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Sample records for constrained acidic alpha-amino

  1. An NMR and ab initio quantum chemical study of acid-base equilibria for conformationally constrained acidic alpha-amino acids in aqueous solution.

    PubMed

    Nielsen, P A; Jaroszewski, J W; Norrby, P O; Liljefors, T

    2001-03-07

    The protonation states of a series of piperidinedicarboxylic acids (PDAs), which are conformationally constrained acidic alpha-amino acids, have been studied by (13)C NMR titration in water. The resulting data have been correlated with theoretical results obtained by HF/6-31+G calculations using the polarizable continuum model (PCM) for the description of water. The PDAs are highly ionizable and contain one or two possible internal hydrogen bonds. In the present study, we show that the PCM model is able to reproduce the relative stabilities of the different protonation states of the PDAs. Furthermore, our results show that prediction of relative pK(a) values for two different types of ionizable functional groups covering a pK(a) range from 1.6 to 12.1 is possible with a high degree of accuracy.

  2. Synthesis of alpha-amino acids

    DOEpatents

    Davis, Jr., Jefferson W.

    1983-01-01

    A method for synthesizing alpha amino acids proceeding through novel intermediates of the formulas: R.sub.1 R.sub.2 C(OSOCl)CN, R.sub.1 R.sub.2 C(Cl)CN and [R.sub.1 R.sub.2 C(CN)O].sub.2 SO wherein R.sub.1 and R.sub.2 are each selected from hydrogen monovalent substituted and unsubstituted hydrocarbon radicals of 1 to 12 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the synthesis methods of the prior art.

  3. Synthesis of alpha-amino acids

    DOEpatents

    Davis, Jr., Jefferson W.

    1983-01-01

    A method for synthesizing alpha amino acids proceding through novel intermediates of the formulas: R.sub.1 R.sub.2 C(OSOCl)CN, R.sub.1 R.sub.2 C(Cl)CN and [R.sub.1 R.sub.2 C(CN)O].sub.2 SO wherein R.sub.1 and R.sub.2 are each selected from hydrogen monovalent substituted and unsubstituted hydrocarbon radicals of 1 to 10 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the snythesis methods of the prior art.

  4. Synthesis of alpha-amino acids

    DOEpatents

    Davis, Jr., Jefferson W.

    1983-01-01

    A method for synthesizing alpha amino acids proceding through novel intermediates of the formulas: R.sub.1 R.sub.2 C(OSOCl)CN, R.sub.1 R.sub.2 C(Cl)CN and [R.sub.1 R.sub.2 C(CN)O].sub.2 SO wherein R.sub.1 and R.sub.2 are each selected from hydrogen monovalent substituted and unsubstituted hydrocarbon radicals of 1 to 12 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the synthesis methods of the prior art.

  5. Synthesis of alpha-amino acids

    DOEpatents

    Davis, J.W. Jr.

    1983-01-25

    A method is described for synthesizing alpha amino acids proceeding through novel intermediates of the formulas: R[sub 1]R[sub 2]C(OSOCl)CN, R[sub 1]R[sub 2]C(Cl)CN and [R[sub 1]R[sub 2]C(CN)O][sub 2]SO wherein R[sub 1] and R[sub 2] are each selected from hydrogen monovalent substituted and unsubstituted hydrocarbon radicals of 1 to 10 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the synthesis methods of the prior art. No Drawings

  6. How to build optically active alpha-amino acids.

    PubMed

    Calmes, M; Daunis, J

    1999-01-01

    Various methodologies published in the literature dealing with alpha-amino carboxylic acid asymmetric synthesis are presented in a digest form. In each case, only some recent or most typical works are mentioned.

  7. An efficient preparation of N-methyl-alpha-amino acids from N-nosyl-alpha-amino acid phenacyl esters.

    PubMed

    Leggio, Antonella; Belsito, Emilia Lucia; De Marco, Rosaria; Liguori, Angelo; Perri, Francesca; Viscomi, Maria Caterina

    2010-03-05

    In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-N-nosyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-alpha-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.

  8. ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)

    PubMed Central

    Pinchuck, Paul; Maurer, Paul H.

    1965-01-01

    The response of mice to synthetic linear polypeptides of known composition but random sequence has been studied. Neither Swiss mice nor a number of inbred strains could respond to copolymers of only 2 amino acids (G60L40, G60A40, G90T10). Upon introduction of as little as 4 mole per cent of a third amino acid, good immune responses were obtained, regardless of the nature of the third amino acid. The level of the immune response to a series of glu-lys-ala polymers increased with increasing alanine content of the polymer. PMID:5849232

  9. ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)

    PubMed Central

    Maurer, Paul H.; Gerulat, Bernard F.; Pinchuck, Paul

    1964-01-01

    A new group of synthetic random polymers of α-L-amino acids has been studied for immunogenicity. With the glutamic acid and alanine copolymers, those consisting of almost equimolar amounts of the two (G60A40 and G40A60) were effective antigens in rabbits whereas those with higher glutamic acid contents (G75A25, G90A10) were poor antigens. The substitution of alanine by valine or leucine (G75V25 and G80Leu20) produced copolymers which were poor antigens in rabbits but effective in guinea pigs. L70A30, although capable of "non-specifically" precipitating serum proteins, was shown not to be antigenic in either rabbits or guinea pigs. The introduction of alanine into glutamic acid and lysine polymers (GLA series) enhanced the immunogenicity of the terpolymers, i.e., GLA30 > GLA20 > GLA10 > GL. The mechanism by which this may be accomplished is discussed as possibly being related to the reduction of the interactions between glutamyl and lysyl residues which allows the carboxyl groups to act as strong immunogenic determinants. PMID:14176288

  10. Soluble polymer supported synthesis of alpha-amino acid derivatives.

    PubMed

    Sauvagnat, B; Kulig, K; Lamaty, F; Lazaro, R; Martinez, J

    2000-01-01

    A Schiff base activated glycine supported on a soluble polymer (poly(ethylene glycol) (PEG)) was readily alkylated with a wide variety of electrophiles in the presence of a carbonate base in acetonitrile. The presence of the polymer provided a phase-transfer catalysis environment which accelerated the reaction. Effects of various carbonate bases and leaving groups have been also studied. Completion of the PEG-supported reaction was obtained without using a large excess of reagents or an extra phase-transfer catalyst, even in the case of unreactive or hindered electrophiles. After cleavage from the polymer, alpha-amino esters are obtained in good yields.

  11. N-carbamoyl-alpha-amino acids rather than free alpha-amino acids formation in the primitive hydrosphere: a novel proposal for the emergence of prebiotic peptides.

    PubMed

    Taillades, J; Beuzelin, I; Garrel, L; Tabacik, V; Bied, C; Commeyras, A

    1998-02-01

    Our previous kinetic and thermodynamic studies upon the reactional system HCHO/HCN/NH3 in aqueous solutions are completed. In the assumed prebiotic conditions of the primitive earth ([HCHO] and [HCN] near 1 g L-1, T = 25 degrees C, pH = 8, [NH3] very low), this system leads to 99.9% of alpha-hydroxyacetonitrile and 0.1% of alpha-aminoacetonitrile (precursor of the alpha-amino acid). The classical base-catalyzed hydration of nitriles, slow and not selective, can not modify significantly this proportion. On the contrary, we found two specific and efficient reactions of alpha-aminonitriles which shift the initial equilibrium in favor of the alpha-aminonitrile pathway. The first reaction catalyzed by formaldehyde generates alpha-aminoamides, precursors of alpha-aminoacids. The second reaction catalyzed by carbon dioxide affords hydantoins, precursors of N-carbamoyl-alpha-aminoacids. In the primitive hydrosphere, where the concentration in carbon dioxide was estimated to be higher than that of formaldehyde, the formation of hydantoins was consequently more efficient. The rates of hydrolysis of the alpha-aminoacetamide and of the hydantoin at pH 8 being very similar, the synthesis of the N-carbamoyl-alpha-amino acid seems then to be the fatal issue of the HCHO/HCN/NH3 system that nature used to perform its evolution. These N-protected alpha-amino acids offer new perspectives in prebiotic chemistry, in particular for the emergence of peptides on the prebiotic earth.

  12. An Ireland-Claisen approach to beta-alkoxy alpha-amino acids.

    PubMed

    Tellam, James P; Kociok-Köhn, Gabriele; Carbery, David R

    2008-11-20

    A diastereoselective Ireland-Claisen approach to beta-alkoxy alpha-amino acid esters is reported. Amino acid esters of enol ethereal allylic alcohols undergo facile syn-selective [3,3]-sigmatropic rearrangement via silyl ketene acetals. Substrate synthesis, rearrangement development, stereoselectivity, and product elaboration are discussed.

  13. Using enantioselective indicator displacement assays to determine the enantiomeric excess of alpha-amino acids.

    PubMed

    Leung, Diana; Folmer-Andersen, J Frantz; Lynch, Vincent M; Anslyn, Eric V

    2008-09-17

    Enantioselective indicator displacement assays (eIDAs) were used for the determination of enantiomeric excess (ee) of alpha-amino acids as an alternative to the labor-intensive technique of chromatography. In this study, eIDAs were implemented by the use of two chiral receptors [(Cu(II)(1)](2+), [Cu(II)(2)](2+)) in conjunction with the indicator chrome azurol S. The two receptors were able to enantioselectively discriminate 13 of the 17 analyzed alpha-amino acids. Enantiomeric excess calibration curves were made using both receptors and then used to analyze true test samples to check the system's ability to determine ee accurately. The proposed method uses a conventional UV-vis spectrophotometer to monitor the colorimetric signal, which allows for a potential high-throughput screening (HTS) method for determining ee. The techniques created consistently produced results accurate enough for rapid preliminary determination of ee.

  14. An easy entry to optically active alpha-amino phosphonic acid derivatives using phase-transfer catalysis (PTC).

    PubMed

    Fini, Francesco; Micheletti, Gabriele; Bernardi, Luca; Pettersen, Daniel; Fochi, Mariafrancesca; Ricci, Alfredo

    2008-09-28

    The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric hydrophosphonylation reaction allows the obtainment of a range of optically active alpha-amino phosphonic acid derivatives directly from alpha-amido sulfones.

  15. Amino acids of the Murchison meteorite. III - Seven carbon acyclic primary alpha-amino alkanoic acids

    NASA Technical Reports Server (NTRS)

    Cronin, John R.; Pizzarello, Sandra

    1986-01-01

    All of the eighteen possible seven-carbon acyclic primary alpha-amino alkanoic acids have been positively identified in a hot-water extract of the Murchison meteorite by the combined use of gas chromatography-mass spectrometry, ion exchange chromatography and reversed-phase chromatography. None of these amino acids has previously been found in meteorites or in any other natural material. They range in concentration from less than or equal to 0.5 to 5.3 nmol/g. Configuration assignments were made for 2-amino-3,4-dimethylpentanoic acid and allo-2-amino-3,4-dimethylpentanoic acid and the diasteromer ratio was determined. Fifty-five amino acids have now been positively identified in the Murchison meteorite, 36 of which are unknown in terrestrial materials. This unique suite of amino acids is characterized by the occurrence of all structural isomers within the two major classes of amino acids represented, by the predominance of branched chain isomers, and by an exponential decline in amount with increasing carbon chain length within homologous series. These characteristics of the Murchison amino acids are suggestive of synthesis before incorporation into a parent body.

  16. Synthesis and transformations of a pyrazole containing alpha, beta-didehydro-alpha-amino acid derivatives.

    PubMed

    Vranicar, L; Pozgan, F; Polanc, S; Kocevar, M

    2003-04-01

    2H-Pyran-2-ones 1 were transformed with various hydrazines into (E)- or (Z)-alpha, beta-didehydro-alpha-amino acid (DDAA) derivatives 4 (and 7) containing a highly substituted pyrazolyl moiety attached at the beta-position. With heterocyclic hydrazines, the products 4 were accompanied also by decarboxylated enamines E-6. In order to separate (E/Z)-mixtures of acids, they were transformed to the corresponding methyl esters 9 and 10 by the application of diazomethane. Catalytic hydrogenation under high pressures with Pd/C as a catalyst resulted in the formation of racemic alanine derivatives 11.

  17. Amino acids of the Murchison meteorite. I - Six carbon acyclic primary alpha-amino alkanoic acids

    NASA Technical Reports Server (NTRS)

    Cronin, J. R.; Gandy, W. E.; Pizzarello, S.

    1981-01-01

    Six of the seven chain isomers of six-carbon acyclic primary alpha-amino alkanoic acids (leucine isomers) have been either identified or confirmed in hot-water extracts of the Murchison meteorite using combined gas chromatography-mass spectrometry (GC-MS) and ion exchange chromatography. 2-Amino-2-ethylbutyric acid, 2-amino-2,3-dimethylbutyric acid, pseudoleucine, and 2-methylnorvaline were positively identified by GC-MS. These amino acids have not been previously reported to occur in natural materials and may be uniquely meteoritic in origin. The presence of leucine and isoleucine (including the diastereoisomer, alloisoleucine) was confirmed. Peaks corresponding to norleucine were seen by ion-exchange and gas chromatography but characteristic mass spectra were not obtained. The alpha-branched chain isomers in this series are quantitatively the most significant. These results are compared with literature data on amino acid synthesis by electrical discharge and Fischer-Tropsch-type catalysis. Neither model system produces an amino acid suite that is completely comparable to that found in the Murchison meteorite.

  18. Molecular Basis of Prodrug Activation by Human Valacyclovirase, an [alpha]-Amino Acid Ester Hydrolase

    SciTech Connect

    Lai, Longsheng; Xu, Zhaohui; Zhou, Jiahai; Lee, Kyung-Dall; Amidon, Gordon L.

    2008-07-08

    Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of {alpha}-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F1. Crystal structures of the enzyme, two mechanistic mutants, and a complex with a product analogue, when combined with biochemical analysis, reveal the key determinants for substrate recognition; that is, a flexible and mostly hydrophobic acyl pocket, a localized negative electrostatic potential, a large open leaving group-accommodating groove, and a pivotal acidic residue, Asp-123, after the nucleophile Ser-122. This is the first time that a residue immediately after the nucleophile has been found to have its side chain directed into the substrate binding pocket and play an essential role in substrate discrimination in serine hydrolases. These results as well as a phylogenetic analysis establish that the enzyme functions as a specific {alpha}-amino acid ester hydrolase. Valacyclovirase is a valuable target for amino acid ester prodrug-based oral drug delivery enhancement strategies.

  19. Kinetics and mechanisms of activation of alpha-amino acid ester prodrugs of camptothecins.

    PubMed

    Song, Lin; Bevins, Robert; Anderson, Bradley D

    2006-07-13

    The alpha-amino acid ester prodrugs of the antitumor agent camptothecin and a more potent, lipophilic silatecan analogue, DB-67, have been shown by NMR spectroscopy and quantitative kinetic analyses to undergo quantitative conversion to their pharmacologically active lactones via a nonenzymatic mechanism that at pH 7.4 is favored over direct hydrolysis. The alternate pathway involves the reversible intramolecular nucleophilic amine attack at the camptothecin E-ring carbonyl to generate a lactam (I) followed by a second intramolecular reaction to produce a bicyclic hemiortho ester (I'). The intermediates were isolated and shown to exist in an apparent equilibrium dominated by the hemiortho ester in DMSO using NMR spectroscopy. The conversion of prodrugs of camptothecin or DB-67 containing either alpha-NH(2) or alpha-NHCH(3) and their corresponding hemiortho esters were monitored versus time in aqueous buffer (pH 3.0 and 7.4) at 37 degrees C, and the kinetic data were fit to a model based on the proposed mechanism. The results indicated that while the prodrugs are relatively stable at pH 3, facile lactone release occurs from both the prodrugs and their corresponding hemiortho ester intermediates under physiological conditions (pH 7.4). The glycinate esters and their hemiortho esters were found to be more cytotoxic than the N-methylglycinates or their corresponding hemiortho ester intermediates in vitro using a human breast cancer cell line (MDA-MB-435S), consistent with their more rapid conversion to active lactone. The pH dependence of the nonenzymatic pathway for conversion of these alpha-amino acid ester prodrugs suggests that they may be useful for tumor-targeting via liposomes, as they can be stabilized in an acidic environment in the core of liposomes and readily convert to the active lactone following their intratumoral release.

  20. Saponification of esters of chiral alpha-amino acids anchored through their amine function on solid support.

    PubMed

    Cantel, Sonia; Desgranges, Stéphane; Martinez, Jean; Fehrentz, Jean-Alain

    2004-06-01

    Anchoring an alpha-amino acid residue by its amine function onto a solid support is an alternative to develop chemistry on its carboxylic function. This strategy can involve the use of amino-acid esters as precursors of the carboxylic function. A complete study on the Wang-resin was performed to determine the non racemizing saponification conditions of anchored alpha-amino esters. The use of LiOH, NaOH, NaOSi(Me)3, various solvents and temperatures were tested for this reaction. After saponification and cleavage from the support, samples were examined through their Marfey's derivatives by reversed phase HPLC to evaluate the percentage of racemization.

  1. Protein design with L- and D-alpha-amino acid structures as the alphabet.

    PubMed

    Durani, Susheel

    2008-10-01

    Summarizing the implications of homochiral structures in interpeptide interactions, not only in the topology but also possibly in the physics of protein folding, this Account provides an overview of the concept of shape-specific protein design using D- and L-(alpha)amino acid structures as the alphabet. The molecular shapes accessible in de novo protein design are stereochemically defined. Indeed, the defining consideration for shape specificity in proteins to be alpha-helix/beta-sheet composites is the L configuration of the alpha-amino acid structures. The stereospecificity in shapes implies that protein shapes may be diversifiable stereochemically, that is, designable de novo, using D and L structures as the alphabet. Indeed, augmented with D enantiomers, Nature's alphabet will expand greatly in the diversity of polypeptide stereoisomers, for example, from 1(30) to 2(30)--that is, from one to ca. one billion--for a modestly sized 30-residue polypeptide. Furthermore, with each isomer having conformers stereospecific to its structure, molecular folds of specific shapes may be approachable sequentially when D and L structures are used as the alphabet. Illustrating the promise, 14-20-residue bracelet-, boat-, canoe-, and cup-shaped molecular folds were designed stereochemically or implemented as specific sequence plans in the D- and L-alpha-amino acid alphabet. In practical terms, canonical poly-L peptide folds were modified to the desired shapes via stereochemical mutations invoking enantiomer symmetries in the Ramachandran phi,psi space as the logic. For example, in designing the boat-shaped fold, the canonical beta-hairpin was reengineered in its flat planar structure via multiple coordinated L-to-D mutations in its position specific cross-strand neighbor residues, upturning its ends enclosing six side chains in a molecular cleft. While affirming the generality of the approach, the 20-residue molecular canoe and the 14-residue molecular cup are also presented as

  2. Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus.

    PubMed

    Cardona-Gómez, Gloria Patricia; Arango-Davila, Cesar; Gallego-Gómez, Juan Carlos; Barrera-Ocampo, Alvaro; Pimienta, Hernan; Garcia-Segura, Luis Miguel

    2006-08-21

    During cerebral ischemia, part of the damage associated with the hyperactivation of glutamate receptors results from the hyperphosphorylation of the microtubule-associated protein Tau. Previous studies have shown that estradiol treatment reduces neural damage after cerebral ischemia. Here, we show that transient occlusion of the middle cerebral artery results in the hyperphosphorylation of Tau and in a significant increase in the association of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and decreased the hyperphosphorylation of Tau and the interaction of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that ischemia produces a strong association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, and estradiol can exert at least part of its neuroprotective activity through inhibition of glycogen synthase kinase-3beta.

  3. Surface active molecules: preparation and properties of long chain n-acyl-l-alpha-amino-omega-guanidine alkyl acid derivatives.

    PubMed

    Infante, R; Dominguez, J G; Erra, P; Julia, R; Prats, M

    1984-12-01

    Synopsis A new route for the synthesis of long chain N(alpha)-acyl-l-alpha-amino-omega-guamdine alkyl acid derivatives, with cationic or amphoteric character has been established. The general formula of these compounds is shown below. A physico-chemical and antimicrobial study of these products as a function of the alkyl ester or sodium salt (R), the straight chain length of the fatty acid residue (x) and the number of carbons between the omega-guanidine and omega-carboxyl group (n) has been investigated. The water solubility, surface tension, critical micelle concentration (c.m.c.) and minimum inhibitory concentration (MIC) against Gram-positive and Gram-negative bacteria (including Pseudomonas) has been determined. Dicyclohexylcarbodiimide has been used to condense fatty acids and alpha-amino-omega-guanidine alkyl acids. In these conditions protection of the omega-guanidine group is not necessary. The main characteristic of this synthetic procedure is the use of very mild experimental conditions (temperature, pH) to form the amide linkage which leads to pure optical compounds in high yield in the absence of electrolytes. The results show that some structural modifications, particularly the protection of the carboxyl group, promote variations of the surfactant and antimicrobial properties. Only those molecules with the blocked carboxyl group (cationic molecules, where R = Me, Et or Pr) showed a good surfactant and antimicrobial activity. When the carboxyl group was unprotected (amphoteric molecules, where R = Na(+)) the resulting compounds were inactive.

  4. Enantioseparation of N-fluorenylmethoxycarbonyl alpha-amino acids on polysaccharide-derived chiral stationary phases by reverse mode liquid chromatography.

    PubMed

    Lee, Kyung-Ah; Yeo, Sujeong; Kim, Kyeong Ho; Lee, Wonjae; Kang, Jong Seong

    2008-04-14

    The enantioseparation of N-protected fluorenylmethoxycarbonyl (N-FMOC) alpha-amino acids was carried out on three polysaccharide-derived chiral stationary phases, such as cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD), amylose tris(3,5-dimethyl-phenylcarbamate) (Chiralpak AD) and cellulose tris(4-methylbenzoate) (Chiralcel OJ), and the influence of acetonitrile composition and pH of the eluents on the enantioseparation in reverse mode chromatography was examined. The best separation of the enantiomers was achieved with 40% acetonitrile in 50mM phosphate buffer at pH 2. However, increasing the composition of acetonitrile to 50% on Chiralcel OD yielded a considerable decrease of retention time with minimum loss of resolution. The elution order of N-FMOC alpha-amino acid enantiomers on Chiralcel OD and OJ were quite different, indicating that both phases could be used in a complementary manner for the separation of the enantiomers of N-FMOC alpha-amino acids. The positive relationship between the capacity factor of N-FMOC alpha-amino acids and the hydrophobicity of amino acids indicated that hydrophobicity plays an important role on the retention of the N-FMOC alpha-amino acids in the reverse mode.

  5. alpha-Hydroxy and alpha-amino acids under possible Hadean, volcanic origin-of-life conditions.

    PubMed

    Huber, Claudia; Wächtershäuser, Günter

    2006-10-27

    To test the theory of a chemoautotrophic origin of life in a volcanic, hydrothermal setting, we explored mechanisms for the buildup of bio-organic compounds by carbon fixation on catalytic transition metal precipitates. We report the carbon monoxide-dependent formation of carbon-fixation products, including an ordered series of alpha-hydroxy and alpha-amino acids of the general formula R-CHA-COOH (where R is H, CH3,C2H5,orHOCH2 and A is OH or NH2) by carbon fixation at 80 degrees to 120 degrees C, catalyzed by nickel or nickel,iron precipitates with carbonyl, cyano, and methylthio ligands as carbon sources, with or without sulfido ligands. Calcium or magnesium hydroxide was added as a pH buffer. The results narrow the gap between biochemistry and volcanic geochemistry and open a new gateway for the exploration of a volcanic, hydrothermal origin of life.

  6. PfEMP1-DBL1alpha amino acid motifs in severe disease states of Plasmodium falciparum malaria.

    PubMed

    Normark, Johan; Nilsson, Daniel; Ribacke, Ulf; Winter, Gerhard; Moll, Kirsten; Wheelock, Craig E; Bayarugaba, Justus; Kironde, Fred; Egwang, Thomas G; Chen, Qijun; Andersson, Björn; Wahlgren, Mats

    2007-10-02

    An infection with Plasmodium falciparum may lead to severe malaria as a result of excessive binding of infected erythrocytes in the microvasculature. Vascular adhesion is mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP1), which is encoded for by highly polymorphic members of the var-gene family. Here, we profile var gene transcription in fresh P. falciparum trophozoites from Ugandan children with malaria through var-specific DBL1alpha-PCR amplification and sequencing. A method for subsectioning region alignments into homology areas (MOTIFF) was developed to examine collected sequences. Specific PfEMP1-DBL1alpha amino acid motifs correlated with rosetting and severe malaria, with motif location corresponding to distinct regions of receptor interaction. The method is potentially applicable to other families of variant proteins and may be useful in identifying sequence-phenotype relationships. The results suggest that certain PfEMP1 sequences are predisposed to inducing severe malaria.

  7. Efficient synthesis of 1-azadienes derived from alpha-aminoesters. Regioselective preparation of alpha-dehydroamino acids, vinylglycines, and alpha-amino acids.

    PubMed

    Palacios, Francisco; Vicario, Javier; Aparicio, Domitila

    2006-09-29

    An efficient synthesis of 1-azadienes derived from alpha-aminoesters is achieved through an aza-Wittig reaction of phosphazenes with beta,gamma-unsaturated alpha-ketoesters. Regioselective 1,2-reduction of these functionalized 1-azadienes affords vinylglycine derivatives, while conjugative 1,4-reduction gives alpha-dehydroamino acid compounds. Reduction of both the carbon-carbon and the imine-carbon-nitrogen double bonds leads to the formation of alpha-amino acid derivatives.

  8. Cloning, sequence analysis, and expression in Escherichia coli of the gene encoding an alpha-amino acid ester hydrolase from Acetobacter turbidans.

    PubMed

    Polderman-Tijmes, Jolanda J; Jekel, Peter A; de Vries, Erik J; van Merode, Annet E J; Floris, René; van der Laan, Jan-Metske; Sonke, Theo; Janssen, Dick B

    2002-01-01

    The alpha-amino acid ester hydrolase from Acetobacter turbidans ATCC 9325 is capable of hydrolyzing and synthesizing beta-lactam antibiotics, such as cephalexin and ampicillin. N-terminal amino acid sequencing of the purified alpha-amino acid ester hydrolase allowed cloning and genetic characterization of the corresponding gene from an A. turbidans genomic library. The gene, designated aehA, encodes a polypeptide with a molecular weight of 72,000. Comparison of the determined N-terminal sequence and the deduced amino acid sequence indicated the presence of an N-terminal leader sequence of 40 amino acids. The aehA gene was subcloned in the pET9 expression plasmid and expressed in Escherichia coli. The recombinant protein was purified and found to be dimeric with subunits of 70 kDa. A sequence similarity search revealed 26% identity with a glutaryl 7-ACA acylase precursor from Bacillus laterosporus, but no homology was found with other known penicillin or cephalosporin acylases. There was some similarity to serine proteases, including the conservation of the active site motif, GXSYXG. Together with database searches, this suggested that the alpha-amino acid ester hydrolase is a beta-lactam antibiotic acylase that belongs to a class of hydrolases that is different from the Ntn hydrolase superfamily to which the well-characterized penicillin acylase from E. coli belongs. The alpha-amino acid ester hydrolase of A. turbidans represents a subclass of this new class of beta-lactam antibiotic acylases.

  9. Partial molar volumes of some alpha-amino acids in aqueous sodium acetate solutions at 308.15 K.

    PubMed

    Wang, J; Yan, Z; Zhuo, K; Lu, J

    1999-08-30

    The apparent molar volumes V(2,phi) have been determined for glycine, DL-alpha-alanine, DL-alpha-amino-n-butyric acid, DL-valine and DL-leucine in aqueous solutions of 0.5, 1.0, 1.5 and 2.0 mol kg(-1) sodium acetate by density measurements at 308.15 K. These data have been used to derive the infinite dilution apparent molar volumes V(0)(2,phi) for the amino acids in aqueous sodium acetate solutions and the standard volumes of transfer, Delta(t)V(0), of the amino acids from water to aqueous sodium acetate solutions. It has been observed that both V(0)(2,phi) and Delta(t)V(0) vary linearly with increasing number of carbon atoms in the alkyl chain of the amino acids. These linear correlations have been utilized to estimate the contributions of the charged end groups (NH(3)(+), COO(-)), CH(2) group and other alkyl chains of the amino acids to V(0)(2,phi) and Delta(t)V(0). The results show that V(0)(2,phi) values for (NH(3)(+), COO(-)) groups increase with sodium acetate concentration, and those for CH(2) are almost constant over the studied sodium acetate concentration range. The transfer volume increases and the hydration number of the amino acids decreases with increasing electrolyte concentrations. These facts indicate that strong interactions occur between the ions of sodium acetate and the charged centers of the amino acids. The volumetric interaction parameters of the amino acids with sodium acetate were calculated in water. The pair interaction parameters are found to be positive and decreased with increasing alkyl chain length of the amino acids, suggesting that sodium acetate has a stronger dehydration effect on amino acids which have longer hydrophobic alkyl chains. These phenomena are discussed by means of the co-sphere overlap model.

  10. Enantiomerically pure trans-beta-lactams from alpha-amino acids via compact fluorescent light (CFL) continuous-flow photolysis.

    PubMed

    Vaske, Yvette S Mimieux; Mahoney, Maximillian E; Konopelski, Joseph P; Rogow, David L; McDonald, William J

    2010-08-18

    Photolysis of alpha-diazo-N-methoxy-N-methyl (Weinreb) beta-ketoamides derived from enantiomerically pure (EP) alpha-amino acids affords the corresponding EP beta-lactams via an intramolecular Wolff rearrangement. The photochemistry is promoted with either standard UV irradiation or through the use of a 100 W compact fluorescent light; the latter affords a safe and environmentally friendly alternative to standard photolysis conditions. A continuous-flow photochemical reactor made from inexpensive laboratory equipment reduced reaction times and was amenable to scale-up. The diastereoselectivity (cis or trans) of the product beta-lactams has been shown to vary from modest to nearly complete. An extremely facile, atom-economical method for the epimerization of the product mixture to the trans isomer, which is generally highly crystalline, has been developed. Evidence for C3 epimerization of Weinreb amide structures via a nonbasic, purely thermal route is presented. Subsequent transformations of both the Weinreb amide at C3 (beta-lactam numbering) and the amino acid side chain at C4 are well-tolerated, allowing for a versatile approach to diverse beta-lactam structures. The technology is showcased in the synthesis of a common intermediate used toward several carbapenem-derived structures starting from unfunctionalized aspartic acid.

  11. Use of Sm(III)-{1,2-propanediamine-N,N,N',N'-tetra(alpha,alpha-dideuterioacetate)} complex for NMR determination of absolute configuration of each alpha-amino acid in peptide hydrolysate mixtures.

    PubMed

    Omata, Kenji; Fujioka, Mika; Kabuto, Kuninobu; Sasaki, Yoichi

    2008-10-28

    (1)H NMR analyses of individual alpha-amino acids in their mixture were simultaneously conducted in the presence of Sm-(pdta-d(8)) in water: high regularity, promising for direct simultaneous determination of absolute configurations of each alpha-amino acids in peptide hydrolysate mixtures, was observed between absolute configuration and the induced shifts.

  12. Polymerization on the rocks: negatively-charged alpha-amino acids

    NASA Technical Reports Server (NTRS)

    Hill, A. R. Jr; Bohler, C.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1998-01-01

    Oligomers of the negatively-charged amino acids, glutamic acid, aspartic acid, and O-phospho-L-serine are adsorbed by hydroxylapatite and illite with affinities that increase with oligomer length. In the case of oligo-glutamic acids adsorbed on hydroxylapatite, addition of an extra residue results in an approximately four-fold increase in the strength of adsorption. Oligomers much longer than the 7-mer are retained tenaciously by the mineral. Repeated incubation of short oligo-glutamic acids adsorbed on hydroxylapatite or illite with activated monomer leads to the accumulation of oligomers at least 45 units long. The corresponding reactions of aspartic acid and O-phospho-L-serine on hydroxylapatite are less effective in generating long oligomers, while illite fails to accumulate substantial amounts of long oligomers of aspartic acid or of O-phospho-L-serine.

  13. Polymerization on the rocks: negatively-charged alpha-amino acids.

    PubMed

    Hill, A R; Böhler, C; Orgel, L E

    1998-06-01

    Oligomers of the negatively-charged amino acids, glutamic acid, aspartic acid, and O-phospho-L-serine are adsorbed by hydroxylapatite and illite with affinities that increase with oligomer length. In the case of oligo-glutamic acids adsorbed on hydroxylapatite, addition of an extra residue results in an approximately four-fold increase in the strength of adsorption. Oligomers much longer than the 7-mer are retained tenaciously by the mineral. Repeated incubation of short oligo-glutamic acids adsorbed on hydroxylapatite or illite with activated monomer leads to the accumulation of oligomers at least 45 units long. The corresponding reactions of aspartic acid and O-phospho-L-serine on hydroxylapatite are less effective in generating long oligomers, while illite fails to accumulate substantial amounts of long oligomers of aspartic acid or of O-phospho-L-serine.

  14. Polymerization on the rocks: negatively-charged alpha-amino acids

    NASA Technical Reports Server (NTRS)

    Hill, A. R. Jr; Bohler, C.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1998-01-01

    Oligomers of the negatively-charged amino acids, glutamic acid, aspartic acid, and O-phospho-L-serine are adsorbed by hydroxylapatite and illite with affinities that increase with oligomer length. In the case of oligo-glutamic acids adsorbed on hydroxylapatite, addition of an extra residue results in an approximately four-fold increase in the strength of adsorption. Oligomers much longer than the 7-mer are retained tenaciously by the mineral. Repeated incubation of short oligo-glutamic acids adsorbed on hydroxylapatite or illite with activated monomer leads to the accumulation of oligomers at least 45 units long. The corresponding reactions of aspartic acid and O-phospho-L-serine on hydroxylapatite are less effective in generating long oligomers, while illite fails to accumulate substantial amounts of long oligomers of aspartic acid or of O-phospho-L-serine.

  15. One pot, rapid and efficient synthesis of water dispersible gold nanoparticles using alpha-amino acids

    NASA Astrophysics Data System (ADS)

    Wangoo, Nishima; Kaur, Sarabjit; Bajaj, Manish; Jain, D. V. S.; Sharma, Rohit K.

    2014-10-01

    A detailed study on the synthesis of spherical and monodispersed gold nanoparticles (AuNPs) using all of the 20 naturally occurring α-amino acids has been reported. The synthesized nanoparticles have been further characterized using various techniques such as absorbance spectroscopy, transmission electron microscopy, dynamic light scattering and nuclear magnetic resonance. Size control of the nanoparticles has been achieved by varying the ratio of the gold ion to the amino acid. These monodispersed water soluble AuNPs synthesized using non-toxic, naturally occurring α-amino acids as reducing and capping/stabilizing agents serve as a remarkable example of green chemistry.

  16. Novel solid-phase synthesis of thiol-terminated-poly(alpha-amino acid)-drug conjugate.

    PubMed

    Palacios, P; Bussat, P; Bichon, D

    1991-01-01

    A new method using a controlled pore glass solid support for the preparation of a thiol-terminated-polymerdrug, notably poly-L-glutamate-daunomycin having a terminal thiol group, is described. The method consists of first polymerizing an ester-protected glutamic acid onto an amino-disulfide functionalized controlled pore glass support. The ester protecting group is then removed, freeing the gamma-carboxyl groups of the grafted polymer which then allows it to react with daunomycin. Finally, the disulfide bond linking the conjugated polymer-drug to the solid support is broken by thiolysis, thus releasing the desired product. The final product consists of only polymer-drug conjugates with terminal thiol groups (global yield 26%). This novel method is much simpler and more elegant than more conventional preparation methods requiring solution phase techniques.

  17. Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-alpha-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141.

    PubMed

    Garg, Neeraj; Li, Yi-Lin; Garcia Collazo, Ana Maria; Litten, Chris; Ryono, Denis E; Zhang, Minsheng; Caringal, Yolanda; Brigance, Robert P; Meng, Wei; Washburn, William N; Agback, Peter; Mellström, Karin; Rehnmark, Stefan; Rahimi-Ghadim, Mahmoud; Norin, Thomas; Grynfarb, Marlena; Sandberg, Johnny; Grover, Gary; Malm, Johan

    2007-08-01

    Based on the scaffold of the pharmacologically selective thyromimetic 2b, structurally a close analog to KB-141 (2a), a number of novel N-acylated-alpha-amino acid derivatives were synthesized and tested in a TR radioligand binding assay as well as in a reporter cell assay. On the basis of TRbeta(1)-isoform selectivity and affinity, as well as affinity to the reporter cell assay, 3d was selected for further studies in the cholesterol-fed rat model. In this model 3d revealed an improved therapeutic window between cholesterol and TSH lowering but decreased margins versus tachycardia compared with 2a.

  18. Synthesis of various 3-substituted 1,2,4-oxadiazole-containing chiral beta 3- and alpha-amino acids from Fmoc-protected aspartic acid.

    PubMed

    Hamzé, Abdallah; Hernandez, Jean-François; Fulcrand, Pierre; Martinez, Jean

    2003-09-19

    Various 3-substituted chiral 1,2,4-oxadiazole-containing Fmoc-beta(3)- and -alpha-amino acids were synthesized from Fmoc-(l or d)-Asp(OtBu)-OH and Fmoc-l-Asp-OtBu, respectively, in three steps (i.e., condensation of an aspartyl derivative with differentially substituted amidoximes, formation of the 1,2,4-oxadiazole, and cleavage of the tert-butyl ester). These compounds represent new series of nonnatural amino acids, which could be used in combinatorial synthesis. A simple protocol has been developed to generate the 1,2,4-oxadiazole ring. Indeed, common methods resulted in cleavage of the Fmoc group or required long reaction times. We found that sodium acetate in refluxing ethanol/water (86 degrees C) was a convenient and efficient catalyst to promote conversion of Fmoc-amino acyl amidoximes to 1,2,4-oxadiazoles, and this procedure proved to be compatible with Fmoc protection. It is shown that these compounds can be prepared without significant loss of enantiomerical purity. Furthermore, the alkaline conditions used to cleave the Fmoc protecting group from these compounds did not induce epimerization of their chiral center.

  19. ESR study of the radicals in X-irradiated L-alpha-amino-n-butyric acid HCl containing 1. 5% L-cysteine HCl

    SciTech Connect

    Shields, H.; Haven, Y.; Hamrick, P.J. Jr.; Ma, Y.

    1988-12-01

    After X-irradiation at room temperature, the radicals in L-alpha-amino-n-butyric acid HCl are CH/sub 3/CH/sub 2/CHCOOH. The beta- and alpha-hyperfine constants are typical of those found in amino acid radicals. On annealing at temperatures near 100 degrees C this carbon-centered radical in samples containing 1.5% cysteine converts to a perthiyl radical, RCH2S(1)S(2). The g-values for the perithiyl radical are 2.0024, 2.0257, and 2.0557. When the field is in the minimum g-value direction, the hyperfine splittings are 50 G for 33S(2) and 32 G for 33S(1).

