. The nonconvex problem of jointly estimating the signal of interest and the covariance matrices is tackled by a computationally efficient fixed-point iteration as well as an approximate variational Bayes solution. The statistical performance of estimators is compared numerically to state-of-the-art estimators from the literature and shown to perform favorably.

Noisy covariance matrices and portfolio optimization

NASA Astrophysics Data System (ADS)

Pafka, S.; Kondor, I.

2002-05-01

According to recent findings [#!bouchaud!#,#!stanley!#], empirical covariance matrices deduced from financial return series contain such a high amount of noise that, apart from a few large eigenvalues and the corresponding eigenvectors, their structure can essentially be regarded as random. In [#!bouchaud!#], e.g., it is reported that about 94% of the spectrum of these matrices can be fitted by that of a random matrix drawn from an appropriately chosen ensemble. In view of the fundamental role of covariance matrices in the theory of portfolio optimization as well as in industry-wide risk management practices, we analyze the possible implications of this effect. Simulation experiments with matrices having a structure such as described in [#!bouchaud!#,#!stanley!#] lead us to the conclusion that in the context of the classical portfolio problem (minimizing the portfolio variance under linear constraints) noise has relatively little effect. To leading order the solutions are determined by the stable, large eigenvalues, and the displacement of the solution (measured in variance) due to noise is rather small: depending on the size of the portfolio and on the length of the time series, it is of the order of 5 to 15%. The picture is completely different, however, if we attempt to minimize the variance under non-linear constraints, like those that arise e.g. in the problem of margin accounts or in international capital adequacy regulation. In these problems the presence of noise leads to a serious instability and a high degree of degeneracy of the solutions.

Nano-Fiber Reinforced Enhancements in Composite Polymer Matrices

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

2009-01-01

Nano-fibers are used to reinforce polymer matrices to enhance the matrix dependent properties that are subsequently used in conventional structural composites. A quasi isotropic configuration is used in arranging like nano-fibers through the thickness to ascertain equiaxial enhanced matrix behavior. The nano-fiber volume ratios are used to obtain the enhanced matrix strength properties for 0.01,0.03, and 0.05 nano-fiber volume rates. These enhanced nano-fiber matrices are used with conventional fiber volume ratios of 0.3 and 0.5 to obtain the composite properties. Results show that nano-fiber enhanced matrices of higher than 0.3 nano-fiber volume ratio are degrading the composite properties.

Convergent evolution of marine mammals is associated with distinct substitutions in common genes

PubMed Central

Zhou, Xuming; Seim, Inge; Gladyshev, Vadim N.

2015-01-01

Phenotypic convergence is thought to be driven by parallel substitutions coupled with natural selection at the sequence level. Multiple independent evolutionary transitions of mammals to an aquatic environment offer an opportunity to test this thesis. Here, whole genome alignment of coding sequences identified widespread parallel amino acid substitutions in marine mammals; however, the majority of these changes were not unique to these animals. Conversely, we report that candidate aquatic adaptation genes, identified by signatures of likelihood convergence and/or elevated ratio of nonsynonymous to synonymous nucleotide substitution rate, are characterized by very few parallel substitutions and exhibit distinct sequence changes in each group. Moreover, no significant positive correlation was found between likelihood convergence and positive selection in all three marine lineages. These results suggest that convergence in protein coding genes associated with aquatic lifestyle is mainly characterized by independent substitutions and relaxed negative selection. PMID:26549748

A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice▿ †

PubMed Central

Fornek, Jamie L.; Gillim-Ross, Laura; Santos, Celia; Carter, Victoria; Ward, Jerrold M.; Cheng, Lily I.; Proll, Sean; Katze, Michael G.; Subbarao, Kanta

2009-01-01

The transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid 627 in the PB2 protein exhibited an increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T-cell receptor activation was impaired at 2 days postinfection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not attributable solely to differences in viral replication in the lungs but to an inefficient immune response early in infection as well. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. The disruption of these factors by a single-amino-acid substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites. PMID:19692471

α-Amino Acid Derived Benzimidazole-Linked Rhodamines: A Case of Substitution Effect at the Amino Acid Site toward Spiro Ring Opening for Selective Sensing of Al3+ Ions.

PubMed

Majumdar, Anupam; Mondal, Subhendu; Daniliuc, Constantin G; Sahu, Debashis; Ganguly, Bishwajit; Ghosh, Sourav; Ghosh, Utpal; Ghosh, Kumaresh

2017-08-07

α-Amino acid derived benzimidazole-linked rhodamines have been synthesized, and their metal ion sensing properties have been evaluated. Experimentally, l-valine- and l-phenylglycine-derived benzimidazole-based rhodamines 1 and 2 selectively recognize Al 3+ ion in aqueous CH 3 CN (CH 3 CN/H 2 O 4/1 v/v, 10 mM tris HCl buffer, pH 7.0) over the other cations by exhibiting color and "turn-on" emission changes. In contrast, glycine-derived benzimidazole 3 remains silent in the recognition event and emphasizes the role of α-substitution of amino acid undertaken in the design. The fact has been addressed on the basis of the single-crystal X-ray structures and theoretical calculations. Moreover, pink 1·Al 3+ and 2·Al 3+ ensembles selectively sensed F - ions over other halides through a discharge of color. Importantly, compounds 1 and 2 are cell permeable and have been used as imaging reagents for the detection of Al 3+ uptake in human lung carcinoma cell line A549.

Effects of two novel amino acid substitutions on the penicillin binding properties of the PBP5 C‑terminal from Enterococcus faecium.