  20. New insulinomimetic zinc(II) complexes of alpha-amino acids and their derivatives with Zn(N2O2) coordination mode.

    PubMed

    Yoshikawa, Y; Ueda, E; Suzuki, Y; Yanagihara, N; Sakurai, H; Kojima, Y

    2001-05-01

    Zinc(II) complexes of alpha-amino acids and their derivatives with a Zn(N2O2) coordination mode were found to have in vitro insulinomimetic activity as estimated with the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine. It was revealed that the insulinomimetic activities of zinc(II) complexes with over-all stability constants (log beta) less than 10.5 are higher than those of ZnSO4 and VOSO4. The high blood glucose level of KK-Ay mice with type 2 diabetes mellitus was lowered by daily intraperitoneal injections of a zinc(II) complex, cis-[Zn(L-Thr)2(H2O)2], for 14 d. The improvement of diabetes mellitus was confirmed with the oral glucose tolerance test.

  1. Quantum-chemical analysis of thermodynamics of two-dimensional cluster formation of alpha-amino acids at the air/water interface.

    PubMed

    Vysotsky, Yu B; Fomina, E S; Belyaeva, E A; Aksenenko, E V; Vollhardt, D; Miller, R

    2009-12-31

    The semiempirical quantum-chemical PM3 method is used to calculate the thermodynamic parameters of clusterization of the S-form of alpha-amino acids with the general composition C(n)H(2n+1)CHNH(2)COOH (n = 5-15) at 278 and 298 K. It is shown that six stable conformations of monomers exist, for which the thermodynamic parameters (enthalpy and Gibbs' energy) of the formation and absolute entropy are calculated. The correlation dependencies of the calculated parameters on the alkyl chain length are found to be linear. The structures of the monomers are used to build larger clusters (dimers, tetramers, hexamers). For all small clusters (comprised of two to six molecules), the thermodynamic parameters of formation and clusterization are calculated. It is shown that for tetramers and hexamers the enthalpy, entropy, and Gibbs' energy of clusterization are linearly dependent on the alkyl chain length, whereas for the dimers these dependencies are stepwise. The thermodynamic characteristics of clusterization of associates tilted by angles of 9 and 30 degrees with respect to the normal to the interface are calculated. It is shown that the 30 degrees angle orientation is more energetically advantageous for this class of compounds. The geometric parameters of the unit cell characteristic for the infinite 2D film which corresponds to the most advantageous conformation of the monomer were calculated using the PM3 parametrization to be a = 4.57-4.71 A and b = 5.67-5.75 A, with the angle between the axes theta = 100-103 degrees . These values agree well with the available experimental data. Spontaneous clusterization of alpha-amino acids at the air/water interface at 278 K takes place if the alkyl chain length exceeds 11-12 carbon atoms, whereas for 298 K this clusterization threshold corresponds to 13-14 carbon atoms in the alkyl chain, also in agreement with the experimental data.

  2. Time-resolved FT EPR and optical spectroscopy study on photooxidation of aliphatic alpha-amino acids in aqueous solutions; electron transfer from amino vs carboxylate functional group.

    PubMed

    Tarabek, Peter; Bonifacić, Marija; Beckert, Dieter

    2006-06-08

    Using time-resolved Fourier transform electron paramagnetic resonance, FT EPR, and optical spectroscopy, the photooxidation of glycine, alpha-alanine, alpha-aminoisobutyric acid, and model compounds beta-alanine, methylamine and sodium acetate, by excited triplets of anthraquinone-2,6-disulfonate dianion was studied in aqueous solutions in the pH range 5-13. Anthraquinone radical trianions showing strong emissive spin-polarization (CIDEP) were formed, indicating fast electron transfer from the quenchers to the spin-polarized quinone triplet as the primary reaction. None of the primary radicals formed upon one-electron oxidation of quenchers could be detected at the nanosecond time scale of FT EPR measurements because of their very fast transformation into secondary products. The latter were identified to be decarboxylated alpha-aminoalkyl radicals for alpha-amino acids anions and zwitterions, beta-aminoalkyl radicals for beta-alanine zwitterions, and methyl radicals for acetate anions; corresponding aminyl radicals were the first EPR detectable products from beta-alanine anions and methylamine. Thus, anthraquinone-2,6-disulfonate triplet can take an electron from both NH(2)- and -CO(2)(-) functional groups forming aminium ((+*)NH(2)-) and acyloxyl (-CO(2)(*)) radicals, respectively. Aminium radicals derived from beta-alanine anions and CH(3)-NH(2) stabilize by deprotonation into aminyl radicals, whereas these derived from alpha-amino acids anions are known to suffer ultrafast decarboxylation (tau approximately 10 ps). Analysis of the polarization patterns revealed that decarboxylation from acyloxyl radicals are considerably slower (ns < tau < 0.1 micros). Therefore, in the case of alpha-amino acids, the isoelectronic structures NH(2)-CR(2)-CO(2)(*) and (+*)NH(2)-CR(2)-CO(2)(-) probably do not constitute resonance mesomeric forms of one and the same species and the decarboxylation of aminium radicals is not preceded by the intramolecular carboxylate to amino group

  3. Purification and biochemical characterization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-sensitive L-glutamate receptors of pig brain.

    PubMed Central

    Chang, Y C; Wu, T Y; Li, B F; Gao, L H; Liu, C I; Wu, C L

    1996-01-01

    Two preparations of glutamate receptors were purified from the synaptic junctions of pig brain by a combination of detergent solubilization, anion-exchange chromatography, wheat-germ agglutinin affinity chromatography and sedimentation through sucrose gradients. These preparations were enriched in specific L-[3H]glutamate binding activity (> 5000 pmol of glutamate binding sites/mg of protein), and the rank order of ligand affinity for binding to these preparations was: quisqualate > 6-cyano-7- nitroquinoxaline-2,3-dione > alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) > L-glutamate > kainate > > N-methyl-D-aspartate approximately L-2-amino-4-phosphonobutyrate. SDS/PAGE analysis revealed that more than 80% of the protein in either of these preparations appeared as a single protein band of 106 kDa. Two-dimensional gel electrophoresis further revealed that these 106 kDa proteins consisted of a series of acidic proteins which were recognized by antibodies against rat AMPA receptor subunits. These 106 kDa proteins were also recognized by wheatgerm agglutinin and concanavalin A; in addition, peptide N-glycosidase F treatment of these preparations decreased their size to 99 kDa. Our results suggest that the putative glutamate receptors isolated here are likely to belong to the AMPA subtype of glutamate receptors in pig brain. Using the purification procedure reported here, 5 micrograms of AMPA receptor proteins can be isolated from 250 g of pig brain tissue. PMID:8870648

  4. Modulation of DL-. alpha. -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A sub 2 : A necessary step in long-term potentiation

    SciTech Connect

    Massicotte, G.; Baudry, M. ); Vanderklish, P.; Lynch, G. )

    1991-03-01

    The effects of kainate (KA)-induced epileptic seizures on the binding properites of hippocampal glutamate receptors, on the modulation of DL-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A{sub 2} (PLA{sub 2}), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a singificant decrease in the maximal number of binding sites for ({sup 3}H)AMPA. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA{sub 2}-induced increase in ({sup 3}H)AMPA binding. The results provide evidence in favor of an essential role of PLA{sub 2} in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

  5. DNA cleavage in red light promoted by copper(II) complexes of alpha-amino acids and photoactive phenanthroline bases.

    PubMed

    Patra, Ashis K; Bhowmick, Tuhin; Ramakumar, Suryanarayanarao; Nethaji, Munirathinam; Chakravarty, Akhil R

    2008-12-28

    Ternary copper(II) complexes [Cu(L-trp)(B)(H(2)O)](NO(3)) (1-3) and [Cu(L-phe)(B)(H(2)O)](NO(3)) (4-6) of L-tryptophan (L-trp) and L-phenylalanine (L-phe) having phenanthroline bases (B), viz. 1,10-phenanthroline (phen, 1 and 4), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2 and 5) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3 and 6), were prepared and characterized by physico-chemical techniques. Complexes 3 and 6 were structurally characterized by X-ray crystallography and show the presence of a square pyramidal (4 + 1) CuN(3)O(2) coordination geometry in which the N,O-donor amino acid (L-trp or L-phe) and N,N-donor phenanthroline base bind at the equatorial plane with an aqua ligand coordinated at the elongated axial site. Complex 3 shows significant distortion from the square pyramidal geometry and a strong intramolecular pi-pi stacking interaction between the pendant indole ring of L-trp and the planar dppz aromatic moiety. All the complexes display good binding propensity to the calf thymus DNA giving an order: 3,6 (dppz) > 2,5 (dpq) > 1,4 (phen). The binding constant (K(b)) values are in the range of 2.1 x 10(4)-1.1 x 10(6) mol(-1) with the binding site size (s) values of 0.17-0.63. The phen and dpq complexes are minor groove binders while the dppz analogues bind at the DNA major groove. Theoretical DNA docking studies on 2 and 3 show the close proximity of two photosensitizers, viz. the indole moiety of L-trp and the quinoxaline/phenazine of the dpq/dppz bases, to the complementary DNA strands. Complexes 2 and 3 show oxidative DNA double strand breaks (dsb) of supercoiled (SC) DNA forming a significant quantity of linear DNA along with the nicked circular (NC) form on photoexposure to UV-A light of 365 nm and red light of 647.1 nm (Ar-Kr laser). Complexes 1,5 and 6 show only single strand breaks (ssb) forming NC DNA. The red light induced DNA cleavage involves metal-assisted photosensitization of L-trp and dpq/dppz base resulting in the formation of a reactive

  6. New chiral didehydroamino acid derivatives from a cyclic glycine template with 3,6-dihydro-2H-1,4-oxazin-2-one structure: applications to the asymmetric synthesis of nonproteinogenic alpha-amino acids.

    PubMed

    Chinchilla, R; Falvello, L R; Galindo, N; Nájera, C

    2000-05-19

    New chiral (Z)-alpha,beta-didehydroamino acid (DDAA) derivatives with 3,5-dihydro-2H-1,4-oxazin-2-one structure 11a-f have been stereoselectively prepared after condensation of chiral glycine equivalent 7 with aldehydes in the presence of K(2)CO(3) under mild solid-liquid phase-transfer catalysis reaction conditions. These new systems have been used in diastereoselective cyclopropanation reactions using Corey's ylide for the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids (ACCs) such as allo-corononamic and allo-norcoronamic acids. The hydrogenation reaction of these systems at ambient pressure in the presence of formaldehyde affords saturated oxazinones and N-methylated oxazinones which have been transformed into the N-methyl-alpha-amino acids (N-MAAs) (S)-2-(methylamino)butanoic acid and (S)-N-methylleucine. In addition, the parent alpha, beta-didehydroalanine derivative 11g has been prepared by a direct aminomethylation-elimination sequence from 7 and Eschenmoser's salt and has been used in Diels-Alder cycloaddition with endo selectivity for the synthesis of the enantiomerically pure bicyclic alpha-amino acids (-)-2-aminobicyclo[2.2.1]heptane-2-carboxylic and (-)-2-aminobicyclo[2.2.2]octane-2-carboxylic acids.

  7. Glutamate regulates intracellular calcium and gene expression in oligodendrocyte progenitors through the activation of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

    PubMed Central

    Pende, M; Holtzclaw, L A; Curtis, J L; Russell, J T; Gallo, V

    1994-01-01

    Oligodendrocytes and their progenitors (O-2A) express functional kainate- and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring glutamate receptors. The physiological consequences of activation of these receptors were studied in purified rat cortical O-2A progenitors and in the primary oligodendrocyte cell line CG-4. Changes in the mRNA levels of a set of immediate early genes were studied and were correlated to intracellular Ca2+ concentration, as measured by fura-2 Ca2+ imaging. Both in CG-4 and in cortical O-2A progenitors, basal mRNA levels of NGFI-A were much higher than c-fos, c-jun, or jun-b. Glutamate, kainate, and AMPA greatly increased NGFI-A mRNA and protein by activation of membrane receptors in a Ca(2+)-dependent fashion. Agonists at non-N-methyl-D-aspartate receptors promoted transmembrane Ca2+ influx through voltage-dependent channels as well as kainate and/or AMPA channels. The influx of Ca2+ ions occurring through glutamate-gated channels was sufficient by itself to increase the expression of NGFI-A mRNA. AMPA receptors were found to be directly involved in intracellular Ca2+ and NGFI-A mRNA regulation, because the effects of kainate were greatly enhanced by cyclothiazide, an allosteric modulator that selectively suppresses desensitization of AMPA but not kainate receptors. Our results indicate that glutamate acting at AMPA receptors regulates immediate early gene expression in cells of the oligodendrocyte lineage by increasing intracellular calcium. Consequently, modulation of these receptor channels may have immediate effects at the genomic level and regulate oligodendrocyte development at critical stages. Images PMID:8159727

  8. Positive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor modulators have different impact on synaptic transmission in the thalamus and hippocampus.

    PubMed

    Xia, Yan-Fang; Kessler, Markus; Arai, Amy C

    2005-04-01

    Earlier studies showed that positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors enhance synaptic responses and facilitate synaptic plasticity. Those studies focused mainly on hippocampal functions. However, AMPA receptors have regionally distinct subunit compositions and thus potencies and efficacies of modulators may vary across the brain. The present study compared the effects of CX546 [1-(1,4-benzodioxan-6-ylcarbonyl) piperidine], a benzamide-type modulator, on synaptic transmission in neurons of the reticular thalamic nucleus (RTN), which regulates the firing mode of relay cells in other thalamic nuclei, and on hippocampal CA1 pyramidal cells. CX546 greatly prolonged synaptic responses in CA1 pyramidal cells, but at the same concentration it had only weak modulatory effects in RTN neurons. Effects on miniature excitatory postsynaptic currents (EPSCs) were similar to those on EPSCs in both regions, suggesting that variations in neuronal morphology and transmitter release kinetics do not account for the differences. Relay cells in the ventrobasal thalamus also exhibited weak modulatory effects that were comparable with those in RTN neurons. Regionally different effects on response duration were also observed with CX516 [BDP-12, 1-(quinoxalin-6-ylcarbonyl)piperidine], a second benzamide drug. In contrast, 100 microM cyclothiazide produced comparable synaptic enhancements in hippocampus and RTN. The regional selectivity of benzamide drugs (ampakines) may be explained, at least in part, by a lower potency at thalamic AMPA receptors, perhaps due to the prevalence of the subunits GluR3 and 4. Although regional preferences of the ampakines were modest in their extent, they may be sufficient to be of relevance when considering future therapeutic applications of such compounds.

  9. Differential effect of beta-N-oxalylamino-L-alanine, the Lathyrus sativus neurotoxin, and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate on the excitatory amino acid and taurine levels in the brain of freely moving rats.

    PubMed

    La Bella, V; Piccoli, F

    2000-05-01

    We studied the effect of beta-oxalylamino-L-alanine, a glutamate analog present in Lathyrus sativus seeds and implicated in the etiopathogenesis of neurolathyrism, and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate on the extracellular levels of aspartate, glutamate and taurine in the primary motor cortex of freely moving rats. We found that while both neurotoxins increase the level of aspartate and glutamate, only (+/-)-alpha(-amino-3-hydroxy-5-methylisoxazole-4-propionate is able to modulate the level of taurine. GYKI-52466, a non-competitive non-NMDA antagonist, inhibited beta-oxalylamino-L-alanine-induced increase of aspartate, but not that of glutamate. Conversely, this antagonist proved to be very efficient in blocking the stimulating effect of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate on all three amino acids. We suggest that beta-oxalylamino-L-alanine increases the level of glutamate in vivo by a mechanism not connected to its effect on the non-NMDA receptors, which might involve the inhibition of glutamate transport. This would allow the excitatory neurotransmitter to reach a concentration sufficient to stimulate the non-NMDA receptors, which in their turn mediate the specific release of aspartate. Although the role of aspartate as a neurotransmitter is still under discussion, it might indeed amplify the excitotoxic cascade through its action on NMDA receptors. We speculate that this sequence of events might represent an important step in the molecular cascade leading to the appearance of the selective motoneuron degeneration in neurolathyrism.

  10. Sensory-guided identification of N-(1-methyl-4-oxoimidazolidin-2-ylidene)-alpha-amino acids as contributors to the thick-sour and mouth-drying orosensation of stewed beef juice.

    PubMed

    Sonntag, Tessa; Kunert, Christof; Dunkel, Andreas; Hofmann, Thomas

    2010-05-26

    Sensory-guided fractionation of stewed beef juice using ultrafiltration, gel permeation chromatography, PFPP-HPLC, and HILIC combined with analytical sensory techniques led to the identification of the dipeptides beta-alanyl-N-methyl-L-histidine and beta-alanyl-L-histidine, as well as the creatinine derivatives N-(1-methyl-4-oxoimidazolidin-2-ylidene)aminopropionic acid, N-(1-methyl-4-oxoimidazolidin-2-ylidene)aminoacetic acid, and N-(1-methyl-4-oxoimidazolidin-2-ylidene)amino-4,5,6-trihydroxyhexanoic acid as taste modulators in stewed beef juice. Model experiments demonstrated for the first time that the latter three N-(1-methyl-4-oxoimidazolidin-2-ylidene)-alpha-amino acids are formed by Maillard-type reactions from creatinine and reducing hexoses. Quantitative analysis, followed by taste recombination and omission experiments, revealed that subthreshold concentrations of these taste modulators enhance the typical thick-sour and mouth-drying orosensation and the mouthfulness imparted by stewed beef juice, although none of these compounds exhibited any significant intrinsic taste when tasted individually in water.

  11. Neutral penta- and hexacoordinate silicon(IV) complexes containing two bidentate ligands derived from the alpha-amino acids (S)-alanine, (S)-phenylalanine, and (S)-tert-leucine.

    PubMed

    Cota, Smaranda; Beyer, Matthias; Bertermann, Rüdiger; Burschka, Christian; Götz, Kathrin; Kaupp, Martin; Tacke, Reinhold

    2010-06-11

    The neutral hexacoordinate silicon(IV) complex 6 (SiO(2)N(4) skeleton) and the neutral pentacoordinate silicon(IV) complexes 7-11 (SiO(2)N(2)C skeletons) were synthesized from Si(NCO)(4) and RSi(NCO)(3) (R = Me, Ph), respectively. The compounds were structurally characterized by solid-state NMR spectroscopy (6-11), solution NMR spectroscopy (6 and 10), and single-crystal X-ray diffraction (8 and 11 were studied as the solvates 8 x CH(3)CN and 11 x C(5)H(12) x 0.5 CH(3)CN, respectively). The silicon(IV) complexes 6 (octahedral Si-coordination polyhedron) and 7-11 (trigonal-bipyramidal Si-coordination polyhedra) each contain two bidentate ligands derived from an alpha-amino acid: (S)-alanine, (S)-phenylalanine, or (S)-tert-leucine. The deprotonated amino acids act as monoanionic (6) or as mono- and dianionic ligands (7-11). The experimental investigations were complemented by computational studies of the stereoisomers of 6 and 7.

  12. The stress hormone corticosterone increases synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors via serum- and glucocorticoid-inducible kinase (SGK) regulation of the GDI-Rab4 complex.

    PubMed

    Liu, Wenhua; Yuen, Eunice Y; Yan, Zhen

    2010-02-26

    Corticosterone, the major stress hormone, plays an important role in regulating neuronal functions of the limbic system, although the cellular targets and molecular mechanisms of corticosteroid signaling are largely unknown. Here we show that a short treatment of corticosterone significantly increases alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission and AMPAR membrane trafficking in pyramidal neurons of prefrontal cortex, a key region involved in cognition and emotion. This enhancing effect of corticosterone is through a mechanism dependent on Rab4, the small GTPase-controlling receptor recycling between early endosome and plasma membrane. Guanosine nucleotide dissociation inhibitor (GDI), which regulates the cycle of Rab proteins between membrane and cytosol, forms an increased complex with Rab4 after corticosterone treatment. Corticosterone also triggers an increased GDI phosphorylation at Ser-213 by the serum- and glucocorticoid-inducible kinase (SGK). Moreover, AMPAR synaptic currents and surface expression and their regulation by corticosterone are altered by mutating Ser-213 on GDI. These results suggest that corticosterone, via SGK phosphorylation of GDI at Ser-213, increases the formation of GDI-Rab4 complex, facilitating the functional cycle of Rab4 and Rab4-mediated recycling of AMPARs to the synaptic membrane. It provides a potential mechanism underlying the role of corticosteroid stress hormone in up-regulating excitatory synaptic efficacy in cortical neurons.

  13. Helix formation in preorganized beta/gamma-peptide foldamers: hydrogen-bond analogy to the alpha-helix without alpha-amino acid residues.

    PubMed

    Guo, Li; Almeida, Aaron M; Zhang, Weicheng; Reidenbach, Andrew G; Choi, Soo Hyuk; Guzei, Ilia A; Gellman, Samuel H

    2010-06-16

    We report the first high-resolution structural data for the beta/gamma-peptide 13-helix (i,i+3 C=O...H-N H-bonds), a secondary structure that is formed by oligomers with a 1:1 alternation of beta- and gamma-amino acid residues. Our characterization includes both crystallographic and 2D NMR data. Previous studies suggested that beta/gamma-peptides constructed from conformationally flexible residues adopt a different helical secondary structure in solution. Our design features preorganized beta- and gamma-residues, which strongly promote 13-helical folding by the 1:1 beta/gamma backbone.

  14. Imidazo[1,2-a]pyrazine-3,6-diones derived from alpha-amino acids: a theoretical mechanistic study of their formation via pyrolysis and silica-catalyzed process.

    PubMed

    Contreras-Torres, Flavio F; Basiuk, Vladimir A

    2006-06-15

    Imidazo[1,2-a]pyrazine-3,6-diones are unusual compounds composed of three alpha-amino acid fragments. These bicyclic amidines (BCAs) form under high temperatures or with the use of strong dehydrating reagents. We gave insight into the mechanisms of BCA formation via gas-phase pyrolytic and silica-catalyzed reactions of glycine (Gly) and alpha-aminoisobutyric acid (AIB) with related diketopiperazines (DKPs), using quantum chemical calculations. The entire process requires four steps: (1) O-acylation of DKP with free or silica-bonded amino acid, (2) acyl transfer from the oxygen to the nitrogen atom, (3) intramolecular condensation of the N-acyl DKP into a cyclol, and (4) elimination of water. To study step (1) at silica surface (modeled by H7Si8O12-OH cluster), we employed two-level ONIOM calculations (AM1:UFF, B3LYP/3-21G:UFF and B3LYP/6-31G(d):UFF); all gas-phase reactions were studied at the AM1, B3LYP/3-21G and B3LYP/6-31G(d) levels. The catalytic effect of silica was observed for both Gly and AIB: the activation energy in the O-acylation at the surface was lower by more than 9 kcal mol(-1) as compared to the gas-phase process. Contrary to the exothermic O-acylation, the gas-phase transfer reaction (step 2) was exothermic in both cases, but more favorable for Gly. The cyclocondensation of N-acylated DKPs into BCAs (steps 3 and 4) is endothermic for Gly and exothermic for AIB.

  15. Insights into the mechanisms of ifosfamide encephalopathy: drug metabolites have agonistic effects on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and induce cellular acidification in mouse cortical neurons.

    PubMed

    Chatton, J Y; Idle, J R; Vågbø, C B; Magistretti, P J

    2001-12-01

    Therapeutic value of the alkylating agent ifosfamide has been limited by major side effects including encephalopathy. Although the underlying biochemical processes of the neurotoxic side effects are still unclear, they could be attributed to metabolites rather than to ifosfamide itself. In the present study, the effects of selected ifosfamide metabolites on indices of neuronal activity have been investigated, in particular for S-carboxymethylcysteine (SCMC) and thiodiglycolic acid (TDGA). Because of structural similarities of SCMC with glutamate, the Ca(2+)(i) response of single mouse cortical neurons to SCMC and TDGA was investigated. SCMC, but not TDGA, evoked a robust increase in Ca(2+)(i) concentration that could be abolished by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but only partly diminished by the N-methyl-D-aspartate receptor antagonist 10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK=801). Cyclothiazide (CYZ), used to prevent AMPA/kainate receptor desensitization, potentiated the response to SCMC. Because activation of AMPA/kainate receptors is known to induce proton influx, the intracellular pH (pH(i)) response to SCMC was investigated. SCMC caused a concentration-dependent acidification that was amplified by CYZ. Since H(+)/monocarboxylate transporter (MCT) activity leads to similar cellular acidification, we tested its potential involvement in the pH(i) response. Application of the lactate transport inhibitor quercetin diminished the pH(i) response to SCMC and TDGA by 43 and 51%, respectively, indicating that these compounds may be substrates of MCTs. Taken together, this study indicates that hitherto apparently inert ifosfamide metabolites, in particular SCMC, activate AMPA/kainate receptors and induce cellular acidification. Both processes could provide the biochemical basis of the observed ifosfamide-associated encephalopathy.

  16. Dual role of hydrophobic racemic thioesters of alpha-amino acids in the generation of isotactic peptides and co-peptides in water; implications for the origin of homochirality.

    PubMed

    Illos, Roni A; Clodic, Gilles; Bolbach, Gerard; Weissbuch, Isabelle; Lahav, Meir

    2010-02-01

    Thioesters of alpha-amino acids are considered as plausible monomers for the generation of the primeval peptides. DL-Leucine-thioethyl esters (LeuSEt), where the L-enantiomer was tagged with deuterium atoms, undergo polycondensation in water or in bicarbonate or imidazole buffer solutions to yield mainly heterochiral (atactic) peptides and diketopiperazine, as analyzed by MALDI-TOF and ESI mass-spectrometry. In variance, when polymerization of DL(d(10))-Leu, first activated with N,N'-carbonyldiimidazole, then initiated with ethanethiol or with DL(d(3))-LeuSEt yielded a library of peptides up to 30 detectable residues where those of homochiral sequence (isotactic) are the dominant diastereoisomers. At these conditions, racemic beta-sheets are formed and operate as stereoselective templates in the process of chain-elongation. Isotopic L:L(d(10))-Leu co-peptides were obtained in the polymerization of L(d(10))-Leu with L-LeuSEt. By contrast, mixtures of oligo-D-Leu and oligo-L(d(10))-Leu were obtained in the polymerization of mixtures of D-LeuSEt with activated L(d(10))-Leu. Isotactic co-peptides containing Leu and Val residues were formed in the polymerization of mixtures of activated DL(d(8))-Val with DL(d(3))-LeuSEt in water, implying that the racemic beta-sheets exert regio-enantio-selection but not chemo-selection. A reaction pathway is suggested, where LeuSEt operates both as initiator of the reaction as well as a multimer.

  17. A study of the oligomeric state of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring glutamate receptors in the synaptic junctions of porcine brain.

    PubMed Central

    Wu, T Y; Liu, C I; Chang, Y C

    1996-01-01

    The number of the subunits in an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring L-glutamate receptor in the synaptic junctions of porcine brain was investigated in this study. Upon incubation of the synaptic junctions with three cross-linking regents, dimethyl adipimidate (DMA), dimethyl suberimidate (DMS) and N-succinimidyl-(4-azidophenyl)-1,3'-dithiopropionate (SADP), AMPA receptor subunits in higher-molecular-mass aggregates were detected by immunoblotting. These aggregates migrated as proteins of approx. 200, 300 and 400 kDa. The number and identity of the subunits in a solubilized AMPA receptor were also investigated here. Two samples, W1 and W2, enriched in AMPA receptors were prepared from synaptic junctions by a combination of detergent-solubilization, anion-exchange chromatography and wheatgerm agglutinin affinity chromatography. Hydrodynamic behaviour analyses revealed that the majority of the AMPA receptors in either one of these samples were asymmetrical detergent-surrounded particles with a protein mass around 350 kDa. SDS/PAGE analysis revealed that the majority of AMPA receptors in the W1 sample were comprised of dimers of 106 kDa subunits which were covalently linked by disulphide bonds. Cross-linking these receptors with SADP yielded a new band of approx. 400 kDa. The results obtained here, either from the studies of AMPA receptors embedding in synaptic junctions or from those of detergent-solubilized and partially purified receptors, suggest that AMPA receptors contain a basic core structure comprising of four 106 kDa subunits. PMID:8920974

  18. Linking supply to demand: the neuronal monocarboxylate transporter MCT2 and the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptor GluR2/3 subunit are associated in a common trafficking process.

    PubMed

    Pierre, Karin; Chatton, Jean-Yves; Parent, Annabelle; Repond, Cendrine; Gardoni, Fabrizio; Di Luca, Monica; Pellerin, Luc

    2009-05-01

    MCT2 is the major neuronal monocarboxylate transporter (MCT) that allows the supply of alternative energy substrates such as lactate to neurons. Recent evidence obtained by electron microscopy has demonstrated that MCT2, like alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, is localized in dendritic spines of glutamatergic synapses. Using immunofluorescence, we show in this study that MCT2 colocalizes extensively with GluR2/3 subunits of AMPA receptors in neurons from various mouse brain regions as well as in cultured neurons. It also colocalizes with GluR2/3-interacting proteins, such as C-kinase-interacting protein 1, glutamate receptor-interacting protein 1 and clathrin adaptor protein. Coimmunoprecipitation of MCT2 with GluR2/3 and C-kinase-interacting protein 1 suggests their close interaction within spines. Parallel changes in the localization of both MCT2 and GluR2/3 subunits at and beneath the plasma membrane upon various stimulation paradigms were unraveled using an original immunocytochemical and transfection approach combined with three-dimensional image reconstruction. Cell culture incubation with AMPA or insulin triggered a marked intracellular accumulation of both MCT2 and GluR2/3, whereas both tumor necrosis factor alpha and glycine (with glutamate) increased their cell surface immunolabeling. Similar results were obtained using Western blots performed on membrane or cytoplasm-enriched cell fractions. Finally, an enhanced lactate flux into neurons was demonstrated after MCT2 translocation on the cell surface. These observations provide unequivocal evidence that MCT2 is linked to AMPA receptor GluR2/3 subunits and undergoes a similar translocation process in neurons upon activation. MCT2 emerges as a novel component of the synaptic machinery putatively linking neuroenergetics to synaptic transmission.

  19. Synthesis of chiral alpha-amino aldehydes linked by their amine function to solid support.

    PubMed

    Cantel, Sonia; Heitz, Annie; Martinez, Jean; Fehrentz, Jean-Alain

    2004-09-01

    The anchoring of an alpha-amino-acid derivative by its amine function on to a solid support allows some chemical reactions starting from the carboxylic acid function. This paper describes the preparation of alpha-amino aldehydes linked to the support by their amine function. This was performed by reduction with LiAlH4 of the corresponding Weinreb amide linked to the resin. The aldehydes obtained were then involved in Wittig or reductive amination reactions. In addition, the linked Weinreb amide was reacted with methylmagnesium bromide to yield the corresponding ketone. After cleavage from the support, the compounds were obtained in good to excellent yields and characterized.

  20. An easy stereoselective access to beta,gamma-aziridino alpha-amino ester derivatives via mannich reaction of benzophenone imines of glycine esters with N-sulfonyl alpha-chloroaldimines.

    PubMed

    Kiss, Loránd; Mangelinckx, Sven; Sillanpää, Reijo; Fülöp, Ferenc; De Kimpe, Norbert

    2007-09-14

    Mannich-type addition of benzophenone imine glycinates across newly synthesized N-(p-toluenesulfonyl) alpha-chloroaldimines afforded gamma-chloro-alpha,beta-diamino ester derivatives with moderate diastereoselectivity as separable mixtures of anti and syn diastereomers. The gamma-chloro-alpha,beta-diamino esters were efficiently cyclized under basic conditions to the corresponding beta,gamma-aziridino alpha-amino ester derivatives, representing a new class of conformationally constrained heterocyclic alpha,beta-diamino acid derivatives. The relative configuration of the aziridines was determined via X-ray diffraction analysis. Mechanisms and intermediate transition states to explain the stereochemical outcome of the Mannich reaction with different substrates or under different conditions are proposed. The synthetic importance of the beta,gamma-aziridino alpha-amino ester derivatives is demonstrated by their conversion into the corresponding Boc-protected derivatives and ring opening reactions to alpha,beta-diamino esters and a gamma-amino alpha,beta-unsaturated amino ester.

  1. Peptide backbone folding induced by the C(alpha)-tetrasubstituted cyclic alpha-amino acids 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) and 1-aminocyclopentane-1-carboxylic acid (Ac5c). A joint computational and experimental study.

    PubMed

    Aschi, Massimiliano; Lucente, Gino; Mazza, Fernando; Mollica, Adriano; Morera, Enrico; Nalli, Marianna; Paglialunga Paradisi, Mario

    2003-06-07

    The conformational study of a new group of synthetic peptides containing 4-amino-1,2-dithiolane-4-carboxylic acid (Adt), a cysteine-related achiral residue, has been carried out through a joint application of computational and experimental methodologies. Molecular Dynamics simulations clearly suggest the tendency of this molecule to adopt a gamma-turn conformation in vacuum and help in analyzing the complex and crucial conformational behaviour of the dithiolane ring which appears to preferentially adopt a C(S)-like structure. Electronic structure calculations carried out in solution using the Density Functional Theory also indicate the preservation of the gamma-like folding in apolar solvents and the helix-like one in more polar solvents. A comparison with the achiral 1-aminocycloalkane-1-carboxylic acid (Ac5c) has been carried out using the same computational tools. NMR and IR data on dipeptide derivatives containing the Adt or Ac5c residue show that in chloroform solution all the models prefer a gamma-turn structure, centered at the cyclic residue, stabilized by an intramolecular H-bond, whereas in a more polar solvent, i.e. dimethyl sulfoxide, this folding is not maintained. The experimental conformational studies, extended to N-Boc protected tripeptides, clearly indicate the remarkable tendency of both the five-membered C(alpha)-tetrasubstituted cyclic amino acids Adt and Ac5c to induce the gamma-turn structure also in models able to adopt the beta-bend conformation.

  2. Catalytic asymmetric synthesis of {alpha}-amino phosphonates using lanthanoid-potassium-BINOL complexes

    SciTech Connect

    Sasai, Hiroaki; Arai, Shigeru; Shibasaki, Masakatsu

    1995-10-20

    {alpha}-Amino phosphonic acids 3 are interesting compounds in the design of enzyme inhibitors. The concept of mimicking tetrahedral transition states of enzyme-medicated peptide bond hydrolysis previously led to the successful design and synthesis of phosphonamide-containing peptides as a promising new class of proteinase inhibitors. It is not surprising that the absolute configuration of the {alpha}-carbon strongly influences the biological properties of 3. Several methods for the synthesis of optically active {alpha}-aminophosphonic acids have been published. The authors report here the first example of a catalytic asymmetric hydrophosphonylation to imines using lanthanoid-potassium-BINOL heterobimetallic complexes (LnPB, Ln = lanthanoid metal), which gives optically active {alpha}-amino phosphonates in modest to high enantiometric excess. 17 refs., 1 tab.

  3. Ovine prolactin and human growth hormone derivatives. Specific modification of their alpha-amino groups.

    PubMed

    Caridad, J J; Nowicki, C; Santomé, J A; Wolfenstein-Todel, C

    1988-06-01

    The alpha-amino group of ovine prolactin (oPRL) and human growth hormone (hGH) was selectively modified by transamination with glyoxylic acid. No difference was found in the binding capacity of transaminated oPRL to rat liver lactogenic receptors with respect to its control, although both samples showed a decrease in its binding capacity with reference to the native hormone. This decrease was due to conformational changes caused by the reaction conditions and not by the transamination itself, as shown by the circular dichroism spectra. Transaminated hGH retained the full binding capacity of the hormone. These results suggest that the alpha-amino group is not relevant for the binding to lactogenic liver receptors in both lactogenic hormones.

  4. Synthesis and utilization of chiral alpha-methylated alpha-amino acids with a carboxyalkyl side chain in the design of novel Grb2-SH2 peptide inhibitors free of phosphotyrosine.

    PubMed

    Long, Ya-Qiu; Xue, Ting; Song, Yan-Li; Liu, Zu-Long; Huang, Shao-Xu; Yu, Qiang

    2008-10-23

    The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. To improve the potency and bioavailability of the Grb2-SH2 inhibitors, the chiral alpha-methyl-alpha-carboxyalkyl amino acid [(alpha-Me)Aa] was designed to cover dual structural and functional features separately contributed by 1-aminocyclohexanecarboxylic acid (Ac6c) and alpha-aminoadipic acid (Adi) in position Y + 1. The enantiopure l(or D)-(alpha-Me)Aa bearing various chain length carboxylalkyl side chain was conveniently synthesized by an optimized oxazolidinone methodology. The incorporation of (S)-(alpha-Me)Aa into the non-pTyr-containing peptide framework with a 5-amino acid sequence binding motif of X (-2)-Leu-(3'-substituted-Tyr) (0)-X (+1)-Asn really improved the inhibitory activity, affording potent (R)-sulfoxide-bridged cyclic and an open-chain series of pentapeptide inhibitors of Grb2-SH2 domain (IC 50 = 1.1-5.8 microM). More significantly, these (alpha-Me)Aa incorporated peptide inhibitors showed excellent activities in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with low micromolar IC 50 values, owing to the reduced peptidic nature and absence of pTyr or pTyr mimetics.

  5. Novel alpha-hydroxyethyl-polystyrene, alpha-chloroethyl-polystyrene and alpha-amino-oxyethyl-polystyrene linkers on the Multipin solid support for solid-phase organic synthesis.

    PubMed

    Bui, C T; Maeji, N J; Bray, A M

    A simple method for the generation of three novel linkers, alpha-hydroxyethyl-polystyrene, alpha-chloroethyl-polystyrene and alpha-amino-oxyethyl-polystyrene on Multipin supports (SynPhase Crowns) has been developed. Applications of these linkers have been successfully demonstrated for solid-phase synthesis of dipeptide, oxime, and hydroxamic acid compounds in good yields and purities.

  6. Methyl 2-((succinimidooxy)carbonyl)benzoate (MSB): a new, efficient reagent for N-phthaloylation of amino acid and peptide derivatives.

    PubMed

    Casimir, J Richard; Guichard, Gilles; Briand, Jean-Paul

    2002-05-31

    A new, efficient, and readily available reagent, methyl 2-((succinimidooxy)carbonyl)benzoate (MSB), for N-phthaloylation of amino acids and amino acid derivatives is described. The phthaloylation procedure is simple and racemization-free and gives excellent results with alpha-amino acids, alpha-amino alcohols, dipeptides, alpha-amino carboxamides, and alpha-amino esters.

  7. Constrained Multistate Sequence Design for Nucleic Acid Reaction Pathway Engineering.

    PubMed

    Wolfe, Brian R; Porubsky, Nicholas J; Zadeh, Joseph N; Dirks, Robert M; Pierce, Niles A

    2017-03-01

    We describe a framework for designing the sequences of multiple nucleic acid strands intended to hybridize in solution via a prescribed reaction pathway. Sequence design is formulated as a multistate optimization problem using a set of target test tubes to represent reactant, intermediate, and product states of the system, as well as to model crosstalk between components. Each target test tube contains a set of desired "on-target" complexes, each with a target secondary structure and target concentration, and a set of undesired "off-target" complexes, each with vanishing target concentration. Optimization of the equilibrium ensemble properties of the target test tubes implements both a positive design paradigm, explicitly designing for on-pathway elementary steps, and a negative design paradigm, explicitly designing against off-pathway crosstalk. Sequence design is performed subject to diverse user-specified sequence constraints including composition constraints, complementarity constraints, pattern prevention constraints, and biological constraints. Constrained multistate sequence design facilitates nucleic acid reaction pathway engineering for diverse applications in molecular programming and synthetic biology. Design jobs can be run online via the NUPACK web application.

  8. Minimal genome encoding proteins with constrained amino acid repertoire

    PubMed Central

    Tsoy, Olga; Yurieva, Marina; Kucharavy, Andrey; O'Reilly, Mary; Mushegian, Arcady

    2013-01-01

    Minimal bacterial gene set comprises the genetic elements needed for survival of engineered bacterium on a rich medium. This set is estimated to include 300–350 protein-coding genes. One way of simplifying an organism with such a minimal genome even further is to constrain the amino acid content of its proteins. In this study, comparative genomics approaches and the results of gene knockout experiments were used to extrapolate the minimal gene set of mollicutes, and bioinformatics combined with the knowledge-based analysis of the structure-function relationships in these proteins and their orthologs, paralogs and analogs was applied to examine the challenges of completely replacing the rarest residue, cysteine. Among several known functions of cysteine residues, their roles in the active centers of the enzymes responsible for deoxyribonucleoside synthesis and transfer RNA modification appear to be crucial, as no alternative chemistry is known for these reactions. Thus, drastic reduction of the content of the rarest amino acid in a minimal proteome appears to be possible, but its complete elimination is challenging. PMID:23873957

  9. The effect of N-substituted alkyl groups on the anticonvulsant activities ofN-Cbz-alpha-amino-N-alkylsuccinimides.

    PubMed

    Lee, J; Son, K; Jung, K; Choi, J; Park, M

    1997-02-01

    For the purpose of defining the effects of theN-substituted alkyl groups on the anticonvulsant activities ofN-Cbz-alpha-aminosuccinimides, various (R)-and(S)-N-alkyl substitutedN-Cbz-alpha-aminosuccinimides (1 and2) were prepared from the corresponding (R)-and(S)-N-Cbz-aspartic acid by using known reaction and were evaluated the anticonvulsant activies in the MES and PTZ tests, including their neurotoxicities. The most active compound in the MES test was(R)-N-Cbz-alpha-amino-N-methylsuccinimide (1b) (ED(50)=52.5 mg/kg, Pl-3.2). And in case of the PTZ test,(R)-N-Cbz-alpha-amino-N-ethylsuccinimide (1c) was the most active compound (ED(50)=32.5 mg/kg, Pl=3.1). The order of anticonvulsant activities of these compounds against the MES test, as judged from the ED(50) values for theR series (1), wasN-methyl >N-isobutyl > non-substituted >N-ethyl,N-allyl >N-benzyl compound; for theS series (2)N-methyl >N-allyl > non-substituted >N-isobutyl >N-ethyl >N-benzyl compound. The anticonvulsant activities in the PTZ tests of these compounds exhibited somewhat different pattern; for theR series (1)N-ethyl >N-methyl >N-isobutyl> non-substituted >N-allyl >N-benzyl compound in order of decreasing activity; forS series (2)N-ethyl >N-allyl, non-substituted >N-isobutyl >N-methyl >N-benzyl compound in order of decreasing activity.

  10. Synthesis of a conformationally constrained δ-amino acid building block.

    PubMed

    O'Reilly, Elaine; Pes, Lara; Ortin, Yannick; Müller-Bunz, Helge; Paradisi, Francesca

    2013-02-01

    Conformationally restricted amino acids are important components in peptidomimetics and drug design. Herein, we describe the synthesis of a novel, non-proteinogenic constrained delta amino acid containing a cyclobutane ring, cis-3(aminomethyl)cyclobutane carboxylic acid (ACCA). The synthesis of the target amino acid was achieved in seven steps, with the key reaction being a base induced intramolecular nucleophilic substitution. A small library of dipeptides was prepared through the coupling of ACCA with proteinogenic amino acids.

  11. Synthesis and biophysical properties of constrained D-altritol nucleic acids (cANA).

    PubMed

    Migawa, Michael T; Prakash, Thazha P; Vasquez, Guillermo; Seth, Punit P; Swayze, Eric E

    2013-09-06

    The first synthesis of constrained altritol nucleic acids (cANA) containing antisense oligonucleotides (ASOs) was carried out to ascertain how conformationally restricting the D-altritol backbone-containing ASO (Me-ANA) would affect their ability to form duplexes with RNA. It was found that the thermal stability was reduced (cANA/RNA -1.1 °C/modification) compared to DNA/RNA, suggesting the constrained system results in a small destabilizing perturbation in the duplex structure.

  12. Phenylalanine ammonia lyase from Arabidopsis thaliana (AtPAL2): a potent enzyme for the synthesis of non-canonical aromatic alpha-amino acids: Part I: Comparative characterization to the enzymes from Petroselinum crispum (PcPAL1) and Rhodosporidium toruloides (RtPAL).

    PubMed

    Dreßen, Alana; Hilberath, Thomas; Mackfeld, Ursula; Billmeier, Arne; Rudat, Jens; Pohl, Martina

    2017-04-06

    Phenylalanine ammonia lyase (PAL) from Arabidopsis thaliana (AtPAL2) was comparatively characterized to the well-studied enzyme from parsley (PcPAL1) and Rhodosporidium toruloides (RtPAL) with respect to kinetic parameters for the deamination and the amination reaction, pH- and temperature optima and the substrate range of the amination reaction. Whereas both plant enzymes are specific for phenylalanine, the bifunctional enzyme from Rhodosporidium toruloides shows KM-values for L-Phe and L-Tyr in the same order of magnitude and, compared to both plant enzymes, a 10-15-fold higher activity. At 30°C all enzymes were sufficiently stable with half-lives of 3.4days (PcPAL1), 4.6days (AtPAL2) and 9.7days (RtPAL/TAL). Very good results for the amination of various trans-cinnamic acid derivatives were obtained using E. coli cells as whole cell biocatalysts in ammonium carbonate buffer. Investigation of the substrate ranges gave interesting results for the newly tested enzymes from A. thaliana and R. toruloides. Only the latter accepts besides 4-hydroxy-CA also 3-methoxy-4-hydroxy-CA as a substrate, which is an interesting intermediate for the formation of pharmaceutically relevant L-Dopa. AtPAL2 is a very good catalyst for the formation of (S)-3-F-Phe, (S)-4-F-Phe and (S)-2-Cl-Phe. Such non-canonical amino acids are valuable building blocks for the formation of various drug molecules.

  13. Phosphorus constrains accelerated nitrogen cycling in limed acidic forests

    NASA Astrophysics Data System (ADS)

    Deforest, J. L.; Shaw, A. N.; Kluber, L. A.; Burke, D. J.; Carrino-Kyker, S. R.; Smemo, K. A.

    2011-12-01

    Anthropogenic deposition can increase phosphorus (P) limitation by abiotic and biotic means. Soil acidification can remove P from available pools and nitrogen (N) deposition can increase the demand for P. We reason that chronic acidic deposition is promoting P limitation in acidic hardwood forests and thereby altering N cycling. The objectives of this study were to investigate the interactive influence of P availability and soil pH on N and P cycling and availability to determine if the response varies between two physiographic regions experiencing similar chronic acidic deposition. We addressed these objectives by experimentally manipulating soil pH, P, or both in strongly acidic glaciated and unglaciated hardwood forests in eastern Ohio, USA. Our results suggest complex interactions between P, soil pH, and the N cycle. Glaciated soils were found to be more N-saturated with nitrification rates 18 times greater than in unglaciated soils. Elevating pH, with or without added P, doubled nitrification rates in glaciated soils. For unglaciated soils, raising pH increased nitrification 10-fold, but increased nitrification only 5-fold in combination with P. This result suggests raising soil pH lowered the demand of soil N, or directly stimulated nitrifying activity, and that increasing P availability could limit N availability. To various degrees, readily available P was geochemically or biologically immobilized in all treatments, suggesting chronic P deficiency in these ecosystems. Phosphorus immobilization decreased as soil pH was elevated, but elevated P either had no effect (glaciated) or doubled P immobilization rates (unglaciated). These results suggest that raising soil pH reduces microbial P limitation for phosphate, whereas adding P appears to make phosphate scarcer. We suggest that P plays an important role in N transformations and cycling, but appears more important in unglaciated soils than in glaciated soils. Chronic soil acidification may have a greater

  14. A straightforward three-component synthesis of alpha-amino esters containing a phenylalanine or a phenylglycine scaffold.

    PubMed

    Haurena, Caroline; Le Gall, Erwan; Sengmany, Stéphane; Martens, Thierry; Troupel, Michel

    2010-04-16

    A range of alpha-amino esters has been synthesized in good to high yields using a straightforward three-component reaction among preformed or in situ generated aromatic or benzylic organozinc reagents, primary or secondary amines, and ethyl glyoxylate. The procedure, which is characterized by its simplicity, allows the concise synthesis of esters bearing a phenylglycine or a phenylalanine scaffold.

  15. Phenylalanine ammonia lyase from Arabidopsis thaliana (AtPAL2): A potent MIO-enzyme for the synthesis of non-canonical aromatic alpha-amino acids.: Part II: Application in different reactor concepts for the production of (S)-2-chloro-phenylalanine.

    PubMed

    Dreßen, Alana; Hilberath, Thomas; Mackfeld, Ursula; Rudat, Jens; Pohl, Martina

    2017-09-20

    Phenylalanine ammonia lyase (PAL) from Arabidopsis thaliana (AtPAL2) is in general a very good catalyst for the amination of fluoro- and chloro-cinnamic acid derivatives yielding halogenated (S)-phenylalanine derivatives with ≥85% conversion and excellent ee values >99%. We have studied the application of this enzyme as whole cell biocatalyst and immobilized on the cellulose carrier Avicel(®) for the production of the hypertension drug precursor (S)-2-chloro-phenylalanine using batch, fed-batch, as well as continuous membrane reactor and plug-flow reactor. For immobilization, a C-terminal fusion of the enzyme with a carbohydrate binding module (CBM) was produced, which selectively binds to Avicel(®) directly from crude cell extracts, thus enabling a fast and cheap immobilization, stabilization and recycling of the enzyme. 1g Avicel was loaded with 10mg enzyme. Best results were obtained with whole cells using the continuous membrane reactor (47gproduct/gDryCellWeight) and using the immobilized enzyme in a repetitive fed-batch (274gproduct/gimmobilized enzyme) or in a continuous plug-flow reactor (288gproduct/gimmobilize enzyme). Therewith the productivity of AtPAL2 outperforms the established fed-batch process at DSM using PAL from Rhodotorula glutinis in E. coli as whole cell biocatalyst with a productivity of 0.14gproduct/gWetCellWeight (ca. 0.7gproduct/gDryCellWeight) (de Lange et al., 2011; doi:10.1002/cctc.201000435). Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Lanthanum(III) and praseodymium(III) derivatives with dithiocarbamates derived from alpha-amino acids.

    PubMed

    Rai, Anita; Sengupta, Soumitra K; Pandey, Om P

    2006-06-01

    Lanthanum(III) and praseodymium(III) complexes with dithiocarbamates have been synthesized by the reactions of lanthanum(III) and praseodymium(III) chloride with barium dithiocarbamate and complexes of type [LnCl(L)H2O]n have been obtained (where Ln=La(III) or Pr(III); L=barium salt of dithiocarbamate derived from glycine, L-leucine, L-valine, DL-alanine). The complexes have been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H NMR spectral studies. The presence of coordinated water molecule is inferred from thermogravimetric analysis which indicates the loss of one water molecule at 150-170 degrees C. The oscillator strength, Judd-Ofelt intensity parameter, stimulated emission cross-section, etc. have been obtained for different transitions of Pr3+.

  17. Enzymic synthesis of L-lysine from DL-alpha-amino-epsilon-caprolactam by new microbial strains.

    PubMed

    Plhácková, K; Vojtísek, V; Plachý, J

    1982-01-01

    The production of L-lysine from DL-alpha-amino-epsilon-caprolactam (DL-ACL) by new strains producing L-alpha-amino-epsilon-caprolactamase and aminocaprolactam racemase is described. Optimal conditions for hydrolysis of L-ACL by Cryptococcus sp. and for racemization of ACL by cells of a strain isolated in nature and identified as Pseudomonas sp. were determined. Synthesis of L-alpha-amino-epsilon-caprolactamase is induced by DL-ACL or L-lysine with the same effectivity. A positive effect of phosphates (potassium salts) on reduction of the induction lag was detected, the synthesis of this enzyme was found to be repressed by glucose and some possibilities of the reversion of this repressive effect were demonstrated. Under conditions optimal for the production of both enzymes a quantitative theoretical conversion of 10% aqueous DL-ACL to L-lysine by a mixture of native cells in a mass ratio of 1 : 2 (producer of ACL-hydrolase to producer of ACL-racemase) occurred in 8 h at 40 degrees C and pH 8.0.

  18. CycloPs: generating virtual libraries of cyclized and constrained peptides including nonnatural amino acids.

    PubMed

    Duffy, Fergal J; Verniere, Mélanie; Devocelle, Marc; Bernard, Elise; Shields, Denis C; Chubb, Anthony J

    2011-04-25

    We introduce CycloPs, software for the generation of virtual libraries of constrained peptides including natural and nonnatural commercially available amino acids. The software is written in the cross-platform Python programming language, and features include generating virtual libraries in one-dimensional SMILES and three-dimensional SDF formats, suitable for virtual screening. The stand-alone software is capable of filtering the virtual libraries using empirical measurements, including peptide synthesizability by standard peptide synthesis techniques, stability, and the druglike properties of the peptide. The software and accompanying Web interface is designed to enable the rapid generation of large, structurally diverse, synthesizable virtual libraries of constrained peptides quickly and conveniently, for use in virtual screening experiments. The stand-alone software, and the Web interface for evaluating these empirical properties of a single peptide, are available at http://bioware.ucd.ie .

  19. Does Aspartic Acid Racemization Constrain the Depth Limit of the Subsurface Biosphere?

    NASA Technical Reports Server (NTRS)

    Onstott, T C.; Magnabosco, C.; Aubrey, A. D.; Burton, A. S.; Dworkin, J. P.; Elsila, J. E.; Grunsfeld, S.; Cao, B. H.; Hein, J. E.; Glavin, D. P.; hide

    2013-01-01

    Previous studies of the subsurface biosphere have deduced average cellular doubling times of hundreds to thousands of years based upon geochemical models. We have directly constrained the in situ average cellular protein turnover or doubling times for metabolically active micro-organisms based on cellular amino acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic acid racemization rate. Application of this method to planktonic microbial communities collected from deep fractures in South Africa yielded maximum cellular amino acid turnover times of approximately 89 years for 1 km depth and 27 C and 1-2 years for 3 km depth and 54 C. The latter turnover times are much shorter than previously estimated cellular turnover times based upon geochemical arguments. The aspartic acid racemization rate at higher temperatures yields cellular protein doubling times that are consistent with the survival times of hyperthermophilic strains and predicts that at temperatures of 85 C, cells must replace proteins every couple of days to maintain enzymatic activity. Such a high maintenance requirement may be the principal limit on the abundance of living micro-organisms in the deep, hot subsurface biosphere, as well as a potential limit on their activity. The measurement of the D/L of aspartic acid in biological samples is a potentially powerful tool for deep, fractured continental and oceanic crustal settings where geochemical models of carbon turnover times are poorly constrained. Experimental observations on the racemization rates of aspartic acid in living thermophiles and hyperthermophiles could test this hypothesis. The development of corrections for cell wall peptides and spores will be required, however, to improve the accuracy of these estimates for environmental samples.

  20. Does aspartic acid racemization constrain the depth limit of the subsurface biosphere?

    SciTech Connect

    Onstott, T. C.; Aubrey, A.D.; Kieft, T L; Silver, B J; Phelps, Tommy Joe; Van Heerden, E.; Opperman, D. J.; Bada, J L.

    2014-01-01

    Previous studies of the subsurface biosphere have deduced average cellular doubling times of hundreds to thousands of years based upon geochemical models. We have directly constrained the in situ average cellular protein turnover or doubling times for metabolically active micro-organisms based on cellular amino acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic acid racemization rate. Application of this method to planktonic microbial communities collected from deep fractures in South Africa yielded maximum cellular amino acid turnover times of ~89 years for 1 km depth and 27 C and 1 2 years for 3 km depth and 54 C. The latter turnover times are much shorter than previously estimated cellular turnover times based upon geochemical arguments. The aspartic acid racemization rate at higher temperatures yields cellular protein doubling times that are consistent with the survival times of hyperthermophilic strains and predicts that at temperatures of 85 C, cells must replace proteins every couple of days to maintain enzymatic activity. Such a high maintenance requirement may be the principal limit on the abundance of living micro-organisms in the deep, hot subsurface biosphere, as well as a potential limit on their activity. The measurement of the D/L of aspartic acid in biological samples is a potentially powerful tool for deep, fractured continental and oceanic crustal settings where geochemical models of carbon turnover times are poorly constrained. Experimental observations on the racemization rates of aspartic acid in living thermophiles and hyperthermophiles could test this hypothesis. The development of corrections for cell wall peptides and spores will be required, however, to improve the accuracy of these estimates for environmental samples.

  1. Does aspartic acid racemization constrain the depth limit of the subsurface biosphere?

    PubMed

    Onstott, T C; Magnabosco, C; Aubrey, A D; Burton, A S; Dworkin, J P; Elsila, J E; Grunsfeld, S; Cao, B H; Hein, J E; Glavin, D P; Kieft, T L; Silver, B J; Phelps, T J; van Heerden, E; Opperman, D J; Bada, J L

    2014-01-01

    Previous studies of the subsurface biosphere have deduced average cellular doubling times of hundreds to thousands of years based upon geochemical models. We have directly constrained the in situ average cellular protein turnover or doubling times for metabolically active micro-organisms based on cellular amino acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic acid racemization rate. Application of this method to planktonic microbial communities collected from deep fractures in South Africa yielded maximum cellular amino acid turnover times of ~89 years for 1 km depth and 27 °C and 1-2 years for 3 km depth and 54 °C. The latter turnover times are much shorter than previously estimated cellular turnover times based upon geochemical arguments. The aspartic acid racemization rate at higher temperatures yields cellular protein doubling times that are consistent with the survival times of hyperthermophilic strains and predicts that at temperatures of 85 °C, cells must replace proteins every couple of days to maintain enzymatic activity. Such a high maintenance requirement may be the principal limit on the abundance of living micro-organisms in the deep, hot subsurface biosphere, as well as a potential limit on their activity. The measurement of the D/L of aspartic acid in biological samples is a potentially powerful tool for deep, fractured continental and oceanic crustal settings where geochemical models of carbon turnover times are poorly constrained. Experimental observations on the racemization rates of aspartic acid in living thermophiles and hyperthermophiles could test this hypothesis. The development of corrections for cell wall peptides and spores will be required, however, to improve the accuracy of these estimates for environmental samples. © 2013 John Wiley & Sons Ltd.

  2. Synthesis and pharmacological evaluation of novel conformationally constrained homologues of glutamic acid.

    PubMed

    Conti, Paola; Caligiuri, Antonio; Pinto, Andrea; Roda, Gabriella; Tamborini, Lucia; Nielsen, Birgitte; Madsen, Ulf; Frydenvang, Karla; Colombo, Alessio; De Micheli, Carlo

    2007-08-01

    Twelve novel conformationally constrained homologues of glutamic acid have been synthesized and pharmacologically characterized at ionotropic glutamate receptors (iGluRs). Synthesis of the target compounds involved 1,3-dipolar cycloaddition of nitrile oxides to suitable dipolarophiles. The structure to the compounds has been assigned by (1)H NMR and, in the case of derivatives (+/-)-4a, (+/-)-4b, (+/-)-5a, and (+/-)-5b, by means of an X-ray crystallographic analysis carried out on intermediate (+/-)-12a. The synthesized amino acids were found to be without affinity (K(i)/IC(50)>100microM) for iGluRs with the exception of compounds (+/-)-4b and (+/-)-5b, which showed a modest affinity for NMDA receptors (K(i)=34 and 13microM, respectively). The results indicate that the increased conformational constraints introduced by the cyclopropane ring and the spiro-attached proline ring are both detrimental to the pharmacological activity.

  3. Access to enantioenriched alpha-amino esters via rhodium-catalyzed 1,4-addition/enantioselective protonation.

    PubMed

    Navarre, Laure; Martinez, Rémi; Genet, Jean-Pierre; Darses, Sylvain

    2008-05-14

    Conjugate addition of potassium trifluoro(organo)borates 2 to dehydroalanine derivatives 1, mediated by a chiral rhodium catalyst and in situ enantioselective protonation, afforded straightforward access to a variety of protected alpha-amino esters 3 with high yields and enantiomeric excesses up to 95%. Among the tested chiral ligands and proton sources, Binap, in combination with guaiacol (2-methoxyphenol), an inexpensive and nontoxic phenol, afforded the highest asymmetric inductions. Organostannanes have also shown to participate in this reaction. By a fine-tuning of the ester moiety, and using Difluorophos as chiral ligand, increased levels of enantioselectivity, generally close to 95%, were achieved. Deuterium labeling experiments revealed, and DFT calculation supported, an unusual mechanism involving a hydride transfer from the amido substituent to the alpha carbon explaining the high levels of enantioselectivity attained in controlling this alpha chiral center.

  4. Evidence from Meteorites for Multiple Possible Amino Acid Alphabets for the Origins of Life

    NASA Technical Reports Server (NTRS)

    Burton, A. S.; Elsila, J. E.; Callahan, M. P.; Glavin, D. P.; Dworkin, J. P.

    2015-01-01

    A key question for the origins of life is understanding which amino acids made up the first proteins synthesized during the origins of life. The canonical set of 20 - 22 amino acids used in proteins are all alpha-amino, alpha-hydrogen isomers that, nevertheless, show considerable variability in properties including size, hydrophobicity, and ionizability. Abiotic amino acid synthesis experiments such as Miller-Urey spark discharge reactions produce a set of up to 23 amino acids, depending on starting materials and reaction conditions, with significant abundances of both alpha- and non-alpha-amino acid isomers. These two sets of amino acids do not completely overlap; of the 23 spark discharge amino acids, only 11 are used in modern proteins. Furthermore, because our understanding of conditions on the early Earth are limited, it is unclear which set(s) of conditions employed in spark discharge or hydrothermal reactions are correct, leaving us with significant uncertainty about the amino acid alphabet available for the origins of life on Earth. Meteorites, the surviving remnants of asteroids and comets that fall to the Earth, offer the potential to study authentic samples of naturally-occurring abiotic chemistry, and thus can provide an alternative approach to constraining the amino acid library during the origins of life.

  5. Design, synthesis, and biological evaluation of conformationally constrained aci-reductone mimics of arachidonic acid.

    PubMed

    Hopper, A T; Witiak, D T; Ziemniak, J

    1998-02-12

    An efficient and convergent synthesis has been developed for the production of 3,4-dihydroxy-5-[4-(2-((2Z)-hexenyl)phenyl)-3-(1Z)-but enyl]-2 (5H)-furanone (12d). This hydrophobic antioxidant is a stable conformationally constrained mimic of arachidonic acid (AA) (1) and its respective aci-reductone analogue (2). Pd(0)-catalyzed cross-coupling of 5-(3-butynyl)-3,4-dihydroxy-2(5H)-furanone (7) with 2-((2Z)-hexenyl)iodobenzene (8d) followed by Lindlar catalyzed hydrogenation produces 12d. Butynyl intermediate 7 is prepared from 2-(benzyloxy)-5-deoxyascorbic acid (15) by iodination (I2, PPh3, Imd), iodo substitution with lithium acetylide ethylenediamine complex (LiAEDA, HMPA, -5 degrees C), and benzyl group cleavage (Ac2O, Pyr, BCl3). The utility of this synthetic method was demonstrated by the synthesis of analogues 10e-k. Biological testing revealed that certain of these antioxidants inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) with comparable efficacy as reported for aspirin and zileuton, respectively. The antioxidant activity of these aci-reductones, measured as a function of their inhibitory effect on CCl4-induced lipid peroxidation of hepatic microsomes, exceeds that produced by alpha-tocopherol. Synthetic routes and initial structure-activity relationships (SAR) for these novel mixed functioning antioxidants are presented.

  6. Bicyclic glutamic acid derivatives.

    PubMed

    Meyer, Udo; Bisel, Philippe; Weckert, Edgar; Frahm, August Wilhelm

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

  7. Thiopeptide synthesis. {alpha}-amino thionoacid derivatives of nitrobenzotriazole as thioacylating agents

    SciTech Connect

    Shalaby, M.A.; Grote, C.W.; Rapoport, H.

    1996-12-13

    There has been considerable interest recently in the synthesis and properties of thiopeptides in which the -CSNH- group replaces one or more peptide bonds. These modified peptides have demonstrated increased activity in vivo as biological response modifiers, neuro-effectors, and immunomodulators due to the stability of their thioamide bonds toward enzymatic degradation as compared to that of their oxygenated counterpart. Synthetic routes employed to prepare these thiopeptides included replacement of oxygen by sulfur using P{sub 4}S{sub 10} or Lawesson`s phosphetane disulfide reagent, and thioesters or dithioesters of N-protected amino acids. Several procedures also have been reported for monothionation of peptides using N-protected amino monothioacids and benzotriazolyloxytris(pyrrolidino) phosphonium hexafluorophosphate (PYBOP) and some of its derivatives. Unfortunately, these methods displayed lack of reaction site specificity, low yields and purity because of side reactions, and loss of enantiomeric integrity in the final product, apparently because of racemization induced by the thioacylating agents. Recently, major improvement was described for the site specific incorporation of thioamide linkages into a growing peptide under mild conditions using thioacylbenzimidazolinones of amino acid derivatives as thioacylating agents. This method proceeds with about 2% loss of enantiomeric purity, as demonstrated by HPLC analysis of the reaction product 10a, formed in reaction with {alpha}-methylbenzylamine. This procedure, although superior to previous methods, still suffers from the formation of benzimidazole 2 as a significant byproduct, and the overall yield for the four-step process was only about 20%. Furthermore, recent attempt to use this procedure failed due to the limited reactivity of the benzimidazolinone 4 as a thioacylating agent. To overcome these limitations, the authors have developed a new method for thiopeptide synthesis. 12 refs.

  8. Evidence for a Dual Role of an Active Site Histidine in [alpha]-Amino-[beta]-carboxymuconate-[epsilon]-semialdehyde Decarboxylase

    SciTech Connect

    Huo, Lu; Fielding, Andrew J.; Chen, Yan; Li, Tingfeng; Iwaki, Hiroaki; Hosler, Jonathan P.; Chen, Lirong; Hasegawa, Yoshie; Que, Jr., Lawrence; Liu, Aimin

    2012-10-09

    The previously reported crystal structures of {alpha}-amino-{beta}-carboxymuconate-{epsilon}-semialdehyde decarboxylase (ACMSD) show a five-coordinate Zn(II)(His){sub 3}(Asp)(OH{sub 2}) active site. The water ligand is H-bonded to a conserved His228 residue adjacent to the metal center in ACMSD from Pseudomonas fluorescens (PfACMSD). Site-directed mutagenesis of His228 to tyrosine and glycine in this study results in a complete or significant loss of activity. Metal analysis shows that H228Y and H228G contain iron rather than zinc, indicating that this residue plays a role in the metal selectivity of the protein. As-isolated H228Y displays a blue color, which is not seen in wild-type ACMSD. Quinone staining and resonance Raman analyses indicate that the blue color originates from Fe(III)-tyrosinate ligand-to-metal charge transfer. Co(II)-substituted H228Y ACMSD is brown in color and exhibits an electron paramagnetic resonance spectrum showing a high-spin Co(II) center with a well-resolved {sup 59}Co (I = 7/2) eight-line hyperfine splitting pattern. The X-ray crystal structures of as-isolated Fe-H228Y (2.8 {angstrom}) and Co-substituted (2.4 {angstrom}) and Zn-substituted H228Y (2.0 {angstrom} resolution) support the spectroscopic assignment of metal ligation of the Tyr228 residue. The crystal structure of Zn-H228G (2.6 {angstrom}) was also determined. These four structures show that the water ligand present in WT Zn-ACMSD is either missing (Fe-H228Y, Co-H228Y, and Zn-H228G) or disrupted (Zn-H228Y) in response to the His228 mutation. Together, these results highlight the importance of His228 for PfACMSD's metal specificity as well as maintaining a water molecule as a ligand of the metal center. His228 is thus proposed to play a role in activating the metal-bound water ligand for subsequent nucleophilic attack on the substrate.

  9. Laboratory and field measurements to constrain atmospheric sources of acetic and formic acids

    NASA Astrophysics Data System (ADS)

    Baasandorj, M.; Hu, L.; Mitroo, D.; Martinez, R.; Walker, M.; Williams, B. J.; Millet, D. B.

    2013-12-01

    Acetic and formic acids are the most abundant organic acids in the atmosphere. They play an important role in atmospheric aqueous chemistry as they can influence the acidity of precipitation, cloud droplets, and atmospheric aerosols. Sources of these acids are highly uncertain, but include secondary production from VOC oxidation, direct emissions, and possibly organic aerosol aging. Here we present measurements of formic and acetic acid, along with a suite of other gas and particle phase species, from a field study in St. Louis during summer 2013. Calibration procedures and results are discussed, and we interpret the ambient formic and acetic acid measurements in terms of patterns of variability and implied constraints on sources. Finally, we present results from oxidative aging experiments on both ambient and test organic aerosol designed to assess the importance of this mechanism as a source of gas-phase carboxylic acids.

  10. Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues.

    PubMed

    Tamborini, Lucia; Cullia, Gregorio; Nielsen, Birgitte; De Micheli, Carlo; Conti, Paola; Pinto, Andrea

    2016-11-15

    Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead for the development of a new class of NMDA antagonists. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Expression of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) GluR2/3 receptors in the developing rat pineal gland.

    PubMed

    Kaur, C; Sivakumar, V; Ling, E A

    2005-10-01

    The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate (GluR2/3) receptors and N-methyl-D-aspartate receptor subtype 1 (NMDAR1) was carried out by immunohistochemistry, double immunofluorescence and real-time RT-PCR analysis in the pineal glands of 1-day to 6-wk-old rats in the present study. GluR2/3 immunopositive cells were distributed throughout the pineal gland and showed branching processes in all age groups. The NMDAR1 immunoreactivity, however, was observed in fewer branched cells. A constitutive mRNA expression of NMDAR1, GluR2 and GluR3 was detected in the pineal glands of various ages and showed no significant difference between the age groups studied. Immunohistochemical and double immunofluorescence results showed that the GluR2/3 were mainly expressed and co-localized with OX-42-positive microglia/macrophages and the glial fibrillary acidic protein (GFAP)-positive astrocytes. Co-localization of NMDAR1 with OX-42- and GFAP-positive cells was much less. The expression of these receptors on the glial cells suggests that they may be involved in the development and growth of the pineal gland in the early postnatal period (1 day to 3 wk) and subsequently in the regulation of melatonin synthesis.

  12. Modulation of N-methyl-D-aspartate and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) responses of spinal nociceptive neurons by a N-terminal fragment of substance P.

    PubMed

    Budai, D; Wilcox, G L; Larson, A A

    1992-06-17

    The effects of an N-terminal fragment of substance P, substance P-(1-7) [SP-(1-7)], on the responses of dorsal horn nociceptive neurons to N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) were tested by combined single-unit extracellular recordings/microiontophoresis. While SP-(1-7) had no effects when applied by itself, it was a potent and long-lasting modulator of both NMDA- and AMPA-mediated excitation of spinal dorsal horn nociceptive neurons. NMDA responses were transiently decreased (by an average of 36% of control at minimum) by SP-(1-7) followed by a more sustained increase (by 76% at maximum). In contrast, AMP responses were only increased by SP-(1-7) (by 81% at maximum). It is hypothesized that the actions of SP-(1-7) on excitatory amino acid (EAA) responses of dorsal horn nociceptive neurons reflect a novel mechanism by which SP and EAAs interact to modulate pain transmission.

  13. Expedited Phonon Transfer in Interfacially Constrained Polymer Chain along Self-Organized Amino Acid Crystals.

    PubMed

    Mu, Liwen; Li, Yifan; Mehra, Nitin; Ji, Tuo; Zhu, Jiahua

    2017-04-05

    In this work, poly(vinyl alcohol) (PVA)/amino acid (AA) composites were prepared by a self-organized crystallization process. Five different AAs (cysteine, aspartic acid, glutamic acid, ornithine, and lysine) were selected based on their similar functional groups but different molecular structures. The different PVA-AA interactions in the five PVA/AA composites lead to two crystal patterns, i.e., continuous network (cysteine and lysine) and discrete particles (glutamic acid, ornithine, and aspartic acid). Scanning thermal microscopy is then applied to map the distribution of thermal conduction in these composites. It is found that the interface surrounding the crystals plays a dominating role in phonon transport where the polymer chains are greatly restrained by the interfacial confinement effect. Continuous crystal network builds up a continuous interface that facilitates phonon transfer while phonon scattering occurs in discrete crystalline structures. Significantly improved thermal conductivity of ∼0.7 W/m·K is observed in PVA/cysteine composite with AA loading of 8.4 wt %, which corresponds to a 170% enhancement as compared to pure PVA. The strong PVA-AA molecular interaction and self-organized crystal structure are considered the major reasons for the unique interface property and superior thermal conductivity.

  14. Some of the amino acid chemistry going on in the Laboratory of Amino Acids, Peptides and Proteins.

    PubMed

    Bouifraden, S; Drouot, C; el Hadrami, M; Guenoun, F; Lecointe, L; Mai, N; Paris, M; Pothion, C; Sadoune, M; Sauvagnat, B; Amblard, M; Aubagnac, J L; Calmes, M; Chevallet, P; Daunis, J; Enjalbal, C; Fehrentz, J A; Lamaty, F; Lavergne, J P; Lazaro, R; Rolland, V; Roumestant, M L; Viallefont, P; Vidal, Y; Martinez, J

    1999-01-01

    Some of the chemistry of amino acids going on in our laboratory (Laboratoire des Amino acides Peptides et Protéines) is described as well as some mass spectrometry methodology for their characterization particularly on solid supports. Several aspects are presented including: (i) the stereoselective synthesis of natural and unnatural amino acids using 2-hydroxypinan-3-one as chiral auxiliary; (ii) the stereoselective synthesis of natural and unnatural amino acids by deracemization of alpha-amino acids via their ketene derivatives; (iii) the synthesis of alpha-aryl-alpha-amino acids via reaction of organometallics with a glycine cation; (iv) the diastereoselective synthesis of glycosyl-alpha-amino acids; (v) the synthesis of beta-amino acids using alpha-aminopyrrolidinopiperazinediones as chiral templates; (vi) the reactivity of urethane-N-protected N-carboxyanhydrides. To characterize natural and non natural amino acids through their immonium ions by mass spectrometry, some methodology is also described.

  15. The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis.

    PubMed

    Garavaglia, Silvia; Perozzi, Silvia; Galeazzi, Luca; Raffaelli, Nadia; Rizzi, Menico

    2009-11-01

    The enzyme alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is a zinc-dependent amidohydrolase that participates in picolinic acid (PA), quinolinic acid (QA) and NAD homeostasis. Indeed, the enzyme stands at a branch point of the tryptophan to NAD pathway, and determines the final fate of the amino acid, i.e. transformation into PA, complete oxidation through the citric acid cycle, or conversion into NAD through QA synthesis. Both PA and QA are key players in a number of physiological and pathological conditions, mainly affecting the central nervous system. As their relative concentrations must be tightly controlled, modulation of ACMSD activity appears to be a promising prospect for the treatment of neurological disorders, including cerebral malaria. Here we report the 2.0 A resolution crystal structure of human ACMSD in complex with the glycolytic intermediate 1,3-dihydroxyacetonephosphate (DHAP), refined to an R-factor of 0.19. DHAP, which we discovered to be a potent enzyme inhibitor, resides in the ligand binding pocket with its phosphate moiety contacting the catalytically essential zinc ion through mediation of a solvent molecule. Arg47, Asp291 and Trp191 appear to be the key residues for DHAP recognition in human ACMSD. Ligand binding induces a significant conformational change affecting a strictly conserved Trp-Met couple, and we propose that these residues are involved in controlling ligand admission into ACMSD. Our data may be used for the design of inhibitors with potential medical interest, and suggest a regulatory link between de novo NAD biosynthesis and glycolysis.

  16. Discovery of Azetidinone Acids as Conformationally-Constrained Dual PPARalpha/gamma Agonists

    SciTech Connect

    Wang, W.; Devasthale, P; Farrelly, D; Gu, L; Harrity, T; Cap, M; Chu, C; Kunselman, L; Morgan, N; et. al.

    2008-01-01

    A novel class of azetidinone acid-derived dual PPAR{alpha}/{gamma} agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARa and PPAR? receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

  17. Synthesis of oxytocin antagonists containing conformationally constrained amino acids in position 2.

    PubMed

    Tóth, G K; Bakos, K; Penke, B; Pávó, I; Varga, C; Török, G; Péter, A; Fülöp, F

    1999-03-08

    Analogues of oxytocin containing D-Trp, 2-amino-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (Atc) or 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (Car) with R or S configurations in position 2 were synthetized, and their receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat kidney inner medulla plasma membranes. The peptides were synthetized in the solid phase by using racemates of Car and Atc. The resulting diastereomeric mixtures were separated by means of RP-HPLC. The binding to the oxytocin receptor was somewhat decreased for the Atc isomers and dramatically decreased for both R- and S-Car, while the D-Trp-containing analogue displayed a relatively high receptor affinity. However, the V1 receptor affinities were almost the same as those of the parent peptide for the Car-containing analogues and dramatically decreased for the S-Atc substituted analogue, which has a relatively high OT/V1 receptor selectivity of 44.5.

  18. Pyridoxine-dependent seizures caused by alpha amino adipic semialdehyde dehydrogenase deficiency: the first polish case with confirmed biochemical and molecular pathology.

    PubMed

    Kaczorowska, Magdalena; Kmiec, Tomasz; Jakobs, Cornelis; Kacinski, Marek; Kroczka, Slawomir; Salomons, Gajja S; Struys, Eduard A; Jozwiak, Sergiusz

    2008-12-01

    Pyridoxine-dependent seizures are a rare condition recognized when numerous seizures respond to pyridoxine treatment and recur on pyridoxine withdrawal. For decades the diagnosis was confirmed only with pyridoxine treatment withdrawal trial. Recently described biochemical and molecular pathology improved the diagnostic process for those cases in which seizures are caused by alpha amino adipic semialdehyde dehydrogenase deficiency. This article presents a girl with recurrent status epilepticus episodes resistant to phenobarbital and phenytoin and partly responding to midazolam. Eventually the seizures were completely controlled with pyridoxine; however, due to the severe condition of this child when seizing, no trial of withdrawal has been performed. The diagnosis of pyridoxine-dependent seizures was confirmed with biochemical and molecular testing revealing elevated alpha-AASA excretion and the presence of 2 different mutations in the antiquitin ( ALDH7A1) gene. Due to the availability of reliable laboratory testing, confirmation of the diagnosis was made without the life-threatening trial of pyridoxine withdrawal.