PubMed

Zhou, Chengjiang; Niu, Haiying; Yu, Hui; Zhou, Lishe; Wang, Zhanli

2015-10-01

The low‑affinity penicillin‑binding protein (PBP)5 is responsible for resistance to β‑lactam antibiotics in Enterococcus faecium. (E. faecium). In order to evaluate more fully the potential of this species for the development of resistance to β-lactam antibiotics, the present study aimed to examine the extent of penicillin-binding protein (PBP) variations in a collection of clinical E. faecium isolates. In the present study, the C‑terminal domain of PBP5 (PBP5‑CD) of 13 penicillin‑resistant clinical isolates of E. faecium were sequenced and the correlation between penicillin resistance and particular amino acid changes were analyzed. The present study identified for the first time, to the best of our knowledge, two novel substitutions (Tyr460Phe and Ala462Thr or Val462Thr) of E. faecium PBP5‑CD. The covalent interaction between penicillin and PBP5‑CD was also investigated using homology modeling and molecular docking methods. The theoretical calculation revealed that Phe460 and Thr462 were involved in penicillin binding, suggesting that substitutions at these positions exert effects on the affinity for penicillin, and this increased affinity translates into lower resistance in vitro.

Amino acid substitutions in subunit 9 of the mitochondrial ATPase complex of Saccharomyces cerevisiae. Sequence analysis of a series of revertants of an oli1 mit- mutant carrying an amino acid substitution in the hydrophilic loop of subunit 9.

PubMed

Willson, T A; Nagley, P

1987-09-01

This work concerns a biochemical genetic study of subunit 9 of the mitochondrial ATPase complex of Saccharomyces cerevisiae. Subunit 9, encoded by the mitochondrial oli1 gene, contains a hydrophilic loop connecting two transmembrane stems. In one particular oli1 mit- mutant 2422, the substitution of a positively charged amino acid in this loop (Arg39----Met) renders the ATPase complex non-functional. A series of 20 revertants, selected for their ability to grow on nonfermentable substrates, has been isolated from mutant 2422. The results of DNA sequence analysis of the oli1 gene in each revertant have led to the recognition of three groups of revertants. Class I revertants have undergone a same-site reversion event: the mutant Met39 is replaced either by arginine (as in wild-type) or lysine. Class II revertants maintain the mutant Met39 residue, but have undergone a second-site reversion event (Asn35----Lys). Two revertants showing an oligomycin-resistant phenotype carry this same second-site reversion in the loop region together with a further amino acid substitution in either of the two membrane-spanning segments of subunit 9 (either Gly23----Ser or Leu53----Phe). Class III revertants contain subunit 9 with the original mutant 2422 sequence, and additionally carry a recessive nuclear suppressor, demonstrated to represent a single gene. The results on the revertants in classes I and II indicate that there is a strict requirement for a positively charged residue in the hydrophilic loop close to the boundary of the lipid bilayer. The precise location of this positive charge is less stringent; in functional ATPase complexes it can be found at either residue 39 or 35. This charged residue is possibly required to interact with some other component of the mitochondrial ATPase complex. These findings, together with hydropathy plots of subunit 9 polypeptides from normal, mutant and revertant strains, led to the conclusion that the hydrophilic loop in normal subunit 9

Amino acid and nucleotide recurrence in aligned sequences: synonymous substitution patterns in association with global and local base compositions.

PubMed

Nishizawa, M; Nishizawa, K

2000-10-01

The tendency for repetitiveness of nucleotides in DNA sequences has been reported for a variety of organisms. We show that the tendency for repetitive use of amino acids is widespread and is observed even for segments conserved between human and Drosophila melanogaster at the level of >50% amino acid identity. This indicates that repetitiveness influences not only the weakly constrained segments but also those sequence segments conserved among phyla. Not only glutamine (Q) but also many of the 20 amino acids show a comparable level of repetitiveness. Repetitiveness in bases at codon position 3 is stronger for human than for D.melanogaster, whereas local repetitiveness in intron sequences is similar between the two organisms. While genes for immune system-specific proteins, but not ancient human genes (i.e. human homologs of Escherichia coli genes), have repetitiveness at codon bases 1 and 2, repetitiveness at codon base 3 for these groups is similar, suggesting that the human genome has at least two mechanisms generating local repetitiveness. Neither amino acid nor nucleotide repetitiveness is observed beyond the exon boundary, denying the possibility that such repetitiveness could mainly stem from natural selection on mRNA or protein sequences. Analyses of mammalian sequence alignments show that while the 'between gene' GC content heterogeneity, which is linked to 'isochores', is a principal factor associated with the bias in substitution patterns in human, 'within gene' heterogeneity in nucleotide composition is also associated with such bias on a more local scale. The relationship amongst the various types of repetitiveness is discussed.

Amino acid and nucleotide recurrence in aligned sequences: synonymous substitution patterns in association with global and local base compositions

PubMed Central

Nishizawa, Manami; Nishizawa, Kazuhisa

2000-01-01

The tendency for repetitiveness of nucleotides in DNA sequences has been reported for a variety of organisms. We show that the tendency for repetitive use of amino acids is widespread and is observed even for segments conserved between human and Drosophila melanogaster at the level of >50% amino acid identity. This indicates that repetitiveness influences not only the weakly constrained segments but also those sequence segments conserved among phyla. Not only glutamine (Q) but also many of the 20 amino acids show a comparable level of repetitiveness. Repetitiveness in bases at codon position 3 is stronger for human than for D.melanogaster, whereas local repetitiveness in intron sequences is similar between the two organisms. While genes for immune system-specific proteins, but not ancient human genes (i.e. human homologs of Escherichia coli genes), have repetitiveness at codon bases 1 and 2, repetitiveness at codon base 3 for these groups is similar, suggesting that the human genome has at least two mechanisms generating local repetitiveness. Neither amino acid nor nucleotide repetitiveness is observed beyond the exon boundary, denying the possibility that such repetitiveness could mainly stem from natural selection on mRNA or protein sequences. Analyses of mammalian sequence alignments show that while the ‘between gene’ GC content heterogeneity, which is linked to ‘isochores’, is a principal factor associated with the bias in substitution patterns in human, ‘within gene’ heterogeneity in nucleotide composition is also associated with such bias on a more local scale. The relationship amongst the various types of repetitiveness is discussed. PMID:11000273

Influence of Al substitution on magnetism and adsorption properties of hematite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, Shanshan; Kang, Feifei; Yang, Xin

2015-08-15

A series of Al-substituted hematite was prepared. The structures and properties of as-prepared samples were characterized by various techniques. The magnetic property of the samples was determined and the adsorption of three dyes Acid Blue 74, Methylene Blue and Phenol Red onto the samples was investigated. The results showed that Al incorporation into the crystal structure of hematite occurs via isomorphous ionic substitution of Al for Fe. With increasing Al content, the particle size of samples decreases, the magnetization increases and the remanent magnetization remains unchanged. The coercivity of the samples increases with Al substitution up to n{sub Al}/n{sub Fe}more » 0.03, and then decreases as Al content further increases. Compared with Al-free hematite, Al-substituted samples exhibit better adsorption ability to all of the three dyes. The adsorption rates of the three dyes on the surface of Al substituted samples depend on the structure of dye, pH and Al content in hematite. - Graphical abstract: Effect of Al on the structure, magnetic properties and adsorption performance of hematite was investigated. - Highlights: • A series of Al-substituted α-Fe{sub 2}O{sub 3} was prepared. • Effect of Al content on the crystal structure and magnetic property of hematite was investigated. • Al-substituted hematite exhibits better adsorption ability than hematite.« less

Composite glycerol/graphite/aromatic acid matrices for thin-layer chromatography/matrix-assisted laser desorption/ionization mass spectrometry of heterocyclic compounds.

PubMed

Esparza, Cesar; Borisov, R S; Varlamov, A V; Zaikin, V G

2016-10-28

New composite matrices have been suggested for the analysis of mixtures of different synthetic organic compounds (N-containing heterocycles and erectile dysfunction drugs) by thin layer chromatography/matrix-assisted laser desorption ionization time-of-flight mass spectrometry (TLC/MALDI-TOF). Different mixtures of classical MALDI matrices and graphite particles dispersed in glycerol were used for the registration of MALDI mass spectra directly from TLC plates after analytes separation. In most of cases, the mass spectra possessed [M+H] + ions; however, for some analytes only [M+Na] + and [M+K] + ions were observed. These ions have been used to generate visualized TLC chromatograms. The described approach increases the desorption/ionization efficiencies of analytes separated by TLC, prevent spot blurring, simplifies and decrease time for sample preparation. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptation of tick-borne encephalitis virus from human brain to different cell cultures induces multiple genomic substitutions.

PubMed

Ponomareva, Eugenia P; Ternovoi, Vladimir A; Mikryukova, Tamara P; Protopopova, Elena V; Gladysheva, Anastasia V; Shvalov, Alexander N; Konovalova, Svetlana N; Chausov, Eugene V; Loktev, Valery B

2017-10-01

The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins. The substitutions NS2a 1067 (Asn → Asp), NS2a 1168 (Leu → Val) in the N-terminus of NS2a and NS3 1745 (His → Gln) in the helicase domain of NS3 were found in all selected variants. We postulate that multiple substitutions in the NS2a, NS3 and NS5 genes play a key role in adaptation of TBEV to different cells.

Diamines and polyimides containing pendent ethynyl groups

NASA Technical Reports Server (NTRS)

Hergenrother, Paul M. (Inventor); Jensen, Brian J. (Inventor)

1994-01-01

Diamines containing pendent ethynyl and substituted ethynyl groups are synthesized. These diamines are reacted with dianhydrides to form polyamide acids, which are chemically or thermally cyclodehydrated to form polyimides and copolyimides with pendent ethynyl groups. Upon heating, the pendent ethynyl groups react to form crosslinked resins that are useful as adhesives, composite matrices, coatings, moldings, and films.

The asymptotic spectra of banded Toeplitz and quasi-Toeplitz matrices

NASA Technical Reports Server (NTRS)

Beam, Richard M.; Warming, Robert F.

1991-01-01

Toeplitz matrices occur in many mathematical, as well as, scientific and engineering investigations. This paper considers the spectra of banded Toeplitz and quasi-Toeplitz matrices with emphasis on non-normal matrices of arbitrarily large order and relatively small bandwidth. These are the type of matrices that appear in the investigation of stability and convergence of difference approximations to partial differential equations. Quasi-Toeplitz matrices are the result of non-Dirichlet boundary conditions for the difference approximations. The eigenvalue problem for a banded Toeplitz or quasi-Toeplitz matrix of large order is, in general, analytically intractable and (for non-normal matrices) numerically unreliable. An asymptotic (matrix order approaches infinity) approach partitions the eigenvalue analysis of a quasi-Toeplitz matrix into two parts, namely the analysis for the boundary condition independent spectrum and the analysis for the boundary condition dependent spectrum. The boundary condition independent spectrum is the same as the pure Toeplitz matrix spectrum. Algorithms for computing both parts of the spectrum are presented. Examples are used to demonstrate the utility of the algorithms, to present some interesting spectra, and to point out some of the numerical difficulties encountered when conventional matrix eigenvalue routines are employed for non-normal matrices of large order. The analysis for the Toeplitz spectrum also leads to a diagonal similarity transformation that improves conventional numerical eigenvalue computations. Finally, the algorithm for the asymptotic spectrum is extended to the Toeplitz generalized eigenvalue problem which occurs, for example, in the stability of Pade type difference approximations to differential equations.