  19. Preferential labeling of alpha-amino N-terminal groups in peptides by biotin: application to the detection of specific anti-peptide antibodies by enzyme immunoassays.

    PubMed

    Sélo, I; Négroni, L; Créminon, C; Grassi, J; Wal, J M

    1996-12-15

    Experimental conditions (pH 6.5, 24 h reaction, peptide:biotin ratio 1:5) were defined for preferential incorporation of the biotin molecule in the N-terminal alpha-amino group of peptides. This strategy could be helpful in numerous applications when an entire peptide chain must remain accessible for antibody or receptor binding. We illustrate this advantage in a solid-phase enzyme immunoassay designed to detect antibodies specific for bovine beta-lactoglobulin present in rabbit or human sera. This test involves synthetic peptides biotinylated in different positions and immobilized on a solid phase. The use of biotin/streptavidin interactions permitted more efficient detection of specific anti-peptide antibodies than solid phases prepared using conventional passive-adsorption techniques. The highest levels of antibody binding were measured when biotinylation occurred at the N-terminal extremity of immobilized peptides.

  20. Structural Analysis of a β-Helical Protein Motif Stabilized by Targeted Replacements with Conformationally Constrained Amino Acids

    PubMed Central

    Ballano, Gema; Zanuy, David; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos

    2009-01-01

    Here we study conformational stabilization induced in a β-helical nanostructure by position-specific mutations. The nanostructure is constructed through the self-assembly of the β-helical building block excised from E. coli galactoside acetyltransferase (PDB code 1krr, chain A; residues 131-165). The mutations involve substitutions by cyclic, conformationally constrained amino acids. Specifically, a complete structural analysis of the Pro-Xaa-Val sequence [with Xaa being Gly, Ac3c (1-aminocyclopropane-1-carboxylic acid) and Ac5c (1-aminocyclopentane-1-carboxylic acid)], corresponding to the 148-150 loop region in the wild-type (Gly) and mutated (Ac3c and Ac5c) 1krr, has been performed using Molecular Dynamics simulations and X-ray crystallography. Simulations have been performed for the wild-type and mutants of three different systems, namely the building block, the nanoconstruct and the isolated Pro-Xaa-Val tripeptide. Furthermore, the crystalline structures of five peptides of Pro-Xaa-Val or Xaa-Val sequences have been solved by X-ray diffraction analysis and compared with theoretical predictions. Both the theoretical and crystallographic studies indicate that the Pro-Acnc-Val sequences exhibit a high propensity to adopt turn-like conformations, and this propensity is little affected by the chemical environment. Overall, the results indicate that replacement of Gly149 by Ac3c or Ac5c significantly reduce the conformational flexibility of the target site enhancing the structural specificity of the building block and the nanoconstruct derived from the 1krr β-helical motif. PMID:18811190

  1. Conformational studies of γ-turn in pseudopeptides containing α-amino acid and conformationally constrained meta amino benzoic acid/meta nitro aniline

    NASA Astrophysics Data System (ADS)

    Dutt Konar, Anita

    2013-03-01

    Reverse turns (commonly β-turns and γ-turns), a common motif in proteins and peptides, have attracted attention due to their relevance in a wide variety of biological processes. In an attempt to artificially imitate and stabilize these turns in short acyclic peptides, a series of N-terminally protected pseudopeptides comprising of an α-amino acid and conformationally constrained meta amino benzoic acid (mABA)/meta nitro aniline (mNA) (peptides I-VI) have been synthesized. The molecules were well characterized by various spectroscopic techniques and subjected to a systematic conformational analysis. Our experimental results reveal that only pseudopeptides I and II with methyl as the sidechain, tertiary butyloxy carbonyl as the N-terminal protecting group and (mABA)/(mNA) at the C-terminus adopt γ-turn conformations in solid state as well as in solution. Even slight modification of any of the stated conditions donot support the formation of this γ-turn architecture in the solid state. Interestingly, the peptides III-V which displays extended conformation in solid state forms γ-turn structure in solution. Thus this result reflects the importance of co-operative steric interactions amongst various amino acid residues in stabilizing a particular conformation in peptides in different phases (solid and solution). This report may open a new avenue in introducing γ-turn motifs within the bioactive conformation of selected peptides.

  2. Chance-constrained/stochastic linear programming model for acid rain abatement—I. Complete colinearity and noncolinearity

    NASA Astrophysics Data System (ADS)

    Ellis, J. H.; McBean, E. A.; Farquhar, G. J.

    A Linear Programming model is presented for development of acid rain abatement strategies in eastern North America. For a system comprised of 235 large controllable point sources and 83 uncontrolled area sources, it determines the least-cost method of reducing SO 2 emissions to satisfy maximum wet sulfur deposition limits at 20 sensitive receptor locations. In this paper, the purely deterministic model is extended to a probabilistic form by incorporating the effects of meteorologic variability on the long-range pollutant transport processes. These processes are represented by source-receptor-specific transfer coefficients. Experiments for quantifying the spatial variability of transfer coefficients showed their distributions to be approximately lognormal with logarithmic standard deviations consistently about unity. Three methods of incorporating second-moment random variable uncertainty into the deterministic LP framework are described: Two-Stage Programming Under Uncertainty (LPUU), Chance-Constrained Programming (CCP) and Stochastic Linear Programming (SLP). A composite CCP-SLP model is developed which embodies the two-dimensional characteristics of transfer coefficient uncertainty. Two probabilistic formulations are described involving complete colinearity and complete noncolinearity for the transfer coefficient covariance-correlation structure. Complete colinearity assumes complete dependence between transfer coefficients. Complete noncolinearity assumes complete independence. The completely colinear and noncolinear formulations are considered extreme bounds in a meteorologic sense and yield abatement strategies of largely didactic value. Such strategies can be characterized as having excessive costs and undesirable deposition results in the completely colinear case and absence of a clearly defined system risk level (other than expected-value) in the noncolinear formulation.

  3. Glutamate regulates Oct-2 DNA-binding activity through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in cultured chick Bergmann glia cells.

    PubMed

    Méndez, J Alfredo; López-Bayghen, Esther; Rojas, Fausto; Hernández, María Elena; Ortega, Arturo

    2004-02-01

    Ionotropic glutamate receptors in cerebellar Bergmann glial cells are linked to transcriptional regulation and, by these means, are thought to play an important role in plasticity, learning and memory and in several neuropathologies. Within the CNS, the transcription factors of the POU family bind their target DNA sequences after a growth factor-dependent phosphorylation-dephosphorylation cascade. Exposure of cultured Bergmann glial cells to glutamate leads to a time- and dose-dependent increase in Oct-2 DNA-binding activity. The use of specific pharmacological tools established the involvement of Ca2+-permeable alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors. Furthermore, the signaling cascade includes phosphatidyl inositol 3-kinase as well as protein kinase C activation. Interestingly, transcriptional as well as translational inhibitors abolish the glutamate effect, suggesting a transcriptional up-regulation of the oct-2 gene. These data demonstrate that Oct-2 expression is not restricted to neurons and further strengthen the notion that the glial glutamate receptors participate in the modulation of glutamatergic cerebellar neurotransmission.

  4. Acylation of the alpha-amino group in neuropeptide Y(12-36) increases binding affinity for the Y2 receptor.

    PubMed

    Murase, S; Yumoto, N; Petukhov, M G; Yoshikawa, S

    1996-01-01

    Competition assays using three series of analogs of neuropeptide Y (NPY) ([Xaa11]NPY(11-36), [Xaa12]NPY(12-36), and [Xaa13]NPY(13-36) revealed that the binding affinity for the Y2 receptor was considerably lowered by truncation of residue 11. Upon acetylation or succinylation of the alpha-amino group, the binding affinity of [Xaa12]NPY(12-36) recovered to a level similar to that of [Xaa11]NPY(11-36). No significant difference was observed between the increases caused by acetylation and those caused by succinylation, suggesting that the increase in binding affinity cannot be explained by the change in the net charge at the N-terminus as a consequence of the modification. The scattered data points on a plot of the alpha-helix content vs. IC50 of all these analogs revealed the absence of any apparent relationship, an indication that prior formation of the alpha-helix is not necessary for binding to the Y2 receptor. It has been widely accepted that fewer than 12 residues from the C-terminus are directly involved in binding of NPY to the Y2 receptor, while the remaining part of NPY only assists in the adoption of a favorable conformation by the C-terminal hexapeptide for recognition by the receptor. However, the present results suggest that the region around residue 12 does not project from the Y2 receptor.

  5. Metabolism of citric acid production by Aspergillus niger: model definition, steady-state analysis and constrained optimization of citric acid production rate.

    PubMed

    Alvarez-Vasquez, F; González-Alcón, C; Torres, N V

    2000-10-05

    In an attempt to provide a rational basis for the optimization of citric acid production by A. niger, we developed a mathematical model of the metabolism of this filamentous fungus when in conditions of citric acid accumulation. The present model is based in a previous one, but extended with the inclusion of new metabolic processes and updated with currently available kinetic data. Among the different alternatives to represent the system behavior we have chosen the S-system representation within power-law formalism. This type of representation allows us to verify not only the ability of the model to exhibit a stable steady state of the integrated system but also the robustness and quality of the representation. The model analysis is shown to be self-consistent, with a stable steady state, and in good agreement with experimental evidence. Moreover, the model representation is sufficiently robust, as indicated by sensitivity and steady-state and dynamic analyses. From the steady-state results we concluded that the range of accuracy of the S-system representation is wide enough to model realistic deviations from the nominal steady state. The dynamic analysis indicated a reasonable response time, which provided further indication that the model is adequate. The extensive assessment of the reliability and quality of the model put us in a position to address questions of optimization of the system with respect to increased citrate production. We carried out the constrained optimization of A. niger metabolism with the goal of predicting an enzyme activity profile yielding the maximum rate of citrate production, while, at the same time, keeping all enzyme activities within predetermined, physiologically acceptable ranges. The optimization is based on a method described and tested elsewhere that utilizes the fact that the S-system representation of a metabolic system becomes linear at steady state, which allows application of linear programming techniques. Our results show

  6. Mixed oligoureas based on constrained bicyclic and acyclic β-amino acids derivatives: on the significance of the subunit configuration for folding.

    PubMed

    André, Christophe; Legrand, Baptiste; Moulat, Laure; Wenger, Emmanuel; Didierjean, Claude; Aubert, Emmanuel; Averlant-Petit, Marie Christine; Martinez, Jean; Amblard, Muriel; Calmes, Monique

    2013-12-09

    The combination of a non-functionalized constrained bicyclo[2.2.2]octane motif along with urea linkages allowed the formation of a highly rigid 2.5(12/14) helical system both in solution and the solid state. In this work, we aimed at developing stable and functionalized systems as promising materials for biological applications in investigating the impact of this constrained motif and its configuration on homo and heterochiral mixed-oligourea helix formation. Di-, tetra-, hexa-, and octa-oligoureas alternating the highly constrained bicyclic motif of (R) or (S) configuration with acyclic (S)-β(3)-amino acid derivatives were constructed. Circular dichroism (CD), NMR experiments, and the X-ray crystal structure of the octamer unequivocally proved that the alternating heterochiral R/S sequences form a stable left-handed 2.5-helix in contrast to the mixed (S/S)-oligoureas, which did not adopt any defined secondary structure. We observed that the (-)-synclinal conformation around the C(α)-C(β) bond of the acyclic residues, although sterically less favorable than the (+)-synclinal conformation, was imposed by the (R)-bicyclic amino carbamoyl (BAC) residue. This highlighted the strong ability of the BAC residue to drive helical folding in heterochiral compounds. The role of the stereochemistry of the BAC unit was assessed and a model was proposed to explain the misfolding of the S/S sequences. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.

    PubMed

    Ahmed, Ahmed H; Oswald, Robert E

    2010-03-11

    Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.

  8. Synthesis of both enantiomers of hemiesters by enantioselective methanolysis of meso cyclic anhydrides catalyzed by alpha-amino acid-derived chiral thioureas.

    PubMed

    Manzano, Rubén; Andrés, José M; Muruzábal, María-Dolores; Pedrosa, Rafael

    2010-08-06

    Both ureas and thioureas derived from L- or D-valine act as bifunctional organocatalysts able to induce the enantioselective alcoholysis of mono-, bi-, and tricyclic meso anhydrides. The desymmetrization occurs in near quantitative yields and excellent enantiomeric ratios (up to >99:<1) under low catalyst loading. Both enantiomers of the hemiesters can be directly obtained by changing the configuration of the catalyst.

  9. Rigid nonproteinogenic cyclic amino acids as ligands for glutamate receptors: trans-tris(homoglutamic) acids.

    PubMed

    Meyer, Udo; Bisel, Philippe; Bräuner-Osborne, Hans; Madsen, Ulf; Höfner, Georg; Wanner, Klaus Th; Frahm, August Wilhelm

    2005-02-01

    The second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids reported herein proceeds via Strecker reaction of chiral ketimines, obtained from condensation of racemic 2-ethoxycarbonylmethylcyclopentanone and commercially available (S)- and (R)-1-phenylethylamine, respectively. In the key stereodifferentiating step, the cyanide addition leads to mixtures of diastereomeric alpha-amino nitrile-esters, the composition of which is independent of the reaction temperature and the type of the solvent, respectively. Hydrolysis of the alpha-amino nitrile-esters with concentrated H(2)SO(4) yielded diastereomeric mixtures of secondary alpha-amino amido-esters, which after separation were hydrogenolyzed and hydrolyzed each to the enantiomeric trans-1-amino-2-carboxymethylcyclopentanecarboxylic acids. Their configuration was completely established by NMR methods, CD spectra, and X-ray analysis of the trans-1S,2R-configured secondary alpha-amino amido-ester. In receptor binding assays and functional tests, trans-1S,2R-1-amino-2-carboxymethylcyclopentanecarboxylic acid hydrochloride was found to behave as a selective mGluR(2)-antagonist without relevant binding properties at iGluRs. Copyright 2005 Wiley-Liss, Inc.

  10. Phosphate Stability in Diagenetic Fluids Constrains the Acidic Alteration Model for Lower Mt. Sharp Sedimentary Rocks in Gale Crater, Mars

    NASA Technical Reports Server (NTRS)

    Berger, J. A.; Schmidt, M. E.; Izawa, M. R. M.; Gellert, R.; Ming, D. W.; Rampe, E. B.; VanBommel, S. J.; McAdam, A. C.

    2016-01-01

    The Mars rover Curiosity has encountered silica-enriched bedrock (as strata and as veins and associated halos of alteration) in the largely basaltic Murray Fm. of Mt. Sharp in Gale Crater. Alpha Particle X-ray Spectrometer (APXS) investigations of the Murray Fm. revealed decreasing Mg, Ca, Mn, Fe, and Al, and higher S, as silica increased (Fig. 1). A positive correlation between SiO2 and TiO2 (up to 74.4 and 1.7 wt %, respectively) suggests that these two insoluble elements were retained while acidic fluids leached more soluble elements. Other evidence also supports a silica-retaining, acidic alteration model for the Murray Fm., including low trace element abundances consistent with leaching, and the presence of opaline silica and jarosite determined by CheMin. Phosphate stability is a key component of this model because PO4 3- is typically soluble in acidic water and is likely a mobile ion in diagenetic fluids (pH less than 5). However, the Murray rocks are not leached of P; they have variable P2O5 (Fig. 1) ranging from average Mars (0.9 wt%) up to the highest values in Gale Crater (2.5 wt%). Here we evaluate APXS measurements of Murray Fm. bedrock and veins with respect to phosphate stability in acidic fluids as a test of the acidic alteration model for the Lower Mt. Sharp rocks.

  11. Enantioselective high-performance liquid chromatographic separation of N-methyloxycarbonyl unsaturated amino acids on macrocyclic glycopeptide stationary phases.

    PubMed

    Boesten, J M M; Berkheij, M; Schoemaker, H E; Hiemstra, H; Duchateau, A L L

    2006-03-03

    This paper describes the enantiomeric resolution of a series of unsaturated N-methyloxycarbonyl-alpha-H-alpha-amino acids (N-MOC-alpha-amino acids) on macrocyclic glycopeptide stationary phases by means of high-performance liquid chromatography (HPLC). Three types of glycopeptide phases, i.e. Chirobiotic T, V and R, were evaluated in both reversed-phase (RP) and polar ionic mode (PIM). The best results in terms of enantioselectivity and resolution were obtained on Chirobiotic R phase, with the PIM mobile phase giving the highest resolution per min. Investigation of the pH of the reversed-phase mobile phase in the pH range 4.1-5.9 showed little effect on enantioselectivity. The method was applied for monitoring the conversion and product enantiomeric excess of an enzymatic hydrolysis reaction using N-MOC-alpha-H-alpha-amino acid esters as substrate.

  12. The Role of the Local Conformation of a Cyclically Constrained β-AMINO Acid in the Secondary Structures of a Mixed α/β Diastereomer Pair

    NASA Astrophysics Data System (ADS)

    Blodgett, Karl N.; Zwier, Timothy S.

    2017-06-01

    Synthetic foldamers are non-natural polymers designed to fold into unique secondary structures that either mimic nature's preferred secondary structures, or expand their possibilities. Among the most studied synthetic foldamers are β-peptides, which lengthen the distance between amide groups from the single substituted carbon spacer in α-peptides by one (β) additional carbon. Cyclically constrained β-amino acids can impart rigidity to the secondary structure of oligomers by locking in a particular conformation. The β-residue cis-2-aminocyclohexanecarboxylic acid (cis-ACHC) is one such amino acid which has been shown to drive vastly different secondary structures as a function of the local conformation of the cyclohexane ring. We present data on two diastereomers of the mixed α/β tri-peptide Ac-Ala-β_{ACHC}-Ala-NHBn which differ from one another by the chirality along the ACHC residue (SRSS vs. SSRS). The first oligomer is known to crystallize to a 9/11 mixed helix while the second forms no intramolecular hydrogen bonds in the crystal state. This talk will describe the conformation-specific IR and UV spectroscopy of the above two diastereomers under jet cooled conditions in the gas phase. Assignments based on comparison with calculations show the presence of incipient 9/11 mixed helices and competing structures containing more tightly folded hydrogen-bonded networks. The calculated global minimum structures are observed in each case, and in each case these folded structures are reminiscent of a β-turn.

  13. Non-racemic amino acids in the Murray and Murchison meteorites.

    PubMed

    Pizzarello, S; Cronin, J R

    2000-01-01

    Small (1.0-9.2%) L-enantiomer excesses were found in six alpha-methyl-alpha-amino alkanoic acids from the Murchison (2.8-9.2%) and Murray (1.0-6.0%) carbonaceous chondrites by gas chromatography-mass spectroscopy of their N-trifluoroacetyl or N-pentafluoropropyl isopropyl esters. These amino acids [2-amino-2,3-dimethylpentanoic acid (both diastereomers), isovaline, alpha-methyl norvaline, alpha-methyl valine, and alpha-methyl norleucine] are either unknown or rare in the terrestrial biosphere. Enantiomeric excesses were either not observed in the four alpha-H-alpha-amino alkanoic acids analyzed (alpha-amino-n-butyric acid, norvaline, alanine, and valine) or were attributed to terrestrial contamination. The substantial excess of L-alanine reported by others was not found in the alanine in fractionated extracts of either meteorite. The enantiomeric excesses reported for the alpha-methyl amino acids may be the result of partial photoresolution of racemic mixtures caused by ultraviolet circularly polarized light in the presolar cloud. The alpha-methyl-alpha-amino alkanoic acids could have been significant in the origin of terrestrial homochirality given their resistance to racemization and the possibility for amplification of their enantiomeric excesses suggested by the strong tendency of their polymers to form chiral secondary structure.

  14. Highly efficient coupling of beta-substituted aminoethane sulfonyl azides with thio acids, toward a new chemical ligation reaction.

    PubMed

    Merkx, Remco; Brouwer, Arwin J; Rijkers, Dirk T S; Liskamp, Rob M J

    2005-03-17

    [reaction: see text] A highly efficient coupling of protected beta-substituted aminoethane sulfonyl azides with thio acids is reported. In the case of peptide thio acids, this method encompasses a new chemoselective ligation method. Furthermore, the resulting alpha-amino acyl sulfonamides can be alkylated with suitable electrophiles to obtain densely functionalized sulfonamide scaffolds.

  15. Design of novel neurokinin 1 receptor antagonists based on conformationally constrained aromatic amino acids and discovery of a potent chimeric opioid agonist-neurokinin 1 receptor antagonist

    PubMed Central

    Ballet, Steven; Feytens, Debby; Buysse, Koen; Chung, Nga N.; Lemieux, Carole; Tumati, Suneeta; Keresztes, Attila; Van Duppen, Joost; Lai, Josephine; Varga, Eva; Porreca, Frank; Schiller, Peter W.; Broeck, Jozef Vanden; Tourwé, Dirk

    2011-01-01

    A screening of conformationally constrained aromatic amino acids as base cores for the preparation of new NK1 receptor antagonists resulted in the discovery of three new NK1 receptor antagonists, 19 [Ac-Aba-Gly-NH-3′,5′-(CF3)2-Bn], 20 [Ac-Aba-Gly-NMe-3′,5′-(CF3)2-Bn] and 23 [Ac-Tic-NMe-3′,5′-(CF3)2-Bn], which were able to counteract the agonist effect of substance P, the endogenous ligand of NK1R. The most active NK1 antagonist of the series, 20 [Ac-Aba-Gly-NMe-3′,5′-(CF3)2-Bn], was then used in the design of a novel, potent chimeric opioid agonist-NK1 receptor antagonist, 35 [Dmt-D-Arg-Aba-Gly-NMe-3′,5′-(CF3)2-Bn], which combines the N-terminus of the established Dmt1-DALDA agonist opioid pharmacophore (H-Dmt-D-Arg-Phe-Lys-NH2) and 20, the NK1R ligand. The opioid component of the chimeric compound 35, i.e. Dmt-D-Arg-Aba-Gly-NH2 36, also proved to be an extremely potent and balanced μ- and δ opioid receptor agonist with subnanomolar binding and in vitro functional activity. PMID:21413804

  16. Carboxylic Acids as Indicators of Parent Body Conditions

    NASA Astrophysics Data System (ADS)

    Lerner, N. R.

    1995-09-01

    Alpha-hydroxy and alpha-amino carboxylic acids found on the Murchison meteorite are deuterium enriched [1]. It is postulated that they arose from a common interstellar source: the reaction of carbonyl compounds in an aqueous mixture containing HCN and NH3. Carbonyl compounds react with HCN to form alph-hydroxy nitriles, RR'CO + HCN <--> RR'C(OH)CN. If ammonia is also present, the alpha-hydroxy nitriles will exist in equilibirum with the alpha-amino nitriles, RR'C(OH)CN +NH3 .<--> RRCNH2CN + H2O. Both nitriles are hydrolyzed by water to form carboxylic acids: RR'C(OH)CN + H2O --> RR'C(OH)CO2H and RR'C(NH2)CN + H2O --> RR'C(NH2)CO2H. Carbonyl compounds observed in the interstellar medium have been shown to be deuterium enriched [2]. The combined alpha-amino acids found on Murchison have deltaD = +1751 o/oo while the combined alpha-hydroxy acids have deltaD = +573. o/oo [1]. This large discrepancy in deltaD values does not preclude common precursors for the alpha-amino acids and the alpha-hydroxy acids. Different relative amounts of specific alpha-amino and alpha-hydroxy acids could lead to quite different combined D/H ratios. If the alpha-hydroxy acids lose significantly more deuterium during synthesis than the alpha-amino acids or if they have a higher rate of H/D exchange with liquid water than alpha-amino acids, the alpha-hydroxy acids would be isotopically lighter than the alpha-amino acids, because the water responsible for the aqueous alteration of the Murchison parent body was deuterium depleted with deltaD = -100. o/oo [3]. To determine between these alternative mechanisms we measured the rates of hydrogen-deuterium exchange of glycolic acid (the alpha-hydroxy analog of glycine), lactic acid (the alpha-hydroxy analog of alanine), and alpha-hydroxy isobutyric acid have been measured in D2O as a function of pH, temperature and the presence of Allende or Murchison minerals. No detectable H/D exchange was observed. Glycine subjected to similar conditons exchanged

  17. Reasons for the occurrence of the twenty coded protein amino acids

    NASA Technical Reports Server (NTRS)

    Weber, A. L.; Miller, S. L.

    1981-01-01

    Factors involved in the selection of the 20 protein L-alpha-amino acids during chemical evolution and the early stages of Darwinian evolution are discussed. The selection is considered on the basis of the availability in the primitive ocean, function in proteins, the stability of the amino acid and its peptides, stability to racemization, and stability on the transfer RNA. It is concluded that aspartic acid, glutamic acid, arginine, lysine, serine and possibly threonine are the best choices for acidic, basic and hydroxy amino acids. The hydrophobic amino acids are reasonable choices, except for the puzzling absences of alpha-amino-n-butyric acid, norvaline and norleucine. The choices of the sulfur and aromatic amino acids seem reasonable, but are not compelling. Asparagine and glutamine are apparently not primitive. If life were to arise on another planet, it would be expected that the catalysts would be poly-alpha-amino acids and that about 75% of the amino acids would be the same as on the earth.

  18. Reasons for the occurrence of the twenty coded protein amino acids

    NASA Technical Reports Server (NTRS)

    Weber, A. L.; Miller, S. L.

    1981-01-01

    Factors involved in the selection of the 20 protein L-alpha-amino acids during chemical evolution and the early stages of Darwinian evolution are discussed. The selection is considered on the basis of the availability in the primitive ocean, function in proteins, the stability of the amino acid and its peptides, stability to racemization, and stability on the transfer RNA. It is concluded that aspartic acid, glutamic acid, arginine, lysine, serine and possibly threonine are the best choices for acidic, basic and hydroxy amino acids. The hydrophobic amino acids are reasonable choices, except for the puzzling absences of alpha-amino-n-butyric acid, norvaline and norleucine. The choices of the sulfur and aromatic amino acids seem reasonable, but are not compelling. Asparagine and glutamine are apparently not primitive. If life were to arise on another planet, it would be expected that the catalysts would be poly-alpha-amino acids and that about 75% of the amino acids would be the same as on the earth.

  19. Carboxylic Acids as Indicators of Parent Body Conditions

    NASA Technical Reports Server (NTRS)

    Lerner N. R.; Chang, Sherwood (Technical Monitor)

    1995-01-01

    Alpha-hydroxy and alpha-amino carboxylic acids found on the Murchison meteorite are deuterium enriched. It is postulated that they arose from a common interstellar scurce: the reaction of carbonyl compounds in an aqueous mixture containing HCN and NH3. Carbonyl compounds react with HCN to form alpha-hydroxy nitriles, RR'CO + HCN right and left arrow RR'C(OH)CN. If ammonia is also present, the alpha-hydroxy nitriles will exist in equilibrium with the alpha-amino nitriles, RR'C(OH)CN + NH3 right and left arrow - RRCNH2CN + H2O. Both nitrites are hydrolyzed by water to form carboxylic acids: RR'C(OH)CN + H2O yields RR'C(OH)CO2H and RR'C(NH2)CN + H2O yields RR'C(NH2)CO2H.

  20. Evolution from amino acids - Lunar occurrence of their precursors.

    NASA Technical Reports Server (NTRS)

    Fox, S. W.

    1972-01-01

    Review of the present state of experimentally based concepts of organic evolution from amino acids. Earlier studies of the synthesis of amino acid precursors from meteoritic material, lunar dust, and terrestrial lava are briefly summarized, and laboratory experiments in which polymers of amino acids were obtained either by direct heating of dry amino acids or by heating aqueous solutions of mixtures of amino acids are described. In particular, a process is described by which alpha-amino acids were made to react to form linear chains of proteinoids. It is concluded that a proteinoid microsystem was a common ancestor of all life on earth.

  1. Selective Michael-aldol reaction by use of sterically hindered aluminum aryloxides as Lewis acids: an easy approach to cyclobutane amino acids.

    PubMed

    Avenoza, Alberto; Busto, Jesús H; Canal, Noelia; Peregrina, Jesús M; Pérez-Fernández, Marta

    2005-08-04

    A formal [2 + 2] cycloaddition of 2-amidoacrylates with monosubstituted donor olefins, including its asymmetric version, is described. The stereoselectivity of this reaction can be modulated by the use of sterically hindered aluminum aryloxides or methylaluminoxane as Lewis acids. The reaction was applied to the synthesis of both stereoisomers of 2-benzyloxycyclobutane-alpha-amino acid, which are protected serine analogues c(4)Ser(OBn).

  2. Roles of fragile X mental retardation protein in dopaminergic stimulation-induced synapse-associated protein synthesis and subsequent alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) receptor internalization.

    PubMed

    Wang, Hansen; Kim, Susan S; Zhuo, Min

    2010-07-09

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.

  3. Early continuous white noise exposure alters l-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit glutamate receptor 2 and gamma-aminobutyric acid type a receptor subunit beta3 protein expression in rat auditory cortex.

    PubMed

    Xu, Jinghong; Yu, Liping; Zhang, Jiping; Cai, Rui; Sun, Xinde

    2010-02-15

    Auditory experience during the postnatal critical period is essential for the normal maturation of auditory function. Previous studies have shown that rearing infant rat pups under conditions of continuous moderate-level noise delayed the emergence of adult-like topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) beyond normal developmental benchmarks and indefinitely blocked the closure of a brief, critical-period window. To gain insight into the molecular mechanisms of these physiological changes after noise rearing, we studied expression of the AMPA receptor subunit GluR2 and GABA(A) receptor subunit beta3 in the auditory cortex after noise rearing. Our results show that continuous moderate-level noise rearing during the early stages of development decreases the expression levels of GluR2 and GABA(A)beta3. Furthermore, noise rearing also induced a significant decrease in the level of GABA(A) receptors relative to AMPA receptors. However, in adult rats, noise rearing did not have significant effects on GluR2 and GABA(A)beta3 expression or the ratio between the two units. These changes could have a role in the cellular mechanisms involved in the delayed maturation of auditory receptive field structure and topographic organization of A1 after noise rearing.

  4. Exogenous amino acids as fuel in shock.

    PubMed

    Daniel, A M; Kapadia, B; MacLean, L D

    1982-01-01

    It has been suggested that in shock branched-chain amino acids are preferentially oxidized resulting in continued proteolysis and stimulated gluconeogenesis. To determine if exogenous amino acids could be used as fuel in shock, dogs rendered hypotensive by controlled cardiac tamponade and normotensive controls were infused with amino acid mixtures and individual amino acids. When Nephramine, a mixture rich in branched-chain amino acids, was infused, plasma alpha-amino nitrogen levels rose but urea output did not increase in either the control state or in shock, suggesting that these amino acids were not rapidly deaminated to serve as fuels. Travasol, which in addition contained large amounts of alanine and glycine, tripled urea output in the controls and doubled it in shock. The limit of urea production was reached in both groups at 35 mumoles urea/minute/kg. In the Travasol-infused animals plasma alpha-amino nitrogen levels were maintained in normotension but rose sharply in shock. When glycine alone was infused into five dogs in shock urea production rate was 30.6 + 2.1 mumoles/minute/kg; with alanine the same value was 22.5 + 2.2 mumoles/minute/kg. In both cases plasma alpha-amino nitrogen levels were high, suggesting that transport of these amino acids into the cell was slow in shock. In four dogs in shock glycine-14C was added to the glycine infusate as a tracer. At radioactive equilibrium 28% of the label infused appeared in CO2; another 22% appeared in glucose. It is concluded that of all the amino acids tested only glycine and alanine are deaminated rapidly enough to serve as exogenous fuels in shock.

  5. Polymerization of beta-amino acids in aqueous solution

    NASA Technical Reports Server (NTRS)

    Liu, R.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1998-01-01

    We have compared carbonyl diimidazole (CDI) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as activating agents for the oligomerization of negatively-charged alpha- and beta-amino acids in homogeneous aqueous solution. alpha-Amino acids can be oligomerized efficiently using CDI, but not by EDAC. beta-Amino acids can be oligomerized efficiently using EDAC, but not by CDI. Aspartic acid, an alpha- and beta-dicarboxylic acid is oligomerized efficiently by both reagents. These results are explained in terms of the mechanisms of the reactions, and their relevance to prebiotic chemistry is discussed.

  6. Polymerization of beta-amino acids in aqueous solution

    NASA Technical Reports Server (NTRS)

    Liu, R.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1998-01-01

    We have compared carbonyl diimidazole (CDI) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as activating agents for the oligomerization of negatively-charged alpha- and beta-amino acids in homogeneous aqueous solution. alpha-Amino acids can be oligomerized efficiently using CDI, but not by EDAC. beta-Amino acids can be oligomerized efficiently using EDAC, but not by CDI. Aspartic acid, an alpha- and beta-dicarboxylic acid is oligomerized efficiently by both reagents. These results are explained in terms of the mechanisms of the reactions, and their relevance to prebiotic chemistry is discussed.

  7. Deuterium Enrichment of Amino and Hydroxy Acids Found in the Murchison Meteorite: Constraints on Parent Body Conditions

    NASA Technical Reports Server (NTRS)

    Lerner, Narcinda R.; Chang, Sherwood (Technical Monitor)

    1997-01-01

    The alpha-amino and alpha-hydroxy acids found in the Murchison carbonaceous chondrite are deuterium enriched. These compounds are thought to have originated from common deuterium enriched carbonyl precursors, by way of a Strecker synthesis which took place in a solution of HCN, NH3, and carbonyl compounds during the period of aqueous alteration of the meteorite parent body. However, the hydroxy acids found on Murchison are less deuterium enriched than the amino acids. With the objective of determining if the discrepancy in deuterium enrichment between the amino acids and the hydroxy acids found on Murchison is consistent with their formation in a Strecker synthesis, we have measured the deuterium content of alpha-amino and alpha-hydroxy acids produced in solutions of deuterated carbonyl compounds, KCN and NH4Cl, and also in mixtures of such solutions and Allende dust at 263 K and 295 K. Retention of the isotopic signature of the starting carbonyl by both alpha amino acids and alpha hydroxy acids is more dependent upon temperature, concentration and pH than upon the presence of meteorite dust in the solution. The constraints these observations place on Murchison parent body conditions will be discussed.

  8. Production of free amino acids and gamma-aminobutyric acid by autolysis reactions from wheat bran.

    PubMed

    Nogata, Yoichi; Nagamine, Takashi

    2009-02-25

    To find added value for wheat-milling byproduct, an approach for producing free amino acids and gamma-aminobutyric acid (GABA) was examined. Milled whole grain, bran, shorts, red dog, and 60% extracted flour all released amino acids using a water-soaking treatment. Little difference was found in amino acid production yield from whole grain between the soft and hard wheat cultivars investigated. Among the milled fractions, shorts produced the largest amount of total amino acids followed by bran, red dog, and 60% extracted flour in decreasing order. From the byproduct fraction (mixture of bran and shorts), leucine (Leu), arginine (Arg), valine (Val), lysine (Lys), glutamine (Gln), phenylalanine (Phe), isoleucine (Ile), and GABA were produced at 486, 421, 316, 329, 321, 279, 227, and 118 mg/100 g, respectively, in 120 h at 40 degrees C. Optimal pH for the byproduct fraction was 3.5-5.0 for alpha-amino acids and 5.5 for GABA. The production levels rose with increasing temperature up to 40-50 degrees C for alpha-amino acids and up to 40 degrees C for GABA. The yield of all amino acids increased in the experimented period until 120 h except for aspartic acid (Asp) and asparagine (Asn). Thus, wheat-milling byproducts have the potential to become effective materials for developing foods enriched in branched-chain amino acids (BCAA), Arg, Lys, Gln, Phe, and GABA.

  9. Elevation of serum levels of beta-aminoisobutyric acid in uremic patients and the toxicity of the amino acid.

    PubMed

    Gejyo, F; Kinoshita, Y; Ikenaka, T

    1977-12-01

    A reliable method for the determination of beta-aminoisobutyric acid in serum was developed utilizing an automated amino acid analyzer. The serum concentrations of beta-aminoisobutyric acid were determined in 20 normal subjects and in 71 uremic patients. The mean serum level of beta-aminoisobutyric acid was markedly increased in the uremic patients to 0.856 +/- 0.910 (mean +/- SD) mg/100 ml as compared with a normal value of 0.026 +/- 0.027 mg/100 ml. The distribution of serum beta-aminoisobutyric acid level in uremic patients was wide-spread, and there was no correlation between the serum levels of the amino acid and those of urea nitrogen, creatinine and uric acid. The toxicity of beta-aminoisobutyric acid on mice with acute renal failure induced by uranyl acetate was investigated and compared with that of alpha-amino-n-butyric acid and gamma-amino-n-butyric acid. All mice given more than 4 g/kg body wt of beta-aminoisobutyric acid showed twitching and cramps, and some of them died. However, the control mice given an equivalent dose of alpha-amino-n-butyric acid or gamma-amino-n-butyric acid showed no change. These results suggest that beta-aminoisobutyric acid might be a factor influencing the development and progression of uremic toxemia.

  10. Constraining Galileon inflation

    SciTech Connect

    Regan, Donough; Anderson, Gemma J.; Hull, Matthew; Seery, David E-mail: G.Anderson@sussex.ac.uk E-mail: D.Seery@sussex.ac.uk

    2015-02-01

    In this short paper, we present constraints on the Galileon inflationary model from the CMB bispectrum. We employ a principal-component analysis of the independent degrees of freedom constrained by data and apply this to the WMAP 9-year data to constrain the free parameters of the model. A simple Bayesian comparison establishes that support for the Galileon model from bispectrum data is at best weak.

  11. Characterization of a broad-scope amino acid transport system in sand dollars

    SciTech Connect

    Davis, J.P.; Bellis, S.; Stephens, G.C. )

    1988-03-01

    Both echinoderm embryos and adults take up {sup 14}C-labelled-{alpha}-amino acids by an apparent broad-scope transport system. This transporter can be characterized as follows: alanine transport is not blocked by {alpha}-(methylamino)isobutyric acid. Leucine and other lipophilic neutral amino acids are preferentially transported. Transport is sodium dependent and blocked by 2-aminobicyclo-(2,2,1)heptane-2-carboxyclic acid. Lysine and aspartate transport is inhibited by lipophilic neutral amino acids. Taurine, a {beta}-neutral amino acid is translocated via a second and independent carrier.

  12. Amino Acid Chemistry as a Link Between Small Solar System Bodies and Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Ehrenfreund, Pascale; Botta, Oliver; Cooper, George; Bada, Jeffrey L.