Ultra-superovulation for the CRISPR-Cas9-mediated production of gene-knockout, single-amino-acid-substituted, and floxed mice.

PubMed

Nakagawa, Yoshiko; Sakuma, Tetsushi; Nishimichi, Norihisa; Yokosaki, Yasuyuki; Yanaka, Noriyuki; Takeo, Toru; Nakagata, Naomi; Yamamoto, Takashi

2016-08-15

Current advances in producing genetically modified mice using genome-editing technologies have indicated the need for improvement of limiting factors including zygote collection for microinjection and their cryopreservation. Recently, we developed a novel superovulation technique using inhibin antiserum and equine chorionic gonadotropin to promote follicle growth. This method enabled the increased production of fertilized oocytes via in vitro fertilization compared with the conventional superovulation method. Here, we verify that the ultra-superovulation technique can be used for the efficient generation of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated knockout mice by microinjection of plasmid vector or ribonucleoprotein into zygotes. We also investigated whether single-amino-acid-substituted mice and conditional knockout mice could be generated. Founder mice bearing base substitutions were generated more efficiently by co-microinjection of Cas9 protein, a guide RNA and single-stranded oligodeoxynucleotide (ssODN) than by plasmid microinjection with ssODN. The conditional allele was successfully introduced by the one-step insertion of an ssODN designed to carry an exon flanked by two loxP sequences and homology arms using a double-cut CRISPR-Cas9 strategy. Our study presents a useful method for the CRISPR-Cas9-based generation of genetically modified mice from the viewpoints of animal welfare and work efficiency. © 2016. Published by The Company of Biologists Ltd.

A single amino acid substitution in the Bombyx-specific mucin-like membrane protein causes resistance to Bombyx mori densovirus.

PubMed

Ito, Katsuhiko; Kidokoro, Kurako; Katsuma, Susumu; Sezutsu, Hideki; Uchino, Keiro; Kobayashi, Isao; Tamura, Toshiki; Yamamoto, Kimiko; Mita, Kazuei; Shimada, Toru; Kadono-Okuda, Keiko

2018-05-09

Bombyx mori densovirus type 1 (BmDV) is a pathogen that causes flacherie disease in the silkworm. The absolute nonsusceptibility to BmDV among certain silkworm strains is determined independently by two genes, nsd-1 and Nid-1. However, neither of these genes has been molecularly identified to date. Here, we isolated the nsd-1 gene by positional cloning and characterized the properties of its product, NSD-1. Sequence and biochemical analyses revealed that this gene encodes a Bombyx-specific mucin-like glycoprotein with a single transmembrane domain. The NSD-1 protein was specifically expressed in the larval midgut epithelium, the known infection site of BmDV. Sequence analysis of the nsd-1 gene from 13 resistant and 12 susceptible strains suggested that a specific arginine residue in the extracellular tail of the NSD-1 protein was common among susceptible strains. Germline transformation of the susceptible-type nsd-1 (with a single nucleotide substitution) conferred partial susceptibility to resistant larvae, indicating that the +  nsd-1 gene is required for the susceptibility of B. mori larvae to BmDV and the susceptibility is solely a result of the substitution of a single amino acid with arginine. Taken together, our results provide striking evidence that a novel membrane-bound mucin-like protein functions as a cell-surface receptor for a densovirus.

Design, synthesis, and evaluation of a novel series of alpha-substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor (PPAR) alpha/delta dual agonists for the treatment of metabolic syndrome.

PubMed

Kasuga, Jun-ichi; Yamasaki, Daisuke; Araya, Yoko; Nakagawa, Aya; Makishima, Makoto; Doi, Takefumi; Hashimoto, Yuichi; Miyachi, Hiroyuki

2006-12-15

A series of alpha-alkyl-substituted phenylpropanoic acids was prepared as dual agonists of peroxisome proliferator-activated receptors alpha and delta (PPARalpha/delta). Structure-activity relationship studies indicated that the shape of the linking group and the shape of the substituent at the distal benzene ring play key roles in determining the potency and the selectivity of PPAR subtype transactivation. Structure-activity relationships among the amide series (10) and the reversed amide series (13) are similar, but not identical, especially in the case of the compounds bearing a bulky hydrophobic substituent at the distal benzene ring, indicating that the hydrophobic tail part of the molecules in these two series binds at somewhat different positions in the large binding pocket of PPAR. alpha-Alkyl-substituted phenylpropanoic acids of (S)-configuration were identified as potent human PPARalpha/delta dual agonists. Representative compounds exhibited marked nuclear receptor selectivity for PPARalpha and PPARdelta. Subtype-selective PPAR activation was also examined by analysis of the mRNA expression of PPAR-regulated genes.

Amino acid substitutions in the heptad repeat A and C regions of the F protein responsible for neurovirulence of measles virus Osaka-1 strain from a patient with subacute sclerosing panencephalitis.