    2000-01-01

    Establishing chemical links between meteorites and small solar system bodies, such as comets and asteroids, provides a tool for investigating the processes that occurred during the formation of the solar system. Carbonaceous meteorites are of particular interest, since they may have seeded the early Earth with a variety of prebiotic organic compounds including amino acids, purines and pyrimidines, which are thought to be necessary for the origin of life. Here we report the results of high-performance liquid chromatography (HPLC) based amino acid analyses of the acid-hydrolyzed hot water extracts from pristine interior pieces of the CI carbonaceous chondrites Orgueil and Ivuna and the CM meteorites Murchison and Murray. We found that the CI meteorites Orgueil and Ivuna contained high abundances of beta-alanine and glycine, while only traces of other amino acids like alanine, alpha-amino-n-butryic acid (ABA) and alpha-aminoisobutyric acid (AIB) were detected in these meteorites. Carbon isotopic measurements of beta-alanine and glycine in Orgueil by gas chromatography combustion-isotope ratio mass spectrometry clearly indicate an extraterrestrial origin of these amino acids. The amino acid composition of Orgueil and Ivuna was strikingly different from the CM chondrites Murchison and Murray. The most notable difference was the high relative abundance of B-alanine in Orgueil and Ivuna compared to Murchison and Murray. Furthermore, AIB, which is one of the most abundant amino acids found in Murchison and Murray, was present in only trace amounts in Orgueil and Ivuna. Our amino acid data strongly suggest that the CI meteorites Orgueil and Ivuna came from a different type of parent body than the CM meteorites Murchison and Murray, possibly from an extinct comet. It is generally thought that carbonaceous meteorites are fragments of larger asteroidal bodies delivered via near Earth objects (NEO). Orbital and dynamic studies suggest that both fragments of main belt asteroids

  13. Amino Acid Chemistry as a Link Between Small Solar System Bodies and Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Ehrenfreund, Pascale; Botta, Oliver; Cooper, George; Bada, Jeffrey L.

    2000-01-01

    Establishing chemical links between meteorites and small solar system bodies, such as comets and asteroids, provides a tool for investigating the processes that occurred during the formation of the solar system. Carbonaceous meteorites are of particular interest, since they may have seeded the early Earth with a variety of prebiotic organic compounds including amino acids, purines and pyrimidines, which are thought to be necessary for the origin of life. Here we report the results of high-performance liquid chromatography (HPLC) based amino acid analyses of the acid-hydrolyzed hot water extracts from pristine interior pieces of the CI carbonaceous chondrites Orgueil and Ivuna and the CM meteorites Murchison and Murray. We found that the CI meteorites Orgueil and Ivuna contained high abundances of beta-alanine and glycine, while only traces of other amino acids like alanine, alpha-amino-n-butryic acid (ABA) and alpha-aminoisobutyric acid (AIB) were detected in these meteorites. Carbon isotopic measurements of beta-alanine and glycine in Orgueil by gas chromatography combustion-isotope ratio mass spectrometry clearly indicate an extraterrestrial origin of these amino acids. The amino acid composition of Orgueil and Ivuna was strikingly different from the CM chondrites Murchison and Murray. The most notable difference was the high relative abundance of B-alanine in Orgueil and Ivuna compared to Murchison and Murray. Furthermore, AIB, which is one of the most abundant amino acids found in Murchison and Murray, was present in only trace amounts in Orgueil and Ivuna. Our amino acid data strongly suggest that the CI meteorites Orgueil and Ivuna came from a different type of parent body than the CM meteorites Murchison and Murray, possibly from an extinct comet. It is generally thought that carbonaceous meteorites are fragments of larger asteroidal bodies delivered via near Earth objects (NEO). Orbital and dynamic studies suggest that both fragments of main belt asteroids

  14. Choosing health, constrained choices.

    PubMed

    Chee Khoon Chan

    2009-12-01

    In parallel with the neo-liberal retrenchment of the welfarist state, an increasing emphasis on the responsibility of individuals in managing their own affairs and their well-being has been evident. In the health arena for instance, this was a major theme permeating the UK government's White Paper Choosing Health: Making Healthy Choices Easier (2004), which appealed to an ethos of autonomy and self-actualization through activity and consumption which merited esteem. As a counterpoint to this growing trend of informed responsibilization, constrained choices (constrained agency) provides a useful framework for a judicious balance and sense of proportion between an individual behavioural focus and a focus on societal, systemic, and structural determinants of health and well-being. Constrained choices is also a conceptual bridge between responsibilization and population health which could be further developed within an integrative biosocial perspective one might refer to as the social ecology of health and disease.

  15. Constraining the dark fluid

    SciTech Connect

    Kunz, Martin; Liddle, Andrew R.; Parkinson, David; Gao Changjun

    2009-10-15

    Cosmological observations are normally fit under the assumption that the dark sector can be decomposed into dark matter and dark energy components. However, as long as the probes remain purely gravitational, there is no unique decomposition and observations can only constrain a single dark fluid; this is known as the dark degeneracy. We use observations to directly constrain this dark fluid in a model-independent way, demonstrating, in particular, that the data cannot be fit by a dark fluid with a single constant equation of state. Parametrizing the dark fluid equation of state by a variety of polynomials in the scale factor a, we use current kinematical data to constrain the parameters. While the simplest interpretation of the dark fluid remains that it is comprised of separate dark matter and cosmological constant contributions, our results cover other model types including unified dark energy/matter scenarios.

  16. Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats.

    PubMed

    Damgaard, Trine; Larsen, Dorrit Bjerg; Hansen, Suzanne L; Grayson, Ben; Neill, Jo C; Plath, Niels

    2010-02-11

    Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclidine (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Previous studies have shown that sub-chronic PCP induces an enduring episodic memory deficit in female Lister Hooded rats in the novel object recognition (NOR) task. Here we show that positive modulation of AMPA receptor (AMPAR) mediated glutamate transmission alleviates cognitive deficits induced by sub-chronic PCP treatment. Female Lister hooded rats were treated sub-chronically with either vehicle (0.9% saline) or PCP (2mg/kg two doses per day for 7 days), followed by a 7 days washout period. 30 min prior to the acquisition trial of the NOR task animals were dosed with either vehicle, CX546 (10, 40 or 80 mg/kg) or CX516 (0.5, 2.5, 10, 40 or 80 mg/kg). Our results show that sub-chronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this disruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment of cognitive deficits in schizophrenia.

  17. Pharmacology of the inhibitory glycine receptor: agonist and antagonist actions of amino acids and piperidine carboxylic acid compounds.

    PubMed

    Schmieden, V; Betz, H

    1995-11-01

    To define structure-activity relations for ligands binding to the inhibitory glycine receptor (GlyR), the agonistic and antagonistic properties of alpha- and beta-amino acids were analyzed at the recombinant human alpha 1 GlyR expressed in Xenopus oocytes. The agonistic activity of alpha-amino acids exhibited a marked stereoselectivity and was highly susceptible to substitutions at the C alpha-atom. In contrast, alpha-amino acid antagonism was not enantiomer dependent and was influenced little by C alpha-atom substitutions. The beta-amino acids taurine, beta-aminobutyric acid (beta-ABA), and beta-aminoisobutyric acid (beta-AIBA) are partial agonists at the GlyR. Low concentrations of these compounds competitively inhibited glycine responses, whereas higher concentrations elicited a significant membrane current. Nipecotic acid, which contains a trans-beta-amino acid configuration, behaved as purely competitive GlyR antagonist. Our data are consistent with the existence of a common binding site for all amino acid agonists and antagonists, at which the functional consequences of binding depend on the particular conformation a given ligand adopts within the binding pocket. In the case of beta-amino acids, the trans conformation appears to mediate antagonistic receptor binding, and the cis conformation appears to mediate agonistic receptor binding. This led us to propose that the partial agonist activity of a given beta-amino acid is determined by the relative mole fractions of the respective cis/trans conformers.

  18. Synthesis of constrained analogues of tryptophan

    PubMed Central

    Negrato, Marco; Abbiati, Giorgio; Dell’Acqua, Monica

    2015-01-01

    Summary A Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues. PMID:26664620

  19. Synthesis of conformationally constrained tricyclic beta-lactam enantiomers through Ugi four-center three-component reactions of a monoterpene-based beta-amino acid.

    PubMed

    Szakonyi, Zsolt; Sillanpää, Reijo; Fülöp, Ferenc

    2010-02-01

    (1R,2R,3S,4R)-2-Amino-6,6-dimethylbicyclo[3.1.1]heptane-3-carboxylic acid 1 was reacted with three aldehydes and two isocyanides in methanol, in water, and under solvent-free conditions to prepare enantiomeric beta-lactams via U-4C-3CRs. The yields in methanol were found to be from acceptable to good. High diastereoselectivities of the reactions were observed, and the diastereoisomers were successfully separated in most cases. In water or under solvent-free conditions, the yields were similar to those in methanol when the aldehyde was pivalaldehyde or propionaldehyde. The advantages of water are the facile isolation of the precipitated product and the shorter reaction time.

  20. Constrained control allocation

    NASA Technical Reports Server (NTRS)

    Durham, Wayne C.

    1992-01-01

    This paper addresses the problem of the allocation of several flight controls to the generation of specified body-axis moments. The number of controls is greater than the number of moments being controlled, and the ranges of the controls are constrained to certain limits. The controls are assumed to be individually linear in their effect throughout their ranges of motion, and independent of one another in their effects. The geometries of the subset of the constrained controls and of its image in moment space are examined. A direct method of allocating these several controls is presented, that guarantees the maximum possible moment is generated within the constraints of the controls. The results are illustrated by an example problem involving three controls and two moments.

  1. Constrained noninformative priors

    SciTech Connect

    Atwood, C.L.

    1994-10-01

    The Jeffreys noninformative prior distribution for a single unknown parameter is the distribution corresponding to a uniform distribution in the transformed model where the unknown parameter is approximately a location parameter. To obtain a prior distribution with a specified mean but with diffusion reflecting great uncertainty, a natural generalization of the noninformative prior is the distribution corresponding to the constrained maximum entropy distribution in the transformed model. Examples are given.

  2. Adipic acid increases plasma lysine but does not improve the efficiency of lysine utilization in swine.

    PubMed

    van Kempen, T A; van Heugten, E; Trottier, N L

    2001-09-01

    Adipic acid, upon catabolism, results in intermediates that bear a structural similarity to lysine degradation products. The objectives of this research were to determine whether adipic acid affects lysine concentrations in plasma and to evaluate whether adipic acid improves the efficiency of lysine utilization in pigs. In Exp. 1, nursery pigs (n = 14) were fed (for a period of 7 d) either a standard nursery diet or the same diet supplemented with 1% adipic acid to assess effects on plasma amino acid concentrations (plasma collected on d 7). In Exp. 2, nursery pigs (n = 56) were fed (for a period of 15 d) either a control diet or the same diet but deficient in either lysine, threonine, or tryptophan with or without supplemental adipic acid to assess the effects of adipic acid on the efficiency of amino acid utilization. The results from Exp. 1 showed that adipic acid increased plasma lysine (by 18%) but not alpha-amino adipic acid, an intermediate in lysine degradation. Experiment 2 demonstrated that adipic acid did not increase the efficiency of utilization of lysine, threonine, or tryptophan. The lack of effects on alpha-amino adipic acid in Exp. 1 and the lack of a positive effect on the efficiency of utilization of lysine, threonine, and tryptophan suggest that adipic acid does not inhibit the mitochondrial uptake of lysine and(or) its degradation in the mitochondrion. It is concluded that feeding adipic acid increases plasma lysine but does not improve the efficiency of lysine utilization.

  3. The spark discharge synthesis of amino acids from various hydrocarbons

    NASA Technical Reports Server (NTRS)

    Ring, D.; Miller, S. L.

    1984-01-01

    The spark discharge synthesis of amino acids using an atmosphere of CH4+N2+H2O+NH3 has been investigated with variable pNH3. The amino acids produced using higher hydrocarbons (ethane, ethylene, acetylene, propane, butane, and isobutane) instead of CH4 were also investigated. There was considerable range in the absolute yields of amino acids, but the yields relative to glycine (or alpha-amino-n-butyric acid) were more uniform. The relative yields of the C3 to C6 aliphatic alpha-amino acids are nearly the same (with a few exceptions) with all the hydrocarbons. The glycine yields are more variable. The precursors to the C3-C6 aliphatic amino acids seem to be produced in the same process, which is separate from the synthesis of glycine precursors. It may be possible to use these relative yields as a signature for a spark discharge synthesis provided corrections can be made for subsequent decomposition events (e.g. in the Murchison meteorite).

  4. The spark discharge synthesis of amino acids from various hydrocarbons

    NASA Technical Reports Server (NTRS)

    Ring, D.; Miller, S. L.

    1984-01-01

    The spark discharge synthesis of amino acids using an atmosphere of CH4+N2+H2O+NH3 has been investigated with variable pNH3. The amino acids produced using higher hydrocarbons (ethane, ethylene, acetylene, propane, butane, and isobutane) instead of CH4 were also investigated. There was considerable range in the absolute yields of amino acids, but the yields relative to glycine (or alpha-amino-n-butyric acid) were more uniform. The relative yields of the C3 to C6 aliphatic alpha-amino acids are nearly the same (with a few exceptions) with all the hydrocarbons. The glycine yields are more variable. The precursors to the C3-C6 aliphatic amino acids seem to be produced in the same process, which is separate from the synthesis of glycine precursors. It may be possible to use these relative yields as a signature for a spark discharge synthesis provided corrections can be made for subsequent decomposition events (e.g. in the Murchison meteorite).

  5. Characteristics and formation of amino acids and hydroxy acids of the Murchison meteorite

    NASA Technical Reports Server (NTRS)

    Cronin, J. R.; Cooper, G. W.; Pizzarello, S.

    1995-01-01

    Eight characteristics of the unique suite of amino acids and hydroxy acids found in the Murchison meteorite can be recognized on the basis of detailed molecular and isotopic analyses. The marked structural correspondence between the alpha-amino acids and alpha-hydroxy acids and the high deuterium/hydrogen ratio argue persuasively for their formation by aqueous phase Strecker reactions in the meteorite parent body from presolar, i.e., interstellar, aldehydes, ketones, ammonia, and hydrogen cyanide. The characteristics of the meteoritic suite of amino acids and hydroxy acids are briefly enumerated and discussed with regard to their consonance with this interstellar-parent body formation hypothesis. The hypothesis has interesting implications for the organic composition of both the primitive parent body and the presolar nebula.

  6. Characteristics and formation of amino acids and hydroxy acids of the Murchison meteorite

    NASA Technical Reports Server (NTRS)

    Cronin, J. R.; Cooper, G. W.; Pizzarello, S.

    1995-01-01

    Eight characteristics of the unique suite of amino acids and hydroxy acids found in the Murchison meteorite can be recognized on the basis of detailed molecular and isotopic analyses. The marked structural correspondence between the alpha-amino acids and alpha-hydroxy acids and the high deuterium/hydrogen ratio argue persuasively for their formation by aqueous phase Strecker reactions in the meteorite parent body from presolar, i.e., interstellar, aldehydes, ketones, ammonia, and hydrogen cyanide. The characteristics of the meteoritic suite of amino acids and hydroxy acids are briefly enumerated and discussed with regard to their consonance with this interstellar-parent body formation hypothesis. The hypothesis has interesting implications for the organic composition of both the primitive parent body and the presolar nebula.

  7. Constrained space camera assembly

    DOEpatents

    Heckendorn, Frank M.; Anderson, Erin K.; Robinson, Casandra W.; Haynes, Harriet B.

    1999-01-01

    A constrained space camera assembly which is intended to be lowered through a hole into a tank, a borehole or another cavity. The assembly includes a generally cylindrical chamber comprising a head and a body and a wiring-carrying conduit extending from the chamber. Means are included in the chamber for rotating the body about the head without breaking an airtight seal formed therebetween. The assembly may be pressurized and accompanied with a pressure sensing means for sensing if a breach has occurred in the assembly. In one embodiment, two cameras, separated from their respective lenses, are installed on a mounting apparatus disposed in the chamber. The mounting apparatus includes means allowing both longitudinal and lateral movement of the cameras. Moving the cameras longitudinally focuses the cameras, and moving the cameras laterally away from one another effectively converges the cameras so that close objects can be viewed. The assembly further includes means for moving lenses of different magnification forward of the cameras.

  8. Thermal copoly/amino acids/ as inhibitors of glyoxalase I

    NASA Technical Reports Server (NTRS)

    Fox, S. W.; Syren, R. M.; Windsor, C. R.

    1979-01-01

    A number of copoly(alpha-amino acids) have been prepared thermally; some have been found to function as inhibitors of glyoxalase I, an enzyme which occupies a central position in Szent-Gyorgyi's theory of tumour genesis. These polymers are also of interest in the search for synthetic peptides having carcinostatic activity, since many natural peptides are active. The way in which the inhibitory activity varies with composition of the synthetic polymers has been investigated. Various properties (hydrophobicity, molecular weight, UV absorption, kinetic type) have been examined in a search for correlates of inhibitory activity.

  9. Constraining the Littlest Higgs

    SciTech Connect

    Petriello, Frank J

    2002-11-18

    Little Higgs models offer a new way to address the hierarchy problem, and give rise to a weakly-coupled Higgs sector. These theories predict the existence of new states which are necessary to cancel the quadratic divergences of the Standard Model. The simplest version of these models, the Littlest Higgs, is based on an SU(5)/SO(5) non-linear sigma model and predicts that four new gauge bosons, a weak isosinglet quark, t{prime}, with Q=2/3, as well as an isotriplet scalar field exist at the TeV scale. We consider the contributions of these new states to precision electroweak observables, and examine their production at the Tevatron. We thoroughly explore the parameter space of this model and find that small regions are allowed by the precision data where the model parameters take on their natural values. These regions are, however, excluded by the Tevatron data. Combined, the direct and indirect effects of these new states constrain the ''decay constant'' f {approx}> 3.5 TeV and m{sub t{prime}} {approx}> 10 TeV. These bounds imply that significant fine-tuning be present in order for this model to resolve the hierarchy problem.

  10. Early cosmology constrained

    NASA Astrophysics Data System (ADS)

    Verde, Licia; Bellini, Emilio; Pigozzo, Cassio; Heavens, Alan F.; Jimenez, Raul

    2017-04-01

    We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter ΩMR < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < Neff < 3.2 when imposing flatness. Our constraints thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is rs = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to rs = 150 ± 5 Mpc.

  11. Constrained space camera assembly

    DOEpatents

    Heckendorn, F.M.; Anderson, E.K.; Robinson, C.W.; Haynes, H.B.

    1999-05-11

    A constrained space camera assembly which is intended to be lowered through a hole into a tank, a borehole or another cavity is disclosed. The assembly includes a generally cylindrical chamber comprising a head and a body and a wiring-carrying conduit extending from the chamber. Means are included in the chamber for rotating the body about the head without breaking an airtight seal formed therebetween. The assembly may be pressurized and accompanied with a pressure sensing means for sensing if a breach has occurred in the assembly. In one embodiment, two cameras, separated from their respective lenses, are installed on a mounting apparatus disposed in the chamber. The mounting apparatus includes means allowing both longitudinal and lateral movement of the cameras. Moving the cameras longitudinally focuses the cameras, and moving the cameras laterally away from one another effectively converges the cameras so that close objects can be viewed. The assembly further includes means for moving lenses of different magnification forward of the cameras. 17 figs.

  12. Effects of amino acid additives during hemodialysis of children.

    PubMed

    Abitbol, C L; Mrozinska, K; Mandel, S; McVicar, M; Wapnir, R A

    1984-01-01

    The intradialytic losses into the dialysate of free amino acids (AA) and alpha-amino nitrogen were determined during the dialysis of three children. Variations in plasma AA were determined pre- and postdialysis. The effect of these losses with the addition of an Abbott General Amino Acid Mixture to the dialysate in concentrations of 8.5, 17, and 34 mg/100 ml was studied. The major determinant of AA losses was the plasma concentration of the AA before beginning the dialysis treatment. Dialysance of individual AA varied inversely with their molecular weights. A zero flux of alpha-amino nitrogen occurred at a derived concentration of 22 mg/100 ml of the AA additive in the dialysate. Plasma concentrations of nonessential amino acids were little affected by the dialysate additive. In contrast, total essential amino acid nitrogen which fell during baseline dialyses showed significant improvement when the AA solution was added to the dialysate. This study suggests that the addition of AA to the dialysate bath may be effective in decreasing AA nitrogen losses during dialysis.

  13. Power-constrained supercomputing

    NASA Astrophysics Data System (ADS)

    Bailey, Peter E.

    As we approach exascale systems, power is turning from an optimization goal to a critical operating constraint. With power bounds imposed by both stakeholders and the limitations of existing infrastructure, achieving practical exascale computing will therefore rely on optimizing performance subject to a power constraint. However, this requirement should not add to the burden of application developers; optimizing the runtime environment given restricted power will primarily be the job of high-performance system software. In this dissertation, we explore this area and develop new techniques that extract maximum performance subject to a particular power constraint. These techniques include a method to find theoretical optimal performance, a runtime system that shifts power in real time to improve performance, and a node-level prediction model for selecting power-efficient operating points. We use a linear programming (LP) formulation to optimize application schedules under various power constraints, where a schedule consists of a DVFS state and number of OpenMP threads for each section of computation between consecutive message passing events. We also provide a more flexible mixed integer-linear (ILP) formulation and show that the resulting schedules closely match schedules from the LP formulation. Across four applications, we use our LP-derived upper bounds to show that current approaches trail optimal, power-constrained performance by up to 41%. This demonstrates limitations of current systems, and our LP formulation provides future optimization approaches with a quantitative optimization target. We also introduce Conductor, a run-time system that intelligently distributes available power to nodes and cores to improve performance. The key techniques used are configuration space exploration and adaptive power balancing. Configuration exploration dynamically selects the optimal thread concurrency level and DVFS state subject to a hardware-enforced power bound

  14. Constraining Dark Energy

    NASA Astrophysics Data System (ADS)

    Abrahamse, Augusta

    2010-12-01

    Future advances in cosmology will depend on the next generation of cosmological observations and how they shape our theoretical understanding of the universe. Current theoretical ideas, however, have an important role to play in guiding the design of such observational programs. The work presented in this thesis concerns the intersection of observation and theory, particularly as it relates to advancing our understanding of the accelerated expansion of the universe (or the dark energy). Chapters 2 - 4 make use of the simulated data sets developed by the Dark Energy Task Force (DETF) for a number of cosmological observations currently in the experimental pipeline. We use these forecast data in the analysis of four quintessence models of dark energy: the PNGB, Exponential, Albrecht-Skordis and Inverse Power Law (IPL) models. Using Markov Chain Monte Carlo sampling techniques we examine the ability of each simulated data set to constrain the parameter space of these models. We examine the potential of the data for differentiating time-varying models from a pure cosmological constant. Additionally, we introduce an abstract parameter space to facilitate comparison between models and investigate the ability of future data to distinguish between these quintessence models. In Chapter 5 we present work towards understanding the effects of systematic errors associated with photometric redshift estimates. Due to the need to sample a vast number of deep and faint galaxies, photometric redshifts will be used in a wide range of future cosmological observations including gravitational weak lensing, baryon accoustic oscillations and type 1A supernovae observations. The uncertainty in the redshift distributions of galaxies has a significant potential impact on the cosmological parameter values inferred from such observations. We introduce a method for parameterizing uncertainties in modeling assumptions affecting photometric redshift calculations and for propagating these

  15. Line constrained between two curves

    NASA Astrophysics Data System (ADS)

    Ahmad, Afida; Ali, Jamaludin Md.

    2013-04-01

    In this paper, the method of finding the line constrained between two quadratic Bezier curves and also finding the line constrained between a quadratic Bezier curve and a circle is presented. The application of the line constrained can be used in the construction of railway tracks between any obstacle or rolling a ball to the other side of a wall in a way that it just touches the wall. The method used is by using equal root properties of a quadratic equation in order to find one point where the line touches the curve. The work examples involved different curve orientations and different circle positions. Mathematica software is used to compute the solutions for the line constrained and present the solutions graphically. By using the method proposed, the number of intersection points obtained is used to determine the number of lines constrained between two curves and between a curve and a circle. The conclusion on whether all lines are acceptable to be considered as the line constrained are depending on the application of the line.

  16. Imino Acids in the Murchison Meteorite: Evidence of Strecker Reactions

    NASA Technical Reports Server (NTRS)

    Lerner, N. R.; Cooper, G. W.

    2003-01-01

    Both alpha-amino acids and alpha-hydroxy acids occur in aqueous extracts of the Murchison carbonaceous meteorite. The Strecker-cyanohydrin reaction, the reaction of carbonyl compounds, cyanide, and ammonia to produce amino and hydroxy acids, has been proposed as a source of such organic acids in meteorites. Such syntheses are consistent with the suggestion that interstellar precursors of meteoritic organic compounds accreted on the meteorite parent body together with other ices. Subsequent internal heating of the parent body melted these ices and led to the formation of larger compounds in synthetic reactions during aqueous alteration, which probably occurred at temperatures between 273K and 298K. In the laboratory, imino acids are observed as important by-products of the Strecker synthesis.

  17. Reappraisal of the 20th-century version of amino acid metabolism.

    PubMed

    Katagiri, Masayuki; Nakamura, Masahiko

    2003-12-05

    In this article, we advocate the radical revision of the 20th-century version of amino acid metabolism as follows. (1) Classic studies on the incorporation of [15N]ammonia into glutamate, once considered to be an epoch-making event, are not distinctive proof of the ability of animals to utilize ammonia for the synthesis of alpha-amino nitrogen. (2) Mammalian glutamate dehydrogenase has been implicated to function as a glutamate-synthesizing enzyme albeit lack of convincing proof. This enzyme, in combination with aminotransferases, is now known to play an exclusive role in the metabolic removal of amino nitrogen and energy production from excess amino acids. (3) Dr. William C Rose's "nutritionally nonessential amino acids" are, of course, essential in cellular metabolism; the nutritional nonessentiality is related to their carbon skeletons, many of which are intermediates of glycolysis or the TCA cycle. Obviously, the prime importance of amino acid nutrition should be the means of obtaining amino nitrogen. (4) Because there is no evidence of the presence of any glutamate-synthesizing enzymes in mammalian tissues, animals must depend on plants and microorganisms for preformed alpha-amino nitrogen. This is analogous to the case of carbohydrates. (5) In contrast, individual essential amino acids, similar to vitamins and essential fatty acids, should be considered important nutrients that must be included regularly in sufficient amounts in the diet.

  18. [The relatioship between decomposition of amino acid chloramines and their structures].

    PubMed

    Roshchupkin, D I; Murina, M A; Petrova, A O; Sergienko, V I

    2009-01-01

    Rate constants of the decomposition of monoamine alpha-amino acid chloramine derivatives were determined by a spectrophotometeric method. Several amino acid chloramines with elevated stability have been found. These included n-chloroglycine, n-chlorovaline, n-chlorothreonine, and n-chloroisoleucine. Their molecular structures are characterized by some characteristic feature at the beta-position. In the case of glycine chloramine, carbon atom at this position is absent, and the chloramine derivatives of three other amino acids possess branched chains. Partial atomic charges of the electrostatic potential (Wang-Ford) for chloramines of alpha-amino acids were computed using the semiempirical quantum-mechanical method AM1. The chloramines with elevated stability have high positive sums of charges of three carbon atoms that are atoms at alpha- and beta-positions and a carboxyl group atom. High partial charge also was obtained for one carbon atom at the beta-position. These computational values may be employed for prediction of the stability of designed amino acid chloramines. One of the important predictions is that the highest atomic charges and stabilities are characteristics of the amino acid chloramines, in which all hydrogen atoms at the beta-position are replaced by carbon-hydrogen chains or hydroxyl groups.

  19. The effect of experimental ischaemia and excitatory amino acid agonists on the GABA and serotonin immunoreactivities in the rabbit retina.

    PubMed

    Osborne, N N; Herrera, A J

    1994-04-01

    The aim of the described experiments was to use immunohistochemistry to visualize the release of GABA from specific retinal amacrine cells following ischaemia and to establish the involvement of defined glutamatergic receptors. In initial experiments, rabbit retinas were exposed in vitro to excitatory amino acid agonists alone or in combination with a putative antagonist, or in physiological solution lacking oxygen and glucose, or in solution containing potassium cyanide for 45 min at 37 degrees C. The nature of the GABA immunoreactivity was then examined by immunohistochemistry. In other in vitro experiments, retinas were first allowed to accumulate exogenous serotonin before exposing the tissues to the combinations as described. These tissues were then processed immunohistochemically for the localization of serotonin. In yet other experiments, the intraocular pressure of a rabbit's eye was raised to about 110 mmHg for 60 min and a reperfusion time of 45 min allowed before dissecting the retina and processing for the localization of GABA immunoreactivity. The other eye served as a control. Of the excitatory amino acid agonists tested, only N-methyl-D-aspartate, kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid caused a change in the GABA immunoreactivity. The N-methyl-D-aspartate effect was specifically antagonized by dizocilpine maleate, dextromethorphan and memantine, and was characterized by a reduction in the number of GABA-immunoreactive perikarya. The GABA "staining" in the inner plexiform layer also appeared as four clear bands. The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- and kainate-induced effects were both antagonized by 6-cyano-2,3-dihydroxy-7-nitroquinoxaline-2,3-dione and partially by kynurenic acid at the concentrations used. Here, the amount of GABA-positive perikarya was greatly reduced and three immunoreactive bands appeared in the inner plexiform layer. However, for low concentrations of alpha-amino-3-hydroxy

  20. Isotopic analyses of amino acids from the Murchison meteorite

    NASA Technical Reports Server (NTRS)

    Pizzarello, S.; Cronin, J. R.; Krishnamurthy, R. V.; Epstein, S.

    1991-01-01

    An account is given of the results of H-2, C-13 isotopic analyses of the Murchison meteorite incorporating an ultrafiltration step to exclude the possibility of fine particulate contaminants. The meteorite's amino acids were chromatographically separated in order to preclude isotopic enrichment by basic compounds other than the amino acids. The results indicate that the Murchison amino acids are isotopically highly unusual; delta-C-13 is elevated by about 40 percent, and delta-D by fully 2500 percent. This high D content of the meteorite's alpha-amino acids may be due to the synthesis of their molecular precursors by low-temperature ion-molecule reactions in an interstellar cloud.

  1. Amino acid sequence of toxin III from Anemonia sulcata.

    PubMed

    Bĕress, L; Wunderer, G; Wachter, E

    1977-08-01

    Toxin III, the smallest toxin component of the poison of the sea anemone Anemonia sulcata, is a polypeptide with 27 amino acids. Its structure is stabilized by three disulfide bridges. The amino acid sequence was determined by solid-phase Edman degradation of the aminoethylated derivative. The peptide was coupled to the carrier, porous glass, by thiourea bridges between the alpha-amino group of arginine-1 and the epsilon-amino group of lysine-26 and the isothiocyanate groups of the carrier. Another fraction of the polypeptide was bound by an acid-amide condensation of the C-terminal valine-27 with the aminopropyl group of the carrier. The sequence of toxin III has no regions homologous to the 47-residue toxin II. Comparison with the known partial sequence of toxin I, which contains 46 amino acids (Wunderer, G. & Eulitz, M., in preparation) also fails to reveal homologies.

  2. Isotopic analyses of amino acids from the Murchison meteorite

    NASA Technical Reports Server (NTRS)

    Pizzarello, S.; Cronin, J. R.; Krishnamurthy, R. V.; Epstein, S.

    1991-01-01

    An account is given of the results of H-2, C-13 isotopic analyses of the Murchison meteorite incorporating an ultrafiltration step to exclude the possibility of fine particulate contaminants. The meteorite's amino acids were chromatographically separated in order to preclude isotopic enrichment by basic compounds other than the amino acids. The results indicate that the Murchison amino acids are isotopically highly unusual; delta-C-13 is elevated by about 40 percent, and delta-D by fully 2500 percent. This high D content of the meteorite's alpha-amino acids may be due to the synthesis of their molecular precursors by low-temperature ion-molecule reactions in an interstellar cloud.

  3. Optimization of retinotopy constrained source estimation constrained by prior

    PubMed Central

    Hagler, Donald J.

    2015-01-01

    Studying how the timing and amplitude of visual evoked responses (VERs) vary between visual areas is important for understanding visual processing but is complicated by difficulties in reliably estimating VERs in individual visual areas using non-invasive brain measurements. Retinotopy constrained source estimation (RCSE) addresses this challenge by using multiple, retinotopically-mapped stimulus locations to simultaneously constrain estimates of VERs in visual areas V1, V2, and V3, taking advantage of the spatial precision of fMRI retinotopy and the temporal resolution of magnetoencephalography (MEG) or electroencephalography (EEG). Nonlinear optimization of dipole locations, guided by a group-constrained RCSE solution as a prior, improved the robustness of RCSE. This approach facilitated the analysis of differences in timing and amplitude of VERs between V1, V2, and V3, elicited by stimuli with varying luminance contrast in a sample of eight adult humans. The V1 peak response was 37% larger than that of V2 and 74% larger than that of V3, and also ~10–20 msec earlier. Normalized contrast response functions were nearly identical for the three areas. Results without dipole optimization, or with other nonlinear methods not constrained by prior estimates were similar but suffered from greater between-subject variability. The increased reliability of estimates offered by this approach may be particularly valuable when using a smaller number of stimulus locations, enabling a greater variety of stimulus and task manipulations. PMID:23868690

  4. Insulin effect on amino acid uptake by unloaded rat hindlimb muscles

    NASA Technical Reports Server (NTRS)

    Jaspers, S. R.; Tischler, M. E.

    1988-01-01

    The effect of insulin on the uptake of alpha-amino-isobutyric acid (AIB) by unloaded rat hindlimb muscles was investigated using soleus and extensor digitorum longus (EDL) muscles from intact and adrenalectomized (ADX) rats that were tail-casted for six days. It was found that, at insulin levels above 0.00001 units/ml, the in vitro rate of AIB uptake by muscles from intact animals was stimulated more in the weight bearing muscles than in unloaded ones. In ADX animals, this differential response to insulin was abolished.

  5. Extraterrestrial Amino Acids in Orgueil and Ivuna: Tracing the Parent Body of CI Type Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Meyer, Michael (Technical Monitor); Ehrenfreund, Pascale; Glavin, Daniel P.; Bota, Oliver; Cooper, George; Bada, Jeffrey

    2001-01-01

    Amino acid analyses using HPLC of pristine interior pieces of the CI carbonaceous chondrites Orgueil and Ivuna have found that beta-alanine, glycine, and gamma-amino-n-butyric acid (ABA) are the most abundant amino acids in these two meteorites, with concentrations ranging from approx. 600 to 2,000 parts per billion (ppb). Other alpha-amino acids such as alanine, alpha-ABA, alpha-aminoisobutyric acid (AIB), and isovaline are present only in trace amounts (less than 200 ppb). Carbon isotopic measurements of beta-alanine and glycine and the presence of racemic (D/L 1) alanine and beta-ABA in Orgueil suggest that these amino acids are extraterrestrial in origin. In comparison to the CM carbonaceous chondrites Murchison and Murray, the amino acid composition of the CIs is strikingly distinct, suggesting that these meteorites came from a different type of parent body, possibly an extinct comet, than did the CM carbonaceous chondrites.

  6. Extraterrestrial Amino Acids in Orgueil and Ivuna: Tracing the Parent Body of CI Type Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Meyer, Michael (Technical Monitor); Ehrenfreund, Pascale; Glavin, Daniel P.; Bota, Oliver; Cooper, George; Bada, Jeffrey

    2001-01-01

    Amino acid analyses using HPLC of pristine interior pieces of the CI carbonaceous chondrites Orgueil and Ivuna have found that beta-alanine, glycine, and gamma-amino-n-butyric acid (ABA) are the most abundant amino acids in these two meteorites, with concentrations ranging from approx. 600 to 2,000 parts per billion (ppb). Other alpha-amino acids such as alanine, alpha-ABA, alpha-aminoisobutyric acid (AIB), and isovaline are present only in trace amounts (less than 200 ppb). Carbon isotopic measurements of beta-alanine and glycine and the presence of racemic (D/L 1) alanine and beta-ABA in Orgueil suggest that these amino acids are extraterrestrial in origin. In comparison to the CM carbonaceous chondrites Murchison and Murray, the amino acid composition of the CIs is strikingly distinct, suggesting that these meteorites came from a different type of parent body, possibly an extinct comet, than did the CM carbonaceous chondrites.

  7. Interactive graphics nonlinear constrained optimization

    NASA Technical Reports Server (NTRS)

    Saouma, V. E.; Sikiotis, E. S.

    1984-01-01

    An interactive computer graphics environment was used for nonlinear constrained optimization analysis. It is found that by combining the power of a digital computer with the subtlety of engineering judgment during program execution, final results can be substantially better than the ones achieved by the numerical algorithm by itself.

  8. The Strecker synthesis from interstellar precursors as a source of amino acids in carbonaceous chondrites: Deuterium retention during synthesis. [Abstract only

    NASA Technical Reports Server (NTRS)

    Lerner, N. R.; Peterson, E.; Chang, S.

    1994-01-01

    Amino acids in the Murchison carbonaceous chondrite are anomalously enriched in deuterium. Synthesis in Strecker reactions from D-enriched interstellar precursors during low temperature aqueous alteration of the parent body has been proposed by Cronin et al. (1988) to account for the isotopic observations. To test this hypothesis, we have measured the retention of deuterium in the glycine, alanine, and alpha-amino isobutyric acid produced, respectively, by reactions of formaldehyde-D2, acetaldehyde-D4, and acetone-D6 with HCN and NH3 in water.

  9. The Strecker synthesis from interstellar precursors as a source of amino acids in carbonaceous chondrites: Deuterium retention during synthesis. [Abstract only

    NASA Technical Reports Server (NTRS)

    Lerner, N. R.; Peterson, E.; Chang, S.

    1994-01-01

    Amino acids in the Murchison carbonaceous chondrite are anomalously enriched in deuterium. Synthesis in Strecker reactions from D-enriched interstellar precursors during low temperature aqueous alteration of the parent body has been proposed by Cronin et al. (1988) to account for the isotopic observations. To test this hypothesis, we have measured the retention of deuterium in the glycine, alanine, and alpha-amino isobutyric acid produced, respectively, by reactions of formaldehyde-D2, acetaldehyde-D4, and acetone-D6 with HCN and NH3 in water.

  10. COBS: COnstrained B-Splines

    NASA Astrophysics Data System (ADS)

    Ng, Pin T.; Maechler, Martin

    2015-05-01

    COBS (COnstrained B-Splines), written in R, creates constrained regression smoothing splines via linear programming and sparse matrices. The method has two important features: the number and location of knots for the spline fit are established using the likelihood-based Akaike Information Criterion (rather than a heuristic procedure); and fits can be made for quantiles (e.g. 25% and 75% as well as the usual 50%) in the response variable, which is valuable when the scatter is asymmetrical or non-Gaussian. This code is useful for, for example, estimating cluster ages when there is a wide spread in stellar ages at a chosen absorption, as a standard regression line does not give an effective measure of this relationship.