PubMed

Ayata, Minoru; Tanaka, Miyuu; Kameoka, Kazuo; Kuwamura, Mitsuru; Takeuchi, Kaoru; Takeda, Makoto; Kanou, Kazuhiko; Ogura, Hisashi

2016-01-01

Measles virus (MV) is the causative agent of subacute sclerosing panencephalitis (SSPE). We previously reported that the F gene of the SSPE Osaka-2 strain is the major determinant of MV neurovirulence. Because the sites and extents of mutations differ among SSPE strains, it is necessary to determine the mutations responsible for the SSPE-specific phenotypes of individual viral strain. In this study, recombinant viruses containing the envelope-associated genes from the SSPE Osaka-1 strain were generated in the IC323 wild-type MV background. Hamsters inoculated with MV containing the H gene of the Osaka-1 strain displayed hyperactivity and seizures, but usually recovered and survived. Hamsters inoculated with MV containing the F gene of the Osaka-1 strain displayed severe neurologic signs and died. Amino acid substitutions in the heptad repeat A and C regions of the F protein, including a methionine-to-valine substitution at amino acid 94, play major roles in neurovirulence. Copyright © 2015 Elsevier Inc. All rights reserved.

Human immunodeficiency virus type 1 resistance to the small molecule maturation inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid is conferred by a variety of single amino acid substitutions at the CA-SP1 cleavage site in Gag.

PubMed

Zhou, Jing; Chen, Chin Ho; Aiken, Christopher

2006-12-01

The compound 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB) potently and specifically inhibits human immunodeficiency virus type 1 (HIV-1) replication by delaying the cleavage of the CA-SP1 junction in Gag, leading to impaired maturation of the viral core. In this study, we investigated HIV-1 resistance to DSB by analyzing HIV-1 mutants encoding a variety of individual amino acid substitutions in the CA-SP1 cleavage site. Three of the substitutions were lethal to HIV-1 replication owing to a deleterious effect on particle assembly. The remaining mutants exhibited a range of replication efficiencies; however, each mutant was capable of replicating in the presence of concentrations of DSB that effectively inhibited wild-type HIV-1. Mutations conferring resistance to DSB also led to impaired binding of the compound to immature HIV-1 virions and loss of DSB-mediated inhibition of cleavage of Gag. Surprisingly, two of the DSB-resistant mutants retained an intermediate ability to bind the compound, suggesting that binding of DSB to immature HIV-1 particles may not be sufficient for antiviral activity. Overall, our results indicate that Gag amino acids L363 and A364 are critical for inhibition of HIV-1 replication by DSB and suggest that these residues form key contacts with the drug in the context of the assembling HIV-1 particle. These results have implications for the design of and screening for novel inhibitors of HIV-1 maturation.

Crosslinked type II collagen matrices: preparation, characterization, and potential for cartilage engineering.

PubMed

Pieper, J S; van der Kraan, P M; Hafmans, T; Kamp, J; Buma, P; van Susante, J L C; van den Berg, W B; Veerkamp, J H; van Kuppevelt, T H

2002-08-01

The limited intrinsic repair capacity of articular cartilage has stimulated continuing efforts to develop tissue engineered analogues. Matrices composed of type II collagen and chondroitin sulfate (CS), the major constituents of hyaline cartilage, may create an appropriate environment for the generation of cartilage-like tissue. In this study, we prepared, characterized, and evaluated type 11 collagen matrices with and without CS. Type II collagen matrices were prepared using purified, pepsin-treated, type II collagen. Techniques applied to prepare type I collagen matrices were found unsuitable for type II collagen. Crosslinking of collagen and covalent attachment of CS was performed using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. Porous matrices were prepared by freezing and lyophilization, and their physico-chemical characteristics (degree of crosslinking, denaturing temperature, collagenase-resistance, amount of CS incorporated) established. Matrices were evaluated for their capacity to sustain chondrocyte proliferation and differentiation in vitro. After 7 d of culture, chondrocytes were mainly located at the periphery of the matrices. In contrast to type I collagen, type II collagen supported the distribution of cells throughout the matrix. After 14 d of culture, matrices were surfaced with a cartilagenous-like layer, and occasionally clusters of chondrocytes were present inside the matrix. Chondrocytes proliferated and differentiated as indicated by biochemical analyses, ultrastructural observations, and reverse transcriptase PCR for collagen types I, II and X. No major differences were observed with respect to the presence or absence of CS in the matrices.

T135I substitution in the nonstructural protein 2C enhances foot-and-mouth disease virus replication.

PubMed

Yuan, Tiangang; Wang, Haiwei; Li, Chen; Yang, Decheng; Zhou, Guohui; Yu, Li

2017-12-01

The foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays an important role in viral replication, virulence, and host range. It has been shown that deletions of 10 or 19-20 amino acids in the C-terminal half of 3A attenuate serotype O and C FMDVs, which replicate poorly in bovine cells but normally in porcine-derived cells, and the C-terminal half of 3A is not essential for serotype Asia1 FMDV replication in BHK-21 cells. In this study, we constructed a 3A deletion FMDV mutant based on a serotype O FMDV, the wild-type virus O/YS/CHA/05, with a 60-amino acid deletion in the 3A protein sequence, between residues 84 and 143. The rescued virus O/YS/CHA/05-Δ3A exhibited slower growth kinetics and formed smaller plaques compared to O/YS/CHA/05 in both BHK-21 and IBRS-2 cells, indicating that the 60-amino acid deletion in the 3A protein impaired FMDV replication. After 14 passages in BHK-21 cells, the replication capacity of the passaged virus O/YS/CHA/05-Δ3A-P14 returned to a level similar to the wild-type virus, suggesting that amino acid substitutions responsible for the enhanced replication capacity occurred in the genome of O/YS/CHA/05-Δ3A-P14. By sequence analysis, two amino acid substitutions, P153L in VP1 and T135I in 2C, were found in the O/YS/CHA/05-Δ3A-P14 genome compared to the O/YS/CHA/05-Δ3A genome. Subsequently, the amino acid substitutions VP1 P153L and 2C T135I were separately introduced into O/YS/CHA/05-Δ3A to rescue mutant viruses for examining their growth kinetics. Results showed that the 2C T135I instead of the VP1 P153L enhanced the virus replication capacity. The 2C T135I substitution also improved the replication of the wild-type virus, indicating that the effect of 2C T135I substitution on FMDV replication is not associated with the 3A deletion. Furthermore, our results showed that the T135I substitution in the nonstructural protein 2C enhanced O/YS/CHA/05 replication through promoting viral RNA synthesis.