  11. Constrained Multiobjective Biogeography Optimization Algorithm

    PubMed Central

    Mo, Hongwei; Xu, Zhidan; Xu, Lifang; Wu, Zhou; Ma, Haiping

    2014-01-01

    Multiobjective optimization involves minimizing or maximizing multiple objective functions subject to a set of constraints. In this study, a novel constrained multiobjective biogeography optimization algorithm (CMBOA) is proposed. It is the first biogeography optimization algorithm for constrained multiobjective optimization. In CMBOA, a disturbance migration operator is designed to generate diverse feasible individuals in order to promote the diversity of individuals on Pareto front. Infeasible individuals nearby feasible region are evolved to feasibility by recombining with their nearest nondominated feasible individuals. The convergence of CMBOA is proved by using probability theory. The performance of CMBOA is evaluated on a set of 6 benchmark problems and experimental results show that the CMBOA performs better than or similar to the classical NSGA-II and IS-MOEA. PMID:25006591

  12. Constrained minimization for monotonic reconstruction

    SciTech Connect

    Rider, W.J.; Kothe, D.B.

    1996-08-20

    The authors present several innovations in a method for monotonic reconstructions. It is based on the application of constrained minimization techniques for the imposition of monotonicity on a reconstruction. In addition, they present extensions of several classical TVD limiters to a genuinely multidimensional setting. In this case the linear least squares reconstruction method is expanded upon. They also clarify data dependent weighting techniques used with the minimization process.

  13. Nitrone protecting groups for enantiopure N-hydroxyamino acids: synthesis of N-terminal peptide hydroxylamines for chemoselective ligations.

    PubMed

    Medina, S Irene; Wu, Jian; Bode, Jeffrey W

    2010-08-07

    The synthesis of enantiopure N-benzylidene nitrones of N-hydroxy-alpha-amino acids and their incorporation using standard Fmoc-based peptide chemistry into solid-supported peptide chains is described. Deprotection and resin cleavage affords N-terminal peptide hydroxylamines, which are the key substrates for chemoselective ligations with C-terminal peptide alpha-ketoacids. This general route is applicable to a variety of different N-terminal residues and provides a general approach to the solid phase synthesis of peptide hydroxylamines.

  14. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, M.M.; Shoup, T.

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  15. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, Mark M.; Shoup, Timothy

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  16. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, Mark M.; Shoup, Timothy

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  17. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, M.M.; Shoup, T.

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  18. Constrained Stochastic Extended Redundancy Analysis.

    PubMed

    DeSarbo, Wayne S; Hwang, Heungsun; Stadler Blank, Ashley; Kappe, Eelco

    2015-06-01

    We devise a new statistical methodology called constrained stochastic extended redundancy analysis (CSERA) to examine the comparative impact of various conceptual factors, or drivers, as well as the specific predictor variables that contribute to each driver on designated dependent variable(s). The technical details of the proposed methodology, the maximum likelihood estimation algorithm, and model selection heuristics are discussed. A sports marketing consumer psychology application is provided in a Major League Baseball (MLB) context where the effects of six conceptual drivers of game attendance and their defining predictor variables are estimated. Results compare favorably to those obtained using traditional extended redundancy analysis (ERA).

  19. Constraining Lorentz violation with cosmology.

    PubMed

    Zuntz, J A; Ferreira, P G; Zlosnik, T G

    2008-12-31

    The Einstein-aether theory provides a simple, dynamical mechanism for breaking Lorentz invariance. It does so within a generally covariant context and may emerge from quantum effects in more fundamental theories. The theory leads to a preferred frame and can have distinct experimental signatures. In this Letter, we perform a comprehensive study of the cosmological effects of the Einstein-aether theory and use observational data to constrain it. Allied to previously determined consistency and experimental constraints, we find that an Einstein-aether universe can fit experimental data over a wide range of its parameter space, but requires a specific rescaling of the other cosmological densities.

  20. Constraining relativistic viscous hydrodynamical evolution

    SciTech Connect

    Martinez, Mauricio; Strickland, Michael

    2009-04-15

    We show that by requiring positivity of the longitudinal pressure it is possible to constrain the initial conditions one can use in second-order viscous hydrodynamical simulations of ultrarelativistic heavy-ion collisions. We demonstrate this explicitly for (0+1)-dimensional viscous hydrodynamics and discuss how the constraint extends to higher dimensions. Additionally, we present an analytic approximation to the solution of (0+1)-dimensional second-order viscous hydrodynamical evolution equations appropriate to describe the evolution of matter in an ultrarelativistic heavy-ion collision.

  1. Constraining walking and custodial technicolor

    SciTech Connect

    Foadi, Roshan; Frandsen, Mads T.; Sannino, Francesco

    2008-05-01

    We show how to constrain the physical spectrum of walking technicolor models via precision measurements and modified Weinberg sum rules. We also study models possessing a custodial symmetry for the S parameter at the effective Lagrangian level - custodial technicolor - and argue that these models cannot emerge from walking-type dynamics. We suggest that it is possible to have a very light spin-one axial (vector) boson. However, in the walking dynamics the associated vector boson is heavy while it is degenerate with the axial in custodial technicolor.

  2. Method of constrained global optimization

    NASA Astrophysics Data System (ADS)

    Altschuler, Eric Lewin; Williams, Timothy J.; Ratner, Edward R.; Dowla, Farid; Wooten, Frederick

    1994-04-01

    We present a new method for optimization: constrained global optimization (CGO). CGO iteratively uses a Glauber spin flip probability and the Metropolis algorithm. The spin flip probability allows changing only the values of variables contributing excessively to the function to be minimized. We illustrate CGO with two problems-Thomson's problem of finding the minimum-energy configuration of unit charges on a spherical surface, and a problem of assigning offices-for which CGO finds better minima than other methods. We think CGO will apply to a wide class of optimization problems.

  3. Quantum Annealing for Constrained Optimization

    NASA Astrophysics Data System (ADS)

    Hen, Itay; Spedalieri, Federico M.

    2016-03-01

    Recent advances in quantum technology have led to the development and manufacturing of experimental programmable quantum annealers that promise to solve certain combinatorial optimization problems of practical relevance faster than their classical analogues. The applicability of such devices for many theoretical and real-world optimization problems, which are often constrained, is severely limited by the sparse, rigid layout of the devices' quantum bits. Traditionally, constraints are addressed by the addition of penalty terms to the Hamiltonian of the problem, which, in turn, requires prohibitively increasing physical resources while also restricting the dynamical range of the interactions. Here, we propose a method for encoding constrained optimization problems on quantum annealers that eliminates the need for penalty terms and thereby reduces the number of required couplers and removes the need for minor embedding, greatly reducing the number of required physical qubits. We argue the advantages of the proposed technique and illustrate its effectiveness. We conclude by discussing the experimental feasibility of the suggested method as well as its potential to appreciably reduce the resource requirements for implementing optimization problems on quantum annealers and its significance in the field of quantum computing.

  4. Quantum Annealing for Constrained Optimization

    NASA Astrophysics Data System (ADS)

    Hen, Itay; Spedalieri, Federico

    Recent advances in quantum technology have led to the development and manufacturing of experimental programmable quantum annealers that could potentially solve certain quadratic unconstrained binary optimization problems faster than their classical analogues. The applicability of such devices for many theoretical and practical optimization problems, which are often constrained, is severely limited by the sparse, rigid layout of the devices' quantum bits. Traditionally, constraints are addressed by the addition of penalty terms to the Hamiltonian of the problem, which in turn requires prohibitively increasing physical resources while also restricting the dynamical range of the interactions. Here we propose a method for encoding constrained optimization problems on quantum annealers that eliminates the need for penalty terms and thereby removes many of the obstacles associated with the implementation of these. We argue the advantages of the proposed technique and illustrate its effectiveness. We then conclude by discussing the experimental feasibility of the suggested method as well as its potential to boost the encodability of other optimization problems.

  5. Influence of Murchison Minerals on Hydrogen-Deuterium Exchange of Amino Acids

    NASA Astrophysics Data System (ADS)

    Lerner, N. R.

    1993-07-01

    The amino acids found on the Murchison meteorite are deuterium enriched. For the glycine-alanine fraction, delta D = +2448 per mil, and for the alpha-amino isobutyric acid fraction, delta D = +149 per mil [1]. In order to retain such levels of deuterium enrichment, the amino acids found in Murchison must have not only retained the deuterium enrichment of their interstellar precursors (delta D > +1500 per mil [2]) during synthesis, as has been recently shown [3], but they must have also retained their deuterium label during the aqueous alteration phase [4]. By measuring the rates of deuterium exchange of amino acids with D(sub)2O, limits can be set on the length of time and the conditions under which the Murchison parent body experienced an aqueous environment. The rates of hydrogen-deuterium exchange of nondeuterated glycine, alanine, alpha-amino isobutyric acid, and amino diacetic acid have been measured in D(sub)2O as a function of temperature, pH, and the presence of Murchison minerals. In addition to the amino and carboxylic hydrogens, only the alpha- hydrogens of glycine, alanine, and amino diacetic acid are found to exchange. Even for solutions maintained for weeks at temperatures as high as 120 degrees C, no exchange was observed with the hydrogens of the methyl groups of alanine or alpha-amino isobutyric acid. The rate of exchange for alpha-hydrogens of amino acids is first-order with respect to the amino acid concentration. Increasing the pH of the solution markedly increases the rate of exchange. For example, at 115 degrees C and pH 4.0, 7.0, and 10 the rates are 14, 30, and 125 yr^-1 respectively for glycine and 2.0, 3.5, and 14 yr^-1 respectively for alanine. In a pH-6.0 D(sub)2O solution of amino acids containing Murchison dust the rates are 135 yr^-1 for glycine and 32 yr^-1 for alanine, rates close to those for the pH 10 solution. Activation energies for exchange were obtained from Arrhenius plots constructed from measurements made between 70 degrees

  6. Amino acid uptake and energy coupling dependent on photosynthesis in Anacystis nidulans.

    PubMed

    Lee-Kaden, J; Simonis, W

    1982-07-01

    The photoautotrophic cyanobacterium Anacystis nidulans was used to investigate the membrane transport of branched-chain, neutral amino acids and its dependence on photosynthetic reactions. The uptake of alpha-amino [1-14C]isobutyric acid and L-[1-14C]leucine followed Michaelis, Menten kinetics and resulted in an energy-dependent accumulation. As in bacteria, different uptake systems for neutral amino acids were present: two DAG (D-alanine, aminoisobutyric acid, and glycine) systems responsible for uptake of alpha-amino [1-14C]isobutyric acid, and one LIV (leucine, isoleucine, and valine) system, responsible for uptake of leucine. The low-affinity DAG system seemed to be dependent on the presence of Na+ ions. Uptake was enhanced by white light and by monochromatic light of 630 nm. In far red light (717 nm) with and without nitrogen flushing, considerable uptake dependent on light intensity and inhibition by dibromothymoquinone and by high concentrations of KCN were observed. Therefore, the energy generated by photosystem I reactions only could perform this membrane transport. The proton translocator carbonylcyanide m-chlorophenylhydrazone and N,N-dicyclohexylcarbodiimide as an ATPase inhibitor reduced amino acid uptake to a high degree. A pH dependence of aminoisobutyric acid and leucine uptake was obvious, with a maximum at pH 6 to 7 and some at a pH as high as 9.5. At higher pH, increasing concentrations of Na+ K+ and also of triphenylmethylphosphonium ions inhibited the transport of aminoisobutyric acid. These findings are consistent with the assumption that ATP from photosynthetic reactions drives a membrane-bound proton-translocating ATPase producing a proton motive force, consisting at higher pH chiefly in a delta psi amount, which promotes a secondary active H+ or Na+/amino acid symport carrier.

  7. Formal language constrained path problems

    SciTech Connect

    Barrett, C.; Jacob, R.; Marathe, M.

    1997-07-08

    In many path finding problems arising in practice, certain patterns of edge/vertex labels in the labeled graph being traversed are allowed/preferred, while others are disallowed. Motivated by such applications as intermodal transportation planning, the authors investigate the complexity of finding feasible paths in a labeled network, where the mode choice for each traveler is specified by a formal language. The main contributions of this paper include the following: (1) the authors show that the problem of finding a shortest path between a source and destination for a traveler whose mode choice is specified as a context free language is solvable efficiently in polynomial time, when the mode choice is specified as a regular language they provide algorithms with improved space and time bounds; (2) in contrast, they show that the problem of finding simple paths between a source and a given destination is NP-hard, even when restricted to very simple regular expressions and/or very simple graphs; (3) for the class of treewidth bounded graphs, they show that (i) the problem of finding a regular language constrained simple path between source and a destination is solvable in polynomial time and (ii) the extension to finding context free language constrained simple paths is NP-complete. Several extensions of these results are presented in the context of finding shortest paths with additional constraints. These results significantly extend the results in [MW95]. As a corollary of the results, they obtain a polynomial time algorithm for the BEST k-SIMILAR PATH problem studied in [SJB97]. The previous best algorithm was given by [SJB97] and takes exponential time in the worst case.

  8. Exploring constrained quantum control landscapes

    NASA Astrophysics Data System (ADS)

    Moore, Katharine W.; Rabitz, Herschel

    2012-10-01

    The broad success of optimally controlling quantum systems with external fields has been attributed to the favorable topology of the underlying control landscape, where the landscape is the physical observable as a function of the controls. The control landscape can be shown to contain no suboptimal trapping extrema upon satisfaction of reasonable physical assumptions, but this topological analysis does not hold when significant constraints are placed on the control resources. This work employs simulations to explore the topology and features of the control landscape for pure-state population transfer with a constrained class of control fields. The fields are parameterized in terms of a set of uniformly spaced spectral frequencies, with the associated phases acting as the controls. This restricted family of fields provides a simple illustration for assessing the impact of constraints upon seeking optimal control. Optimization results reveal that the minimum number of phase controls necessary to assure a high yield in the target state has a special dependence on the number of accessible energy levels in the quantum system, revealed from an analysis of the first- and second-order variation of the yield with respect to the controls. When an insufficient number of controls and/or a weak control fluence are employed, trapping extrema and saddle points are observed on the landscape. When the control resources are sufficiently flexible, solutions producing the globally maximal yield are found to form connected "level sets" of continuously variable control fields that preserve the yield. These optimal yield level sets are found to shrink to isolated points on the top of the landscape as the control field fluence is decreased, and further reduction of the fluence turns these points into suboptimal trapping extrema on the landscape. Although constrained control fields can come in many forms beyond the cases explored here, the behavior found in this paper is illustrative of

  9. Constrained photophysics of partially and fully encapsulated charge transfer probe (E)-3-(4-Methylaminophenyl) acrylic acid methyl ester inside cyclodextrin nano-cavities: Evidence of cyclodextrins cavity dependent complex stoichiometry

    NASA Astrophysics Data System (ADS)

    Ghosh, Shalini; Jana, Sankar; Guchhait, Nikhil

    2011-12-01

    The polarity sensitive intra-molecular charge transfer (ICT) emission from (E)-3-(4-Methylaminophenyl) acrylic acid methyl ester (MAPAME) is found to show distinct changes once introduced into the nano-cavities of cyclodextrins in aqueous environment. Movement of the molecule from the more polar aqueous environment to the less polar, hydrophobic cyclodextrin interior is marked by the blue shift of the CT emission band with simultaneous fluorescence intensity enhancement. The emission spectral changes on complexation with the α- and β-CD show different stoichiometries as observed from the Benesi-Hildebrand plots. Fluorescence anisotropy and lifetime measurements were performed to probe the different behaviors of MAPAME in aqueous α- and β-CD solutions.

  10. Constrained photophysics of partially and fully encapsulated charge transfer probe (E)-3-(4-Methylaminophenyl) acrylic acid methyl ester inside cyclodextrin nano-cavities: evidence of cyclodextrins cavity dependent complex stoichiometry.

    PubMed

    Ghosh, Shalini; Jana, Sankar; Guchhait, Nikhil

    2011-12-15

    The polarity sensitive intra-molecular charge transfer (ICT) emission from (E)-3-(4-Methylaminophenyl) acrylic acid methyl ester (MAPAME) is found to show distinct changes once introduced into the nano-cavities of cyclodextrins in aqueous environment. Movement of the molecule from the more polar aqueous environment to the less polar, hydrophobic cyclodextrin interior is marked by the blue shift of the CT emission band with simultaneous fluorescence intensity enhancement. The emission spectral changes on complexation with the α- and β-CD show different stoichiometries as observed from the Benesi-Hildebrand plots. Fluorescence anisotropy and lifetime measurements were performed to probe the different behaviors of MAPAME in aqueous α- and β-CD solutions. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. A reexamination of amino acids in lunar soil

    NASA Astrophysics Data System (ADS)

    Brinton, K. L. F.; Bada, J. L.; Arnold, J. R.

    1993-03-01

    Amino acids in lunar soils provide an important indicator of the level of prebiotic organic compounds on the moon. The results provide insight into the chemistry of amino acid precursors, and furthermore, given the flux of carbonaceous material to the moon, we can evaluate the survival of organics upon impact. The amino acid contents of both hydrolyzed and unhydrolyzed hot-water extracts of Apollo 17 lunar soil were determined using ophthaldialdehyde/N-acetyl cysteine (OPA/NAC) derivatization followed by HPLC analysis. Previous studies of lunar amino acids were inconclusive, as the technique used (derivatization with ninhydrin followed by HPLC analysis) was unable to discriminate between cosmogenic amino acids and terrestrial contaminants. Cosmogenic amino acids are racemic, and many of the amino acids found in carbonaceous meteorites such as Murchison, i.e., alpha-amino-i-butyric acid (aib), are extremely rare on Earth. The ninhydrin method does not distinguish amino acid enantiomers, nor does it detect alpha-alkyl amino acids such as aib, whereas the OPA/NAC technique does both.

  12. A reexamination of amino acids in lunar soil

    NASA Technical Reports Server (NTRS)

    Brinton, K. L. F.; Bada, J. L.; Arnold, J. R.

    1993-01-01

    Amino acids in lunar soils provide an important indicator of the level of prebiotic organic compounds on the moon. The results provide insight into the chemistry of amino acid precursors, and furthermore, given the flux of carbonaceous material to the moon, we can evaluate the survival of organics upon impact. The amino acid contents of both hydrolyzed and unhydrolyzed hot-water extracts of Apollo 17 lunar soil were determined using ophthaldialdehyde/N-acetyl cysteine (OPA/NAC) derivatization followed by HPLC analysis. Previous studies of lunar amino acids were inconclusive, as the technique used (derivatization with ninhydrin followed by HPLC analysis) was unable to discriminate between cosmogenic amino acids and terrestrial contaminants. Cosmogenic amino acids are racemic, and many of the amino acids found in carbonaceous meteorites such as Murchison, i.e., alpha-amino-i-butyric acid (aib), are extremely rare on Earth. The ninhydrin method does not distinguish amino acid enantiomers, nor does it detect alpha-alkyl amino acids such as aib, whereas the OPA/NAC technique does both.

  13. A reexamination of amino acids in lunar soil

    NASA Technical Reports Server (NTRS)

    Brinton, K. L. F.; Bada, J. L.; Arnold, J. R.

    1993-01-01

    Amino acids in lunar soils provide an important indicator of the level of prebiotic organic compounds on the moon. The results provide insight into the chemistry of amino acid precursors, and furthermore, given the flux of carbonaceous material to the moon, we can evaluate the survival of organics upon impact. The amino acid contents of both hydrolyzed and unhydrolyzed hot-water extracts of Apollo 17 lunar soil were determined using ophthaldialdehyde/N-acetyl cysteine (OPA/NAC) derivatization followed by HPLC analysis. Previous studies of lunar amino acids were inconclusive, as the technique used (derivatization with ninhydrin followed by HPLC analysis) was unable to discriminate between cosmogenic amino acids and terrestrial contaminants. Cosmogenic amino acids are racemic, and many of the amino acids found in carbonaceous meteorites such as Murchison, i.e., alpha-amino-i-butyric acid (aib), are extremely rare on Earth. The ninhydrin method does not distinguish amino acid enantiomers, nor does it detect alpha-alkyl amino acids such as aib, whereas the OPA/NAC technique does both.

  14. Constraining QGP properties with CHIMERA

    NASA Astrophysics Data System (ADS)

    Garishvili, Irakli; Abelev, Betty; Cheng, Michael; Glenn, Andrew; Soltz, Ron

    2011-10-01

    Understanding essential properties of strongly interacting matter is arguably the most important goal of the relativistic heavy-ion programs both at RHIC and the LHC. In particular, constraining observables such as ratio of shear viscosity to entropy density, η/s, initial temperature, Tinit, and energy density is of critical importance. For this purpose we have developed CHIMERA, Comprehensive Heavy Ion Model Reporting and Evaluation Algorithm. CHIMERA is designed to facilitate global statistical comparison of results from our multi-stage hydrodynamics/hadron cascade model of heavy ion collisions to the key soft observables (HBT, elliptic flow, spectra) measured at RHIC and the LHC. Within this framework the data representing multiple different measurements from different experiments are compiled into single format. One of the unique features of CHIMERA is, that in addition to taking into account statistical errors, it also treats different types of systematic uncertainties. The hydrodynamics/hadron cascade model used in the framework incorporates different initial state conditions, pre-equilibrium flow, the UVH2+1 viscous hydro model, Cooper-Frye freezeout, and the UrQMD hadronic cascade model. The sensitivity of the observables to the equation of state (EoS) is explored using several EoS's in the hydrodynamic evolution. The latest results from CHIMERA, including data from the LHC, will be presented.

  15. Gyrification from constrained cortical expansion

    PubMed Central

    Tallinen, Tuomas; Chung, Jun Young; Biggins, John S.; Mahadevan, L.

    2014-01-01

    The exterior of the mammalian brain—the cerebral cortex—has a conserved layered structure whose thickness varies little across species. However, selection pressures over evolutionary time scales have led to cortices that have a large surface area to volume ratio in some organisms, with the result that the brain is strongly convoluted into sulci and gyri. Here we show that the gyrification can arise as a nonlinear consequence of a simple mechanical instability driven by tangential expansion of the gray matter constrained by the white matter. A physical mimic of the process using a layered swelling gel captures the essence of the mechanism, and numerical simulations of the brain treated as a soft solid lead to the formation of cusped sulci and smooth gyri similar to those in the brain. The resulting gyrification patterns are a function of relative cortical expansion and relative thickness (compared with brain size), and are consistent with observations of a wide range of brains, ranging from smooth to highly convoluted. Furthermore, this dependence on two simple geometric parameters that characterize the brain also allows us to qualitatively explain how variations in these parameters lead to anatomical anomalies in such situations as polymicrogyria, pachygyria, and lissencephalia. PMID:25136099

  16. Constraining the Europa Neutral Torus

    NASA Astrophysics Data System (ADS)

    Smith, Howard T.; Mitchell, Donald; mauk, Barry; Johnson, Robert E.; clark, george

    2016-10-01

    "Neutral tori" consist of neutral particles that usually co-orbit along with their source forming a toroidal (or partial toroidal) feature around the planet. The distribution and composition of these features can often provide important, if not unique, insight into magnetospheric particles sources, mechanisms and dynamics. However, these features can often be difficult to directly detect. One innovative method for detecting neutral tori is by observing Energetic Neutral Atoms (ENAs) that are generally considered produced as a result of charge exchange interactions between charged and neutral particles.Mauk et al. (2003) reported the detection of a Europa neutral particle torus using ENA observations. The presence of a Europa torus has extremely large implications for upcoming missions to Jupiter as well as understanding possible activity at this moon and providing critical insight into what lies beneath the surface of this icy ocean world. However, ENAs can also be produced as a result of charge exchange interactions between two ionized particles and in that case cannot be used to infer the presence of neutral particle population. Thus, a detailed examination of all possible source interactions must be considered before one can confirm that likely original source population of these ENA images is actually a Europa neutral particle torus. For this talk, we examine the viability that the Mauk et al. (2003) observations were actually generated from a neutral torus emanating from Europa as opposed to charge particle interactions with plasma originating from Io. These results help constrain such a torus as well as Europa source processes.

  17. Order-constrained linear optimization.

    PubMed

    Tidwell, Joe W; Dougherty, Michael R; Chrabaszcz, Jeffrey S; Thomas, Rick P

    2017-02-27

    Despite the fact that data and theories in the social, behavioural, and health sciences are often represented on an ordinal scale, there has been relatively little emphasis on modelling ordinal properties. The most common analytic framework used in psychological science is the general linear model, whose variants include ANOVA, MANOVA, and ordinary linear regression. While these methods are designed to provide the best fit to the metric properties of the data, they are not designed to maximally model ordinal properties. In this paper, we develop an order-constrained linear least-squares (OCLO) optimization algorithm that maximizes the linear least-squares fit to the data conditional on maximizing the ordinal fit based on Kendall's τ. The algorithm builds on the maximum rank correlation estimator (Han, 1987, Journal of Econometrics, 35, 303) and the general monotone model (Dougherty & Thomas, 2012, Psychological Review, 119, 321). Analyses of simulated data indicate that when modelling data that adhere to the assumptions of ordinary least squares, OCLO shows minimal bias, little increase in variance, and almost no loss in out-of-sample predictive accuracy. In contrast, under conditions in which data include a small number of extreme scores (fat-tailed distributions), OCLO shows less bias and variance, and substantially better out-of-sample predictive accuracy, even when the outliers are removed. We show that the advantages of OCLO over ordinary least squares in predicting new observations hold across a variety of scenarios in which researchers must decide to retain or eliminate extreme scores when fitting data.

  18. BICEP2 constrains composite inflation

    NASA Astrophysics Data System (ADS)

    Channuie, Phongpichit

    2014-07-01

    In light of BICEP2, we re-examine single field inflationary models in which the inflation is a composite state stemming from various four-dimensional strongly coupled theories. We study in the Einstein frame a set of cosmological parameters, the primordial spectral index ns and tensor-to-scalar ratio r, predicted by such models. We confront the predicted results with the joint Planck data, and with the recent BICEP2 data. We constrain the number of e-foldings for composite models of inflation in order to obtain a successful inflation. We find that the minimal composite inflationary model is fully consistent with the Planck data. However it is in tension with the recent BICEP2 data. The observables predicted by the glueball inflationary model can be consistent with both Planck and BICEP2 contours if a suitable number of e-foldings are chosen. Surprisingly, the super Yang-Mills inflationary prediction is significantly consistent with the Planck and BICEP2 observations.

  19. Constrained navigation for unmanned systems

    NASA Astrophysics Data System (ADS)

    Vasseur, Laurent; Gosset, Philippe; Carpentier, Luc; Marion, Vincent; Morillon, Joel G.; Ropars, Patrice

    2005-05-01

    The French Military Robotic Study Program (introduced in Aerosense 2003), sponsored by the French Defense Procurement Agency and managed by Thales as the prime contractor, focuses on about 15 robotic themes which can provide an immediate "operational add-on value". The paper details the "constrained navigation" study (named TEL2), which main goal is to identify and test a well-balanced task sharing between man and machine to accomplish a robotic task that cannot be performed autonomously at the moment because of technological limitations. The chosen function is "obstacle avoidance" on rough ground and quite high speed (40 km/h). State of the art algorithms have been implemented to perform autonomous obstacle avoidance and following of forest borders, using scanner laser sensor and standard localization functions. Such an "obstacle avoidance" function works well most of the time, BUT fails sometimes. The study analyzed how the remote operator can manage such failures so that the system remains fully operationally reliable; he can act according to two ways: a) finely adjust the vehicle current heading; b) take the control of the vehicle "on the fly" (without stopping) and bring it back to autonomous behavior when motion is secured again. The paper also presents the results got from the military acceptance tests performed on French 4x4 DARDS ATD.

  20. Constrained Allocation Flux Balance Analysis

    PubMed Central

    Mori, Matteo; Hwa, Terence; Martin, Olivier C.

    2016-01-01

    New experimental results on bacterial growth inspire a novel top-down approach to study cell metabolism, combining mass balance and proteomic constraints to extend and complement Flux Balance Analysis. We introduce here Constrained Allocation Flux Balance Analysis, CAFBA, in which the biosynthetic costs associated to growth are accounted for in an effective way through a single additional genome-wide constraint. Its roots lie in the experimentally observed pattern of proteome allocation for metabolic functions, allowing to bridge regulation and metabolism in a transparent way under the principle of growth-rate maximization. We provide a simple method to solve CAFBA efficiently and propose an “ensemble averaging” procedure to account for unknown protein costs. Applying this approach to modeling E. coli metabolism, we find that, as the growth rate increases, CAFBA solutions cross over from respiratory, growth-yield maximizing states (preferred at slow growth) to fermentative states with carbon overflow (preferred at fast growth). In addition, CAFBA allows for quantitatively accurate predictions on the rate of acetate excretion and growth yield based on only 3 parameters determined by empirical growth laws. PMID:27355325

  1. Heterogeneous Distributions of Amino Acids Provide Evidence of Multiple Sources Within the Almahata Sitta Parent Body, Asteroid 2008 TC(sub 3)

    NASA Technical Reports Server (NTRS)

    Burton, Aaron S.; Glavin, Daniel P.; Callahan, Michael P.; Dworkin, Jason P.; Jenniskens, Peter; Shaddad, Muawia H.

    2011-01-01

    Two new fragments of the Almahata Sitta meteorite and a sample of sand from the related strewn field in the Nubian Desert, Sudan, were analyzed for two to six carbon aliphatic primary amino acids by ultrahigh performance liquid chromatography with UV-fluorescence detection and time-of-flight mass spectrometry (LC-FT/ToF-MS). The distribution of amino acids in fragment #25, an H5 ordinary chondrite, and fragment #27, a polymict ureilite, were compared with results from the previously analyzed fragment #4, also a polymict ureilite. All three meteorite fragments contain 180-270 parts-per-billion (ppb) of amino acids, roughly 1000-fold lower than the total amino acid abundance of the Murchison carbonaceous chondrite. All of the Almahata Sitta fragments analyzed have amino acid distributions that differ from the Nubian Desert sand, which primarily contains L-alpha-amino acids. In addition, the meteorites contain several amino acids that were not detected in the sand, indicating that many of the amino acids are extraterrestrial in origin. Despite their petrological differences, meteorite fragments #25 and #27 contain similar amino acid compositions; however, the distribution of amino acids in fragment #27 was distinct from those in fragment #4, even though both arc polymict ureilites from the same parent body. Unlike in CM2 and CR2/3 meteorites, there are low relative abundances of alpha-amino acids in the Almahata Sitta meteorite fragments, which suggest that Strecker-type chemistry was not a significant amino acid formation mechanism. Given the high temperatures that asteroid 2008 TC3 appears to have experienced and lack of evidence for aqueous alteration on the asteroid, it is possible that the extraterrestrial amino acids detected in Almahata Sitta were formed by Fischer-Tropsch/Haber-Bosch type gas-grain reactions at elevated temperatures.

  2. Heterogeneous Distributions of Amino Acids Provide Evidence of Multiple Sources Within the Almahata Sitta Parent Body, Asteroid 2008 TC(sub 3)

    NASA Technical Reports Server (NTRS)

    Burton, Aaron S.; Glavin, Daniel P.; Callahan, Michael P.; Dworkin, Jason P.; Jenniskens, Peter; Shaddad, Muawia H.

    2011-01-01

    Two new fragments of the Almahata Sitta meteorite and a sample of sand from the related strewn field in the Nubian Desert, Sudan, were analyzed for two to six carbon aliphatic primary amino acids by ultrahigh performance liquid chromatography with UV-fluorescence detection and time-of-flight mass spectrometry (LC-FT/ToF-MS). The distribution of amino acids in fragment #25, an H5 ordinary chondrite, and fragment #27, a polymict ureilite, were compared with results from the previously analyzed fragment #4, also a polymict ureilite. All three meteorite fragments contain 180-270 parts-per-billion (ppb) of amino acids, roughly 1000-fold lower than the total amino acid abundance of the Murchison carbonaceous chondrite. All of the Almahata Sitta fragments analyzed have amino acid distributions that differ from the Nubian Desert sand, which primarily contains L-alpha-amino acids. In addition, the meteorites contain several amino acids that were not detected in the sand, indicating that many of the amino acids are extraterrestrial in origin. Despite their petrological differences, meteorite fragments #25 and #27 contain similar amino acid compositions; however, the distribution of amino acids in fragment #27 was distinct from those in fragment #4, even though both arc polymict ureilites from the same parent body. Unlike in CM2 and CR2/3 meteorites, there are low relative abundances of alpha-amino acids in the Almahata Sitta meteorite fragments, which suggest that Strecker-type chemistry was not a significant amino acid formation mechanism. Given the high temperatures that asteroid 2008 TC3 appears to have experienced and lack of evidence for aqueous alteration on the asteroid, it is possible that the extraterrestrial amino acids detected in Almahata Sitta were formed by Fischer-Tropsch/Haber-Bosch type gas-grain reactions at elevated temperatures.

  3. Constrained Peptides as Miniature Protein Structures

    PubMed Central

    Yin, Hang

    2012-01-01

    This paper discusses the recent developments of protein engineering using both covalent and noncovalent bonds to constrain peptides, forcing them into designed protein secondary structures. These constrained peptides subsequently can be used as peptidomimetics for biological functions such as regulations of protein-protein interactions. PMID:25969758

  4. The genetic code constrains yet facilitates Darwinian evolution.

    PubMed

    Firnberg, Elad; Ostermeier, Marc

    2013-08-01

    An important goal of evolutionary biology is to understand the constraints that shape the dynamics and outcomes of evolution. Here, we address the extent to which the structure of the standard genetic code constrains evolution by analyzing adaptive mutations of the antibiotic resistance gene TEM-1 β-lactamase and the fitness distribution of codon substitutions in two influenza hemagglutinin inhibitor genes. We find that the architecture of the genetic code significantly constrains the adaptive exploration of sequence space. However, the constraints endow the code with two advantages: the ability to restrict access to amino acid mutations with a strong negative effect and, most remarkably, the ability to enrich for adaptive mutations. Our findings support the hypothesis that the standard genetic code was shaped by selective pressure to minimize the deleterious effects of mutation yet facilitate the evolution of proteins through imposing an adaptive mutation bias.

  5. Sparsity constrained contrast source inversion.

    PubMed

    Ramirez, Ana B; van Dongen, Koen W A

    2016-09-01

    Ultrasound imaging is used for detecting and characterizing breast lesions. A state of the art imaging method is the contrast source inversion (CSI), which solves the full wave nonlinear inverse problem. However, when the measurements are acquired in noisy environments, CSI can diverge from the correct solution after several iterations. Problems associated with noisy data were originally solved by including total variation (TV) regularization. Unfortunately, for very noisy data, TV regularization alone is not sufficient. In this work, compressed sensing ideas are used to regularize the inversion process by restricting the solution of the CSI method to be sparse in a transformation domain. The proposed method estimates the contrast source and contrast function by minimizing the mean squared error between the measured and modeled data. An extra penalty term is added to measure sparsity in the transformation domain. A second method that combines sparsity of the contrast source and minimal TV in the contrast function is also presented. The proposed methods are tested on noise-free and noisy synthetic data sets representing a scan of a cancerous breast. Numerical experiments show that, for measurements contaminated with 1% noise, the sparsity constrained CSI improves the normalized mean squared error of the reconstructed speed-of-sound profiles up to 36% in comparison with traditional CSI. Also, for measurements contaminated with 5% noise, the proposed methods improve the quality of the reconstruction up to 70% in comparison with the traditional CSI method. Experimental results also show that the methods remain convergent to the correct speed-of-sound profile as the number of iterations increases.

  6. Interaction of metal ions and amino acids - Possible mechanisms for the adsorption of amino acids on homoionic smectite clays

    NASA Technical Reports Server (NTRS)

    Gupta, A.; Loew, G. H.; Lawless, J.

    1983-01-01

    A semiempirical molecular orbital method is used to characterize the binding of amino acids to hexahydrated Cu(2+) and Ni(2+), a process presumed to occur when they are adsorbed in the interlamellar space of homoionic smectite clays. Five alpha-amino acids, beta-alanine, and gamma-aminobutyric acid were used to investigate the metal ion and amino acid specificity in binding. It was assumed that the alpha, beta, and gamma-amino acids would bind as bidentate anionic ligands, forming either 1:1 or 1:2 six-coordinated five, six, and seven-membered-ring chelate complexes, respectively. Energies of complex formation, optimized geometries, and electron and spin distribution were determined; and steric constraints of binding of the amino acids to the ion-exchanged cations in the interlamellar spacing of a clay were examined. Results indicate that hexahydrated Cu(2+) forms more stable complexes than hexahydrated Ni(2+) with all the amino acids studied. However, among these amino acids, complex formation does not favor the adsorption of the biological subset. Calculated energetics of complex formation and steric constraints are shown to predict that 1:1 rather than 1:2 metal-amino acid complexes are generally favored in the clay.

  7. Interaction of metal ions and amino acids - Possible mechanisms for the adsorption of amino acids on homoionic smectite clays

    NASA Technical Reports Server (NTRS)

    Gupta, A.; Loew, G. H.; Lawless, J.

    1983-01-01

    A semiempirical molecular orbital method is used to characterize the binding of amino acids to hexahydrated Cu(2+) and Ni(2+), a process presumed to occur when they are adsorbed in the interlamellar space of homoionic smectite clays. Five alpha-amino acids, beta-alanine, and gamma-aminobutyric acid were used to investigate the metal ion and amino acid specificity in binding. It was assumed that the alpha, beta, and gamma-amino acids would bind as bidentate anionic ligands, forming either 1:1 or 1:2 six-coordinated five, six, and seven-membered-ring chelate complexes, respectively. Energies of complex formation, optimized geometries, and electron and spin distribution were determined; and steric constraints of binding of the amino acids to the ion-exchanged cations in the interlamellar spacing of a clay were examined. Results indicate that hexahydrated Cu(2+) forms more stable complexes than hexahydrated Ni(2+) with all the amino acids studied. However, among these amino acids, complex formation does not favor the adsorption of the biological subset. Calculated energetics of complex formation and steric constraints are shown to predict that 1:1 rather than 1:2 metal-amino acid complexes are generally favored in the clay.

  8. Constrained Galerkin variational integrators and modified constrained symplectic Runge-Kutta methods

    NASA Astrophysics Data System (ADS)

    Wenger, Theresa; Ober-Blöbaum, Sina; Leyendecker, Sigrid

    2017-07-01

    The presented constrained Galerkin variational integrators base on the higher order variational integrators in [1], now applied to holonomically constrained systems and are an extension of the constrained Galerkin methods in [2]. Sufficient conditions are given to obtain a stiffly accurate integration scheme, its structure preserving properties are analysed and the convergence order as well as the computational efficiency are investigated numerically. The equivalence to constrained symplectic Runge-Kutta methods is shown, with focus on a modified constrained symplectic Runge-Kutta method, that was first introduced in [3], there for the unconstrained case.