Asymptotics of eigenvalues and eigenvectors of Toeplitz matrices

NASA Astrophysics Data System (ADS)

Böttcher, A.; Bogoya, J. M.; Grudsky, S. M.; Maximenko, E. A.

2017-11-01

Analysis of the asymptotic behaviour of the spectral characteristics of Toeplitz matrices as the dimension of the matrix tends to infinity has a history of over 100 years. For instance, quite a number of versions of Szegő's theorem on the asymptotic behaviour of eigenvalues and of the so-called strong Szegő theorem on the asymptotic behaviour of the determinants of Toeplitz matrices are known. Starting in the 1950s, the asymptotics of the maximum and minimum eigenvalues were actively investigated. However, investigation of the individual asymptotics of all the eigenvalues and eigenvectors of Toeplitz matrices started only quite recently: the first papers on this subject were published in 2009-2010. A survey of this new field is presented here. Bibliography: 55 titles.

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

Synthesis and Evolution of a Threose Nucleic Acid Aptamer Bearing 7-Deaza-7-Substituted Guanosine Residues.

PubMed

Mei, Hui; Liao, Jen-Yu; Jimenez, Randi M; Wang, Yajun; Bala, Saikat; McCloskey, Cailen; Switzer, Christopher; Chaput, John C

2018-05-02

In vitro selection experiments carried out on artificial genetic polymers require robust and faithful methods for copying genetic information back and forth between DNA and xeno-nucleic acids (XNA). Previously, we have shown that Kod-RI, an engineered polymerase developed to transcribe DNA templates into threose nucleic acid (TNA), can function with high fidelity in the absence of manganese ions. However, the transcriptional efficiency of this enzyme diminishes greatly when individual templates are replaced with libraries of DNA sequences, indicating that manganese ions are still required for in vitro selection. Unfortunately, the presence of manganese ions in the transcription mixture leads to the misincorporation of tGTP nucleotides opposite dG residues in the templating strand, which are detected as G-to-C transversions when the TNA is reverse transcribed back into DNA. Here we report the synthesis and fidelity of TNA replication using 7-deaza-7-modified guanosine base analogues in the DNA template and incoming TNA nucleoside triphosphate. Our findings reveal that tGTP misincorporation occurs via a Hoogsteen base pair in which the incoming tGTP residue adopts a syn conformation with respect to the sugar. Substitution of tGTP for 7-deaza-7-phenyl tGTP enabled the synthesis of TNA polymers with >99% overall fidelity. A TNA library containing the 7-deaza-7-phenyl guanine analogue was used to evolve a biologically stable TNA aptamer that binds to HIV reverse transcriptase with low nanomolar affinity.

Perceptual Optimization of DCT Color Quantization Matrices

NASA Technical Reports Server (NTRS)

Watson, Andrew B.; Statler, Irving C. (Technical Monitor)

1994-01-01

Many image compression schemes employ a block Discrete Cosine Transform (DCT) and uniform quantization. Acceptable rate/distortion performance depends upon proper design of the quantization matrix. In previous work, we showed how to use a model of the visibility of DCT basis functions to design quantization matrices for arbitrary display resolutions and color spaces. Subsequently, we showed how to optimize greyscale quantization matrices for individual images, for optimal rate/perceptual distortion performance. Here we describe extensions of this optimization algorithm to color images.

Detecting Adaptation in Protein-Coding Genes Using a Bayesian Site-Heterogeneous Mutation-Selection Codon Substitution Model.

PubMed

Rodrigue, Nicolas; Lartillot, Nicolas

2017-01-01

Codon substitution models have traditionally attempted to uncover signatures of adaptation within protein-coding genes by contrasting the rates of synonymous and non-synonymous substitutions. Another modeling approach, known as the mutation-selection framework, attempts to explicitly account for selective patterns at the amino acid level, with some approaches allowing for heterogeneity in these patterns across codon sites. Under such a model, substitutions at a given position occur at the neutral or nearly neutral rate when they are synonymous, or when they correspond to replacements between amino acids of similar fitness; substitutions from high to low (low to high) fitness amino acids have comparatively low (high) rates. Here, we study the use of such a mutation-selection framework as a null model for the detection of adaptation. Following previous works in this direction, we include a deviation parameter that has the effect of capturing the surplus, or deficit, in non-synonymous rates, relative to what would be expected under a mutation-selection modeling framework that includes a Dirichlet process approach to account for across-codon-site variation in amino acid fitness profiles. We use simulations, along with a few real data sets, to study the behavior of the approach, and find it to have good power with a low false-positive rate. Altogether, we emphasize the potential of recent mutation-selection models in the detection of adaptation, calling for further model refinements as well as large-scale applications. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Simple, heart-smart substitutions

MedlinePlus

Coronary artery disease - heart smart substitutions; Atherosclerosis - heart smart substitutions; Cholesterol - heart smart substitutions; Coronary heart disease - heart smart substitutions; Healthy diet - heart ...

Calibration and temperature correction of heat dissipation matric potential sensors

USGS Publications Warehouse

Flint, A.L.; Campbell, G.S.; Ellett, K.M.; Calissendorff, C.

2002-01-01

This paper describes how heat dissipation sensors, used to measure soil water matric potential, were analyzed to develop a normalized calibration equation and a temperature correction method. Inference of soil matric potential depends on a correlation between the variable thermal conductance of the sensor's porous ceramic and matric poten-tial. Although this correlation varies among sensors, we demonstrate a normalizing procedure that produces a single calibration relationship. Using sensors from three sources and different calibration methods, the normalized calibration resulted in a mean absolute error of 23% over a matric potential range of -0.01 to -35 MPa. Because the thermal conductivity of variably saturated porous media is temperature dependent, a temperature correction is required for application of heat dissipation sensors in field soils. A temperature correction procedure is outlined that reduces temperature dependent errors by 10 times, which reduces the matric potential measurement errors by more than 30%. The temperature dependence is well described by a thermal conductivity model that allows for the correction of measurements at any temperature to measurements at the calibration temperature.

In Situ Evaluation of Calcium Phosphate Nucleation Kinetics and Pathways during Intra- and Extrafibrillar Mineralization of Collagen Matrices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Doyoon; Lee, Byeongdu; Thomopoulos, Stavros

Calcium phosphate (CaP) nanocrystals nucleate and grow in intrafibrillar and/or extrafibrillar spaces of collagen fibrils during the mineralization of bones and teeth. Little is known about the early stages of CaP nucleation and distribution in fibrillar matrices, despite their significant influence on the physical and chemical structures of tissue-level constructs. Using in situ small angle X-ray scattering (SAXS), we examined the nucleation and growth of CaP within collagen matrices and elucidated how a nucleation inhibitor, polyaspartic acid (pAsp), governs mineralization kinetics and pathways at multiple length scales. In situ SAXS analysis clearly revealed that nucleation sites, kinetically-controlled by the nucleationmore » inhibitor, determined the pathways of CaP morphological transformation. Mineralization with pAsp led to intrafibrillar CaP plates with a spatial distribution gradient through the depth of the matrix. Mineralization without pAsp led initially to spherical aggregates of CaP in the entire extrafibrillar spaces. With time, the spherical aggregates transformed into plates at the outermost surface of the collagen matrix, preventing intrafibrillar mineralization inside. The results illuminate mineral nucleation kinetics and real-time nanoparticle distributions within organic matrices in solutions containing body fluid components. Because the macroscale mechanical properties of collagen matrices depend on their mineral content, phase, and arrangement at the nanoscale, this study contributes to better design and fabrication of biomaterials for regenerative medicine.« less

Reflectionless CMV Matrices and Scattering Theory

NASA Astrophysics Data System (ADS)

Chu, Sherry; Landon, Benjamin; Panangaden, Jane

2015-04-01

Reflectionless CMV matrices are studied using scattering theory. By changing a single Verblunsky coefficient, a full-line CMV matrix can be decoupled and written as the sum of two half-line operators. Explicit formulas for the scattering matrix associated to the coupled and decoupled operators are derived. In particular, it is shown that a CMV matrix is reflectionless iff the scattering matrix is off-diagonal which in turn provides a short proof of an important result of Breuer et al. (Commun Math Phys 295:531-550, 2010). These developments parallel those recently obtained for Jacobi matrices Jakšić et al. (Commun Math Phys 827-838, 2014).

Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench.

PubMed

Talk, Ruaa A; Duperray, Alexia; Li, Xiabing; Coldham, Iain

2016-06-07

Substituted N-tert-butoxycarbonyl (Boc)-1,2,3,4-tetrahydroisoquinolines were prepared and treated with n-butyllithium in THF at -50 °C to test the scope of the metallation and electrophilic quench. The lithiation was optimised by using in situ ReactIR spectroscopy and the rate of rotation of the carbamate was determined. The 1-lithiated intermediates could be trapped with a variety of electrophiles to give good yields of 1-substituted tetrahydroisoquinoline products. Treatment with acid or reduction with LiAlH4 allows conversion to the N-H or N-Me compound. The chemistry was applied to the efficient total syntheses of the alkaloids (±)-crispine A and (±)-dysoxyline.

Molecular cloning and expression of the hyu genes from Microbacterium liquefaciens AJ 3912, responsible for the conversion of 5-substituted hydantoins to alpha-amino acids, in Escherichia coli.

PubMed

Suzuki, Shun'ichi; Takenaka, Yasuhiro; Onishi, Norimasa; Yokozeki, Kenzo

2005-08-01

A DNA fragment from Microbacterium liquefaciens AJ 3912, containing the genes responsible for the conversion of 5-substituted-hydantoins to alpha-amino acids, was cloned in Escherichia coli and sequenced. Seven open reading frames (hyuP, hyuA, hyuH, hyuC, ORF1, ORF2, and ORF3) were identified on the 7.5 kb fragment. The deduced amino acid sequence encoded by the hyuA gene included the N-terminal amino acid sequence of the hydantoin racemase from M. liquefaciens AJ 3912. The hyuA, hyuH, and hyuC genes were heterologously expressed in E. coli; their presence corresponded with the detection of hydantoin racemase, hydantoinase, and N-carbamoyl alpha-amino acid amido hydrolase enzymatic activities respectively. The deduced amino acid sequences of hyuP were similar to those of the allantoin (5-ureido-hydantoin) permease from Saccharomyces cerevisiae, suggesting that hyuP protein might function as a hydantoin transporter.