  9. constrainedKriging: An R-package for customary, constrained and covariance-matching constrained point or block kriging

    NASA Astrophysics Data System (ADS)

    Hofer, Christoph; Papritz, Andreas

    2011-10-01

    The article describes the R-package constrainedKriging, a tool for spatial prediction problems that involve change of support. The package provides software for spatial interpolation by constrained (CK), covariance-matching constrained (CMCK), and customary universal (UK) kriging. CK and CMCK yield approximately unbiased predictions of nonlinear functionals of target quantities under change of support and are therefore an attractive alternative to conditional Gaussian simulations. The constrainedKriging package computes CK, CMCK, and UK predictions for points or blocks of arbitrary shape from data observed at points in a two-dimensional survey domain. Predictions are computed for a random process model that involves a nonstationary mean function (modeled by a linear regression) and a weakly stationary, isotropic covariance function (or variogram). CK, CMCK, and UK require the point-block and block-block averages of the covariance function if the prediction targets are blocks. The constrainedKriging package uses numerically efficient approximations to compute these averages. The article contains, apart from a brief summary of CK and CMCK, a detailed description of the algorithm used to compute the point-block and block-block covariances, and it describes the functionality of the software in detail. The practical use of the package is illustrated by a comparison of universal and constrained lognormal block kriging for the Meuse Bank heavy metal data set.

  10. Compositionally Constraining Elysium Lava Fields

    NASA Astrophysics Data System (ADS)

    Karunatillake, S.; Button, N. E.; Skok, J. R.

    2013-12-01

    Chemical provinces of Mars defined recently [1-3] became possible with the maps of elemental mass fractions generated with Mars Odyssey Gamma and Neutron Spectrometer (GS) data [4,5]. These provide a unique perspective by representing compositional signatures distinctive of the regolith vertically at decimeter depths and laterally at hundreds of kilometer scale. Some provinces overlap compellingly with regions highlighted by other remote sensing observations, such as the Mars Radar Stealth area [3]. The spatial convergence of mutually independent data with the consequent highlight of a region provides a unique opportunity of insight not possible with a single type of remote sensing observation. Among such provinces, previous work [3] highlighted Elysium lava flows as a promising candidate on the basis of convergence with mapped geologic units identifying Elysium's lava fields generally, and Amazonian-aged lava flows specifically. The South Eastern lava flows of Elysium Mons, dating to the recent Amazonian epoch, overlap compellingly with a chemical province of K and Th depletion relative to the Martian midlatitudes. We characterize the composition, geology, and geomorphology of the SE Elysium province to constrain the confluence of geologic and alteration processes that may have contributed to its evolution. We compare this with the North Western lava fields, extending the discussion on chemical products from the thermal evolution of Martian volcanism as discussed by Baratoux et al. [6]. The chemical province, by regional proximity to Cerberus Fossae, may also reflect the influence of recently identified buried flood channels [7] in the vicinity of Orcus Patera. Despite the compelling chemical signature from γ spectra, fine grained unconsolidated sediment hampers regional VNTIR (Visible, Near, and Thermal Infrared) spectral analysis. But some observations near scarps and fresh craters allow a view of small scale mineral content. The judicious synthesis of

  11. Active constrained clustering by examining spectral Eigenvectors

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; desJardins, Marie; Xu, Qianjun

    2005-01-01

    This work focuses on the active selection of pairwise constraints for spectral clustering. We develop and analyze a technique for Active Constrained Clustering by Examining Spectral eigenvectorS (ACCESS) derived from a similarity matrix.

  12. Constrained density functional for noncollinear magnetism

    NASA Astrophysics Data System (ADS)

    Ma, Pui-Wai; Dudarev, S. L.

    2015-02-01

    Energies of arbitrary small- and large-angle noncollinear excited magnetic configurations are computed using a highly accurate constrained density functional theory approach. Numerical convergence and accuracy are controlled by the choice of Lagrange multipliers λI entering the constraining conditions. The penalty part Ep of the constrained energy functional at its minimum is shown to be inversely proportional to λI, enabling a simple, robust, and accurate iterative procedure to be followed to find a convergent solution. The method is implemented as a part of ab initio vasp package, and applied to the investigation of noncollinear B2-like and <001 > double-layer antiferromagnetic configurations of bcc iron, Fe2 dimer, and amorphous iron. Forces acting on atoms depend on the orientations of magnetic moments, and the proposed approach enables constrained self-consistent noncollinear magnetic and structural relaxation of large atomic systems to be carried out.

  13. Active constrained clustering by examining spectral Eigenvectors

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; desJardins, Marie; Xu, Qianjun

    2005-01-01

    This work focuses on the active selection of pairwise constraints for spectral clustering. We develop and analyze a technique for Active Constrained Clustering by Examining Spectral eigenvectorS (ACCESS) derived from a similarity matrix.

  14. Energetic Materials Optimization via Constrained Search

    DTIC Science & Technology

    2015-06-01

    ARL-TR-7304• JUN 2015 US Army Research Laboratory Energetic Materials Optimization via Constrained Search by Berend Christopher Rinderspacher...Army Research Laboratory Energetic Materials Optimization via Constrained Search by Berend Christopher Rinderspacher Weapons and Materials Research...burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions,  searching

  15. On the Constrained Attitude Control Problem

    NASA Technical Reports Server (NTRS)

    Hadaegh, Fred Y.; Kim, Yoonsoo; Mesbahi, Mehran; Singh, Gurkipal

    2004-01-01

    In this paper, we consider various classes of constrained attitude control (CAC) problem in single and multiple spacecraft settings. After categorizing attitude constraints into four distinct types, we provide an overview of the existing approaches to this problem. We then proceed to further expand on a recent algorithmic approach to the CAC problem. The paper concludes with an example demonstrating the viability of the proposed algorithm for a multiple spacecraft constrained attitude reconfiguration scenario.

  16. On the Constrained Attitude Control Problem

    NASA Technical Reports Server (NTRS)

    Hadaegh, Fred Y.; Kim, Yoonsoo; Mesbahi, Mehran; Singh, Gurkipal

    2004-01-01

    In this paper, we consider various classes of constrained attitude control (CAC) problem in single and multiple spacecraft settings. After categorizing attitude constraints into four distinct types, we provide an overview of the existing approaches to this problem. We then proceed to further expand on a recent algorithmic approach to the CAC problem. The paper concludes with an example demonstrating the viability of the proposed algorithm for a multiple spacecraft constrained attitude reconfiguration scenario.

  17. The 3-amino-derivative of gamma-cyclodextrin as chiral selector of Dns-amino acids in electrokinetic chromatography.

    PubMed

    Giuffrida, A; Contino, A; Maccarrone, G; Messina, M; Cucinotta, V

    2009-04-24

    The enantioseparation of the enantiomeric pairs of 10 Dns derivatives of alpha-amino acids was successfully carried out by using for the first time the 3-amino derivative of the gamma-cyclodextrin. The effects of pH and selector concentration on the migration times and the resolutions of analytes were studied in detail. 3-Deoxy-3-amino-2(S),3(R)-gamma-cyclodextrin (GCD3AM) shows very good chiral recognition ability even at very low concentrations at all the three investigated values of pH, as shown by the very large values of selectivity and resolution towards several pairs of amino acids. The role played by the cavity, the substitution site and the protonation equilibria on the observed properties of chiral selectivity, on varying the specific amino acid involved, is discussed.

  18. Isotopic analyses of amino acids from the Murchison meteorite

    SciTech Connect

    Pizzarello, S.; Cronin, J.R. ); Krishnamurthy, R.V.; Epstein, S. )

    1991-03-01

    Previous isotopic analyses of the total amino acids of the Murchison meteorite showed these compounds to be substantially enriched in {sup 2}H, {sup 13}C, and {sup 15}N relative to terrestrial organic matter. These analyses have been repeated ({sup 2}H, {sup 13}C) with inclusion of an ultrafiltration step to exclude the possibility that a fine particulate contaminant carried the isotopic excesses observed in the previous work. In addition, the meteorite amino acids were chromatographically separated to rule out the possibility that the isotopic enrichment of the meteorite extract could reside in basic compounds other than amino acids. The results indicate that the Murchison amino acids are truly isotopically unusual, that the isotopic excesses reside in at least several different amino acids, and that the isotopic contents of some of these amino acids reach values of about +40{per thousand} ({delta}{sup 13}C) and +2,500{per thousand} ({delta}D). If it is assumed that the high deuterium content of the meteroite {alpha}-amino acids is a result of the synthesis of their molecular precursors by low temperature ion-molecule reactions in an interstellar cloud, their formation by aqueous phase Strecker reactions in the parent body is consistent with their general characteristics and with known parent body processes.

  19. Egg Production Constrains Chemical Defenses in a Neotropical Arachnid

    PubMed Central

    Nazareth, Taís M.; Machado, Glauco

    2015-01-01

    Female investment in large eggs increases the demand for fatty acids, which are allocated for yolk production. Since the biosynthetic pathway leading to fatty acids uses the same precursors used in the formation of polyketides, allocation trade-offs are expected to emerge. Therefore, egg production should constrain the investment in chemical defenses based on polyketides, such as benzoquinones. We tested this hypothesis using the harvestman Acutiosoma longipes, which produces large eggs and releases benzoquinones as chemical defense. We predicted that the amount of secretion released by ovigerous females (OFs) would be smaller than that of non-ovigerous females (NOF). We also conducted a series of bioassays in the field and in the laboratory to test whether egg production renders OFs more vulnerable to predation. OFs produce less secretion than NOFs, which is congruent with the hypothesis that egg production constrains the investment in chemical defenses. Results of the bioassays show that the secretion released by OFs is less effective in deterring potential predators (ants and spiders) than the secretion released by NOFs. In conclusion, females allocate resources to chemical defenses in a way that preserves a primary biological function related to reproduction. However, the trade-off between egg and secretion production makes OFs vulnerable to predators. We suggest that egg production is a critical moment in the life of harvestman females, representing perhaps the highest cost of reproduction in the group. PMID:26331946

  20. Outcome and complications of constrained acetabular components.

    PubMed

    Yang, Cao; Goodman, Stuart B

    2009-02-01

    Constrained acetabular liners were developed for the surgical treatment of recurrent instability by holding the femoral head captive within the socket. This article summarizes the data describing constrained component designs, indications, outcome, and complications. Different designs accept head sizes of varying diameter and have differing amounts of rim elevation and offset, allowing slight variations in the range of movement allowed. Complications of constrained acetabular components can be divided into three categories. The first category is directly related to the constraining mechanism such as dislocation, head dissociation from the stem, liner dissociation from the acetabular device, and impingement with or without locking ring breakage. The second category is related to increased constraint such as aseptic component loosening and osteolysis and periprosthetic fracture. The third category includes those cases not associated with increased constraint such as infection, deep vein thrombosis, and periprosthetic fracture. This device is effective at achieving hip stability, but the complications related to the constraining mechanism and increased constraint are of concern. These devices should be used as a salvage measure for the treatment of severe instability.

  1. Constraining weak annihilation using semileptonic D decays

    SciTech Connect

    Ligeti, Zoltan; Luke, Michael; Manohar, Aneesh V.

    2010-08-01

    The recently measured semileptonic D{sub s} decay rate can be used to constrain weak annihilation (WA) effects in semileptonic D and B decays. We revisit the theoretical predictions for inclusive semileptonic D{sub (s)} decays using a variety of quark mass schemes. The most reliable results are obtained if the fits to B decay distributions are used to eliminate the charm quark mass dependence, without using any specific charm mass scheme. Our fit to the available data shows that WA is smaller than commonly assumed. There is no indication that the WA octet contribution (which is better constrained than the singlet contribution) dominates. The results constrain an important source of uncertainty in the extraction of |V{sub ub}| from inclusive semileptonic B decays.

  2. Bayesian evaluation of inequality constrained hypotheses.

    PubMed

    Gu, Xin; Mulder, Joris; Deković, Maja; Hoijtink, Herbert

    2014-12-01

    Bayesian evaluation of inequality constrained hypotheses enables researchers to investigate their expectations with respect to the structure among model parameters. This article proposes an approximate Bayes procedure that can be used for the selection of the best of a set of inequality constrained hypotheses based on the Bayes factor in a very general class of statistical models. The software package BIG is provided such that psychologists can use the approach proposed for the analysis of their own data. To illustrate the approximate Bayes procedure and the use of BIG, we evaluate inequality constrained hypotheses in a path model and a logistic regression model. Two simulation studies on the performance of our approximate Bayes procedure show that it results in accurate Bayes factors. PsycINFO Database Record (c) 2014 APA, all rights reserved

  3. Pattern Search Methods for Linearly Constrained Minimization

    NASA Technical Reports Server (NTRS)

    Lewis, Robert Michael; Torczon, Virginia

    1998-01-01

    We extend pattern search methods to linearly constrained minimization. We develop a general class of feasible point pattern search algorithms and prove global convergence to a Karush-Kuhn-Tucker point. As in the case of unconstrained minimization, pattern search methods for linearly constrained problems accomplish this without explicit recourse to the gradient or the directional derivative. Key to the analysis of the algorithms is the way in which the local search patterns conform to the geometry of the boundary of the feasible region.

  4. Spacecraft inertia estimation via constrained least squares

    NASA Technical Reports Server (NTRS)

    Keim, Jason A.; Acikmese, Behcet A.; Shields, Joel F.

    2006-01-01

    This paper presents a new formulation for spacecraft inertia estimation from test data. Specifically, the inertia estimation problem is formulated as a constrained least squares minimization problem with explicit bounds on the inertia matrix incorporated as LMIs [linear matrix inequalities). The resulting minimization problem is a semidefinite optimization that can be solved efficiently with guaranteed convergence to the global optimum by readily available algorithms. This method is applied to data collected from a robotic testbed consisting of a freely rotating body. The results show that the constrained least squares approach produces more accurate estimates of the inertia matrix than standard unconstrained least squares estimation methods.

  5. Spacecraft inertia estimation via constrained least squares

    NASA Technical Reports Server (NTRS)

    Keim, Jason A.; Acikmese, Behcet A.; Shields, Joel F.

    2006-01-01

    This paper presents a new formulation for spacecraft inertia estimation from test data. Specifically, the inertia estimation problem is formulated as a constrained least squares minimization problem with explicit bounds on the inertia matrix incorporated as LMIs [linear matrix inequalities). The resulting minimization problem is a semidefinite optimization that can be solved efficiently with guaranteed convergence to the global optimum by readily available algorithms. This method is applied to data collected from a robotic testbed consisting of a freely rotating body. The results show that the constrained least squares approach produces more accurate estimates of the inertia matrix than standard unconstrained least squares estimation methods.

  6. Pattern Search Algorithms for Bound Constrained Minimization

    NASA Technical Reports Server (NTRS)

    Lewis, Robert Michael; Torczon, Virginia

    1996-01-01

    We present a convergence theory for pattern search methods for solving bound constrained nonlinear programs. The analysis relies on the abstract structure of pattern search methods and an understanding of how the pattern interacts with the bound constraints. This analysis makes it possible to develop pattern search methods for bound constrained problems while only slightly restricting the flexibility present in pattern search methods for unconstrained problems. We prove global convergence despite the fact that pattern search methods do not have explicit information concerning the gradient and its projection onto the feasible region and consequently are unable to enforce explicitly a notion of sufficient feasible decrease.

  7. Genome wide exploration of the origin and evolution of amino acids

    PubMed Central

    2010-01-01

    Background Even after years of exploration, the terrestrial origin of bio-molecules remains unsolved and controversial. Today, observation of amino acid composition in proteins has become an alternative way for a global understanding of the mystery encoded in whole genomes and seeking clues for the origin of amino acids. Results In this study, we statistically monitored the frequencies of 20 alpha-amino acids in 549 taxa from three kingdoms of life: archaebacteria, eubacteria, and eukaryotes. We found that the amino acids evolved independently in these three kingdoms; but, conserved linkages were observed in two groups of amino acids, (A, G, H, L, P, Q, R, and W) and (F, I, K, N, S, and Y). Moreover, the amino acids encoded by GC-poor codons (F, Y, N, K, I, and M) were found to "lose" their usage in the development from single cell eukaryotic organisms like S. cerevisiae to H. sapiens, while the amino acids encoded by GC-rich codons (P, A, G, and W) were found to gain usage. These findings further support the co-evolution hypothesis of amino acids and genetic codes. Conclusion We proposed a new chronological order of the appearance of amino acids (L, A, V/E/G, S, I, K, T, R/D, P, N, F, Q, Y, M, H, W, C). Two conserved evolutionary paths of amino acids were also suggested: A→G→R→P and K→Y. PMID:20230639

  8. Vibrational analysis of amino acids and short peptides in hydrated media. I. L-glycine and L-leucine.

    PubMed

    Derbel, Najoua; Hernández, Belén; Pflüger, Fernando; Liquier, Jean; Geinguenaud, Frédéric; Jaïdane, Nejmeddine; Lakhdar, Zohra Ben; Ghomi, Mahmoud

    2007-02-15

    Raman scattering and Fourier-transform infrared (FT-IR) attenuated transmission reflectance (ATR) spectra of two alpha-amino acids (alpha-AAs), i.e., glycine and leucine, were measured in H2O and D2O (at neutral pH and pD). This series of observed vibrational data gave us the opportunity to analyze vibrational features of both AAs in hydrated media by density functional theory (DFT) calculations at the B3LYP/6-31++G* level. Harmonic vibrational modes calculated after geometry optimization on the clusters containing each AA and 12 surrounding water molecules, which represent primary models for hydration scheme of amino acids, allowed us to assign the main observed peaks.

  9. Constrained tri-sphere kinematic positioning system

    DOEpatents

    Viola, Robert J

    2010-12-14

    A scalable and adaptable, six-degree-of-freedom, kinematic positioning system is described. The system can position objects supported on top of, or suspended from, jacks comprising constrained joints. The system is compatible with extreme low temperature or high vacuum environments. When constant adjustment is not required a removable motor unit is available.

  10. Constrained superfields from inflation to reheating

    NASA Astrophysics Data System (ADS)

    Dalianis, Ioannis; Farakos, Fotis

    2017-10-01

    We construct effective supergravity theories from customized constrained superfields which provide a setup consistent both for the description of inflation and the subsequent reheating processes. These theories contain the minimum degrees of freedom in the bosonic sector required for single-field inflation.

  11. A Model for Optimal Constrained Adaptive Testing.

    ERIC Educational Resources Information Center

    van der Linden, Wim J.; Reese, Lynda M.

    1998-01-01

    Proposes a model for constrained computerized adaptive testing in which the information in the test at the trait level (theta) estimate is maximized subject to the number of possible constraints on the content of the test. Test assembly relies on a linear-programming approach. Illustrates the approach through simulation with items from the Law…

  12. Rhythmic Grouping Biases Constrain Infant Statistical Learning

    ERIC Educational Resources Information Center

    Hay, Jessica F.; Saffran, Jenny R.

    2012-01-01

    Linguistic stress and sequential statistical cues to word boundaries interact during speech segmentation in infancy. However, little is known about how the different acoustic components of stress constrain statistical learning. The current studies were designed to investigate whether intensity and duration each function independently as cues to…

  13. Automation of constrained-value business forms

    SciTech Connect

    Carson, M.L.; Beaumariage, T.G.; Greitzer, F.L.

    1993-05-01

    Expert systems can improve many business tasks. However, the nature of a constrained-value business form can result in a rule base that contains circular reasoning, unsuitable for expert system implementation. A methodology is presented for restructuring such a rule base for compatibility with a backward-chaining expert system.

  14. Constrained Subjective Assessment of Student Learning

    ERIC Educational Resources Information Center

    Saliu, Sokol

    2005-01-01

    Student learning is a complex incremental cognitive process; assessment needs to parallel this, reporting the results in similar terms. Application of fuzzy sets and logic to the criterion-referenced assessment of student learning is considered here. The constrained qualitative assessment (CQA) system was designed, and then applied in assessing a…

  15. Constrained Subjective Assessment of Student Learning

    ERIC Educational Resources Information Center

    Saliu, Sokol

    2005-01-01

    Student learning is a complex incremental cognitive process; assessment needs to parallel this, reporting the results in similar terms. Application of fuzzy sets and logic to the criterion-referenced assessment of student learning is considered here. The constrained qualitative assessment (CQA) system was designed, and then applied in assessing a…

  16. A universal strategy for visual chiral recognition of α-amino acids with L-tartaric acid-capped gold nanoparticles as colorimetric probes.

    PubMed

    Song, Guoxin; Zhou, Fulin; Xu, Chunli; Li, Baoxin

    2016-02-21

    The ability to recognize and quantify the chirality of alpha-amino acids constitutes the basis of many critical areas for specific targeting in drug development and metabolite probing. It is still challenging to conveniently distinguish the enantiomer of amino acids largely due to the lack of a universal and simple strategy. In this work, we report a strategy for the visual recognition of α-amino acids. It is based on the chirality of L-tartaric acid-capped gold nanoparticles (L-TA-capped AuNPs, ca. 13 nm in diameter). All of 19 right-handed α-amino acids can induce a red-to-blue color change of L-TA-capped AuNP solution, whereas all of the left-handed amino acids (except cysteine) cannot. The chiral recognition can be achieved by the naked eye and a simple spectrophotometer. This method does not require complicated chiral modification, and excels through its low-cost, good availability of materials and its simplicity. Another notable feature of this method is its high generality, and this method can discriminate almost all native α-amino acid enantiomers. This versatile method could be potentially used for high-throughput chiral recognition of amino acids.

  17. Constrained target controllability of complex networks

    NASA Astrophysics Data System (ADS)

    Guo, Wei-Feng; Zhang, Shao-Wu; Wei, Ze-Gang; Zeng, Tao; Liu, Fei; Zhang, Jingsong; Wu, Fang-Xiang; Chen, Luonan

    2017-06-01

    It is of great theoretical interest and practical significance to study how to control a system by applying perturbations to only a few driver nodes. Recently, a hot topic of modern network researches is how to determine driver nodes that allow the control of an entire network. However, in practice, to control a complex network, especially a biological network, one may know not only the set of nodes which need to be controlled (i.e. target nodes), but also the set of nodes to which only control signals can be applied (i.e. constrained control nodes). Compared to the general concept of controllability, we introduce the concept of constrained target controllability (CTC) of complex networks, which concerns the ability to drive any state of target nodes to their desirable state by applying control signals to the driver nodes from the set of constrained control nodes. To efficiently investigate the CTC of complex networks, we further design a novel graph-theoretic algorithm called CTCA to estimate the ability of a given network to control targets by choosing driver nodes from the set of constrained control nodes. We extensively evaluate the CTC of numerous real complex networks. The results indicate that biological networks with a higher average degree are easier to control than biological networks with a lower average degree, while electronic networks with a lower average degree are easier to control than web networks with a higher average degree. We also show that our CTCA can more efficiently produce driver nodes for target-controlling the networks than existing state-of-the-art methods. Moreover, we use our CTCA to analyze two expert-curated bio-molecular networks and compare to other state-of-the-art methods. The results illustrate that our CTCA can efficiently identify proven drug targets and new potentials, according to the constrained controllability of those biological networks.

  18. Inhibited muscle amino acid uptake in sepsis.

    PubMed Central

    Hasselgren, P O; James, J H; Fischer, J E

    1986-01-01

    Amino acid uptake in vivo was determined in soleus (SOL) muscle, diaphragm, heart, and liver following intravenous injection of [3H]-alpha-amino-isobutyric acid ([3H]-AIB) in rats made septic by cecal ligation and puncture (CLP) and in sham-operated controls. Muscle amino acid transport was also measured in vitro by determining uptake of [3H]-AIB in incubated extensor digitorum longus (EDL) and SOL muscles. Results were expressed as distribution ratio between [3H]-AIB in intracellular and extracellular fluid. AIB uptake in vivo was reduced by 90% in SOL and cardiac muscle and by 45% in diaphragm 16 hours after CLP. In contrast, AIB uptake by liver was almost four times higher in septic than in control animals. AIB uptake in vitro was reduced by 18% in EDL 8 hours after CLP but was not significantly altered in SOL at the same time point. Sixteen hours after CLP, AIB uptake was significantly reduced in both muscles, i.e., by 17% in EDL and by 65% in SOL. When muscles from untreated rats were incubated in the presence of plasma from septic animals (16 hours CLP) or from animals injected with endotoxin (2 mg/kg body weight), AIB uptake was reduced. Addition of endotoxin in vitro (2-200 micrograms/ml) to incubated muscles did not affect AIB uptake. The results suggest that sepsis leads to marked impairment of amino acid transport system A in muscle and that this impairment is mediated by a circulating factor that is not endotoxin. Reduced uptake of amino acids by skeletal muscle during sepsis may divert amino acids to the liver for increased gluconeogenesis and protein synthesis. PMID:3963895

  19. Kinetic analysis of the role of histidine chloramines in hypochlorous acid mediated protein oxidation.

    PubMed

    Pattison, David I; Davies, Michael J

    2005-05-17

    Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and chloride ions by the heme enzyme myeloperoxidase (MPO) released from activated leukocytes. In addition to its potent antibacterial effects, excessive HOCl production can lead to host tissue damage, with this implicated in human diseases such as atherosclerosis, cystic fibrosis, and arthritis. HOCl reacts rapidly with biological materials, with proteins being major targets. Chlorinated amines (chloramines) formed from Lys and His side chains and alpha-amino groups on proteins are major products of these reactions; these materials are however also oxidants and can undergo further reactions. In this study, the kinetics of reaction of His side-chain chloramines with other protein components have been investigated by UV/visible spectroscopy and stopped flow methods at pH 7.4 and 22 degrees C, using the chloramines of the model compound 4-imidazoleacetic acid and N-alpha-acetyl-histidine. The second-order rate constants decrease in a similar order (Cys > Met > disulfide bonds > Trp approximately alpha-amino > Lys > Tyr > backbone amides > Arg) to the corresponding reactions of HOCl, but are typically 5-25 times slower. These rate constants are consistent with His side-chain chloramines being important secondary oxidants in HOCl-mediated damage. These studies suggest that formation and subsequent reactions of His side-chain chloramines may be responsible for the targeted secondary modification of selected protein residues by HOCl that has previously been observed experimentally and highlight the importance of chloramine structure on their subsequent reactivity.

  20. CONSTRAINED SPECTRAL CLUSTERING FOR IMAGE SEGMENTATION

    PubMed Central

    Sourati, Jamshid; Brooks, Dana H.; Dy, Jennifer G.; Erdogmus, Deniz

    2013-01-01

    Constrained spectral clustering with affinity propagation in its original form is not practical for large scale problems like image segmentation. In this paper we employ novelty selection sub-sampling strategy, besides using efficient numerical eigen-decomposition methods to make this algorithm work efficiently for images. In addition, entropy-based active learning is also employed to select the queries posed to the user more wisely in an interactive image segmentation framework. We evaluate the algorithm on general and medical images to show that the segmentation results will improve using constrained clustering even if one works with a subset of pixels. Furthermore, this happens more efficiently when pixels to be labeled are selected actively. PMID:24466500

  1. Constraining the Braneworld with Gravitational Wave Observations

    SciTech Connect

    McWilliams, Sean T.

    2010-04-09

    Some braneworld models may have observable consequences that, if detected, would validate a requisite element of string theory. In the infinite Randall-Sundrum model (RS2), the AdS radius of curvature, l, of the extra dimension supports a single bound state of the massless graviton on the brane, thereby reproducing Newtonian gravity in the weak-field limit. However, using the AdS/CFT correspondence, it has been suggested that one possible consequence of RS2 is an enormous increase in Hawking radiation emitted by black holes. We utilize this possibility to derive two novel methods for constraining l via gravitational wave measurements. We show that the EMRI event rate detected by LISA can constrain l at the {approx}1 {mu}m level for optimal cases, while the observation of a single galactic black hole binary with LISA results in an optimal constraint of l{<=}5 {mu}m.

  2. Constraining the braneworld with gravitational wave observations.

    PubMed

    McWilliams, Sean T

    2010-04-09

    Some braneworld models may have observable consequences that, if detected, would validate a requisite element of string theory. In the infinite Randall-Sundrum model (RS2), the AdS radius of curvature, l, of the extra dimension supports a single bound state of the massless graviton on the brane, thereby reproducing Newtonian gravity in the weak-field limit. However, using the AdS/CFT correspondence, it has been suggested that one possible consequence of RS2 is an enormous increase in Hawking radiation emitted by black holes. We utilize this possibility to derive two novel methods for constraining l via gravitational wave measurements. We show that the EMRI event rate detected by LISA can constrain l at the approximately 1 microm level for optimal cases, while the observation of a single galactic black hole binary with LISA results in an optimal constraint of l < or = 5 microm.

  3. Constraining the Braneworld with Gravitational Wave Observations

    NASA Technical Reports Server (NTRS)

    McWilliams, Sean T.

    2011-01-01

    Some braneworld models may have observable consequences that, if detected, would validate a requisite element of string theory. In the infinite Randall-Sundrum model (RS2), the AdS radius of curvature, L, of the extra dimension supports a single bound state of the massless graviton on the brane, thereby reproducing Newtonian gravity in the weak-field limit. However, using the AdS/CFT correspondence, it has been suggested that one possible consequence of RS2 is an enormous increase in Hawking radiation emitted by black holes. We utilize this possibility to derive two novel methods for constraining L via gravitational wave measurements. We show that the EMRI event rate detected by LISA can constrain L at the approximately 1 micron level for optimal cases, while the observation of a single galactic black hole binary with LISA results in an optimal constraint of L less than or equal to 5 microns.

  4. Compilation for critically constrained knowledge bases

    SciTech Connect

    Schrag, R.

    1996-12-31

    We show that many {open_quotes}critically constrained{close_quotes} Random 3SAT knowledge bases (KBs) can be compiled into disjunctive normal form easily by using a variant of the {open_quotes}Davis-Putnam{close_quotes} proof procedure. From these compiled KBs we can answer all queries about entailment of conjunctive normal formulas, also easily - compared to a {open_quotes}brute-force{close_quotes} approach to approximate knowledge compilation into unit clauses for the same KBs. We exploit this fact to develop an aggressive hybrid approach which attempts to compile a KB exactly until a given resource limit is reached, then falls back to approximate compilation into unit clauses. The resulting approach handles all of the critically constrained Random 3SAT KBs with average savings of an order of magnitude over the brute-force approach.

  5. Cosmogenic photons strongly constrain UHECR source models

    NASA Astrophysics Data System (ADS)

    van Vliet, Arjen

    2017-03-01

    With the newest version of our Monte Carlo code for ultra-high-energy cosmic ray (UHECR) propagation, CRPropa 3, the flux of neutrinos and photons due to interactions of UHECRs with extragalactic background light can be predicted. Together with the recently updated data for the isotropic diffuse gamma-ray background (IGRB) by Fermi LAT, it is now possible to severely constrain UHECR source models. The evolution of the UHECR sources especially plays an important role in the determination of the expected secondary photon spectrum. Pure proton UHECR models are already strongly constrained, primarily by the highest energy bins of Fermi LAT's IGRB, as long as their number density is not strongly peaked at recent times.

  6. The totally constrained model: three quantization approaches

    NASA Astrophysics Data System (ADS)

    Gambini, Rodolfo; Olmedo, Javier

    2014-08-01

    We provide a detailed comparison of the different approaches available for the quantization of a totally constrained system with a constraint algebra generating the non-compact group. In particular, we consider three schemes: the Refined Algebraic Quantization, the Master Constraint Programme and the Uniform Discretizations approach. For the latter, we provide a quantum description where we identify semiclassical sectors of the kinematical Hilbert space. We study the quantum dynamics of the system in order to show that it is compatible with the classical continuum evolution. Among these quantization approaches, the Uniform Discretizations provides the simpler description in agreement with the classical theory of this particular model, and it is expected to give new insights about the quantum dynamics of more realistic totally constrained models such as canonical general relativity.

  7. Constraining SUSY GUTs and Inflation with Cosmology

    SciTech Connect

    Rocher, Jonathan

    2006-11-03

    In the framework of Supersymmetric Grand Unified Theories (SUSY GUTs), the universe undergoes a cascade of symmetry breakings, during which topological defects can be formed. We address the question of the probability of cosmic string formation after a phase of hybrid inflation within a large number of models of SUSY GUTs in agreement with particle and cosmological data. We show that cosmic strings are extremely generic and should be used to relate cosmology and high energy physics. This conclusion is employed together with the WMAP CMB data to strongly constrain SUSY hybrid inflation models. F-term and D-term inflation are studied in the SUSY and minimal SUGRA framework. They are both found to agree with data but suffer from fine tuning of their superpotential coupling ({lambda} (less-or-similar sign) 3 x 10-5 or less). Mass scales of inflation are also constrained to be less than M < or approx. 3 x 1015 GeV.

  8. Constraining Neutron Star Matter with Quantum Chromodynamics

    NASA Astrophysics Data System (ADS)

    Kurkela, Aleksi; Fraga, Eduardo S.; Schaffner-Bielich, Jürgen; Vuorinen, Aleksi

    2014-07-01

    In recent years, there have been several successful attempts to constrain the equation of state of neutron star matter using input from low-energy nuclear physics and observational data. We demonstrate that significant further restrictions can be placed by additionally requiring the pressure to approach that of deconfined quark matter at high densities. Remarkably, the new constraints turn out to be highly insensitive to the amount—or even presence—of quark matter inside the stars.

  9. Optimal constrained layer damping with partial coverage

    NASA Astrophysics Data System (ADS)

    Marcelin, J.-L.; Trompette, Ph.; Smati, A.

    1992-12-01

    This paper deals with the optimal damping of beams constrained by viscoelastic layers when only one or several portions of the beam are covered. An efficient finite element model for dynamic analysis of such beams is used. The design variables are the dimensions and prescribed locations of the viscoelastic layers and the objective is the maximum viscoelastic damping factor. The method for nonlinear programming in structural optimization is the so-called method of moving asymptotes.

  10. On the path integral of constrained systems

    SciTech Connect

    Muslih, Sami I.

    2004-10-04

    Constrained Hamiltonian systems are investigated by using Gueler's method. Integration of a set of equations of motion and the action function is discussed. It is shown that the canonical path integral quantization is obtained directly as an integration over the canonical phase-space coordinates without any need to enlarge the initial phase-space by introducing extra- unphysical variables as in the Batalin-Fradkin-Tyutin (BFT) method. The abelian Proca model is analyzed by the two methods.

  11. Constraining neutron star matter with quantum chromodynamics

    SciTech Connect

    Kurkela, Aleksi; Fraga, Eduardo S.; Schaffner-Bielich, Jürgen; Vuorinen, Aleksi

    2014-07-10

    In recent years, there have been several successful attempts to constrain the equation of state of neutron star matter using input from low-energy nuclear physics and observational data. We demonstrate that significant further restrictions can be placed by additionally requiring the pressure to approach that of deconfined quark matter at high densities. Remarkably, the new constraints turn out to be highly insensitive to the amount—or even presence—of quark matter inside the stars.

  12. Constraining neutrino decays with CMBR data

    NASA Astrophysics Data System (ADS)

    Hannestad, Steen

    1998-07-01

    The decay of massive neutrinos to final states containing only invisible particles is poorly constrained experimentally. In this letter we describe the constraints that can be put on neutrino mass and lifetime using CMBR measurements. We find that very tight lifetime limits on neutrinos in the mass range 10 eV - 100 keV can be derived using CMBR data from upcoming satellite measurements.

  13. High-performance liquid chromatography determination of pipecolic acid after precolumn ninhydrin derivatization using domestic microwave.

    PubMed

    Moulin, Michaël; Deleu, Carole; Larher, François Robert; Bouchereau, Alain

    2002-09-15

    A novel procedure to specifically quantify low amounts of pipecolic acid and structurally related compounds in several types of biological materials has been characterized. From crude extracts of various types of biological material, the first step was to clear all low-molecular-weight compounds containing primary amino groups by a treatment of nitrous acid. Using a microwave-assisted reaction, the remaining substances containing secondary amino groups were then derivatized with ninhydrin and made soluble in glacial acetic acid. The derivatives produced were resolved by reverse-phase HPLC and detected by spectrophotometry at 570nm. This procedure allowed more rapid determination of pipecolic acid since microwave heating shortened the time needed for derivatization compared with heating at 95 degrees C in a water bath. The complete analysis of the chromogens for pipecolic acid and related substances was achieved in 20min. Under such conditions, the detection threshold for pipecolic acid was about 20pmol. The suitability of the technique was assessed in various biological matrices known to contain significant amounts of this amino acid. The data obtained are in accordance with those available in the literature. To our knowledge, this is the first method using the ninhydrin reaction in a precolumn, microwave-assisted derivatization procedure for detection and determination of heterocyclic alpha-amino acids.

  14. CONSTRAINING SOURCE REDSHIFT DISTRIBUTIONS WITH GRAVITATIONAL LENSING

    SciTech Connect

    Wittman, D.; Dawson, W. A.

    2012-09-10

    We introduce a new method for constraining the redshift distribution of a set of galaxies, using weak gravitational lensing shear. Instead of using observed shears and redshifts to constrain cosmological parameters, we ask how well the shears around clusters can constrain the redshifts, assuming fixed cosmological parameters. This provides a check on photometric redshifts, independent of source spectral energy distribution properties and therefore free of confounding factors such as misidentification of spectral breaks. We find that {approx}40 massive ({sigma}{sub v} = 1200 km s{sup -1}) cluster lenses are sufficient to determine the fraction of sources in each of six coarse redshift bins to {approx}11%, given weak (20%) priors on the masses of the highest-redshift lenses, tight (5%) priors on the masses of the lowest-redshift lenses, and only modest (20%-50%) priors on calibration and evolution effects. Additional massive lenses drive down uncertainties as N{sub lens}{sup -1/2}, but the improvement slows as one is forced to use lenses further down the mass function. Future large surveys contain enough clusters to reach 1% precision in the bin fractions if the tight lens-mass priors can be maintained for large samples of lenses. In practice this will be difficult to achieve, but the method may be valuable as a complement to other more precise methods because it is based on different physics and therefore has different systematic errors.

  15. Constraining the mass of the Local Group

    NASA Astrophysics Data System (ADS)

    Carlesi, Edoardo; Hoffman, Yehuda; Sorce, Jenny G.; Gottlöber, Stefan

    2017-03-01

    The mass of the Local Group (LG) is a crucial parameter for galaxy formation theories. However, its observational determination is challenging - its mass budget is dominated by dark matter that cannot be directly observed. To meet this end, the posterior distributions of the LG and its massive constituents have been constructed by means of constrained and random cosmological simulations. Two priors are assumed - the Λ cold dark matter model that is used to set up the simulations, and an LG model that encodes the observational knowledge of the LG and is used to select LG-like objects from the simulations. The constrained simulations are designed to reproduce the local cosmography as it is imprinted on to the Cosmicflows-2 data base of velocities. Several prescriptions are used to define the LG model, focusing in particular on different recent estimates of the tangential velocity of M31. It is found that (a) different vtan choices affect the peak mass values up to a factor of 2, and change mass ratios of MM31 to MMW by up to 20 per cent; (b) constrained simulations yield more sharply peaked posterior distributions compared with the random ones; (c) LG mass estimates are found to be smaller than those found using the timing argument; (d) preferred Milky Way masses lie in the range of (0.6-0.8) × 1012 M⊙; whereas (e) MM31 is found to vary between (1.0-2.0) × 1012 M⊙, with a strong dependence on the vtan values used.