Presence and partitioning behavior of polyfluorinated iodine alkanes in environmental matrices around a fluorochemical manufacturing plant: another possible source for perfluorinated carboxylic acids?

PubMed

Ruan, Ting; Wang, Yawei; Wang, Thanh; Zhang, Qinghua; Ding, Lei; Liu, Jiyan; Wang, Chang; Qu, Guangbo; Jiang, Guibin

2010-08-01

The indistinct origins of some ubiquitous perfluorinated alkyl acids have attracted great attention in recent decades. In this present work, even-chained polyfluorinated iodides (PFIs), a group of volatile perfluorinated compounds (PFCs), including four perfluorinated iodine alkanes (FIAs) and three polyfluorinated telomer iodides (FTIs) were confirmed to be present in the environment. A wide concentration range was found for FIAs at 1.41 to 3.08x10(4) pg/L, and for FTIs at 1.39 to 1.32x10(3) pg/L in the ambient air collected around a fluorochemical manufacturing plant in Shandong province, northern China. Whereas for surface soils, most of these PFIs were below detection limits and only small amounts of analytes with higher carbon chain (such as perfluorododecyl iodide and 1H,1H,2H,2H-perfluorodecyl iodide, 16.6-499 pg/g) could be sporadically detected. The presence of the PFIs in different environmental matrices in the investigated area and calculated vapor pressures (0.095-20.4 Torr) verify that they can be considered as volatile organic chemicals and easily be released into the atmosphere. Together with reported degradation ability and long-range transport potential, the identification of these PFIs indicates that unintentional release during the telomer reaction process might also be another route for the formation and distribution of certain polyfluorinated alcohols, aldehydes, and carboxylic acid derivatives under oxidative conditions in the environment.

The Approximation of Two-Mode Proximity Matrices by Sums of Order-Constrained Matrices.

ERIC Educational Resources Information Center

Hubert, Lawrence; Arabie, Phipps

1995-01-01

A least-squares strategy is proposed for representing a two-mode proximity matrix as an approximate sum of a small number of matrices that satisfy certain simple order constraints on their entries. The primary class of constraints considered defines Q-forms for particular conditions in a two-mode matrix. (SLD)

Active-Site Residues of Escherichia coli DNA Gyrase Required in Coupling ATP Hydrolysis to DNA Supercoiling and Amino Acid Substitutions Leading to Novobiocin Resistance

PubMed Central

Gross, Christian H.; Parsons, Jonathan D.; Grossman, Trudy H.; Charifson, Paul S.; Bellon, Steven; Jernee, James; Dwyer, Maureen; Chambers, Stephen P.; Markland, William; Botfield, Martyn; Raybuck, Scott A.

2003-01-01

DNA gyrase is a bacterial type II topoisomerase which couples the free energy of ATP hydrolysis to the introduction of negative supercoils into DNA. Amino acids in proximity to bound nonhydrolyzable ATP analog (AMP · PNP) or novobiocin in the gyrase B (GyrB) subunit crystal structures were examined for their roles in enzyme function and novobiocin resistance by site-directed mutagenesis. Purified Escherichia coli GyrB mutant proteins were complexed with the gyrase A subunit to form the functional A2B2 gyrase enzyme. Mutant proteins with alanine substitutions at residues E42, N46, E50, D73, R76, G77, and I78 had reduced or no detectable ATPase activity, indicating a role for these residues in ATP hydrolysis. Interestingly, GyrB proteins with P79A and K103A substitutions retained significant levels of ATPase activity yet demonstrated no DNA supercoiling activity, even with 40-fold more enzyme than the wild-type enzyme, suggesting that these amino acid side chains have a role in the coupling of the two activities. All enzymes relaxed supercoiled DNA to the same extent as the wild-type enzyme did, implying that only ATP-dependent reactions were affected. Mutant genes were examined in vivo for their abilities to complement a temperature-sensitive E. coli gyrB mutant, and the activities correlated well with the in vitro activities. We show that the known R136 novobiocin resistance mutations bestow a significant loss of inhibitor potency in the ATPase assay. Four new residues (D73, G77, I78, and T165) that, when changed to the appropriate amino acid, result in both significant levels of novobiocin resistance and maintain in vivo function were identified in E. coli. PMID:12604539

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

NASA Astrophysics Data System (ADS)

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.

The Quality Improvement of Emulsion-type Pork Sausages Formulated by Substituting Pork Back fat with Rice Bran Oil

PubMed Central

Yum, Hyeon-Woong; Seo, Jin-Kyu; Jeong, Jin-Yeon; Kim, Gap-Don; Rahman, M. Shafiur; Yang, Han-Sul

2018-01-01

The effects of pork back fat (PBF) substitution with various concentrations of rice bran oil (RBO) (50%, 45%, 40% and 35%) on the physicochemical characteristics and sensory attributes of emulsion-type pork sausages were studied. The modified pork sausages were compared with control sausages produced using PBF only. The sausages with RBO had significantly lower (p<0.05) moisture content than the control sausages. Sausages made from PBF substituted with 40% RBO showed the lowest cooking loss. Substitution of PBF with RBO had no significant effect on the emulsion stability of pork sausages. All sausages with RBO showed significantly lower (p<0.05) hardness values than control sausages. Sausages with RBO also had significantly higher values (p<0.05) of unsaturated fatty acid and polyunsaturated to saturated fatty acid contents than the controls. RBO substitution had no effect on the flavor intensity of sausages, but it improved the tenderness and produced a softer texture. PMID:29725230