  16. Constrained Clustering With Nonnegative Matrix Factorization.

    PubMed

    Zhang, Xianchao; Zong, Linlin; Liu, Xinyue; Luo, Jiebo

    2016-07-01

    Nonnegative matrix factorization (NMF) and symmetric NMF (SymNMF) have been shown to be effective for clustering linearly separable data and nonlinearly separable data, respectively. Nevertheless, many practical applications demand constrained algorithms in which a small number of constraints in the form of must-link and cannot-link are available. In this paper, we propose an NMF-based constrained clustering framework in which the similarity between two points on a must-link is enforced to approximate 1 and the similarity between two points on a cannot-link is enforced to approximate 0. We then formulate the framework using NMF and SymNMF to deal with clustering of linearly separable data and nonlinearly separable data, respectively. Furthermore, we present multiplicative update rules to solve them and show the correctness and convergence. Experimental results on various text data sets, University of California, Irvine (UCI) data sets, and gene expression data sets demonstrate the superiority of our algorithms over existing constrained clustering algorithms.

  17. Constrained Implants in Total Knee Replacement.

    PubMed

    Touzopoulos, Panagiotis; Drosos, Georgios I; Ververidis, Athanasios; Kazakos, Konstantinos

    2015-05-01

    Total knee replacement (TKR) is a successful procedure for pain relief and functional restoration in patients with advanced osteoarthritis. The number of TKRs is increasing, and this has led to an increase in revision surgeries. The key to long-term success in both primary and revision TKR is stability, as well as adequate and stable fixation between components and underlying bone. In the vast majority of primary TKRs and in some revision cases, a posterior cruciate retaining or a posterior cruciate substituting device can be used. In some primary cases with severe deformity or ligamentous instability and in most of the revision cases, a more constrained implant is required. The purpose of this paper is to review the literature concerning the use of condylar constrained knee (CCK) and rotating hinge (RH) implants in primary and revision cases focusing on the indications and results. According to this review, although excellent and very good results have been reported, there are limitations of the existing literature concerning the indications for the use of constrained implants, the absence of long-term results, and the limited comparative studies.

  18. Constrained and joint inversion on unstructured meshes

    NASA Astrophysics Data System (ADS)

    Doetsch, J.; Jordi, C.; Rieckh, V.; Guenther, T.; Schmelzbach, C.

    2015-12-01

    Unstructured meshes allow for inclusion of arbitrary surface topography, complex acquisition geometry and undulating geological interfaces in the inversion of geophysical data. This flexibility opens new opportunities for coupling different geophysical and hydrological data sets in constrained and joint inversions. For example, incorporating geological interfaces that have been derived from high-resolution geophysical data (e.g., ground penetrating radar) can add geological constraints to inversions of electrical resistivity data. These constraints can be critical for a hydrogeological interpretation of the inversion results. For time-lapse inversions of geophysical data, constraints can be derived from hydrological point measurements in boreholes, but it is difficult to include these hard constraints in the inversion of electrical resistivity monitoring data. Especially mesh density and the regularization footprint around the hydrological point measurements are important for an improved inversion compared to the unconstrained case. With the help of synthetic and field examples, we analyze how regularization and coupling operators should be chosen for time-lapse inversions constrained by point measurements and for joint inversions of geophysical data in order to take full advantage of the flexibility of unstructured meshes. For the case of constraining to point measurements, it is important to choose a regularization operator that extends beyond the neighboring cells and the uncertainty in the point measurements needs to be accounted for. For joint inversion, the choice of the regularization depends on the expected subsurface heterogeneity and the cell size of the parameter mesh.

  19. An English language interface for constrained domains

    NASA Technical Reports Server (NTRS)

    Page, Brenda J.

    1989-01-01

    The Multi-Satellite Operations Control Center (MSOCC) Jargon Interpreter (MJI) demonstrates an English language interface for a constrained domain. A constrained domain is defined as one with a small and well delineated set of actions and objects. The set of actions chosen for the MJI is from the domain of MSOCC Applications Executive (MAE) Systems Test and Operations Language (STOL) directives and contains directives for signing a cathode ray tube (CRT) on or off, calling up or clearing a display page, starting or stopping a procedure, and controlling history recording. The set of objects chosen consists of CRTs, display pages, STOL procedures, and history files. Translation from English sentences to STOL directives is done in two phases. In the first phase, an augmented transition net (ATN) parser and dictionary are used for determining grammatically correct parsings of input sentences. In the second phase, grammatically typed sentences are submitted to a forward-chaining rule-based system for interpretation and translation into equivalent MAE STOL directives. Tests of the MJI show that it is able to translate individual clearly stated sentences into the subset of directives selected for the prototype. This approach to an English language interface may be used for similarly constrained situations by modifying the MJI's dictionary and rules to reflect the change of domain.

  20. Constrained inversion of seismo-volcanic events

    NASA Astrophysics Data System (ADS)

    Nocerino, Luciano; D'Auria, Luca; Giudicepietro, Flora; Martini, Marcello

    2014-05-01

    The inversion of seismo-volcanic events is performed to retrieve the source geometry and to determine volumetric budgets of the source. Such observations have shown to be an important tool for the seismological monitoring of volcanoes. We developed a novel technique for the non-linear constrained inversion of low frequency seismo-volcanic events. Unconstrained linear inversion methods work well when a dense network of broadband seismometers is available. We propose a new constrained inversion technique, which has shown to be efficient also in a reduced network configuration and a low signal-noise ratio. The waveform inversion is performed in the frequency domain, constraining the source mechanism during the event to vary only in its magnitude. The eigenvectors orientation and the eigenvalue ratio are kept constant. This significantly reduces the number of parameters to invert, making the procedure more stable. The method has been tested over a synthetic dataset, reproducing realistic very-long-period (VLP) signals Stromboli volcano. We have applied the method to a VLP dataset recorded on Stromboli volcano and to low-frequency earthquakes recorded on Mt.Vesuvius.

  1. Prevention of effects of ethanol on amino acid concentrations in plasma and tissues by hepatic lipotropic factors in rats.

    PubMed

    Stanko, R T; Morse, E L; Adibi, S A

    1979-01-01

    The authors' previous studies have shown that hepatic steatosis of chronic ethanol ingestion in rats can be prevented by adding pyruvate, dihydroxyacetone, and riboflavin to their diet. In this study, the authors investigated the effect of chronic ethanol ingestion, with or without addition of the above metabolites to the diet, on protein and amino acid concentrations in tissues. Rats (120 g) were divided into three groups and fed isocalorically one of the fellowing diets for 30 days: control diet (28% fat, 15% protein, and 57% carbohydrate), ethanol diet (28% fat, 15% protein, 23% carbohydrate, and 24% ethanol), and metabolite diet (ethanol diet plus pyruvate, dihydroxyacetone, and riboflavin). Chronic ethanol ingestion reduced growth of muscle and intestinal mucosa without affecting that of liver and kidney. Among the 15 amino acids measured, chronic ethanol ingestion had the most consistent effect on plasma and tissue concentrations of leucine, alanine and alpha-amino-n-butyrate. The concentration of leucine was increased in muscle, liver, and plasma; that of alpha-amino-n-butyrate was increased in muscle and plasma, whereas that of alanine was decreased in plasma and liver. Addition of pyruvate, dihydroxyacetone, and riboflavin to the ethanol diet either totally or partially prevented ethanol-induced changes in plasma and tissue concentrations of amino acids despite similarity in plasma ethanol levels. Although these metabolites prevented the inhibition of the growth of intestinal mucosa, they were ineffective in blunting the effect of ehtanol on the skeletal muscle. This latter observation suggests that the mechanism of ethanol-induced inhibition of tissue growth is not the same for these tissues.

  2. Comparison of intraduodenal and intravenous administration of amino acids on gastric secretion in healthy subjects and patients with duodenal ulcer.

    PubMed Central

    Konturek, S J; Kwiecień, N; Obtułowicz, W; Mikoś, E; Sito, E; Oleksy, J

    1978-01-01

    The ability of an amino acid mixture given intraduodenally or intravenously to stimulate gastric secretion is compared in healthy subjects and in duodenal ulcer patients. Graded amounts of amino acids by both routes produced a similar increase in acid output in healthy subjects, reaching about 30% of the maximal response to pentagastrin. Serum gastrin concentrations remained virtually unchanged but serum alpha amino acid nitrogen levels were about twice as high with intravenous as with intraduodenal administration. Intravenously administered amino acids produced a significantly higher acid output in patients with duodenal ulcer than in healthy subjects, but did not produce a significant increase in gastric acid or pepsin secretion when combined with a pentagastrin infusion as compared with pentagastrin alone. Cimetidine (2 mg/kg/h) added to intravenous amino acid infusions caused almost complete suppression of acid secretion. This study indicates that amino acids are capable of stimulating gastric secretion after intraduodenal and after intravenous administration. The response to the latter is significantly higher in patients with duodenal ulcer than in healthy subjects, does not appear to involve gastrin release, is not affected by pentagastrin, and is strongly suppressed by histamine H2-blocker. PMID:361509

  3. Protein Structure and Evolution: Are They Constrained Globally by a Principle Derived from Information Theory?

    PubMed Central

    Hatton, Leslie; Warr, Gregory

    2015-01-01

    That the physicochemical properties of amino acids constrain the structure, function and evolution of proteins is not in doubt. However, principles derived from information theory may also set bounds on the structure (and thus also the evolution) of proteins. Here we analyze the global properties of the full set of proteins in release 13-11 of the SwissProt database, showing by experimental test of predictions from information theory that their collective structure exhibits properties that are consistent with their being guided by a conservation principle. This principle (Conservation of Information) defines the global properties of systems composed of discrete components each of which is in turn assembled from discrete smaller pieces. In the system of proteins, each protein is a component, and each protein is assembled from amino acids. Central to this principle is the inter-relationship of the unique amino acid count and total length of a protein and its implications for both average protein length and occurrence of proteins with specific unique amino acid counts. The unique amino acid count is simply the number of distinct amino acids (including those that are post-translationally modified) that occur in a protein, and is independent of the number of times that the particular amino acid occurs in the sequence. Conservation of Information does not operate at the local level (it is independent of the physicochemical properties of the amino acids) where the influences of natural selection are manifest in the variety of protein structure and function that is well understood. Rather, this analysis implies that Conservation of Information would define the global bounds within which the whole system of proteins is constrained; thus it appears to be acting to constrain evolution at a level different from natural selection, a conclusion that appears counter-intuitive but is supported by the studies described herein. PMID:25970335

  4. Protein structure and evolution: are they constrained globally by a principle derived from information theory?

    PubMed

    Hatton, Leslie; Warr, Gregory

    2015-01-01

    That the physicochemical properties of amino acids constrain the structure, function and evolution of proteins is not in doubt. However, principles derived from information theory may also set bounds on the structure (and thus also the evolution) of proteins. Here we analyze the global properties of the full set of proteins in release 13-11 of the SwissProt database, showing by experimental test of predictions from information theory that their collective structure exhibits properties that are consistent with their being guided by a conservation principle. This principle (Conservation of Information) defines the global properties of systems composed of discrete components each of which is in turn assembled from discrete smaller pieces. In the system of proteins, each protein is a component, and each protein is assembled from amino acids. Central to this principle is the inter-relationship of the unique amino acid count and total length of a protein and its implications for both average protein length and occurrence of proteins with specific unique amino acid counts. The unique amino acid count is simply the number of distinct amino acids (including those that are post-translationally modified) that occur in a protein, and is independent of the number of times that the particular amino acid occurs in the sequence. Conservation of Information does not operate at the local level (it is independent of the physicochemical properties of the amino acids) where the influences of natural selection are manifest in the variety of protein structure and function that is well understood. Rather, this analysis implies that Conservation of Information would define the global bounds within which the whole system of proteins is constrained; thus it appears to be acting to constrain evolution at a level different from natural selection, a conclusion that appears counter-intuitive but is supported by the studies described herein.

  5. 21 CFR 888.3780 - Wrist joint polymer constrained prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Wrist joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3780 Wrist joint polymer constrained prosthesis. (a) Identification. A wrist joint polymer constrained prosthesis is a device made...

  6. 21 CFR 888.3720 - Toe joint polymer constrained prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Toe joint polymer constrained prosthesis. 888.3720... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3720 Toe joint polymer constrained prosthesis. (a) Identification. A toe joint polymer constrained prosthesis is a device made of...

  7. 21 CFR 888.3720 - Toe joint polymer constrained prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Toe joint polymer constrained prosthesis. 888.3720... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3720 Toe joint polymer constrained prosthesis. (a) Identification. A toe joint polymer constrained prosthesis is a device made of...

  8. 21 CFR 888.3230 - Finger joint polymer constrained prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Finger joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3230 Finger joint polymer constrained prosthesis. (a) Identification. A finger joint polymer constrained prosthesis is a device...

  9. 21 CFR 888.3780 - Wrist joint polymer constrained prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Wrist joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3780 Wrist joint polymer constrained prosthesis. (a) Identification. A wrist joint polymer constrained prosthesis is a device made...

  10. 21 CFR 888.3230 - Finger joint polymer constrained prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Finger joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3230 Finger joint polymer constrained prosthesis. (a) Identification. A finger joint polymer constrained prosthesis is a device...

  11. 21 CFR 888.3720 - Toe joint polymer constrained prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Toe joint polymer constrained prosthesis. 888.3720... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3720 Toe joint polymer constrained prosthesis. (a) Identification. A toe joint polymer constrained prosthesis is a device made of silicone...

  12. 21 CFR 888.3780 - Wrist joint polymer constrained prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Wrist joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3780 Wrist joint polymer constrained prosthesis. (a) Identification. A wrist joint polymer constrained prosthesis is a device made of...

  13. 21 CFR 888.3780 - Wrist joint polymer constrained prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Wrist joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3780 Wrist joint polymer constrained prosthesis. (a) Identification. A wrist joint polymer constrained prosthesis is a device made of...

  14. 21 CFR 888.3780 - Wrist joint polymer constrained prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Wrist joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3780 Wrist joint polymer constrained prosthesis. (a) Identification. A wrist joint polymer constrained prosthesis is a device made of...

  15. 21 CFR 888.3720 - Toe joint polymer constrained prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Toe joint polymer constrained prosthesis. 888.3720... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3720 Toe joint polymer constrained prosthesis. (a) Identification. A toe joint polymer constrained prosthesis is a device made of silicone...

  16. 21 CFR 888.3720 - Toe joint polymer constrained prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Toe joint polymer constrained prosthesis. 888.3720... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3720 Toe joint polymer constrained prosthesis. (a) Identification. A toe joint polymer constrained prosthesis is a device made of silicone...

  17. 21 CFR 888.3230 - Finger joint polymer constrained prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Finger joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3230 Finger joint polymer constrained prosthesis. (a) Identification. A finger joint polymer constrained prosthesis is a device intended...

  18. 21 CFR 888.3230 - Finger joint polymer constrained prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Finger joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3230 Finger joint polymer constrained prosthesis. (a) Identification. A finger joint polymer constrained prosthesis is a device intended...

  19. 21 CFR 888.3230 - Finger joint polymer constrained prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Finger joint polymer constrained prosthesis. 888... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3230 Finger joint polymer constrained prosthesis. (a) Identification. A finger joint polymer constrained prosthesis is a device intended...

  20. Wastes from bioethanol and beer productions as substrates for l(+) lactic acid production - A comparative study.

    PubMed

    Djukić-Vuković, Aleksandra; Mladenović, Dragana; Radosavljević, Miloš; Kocić-Tanackov, Sunčica; Pejin, Jelena; Mojović, Ljiljana

    2016-02-01

    Waste substrates from bioethanol and beer productions are cheap, abundant and renewable substrates for biorefinery production of lactic acid (LA) and variability in their chemical composition presents a challenge in their valorisation. Three types of waste substrates, wasted bread and wasted potato stillage from bioethanol production and brewers' spent grain hydrolysate from beer production were studied as substrates for the production of l(+) LA and probiotic biomass by Lactobacillus rhamnosus ATCC 7469. The correlation of the content of free alpha amino nitrogen and the production of LA was determined as a critical characteristic of the waste media for efficient LA production by L. rhamnosus on the substrates which contained equal amount of fermentable sugars. A maximal LA productivity of 1.54gL(-1)h(-1) was obtained on wasted bread stillage media, whilst maximal productivities achieved on the potato stillage and brewers' spent grain hydrolysate media were 1.28gL(-1)h(-1)and 0.48gL(-1)h(-1), respectively. A highest LA yield of 0.91gg(-1) was achieved on wasted bread stillage media, followed by the yield of 0.81gg(-1) on wasted potato stillage and 0.34gg(-1) on brewers' spent grain hydrolysate media. The kinetics of sugar consumption in the two stillage substrates were similar while the sugar conversion in brewers' spent grain hydrolysate was slower and less efficient due to significantly lower content of free alpha amino nitrogen. The lignocellulosic hydrolysate from beer production required additional supplementation with nitrogen.

  1. HCV management in resource-constrained countries.

    PubMed

    Lim, Seng Gee

    2017-02-21

    With the arrival of all-oral directly acting antiviral (DAA) therapy with high cure rates, the promise of hepatitis C virus (HCV) eradication is within closer reach. The availability of generic DAAs has improved access to countries with constrained resources. However, therapy is only one component of the HCV care continuum, which is the framework for HCV management from identifying patients to cure. The large number of undiagnosed HCV cases is the biggest concern, and strategies to address this are needed, as risk factor screening is suboptimal, detecting <20% of known cases. Improvements in HCV confirmation through either reflex HCV RNA screening or ideally a sensitive point of care test are needed. HCV notification (e.g., Australia) may improve diagnosis (proportion of HCV diagnosed is 75%) and may lead to benefits by increasing linkage to care, therapy and cure. Evaluations for cirrhosis using non-invasive markers are best done with a biological panel, but they are only moderately accurate. In resource-constrained settings, only generic HCV medications are available, and a combination of sofosbuvir, ribavirin, ledipasvir or daclatasvir provides sufficient efficacy for all genotypes, but this is likely to be replaced with pangenetypic regimens such as sofosbuvir/velpatasvir and glecaprevir/pibrentaasvir. In conclusion, HCV management in resource-constrained settings is challenging on multiple fronts because of the lack of infrastructure, facilities, trained manpower and equipment. However, it is still possible to make a significant impact towards HCV eradication through a concerted effort by individuals and national organisations with domain expertise in this area.

  2. Feature and Pose Constrained Visual Aided Inertial Navigation for Computationally Constrained Aerial Vehicles

    NASA Technical Reports Server (NTRS)

    Williams, Brian; Hudson, Nicolas; Tweddle, Brent; Brockers, Roland; Matthies, Larry

    2011-01-01

    A Feature and Pose Constrained Extended Kalman Filter (FPC-EKF) is developed for highly dynamic computationally constrained micro aerial vehicles. Vehicle localization is achieved using only a low performance inertial measurement unit and a single camera. The FPC-EKF framework augments the vehicle's state with both previous vehicle poses and critical environmental features, including vertical edges. This filter framework efficiently incorporates measurements from hundreds of opportunistic visual features to constrain the motion estimate, while allowing navigating and sustained tracking with respect to a few persistent features. In addition, vertical features in the environment are opportunistically used to provide global attitude references. Accurate pose estimation is demonstrated on a sequence including fast traversing, where visual features enter and exit the field-of-view quickly, as well as hover and ingress maneuvers where drift free navigation is achieved with respect to the environment.

  3. Constrained inflaton due to a complex scalar

    SciTech Connect

    Budhi, Romy H. S.; Kashiwase, Shoichi; Suematsu, Daijiro

    2015-09-14

    We reexamine inflation due to a constrained inflaton in the model of a complex scalar. Inflaton evolves along a spiral-like valley of special scalar potential in the scalar field space just like single field inflation. Sub-Planckian inflaton can induce sufficient e-foldings because of a long slow-roll path. In a special limit, the scalar spectral index and the tensor-to-scalar ratio has equivalent expressions to the inflation with monomial potential φ{sup n}. The favorable values for them could be obtained by varying parameters in the potential. This model could be embedded in a certain radiative neutrino mass model.

  4. Newton modified barrier method in constrained optimization

    NASA Technical Reports Server (NTRS)

    Polyak, R.

    1990-01-01

    In this paper, we develop and investigate the Newton method for solving constrained (non-smooth) optimization problems. This approach is based on the modified barrier functions (MBF) theory and on the global converging step-size version of the Newton method for smooth unconstrained optimization. Due to the excellent properties of the MBF near primal-dual solution, the Newton modified barrier method (NMBM) has a better rate of convergence, better complexity bound, and is much more stable in the final stage of the computational process than the methods which are based on the classical barrier functions (CBF).

  5. Incomplete Dirac reduction of constrained Hamiltonian systems

    SciTech Connect

    Chandre, C.

    2015-10-15

    First-class constraints constitute a potential obstacle to the computation of a Poisson bracket in Dirac’s theory of constrained Hamiltonian systems. Using the pseudoinverse instead of the inverse of the matrix defined by the Poisson brackets between the constraints, we show that a Dirac–Poisson bracket can be constructed, even if it corresponds to an incomplete reduction of the original Hamiltonian system. The uniqueness of Dirac brackets is discussed. The relevance of this procedure for infinite dimensional Hamiltonian systems is exemplified.

  6. Quantization of soluble classical constrained systems

    SciTech Connect

    Belhadi, Z.; Menas, F.; Bérard, A.; Mohrbach, H.

    2014-12-15

    The derivation of the brackets among coordinates and momenta for classical constrained systems is a necessary step toward their quantization. Here we present a new approach for the determination of the classical brackets which does neither require Dirac’s formalism nor the symplectic method of Faddeev and Jackiw. This approach is based on the computation of the brackets between the constants of integration of the exact solutions of the equations of motion. From them all brackets of the dynamical variables of the system can be deduced in a straightforward way.

  7. Constraining nucleon high momentum in nuclei

    NASA Astrophysics Data System (ADS)

    Yong, Gao-Chan

    2017-02-01

    Recent studies at Jefferson Lab show that there are a certain proportion of nucleons in nuclei have momenta greater than the so-called nuclear Fermi momentum pF. Based on the transport model of nucleus-nucleus collisions at intermediate energies, nucleon high momentum caused by the neutron-proton short-range correlations in nuclei is constrained by comparing with π and photon experimental data and considering some uncertainties. The high momentum cutoff value pmax ≤ 2pF is obtained.

  8. Protein biosynthesis with conformationally restricted amino acids

    SciTech Connect

    Mendel, D. Lawrence Berkeley Lab., CA ); Ellman, J.; Schultz, P.G. )

    1993-05-19

    The incorporation of conformationally constrained amino acids into peptides is a powerful approach for generating structurally defined peptides as conformational probes and bioactive agents. The ability to site-specifically introduce constrained amino acids into large polypeptide chains would provide a similar opportunity to probe the flexibility, conformation, folding and stability of proteins. To this end, we have examined the competence of the Escherichia coli protein biosynthetic machinery to incorporate a number of these unnatural amino acids into the 164 residue protein T4 lysozyme (T4L). Results clearly demonstrate that the protein biosynthetic machinery can accommodate a wide variety of conformationally constrained amino acids. The expansion of structural motifs that can be biosynthetically incorporated into proteins to include a large number of conformationally constrained amino acids significantly increases the power of mutagenesis methods as probes of protein structure and function and provides additional insights into the steric requirements of the translational machinery. 13 refs., 2 figs.

  9. Intersecting transcription networks constrain gene regulatory evolution

    PubMed Central

    Sorrells, Trevor R; Booth, Lauren N; Tuch, Brian B; Johnson, Alexander D

    2015-01-01

    Epistasis—the non-additive interactions between different genetic loci—constrains evolutionary pathways, blocking some and permitting others1–8. For biological networks such as transcription circuits, the nature of these constraints and their consequences are largely unknown. Here we describe the evolutionary pathways of a transcription network that controls the response to mating pheromone in yeasts9. A component of this network, the transcription regulator Ste12, has evolved two different modes of binding to a set of its target genes. In one group of species, Ste12 binds to specific DNA binding sites, while in another lineage it occupies DNA indirectly, relying on a second transcription regulator to recognize DNA. We show, through the construction of various possible evolutionary intermediates, that evolution of the direct mode of DNA binding was not directly accessible to the ancestor. Instead, it was contingent on a lineage-specific change to an overlapping transcription network with a different function, the specification of cell type. These results show that analyzing and predicting the evolution of cis-regulatory regions requires an understanding of their positions in overlapping networks, as this placement constrains the available evolutionary pathways. PMID:26153861

  10. Multiple Manifold Clustering Using Curvature Constrained Path

    PubMed Central

    Babaeian, Amir; Bayestehtashk, Alireza; Bandarabadi, Mojtaba

    2015-01-01

    The problem of multiple surface clustering is a challenging task, particularly when the surfaces intersect. Available methods such as Isomap fail to capture the true shape of the surface near by the intersection and result in incorrect clustering. The Isomap algorithm uses shortest path between points. The main draw back of the shortest path algorithm is due to the lack of curvature constrained where causes to have a path between points on different surfaces. In this paper we tackle this problem by imposing a curvature constraint to the shortest path algorithm used in Isomap. The algorithm chooses several landmark nodes at random and then checks whether there is a curvature constrained path between each landmark node and every other node in the neighborhood graph. We build a binary feature vector for each point where each entry represents the connectivity of that point to a particular landmark. Then the binary feature vectors could be used as a input of conventional clustering algorithm such as hierarchical clustering. We apply our method to simulated and some real datasets and show, it performs comparably to the best methods such as K-manifold and spectral multi-manifold clustering. PMID:26375819

  11. Constraining torsion with Gravity Probe B

    SciTech Connect

    Mao Yi; Guth, Alan H.; Cabi, Serkan; Tegmark, Max

    2007-11-15

    It is well-entrenched folklore that all torsion gravity theories predict observationally negligible torsion in the solar system, since torsion (if it exists) couples only to the intrinsic spin of elementary particles, not to rotational angular momentum. We argue that this assumption has a logical loophole which can and should be tested experimentally, and consider nonstandard torsion theories in which torsion can be generated by macroscopic rotating objects. In the spirit of action=reaction, if a rotating mass like a planet can generate torsion, then a gyroscope would be expected to feel torsion. An experiment with a gyroscope (without nuclear spin) such as Gravity Probe B (GPB) can test theories where this is the case. Using symmetry arguments, we show that to lowest order, any torsion field around a uniformly rotating spherical mass is determined by seven dimensionless parameters. These parameters effectively generalize the parametrized post-Newtonian formalism and provide a concrete framework for further testing Einstein's general theory of relativity (GR). We construct a parametrized Lagrangian that includes both standard torsion-free GR and Hayashi-Shirafuji maximal torsion gravity as special cases. We demonstrate that classic solar system tests rule out the latter and constrain two observable parameters. We show that Gravity Probe B is an ideal experiment for further constraining nonstandard torsion theories, and work out the most general torsion-induced precession of its gyroscope in terms of our torsion parameters.

  12. Constraining the Mass of A Galaxy Cluster

    NASA Astrophysics Data System (ADS)

    Cemenenkoff, Nicholas; Rines, Kenneth J.; Geller, Margaret J.; Diaferio, Antonaldo

    2017-01-01

    Accurate cluster masses are critical for understanding dark matter and for using clusters to constrain cosmological parameters. We use the observed surface number density profile and velocity dispersion profile of galaxies in the Coma cluster to constrain its mass profile via Jeans analysis. In particular, we evaluate the robustness of the mass estimate M_200 by using different parametric forms for the distribution of mass and galaxies as well as different models of the orbital anisotropy parameter β (r) . Allowing for variation between the scale radii of the mass profile and the galaxy profile (i.e. relaxing the assumption that galaxies trace mass) does not significantly change the estimate of M 200 . We use a Bayesian approach to construct probability distribution functions of M 200, scale radius, and beta via Markov Chain Monte Carlo (MCMC) sampling. We apply this approach to ensemble clusters stacked by either their Sunyaev-Zel'dovich (SZ) signals or X-ray luminosities to measure the scaling relations of dynamical mass estimates with these mass proxies. Specifically, we test the hypothesis that the apparent deficit of SZ clusters (compared to predictions based on observations of the microwave background) can be explained by a bias of ˜ 60% in the normalization of the scaling relation between SZ signal and mass.

  13. New General Tools for Constrained Geometry Optimizations.

    PubMed

    De Vico, Luca; Olivucci, Massimo; Lindh, Roland

    2005-09-01

    A modification of the constrained geometry optimization method by Anglada and Bofill (Anglada, J. M.; Bofill, J. M. J. Comput. Chem. 1997, 18, 992-1003) is designed and implemented. The changes include the choice of projection, quasi-line-search, and the use of a Rational Function optimization approach rather than a reduced-restricted-quasi-Newton-Raphson method in the optimization step. Furthermore, we show how geometrical constrains can be implemented in an approach based on nonredundant curvilinear coordinates avoiding the inclusion of the constraints in the set of redundant coordinates used to define the internal coordinates. The behavior of the new implementation is demonstrated in geometry optimizations featuring single or multiple geometrical constraints (bond lengths, angles, etc.), optimizations on hyperspherical cross sections (as in the computation of steepest descent paths), and location of energy minima on the intersection subspace of two potential energy surfaces (i.e. minimum energy crossing points). In addition, a novel scheme to determine the crossing point geometrically nearest to a given molecular structure is proposed.

  14. Constraining the halo mass function with observations

    NASA Astrophysics Data System (ADS)

    Castro, Tiago; Marra, Valerio; Quartin, Miguel

    2016-12-01

    The abundances of dark matter haloes in the universe are described by the halo mass function (HMF). It enters most cosmological analyses and parametrizes how the linear growth of primordial perturbations is connected to these abundances. Interestingly, this connection can be made approximately cosmology independent. This made it possible to map in detail its near-universal behaviour through large-scale simulations. However, such simulations may suffer from systematic effects, especially if baryonic physics is included. In this paper, we ask how well observations can constrain directly the HMF. The observables we consider are galaxy cluster number counts, galaxy cluster power spectrum and lensing of Type Ia supernovae. Our results show that Dark Energy Survey is capable of putting the first meaningful constraints on the HMF, while both Euclid and J-PAS (Javalambre-Physics of the Accelerated Universe Astrophysical Survey) can give stronger constraints, comparable to the ones from state-of-the-art simulations. We also find that an independent measurement of cluster masses is even more important for measuring the HMF than for constraining the cosmological parameters, and can vastly improve the determination of the HMF. Measuring the HMF could thus be used to cross-check simulations and their implementation of baryon physics. It could even, if deviations cannot be accounted for, hint at new physics.

  15. Regular Language Constrained Sequence Alignment Revisited

    NASA Astrophysics Data System (ADS)

    Kucherov, Gregory; Pinhas, Tamar; Ziv-Ukelson, Michal

    Imposing constraints in the form of a finite automaton or a regular expression is an effective way to incorporate additional a priori knowledge into sequence alignment procedures. With this motivation, Arslan [1] introduced the Regular Language Constrained Sequence Alignment Problem and proposed an O(n 2 t 4) time and O(n 2 t 2) space algorithm for solving it, where n is the length of the input strings and t is the number of states in the non-deterministic automaton, which is given as input. Chung et al. [2] proposed a faster O(n 2 t 3) time algorithm for the same problem. In this paper, we further speed up the algorithms for Regular Language Constrained Sequence Alignment by reducing their worst case time complexity bound to O(n 2 t 3/logt). This is done by establishing an optimal bound on the size of Straight-Line Programs solving the maxima computation subproblem of the basic dynamic programming algorithm. We also study another solution based on a Steiner Tree computation. While it does not improve the run time complexity in the worst case, our simulations show that both approaches are efficient in practice, especially when the input automata are dense.

  16. Glassy dynamics of kinetically constrained models

    NASA Astrophysics Data System (ADS)

    Ritort, F.; Sollich, P.

    2003-06-01

    We review the use of kinetically constrained models (KCMs) for the study of dynamics in glassy systems. The characteristic feature of KCMs is that they have trivial, often non-interacting, equilibrium behaviour but interesting slow dynamics due to restrictions on the allowed transitions between configurations. The basic question which KCMs ask is therefore how much glassy physics can be understood without an underlying 'equilibrium glass transition'. After a brief review of glassy phenomenology, we describe the main model classes, which include spin-facilitated (Ising) models, constrained lattice gases, models inspired by cellular structures such as soap froths, models obtained via mappings from interacting systems without constraints, and finally related models such as urn, oscillator, tiling and needle models. We then describe the broad range of techniques that have been applied to KCMs, including exact solutions, adiabatic approximations, projection and mode-coupling techniques, diagrammatic approaches and mappings to quantum systems or effective models. Finally, we give a survey of the known results for the dynamics of KCMs both in and out of equilibrium, including topics such as relaxation time divergences and dynamical transitions, nonlinear relaxation, ageing and effective temperatures, cooperativity and dynamical heterogeneities, and finally non-equilibrium stationary states generated by external driving. We conclude with a discussion of open questions and possibilities for future work.

  17. Physically constrained maximum likelihood mode filtering.

    PubMed

    Papp, Joseph C; Preisig, James C; Morozov, Andrey K

    2010-04-01

    Mode filtering is most commonly implemented using the sampled mode shapes or pseudoinverse algorithms. Buck et al. [J. Acoust. Soc. Am. 103, 1813-1824 (1998)] placed these techniques in the context of a broader maximum a posteriori (MAP) framework. However, the MAP algorithm requires that the signal and noise statistics be known a priori. Adaptive array processing algorithms are candidates for improving performance without the need for a priori signal and noise statistics. A variant of the physically constrained, maximum likelihood (PCML) algorithm [A. L. Kraay and A. B. Baggeroer, IEEE Trans. Signal Process. 55, 4048-4063 (2007)] is developed for mode filtering that achieves the same performance as the MAP mode filter yet does not need a priori knowledge of the signal and noise statistics. The central innovation of this adaptive mode filter is that the received signal's sample covariance matrix, as estimated by the algorithm, is constrained to be that which can be physically realized given a modal propagation model and an appropriate noise model. Shallow water simulation results are presented showing the benefit of using the PCML method in adaptive mode filtering.

  18. The Constrained Crystallization of Nylon-6

    NASA Astrophysics Data System (ADS)

    Mohan, Anushree; Tonelli, Alan

    2008-10-01

    Non-covalently bonded crystalline inclusion compounds (ICs) have been formed by threading host cyclic starches, cyclodextrins (CDs) onto guest nylon 6 (N6) chains. When excess N6 is employed, non-stoichiometric (n-s)-N6-CD-ICs with partially uncovered and dangling N6 chains result. While the crystalline CD lattice is stable to ˜300 C, the uncovered and dangling, yet constrained, N6 chains may crystallize below or, as shown below, be molten above ˜225 C. We have been studying the constrained crystallization of the dangling N6 chains in (n-S)-N6-CD-ICs, with comparison to bulk N6 samples, as a function of N6 molecular weights, lengths of uncovered N6 chains, and the CD host used. In the IC channels formed with host α- and γ-CDs containing 6 and 8 glucose units, respectively, single and pairs of side-by-side N6 chains are threaded and included. In the α-CD-ICs the ˜ 0.5 nm channels are separated by ˜ 1.4 nm, while in γ-CD-ICs the ˜ 1 nm channels are ˜ 1.7 nm apart, with each γ-CD channel including 2 N6 chains. N6 chains in the bulk and in the dense (n-s)-N6-CD-IC brushes show distinctly different kinetic and thermodynamic crystallization behaviors.

  19. Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

    PubMed Central

    Koopmanschap, Gijs; Ruijter, Eelco

    2014-01-01

    Summary In the recent past, the design and synthesis of peptide mimics (peptidomimetics) has received much attention. This because they have shown in many cases enhanced pharmacological properties over their natural peptide analogues. In particular, the incorporation of cyclic constructs into peptides is of high interest as they reduce the flexibility of the peptide enhancing often affinity for a certain receptor. Moreover, these cyclic mimics force the molecule into a well-defined secondary structure. Constraint structural and conformational features are often found in biological active peptides. For the synthesis of cyclic constrained peptidomimetics usually a sequence of multiple reactions has been applied, which makes it difficult to easily introduce structural diversity necessary for fine tuning the biological activity. A promising approach to tackle this problem is the use of multicomponent reactions (MCRs), because they can introduce both structural diversity and molecular complexity in only one step. Among the MCRs, the isocyanide-based multicomponent reactions (IMCRs) are most relevant for the synthesis of peptidomimetics because they provide peptide-like products. However, these IMCRs usually give linear products and in order to obtain cyclic constrained peptidomimetics, the acyclic products have to be cyclized via additional cyclization strategies. This is possible via incorporation of bifunctional substrates into the initial IMCR. Examples of such bifunctional groups are N-protected amino acids, convertible isocyanides or MCR-components that bear an additional alkene, alkyne or azide moiety and can be cyclized via either a deprotection–cyclization strategy, a ring-closing metathesis, a 1,3-dipolar cycloaddition or even via a sequence of multiple multicomponent reactions. The sequential IMCR-cyclization reactions can afford small cyclic peptide mimics (ranging from four- to seven-membered rings), medium-sized cyclic constructs or peptidic macrocycles

  20. Vibrational circular dichroism and IR absorption spectra of amino acids: a density functional study.

    PubMed

    Ji, Zhi; Santamaria, Rubén; Garzón, Ignacio L

    2010-03-18

    With density functional theory, vibrational circular dichroism (VCD) and infrared absorption (IR) spectra are obtained at the B3LYP/CC-pVTZ level of theory for 20 alpha-amino acids. The contribution of different vibration modes to the IR and VCD spectra is analyzed. Overall agreement between calculated results for amino acids in gas phase with the available experimental VCD data for matrix-assisted amino acid films is found. The analysis of the calculated IR and VCD spectra indicates that the functional groups in the backbones and side chains of amino acids contribute differently to the spectra line shape. It is obtained that molecular torsions are the characteristic vibrations of the amino acids at the low-frequency regime, whereas the bending of bond angles, the out-of-plane wagging of individual atoms, and some stretching modes dominate the intermediate frequency range. Specific modes like NH(2) scissoring, CO bond stretching, and the (symmetric and asymmetric) stretching of the hydrogen atoms in the NH(2) and OH groups characterize the high-frequency regime. A general trend emerging from these calculations indicates that the rho(OH) rocking and nu(C=O) stretching modes have the highest intensity in the VCD spectra of most amino acids.

  1. Total parenteral nutrition-associated cholestasis in rats: comparison of different amino acid mixtures.

    PubMed

    Belli, D C; Fournier, L A; Lepage, G; Yousef, I; Weber, A M; Tuchweber, B; Roy, C C

    1987-01-01

    It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect.

  2. Electrophysiological evidence for acidic, basic, and neutral amino acid olfactory receptor sites in the catfish

    PubMed Central

    1984-01-01

    Electrophysiological experiments indicate that olfactory receptors of the channel catfish, Ictalurus punctatus, contain different receptor sites for the acidic (A), basic (B), and neutral amino acids; further, at least two partially interacting neutral sites exist, one for the hydrophilic neutral amino acids containing short side chains (SCN), and the second for the hydrophobic amino acids containing long side chains (LCN). The extent of cross-adaptation was determined by comparing the electro-olfactogram (EOG) responses to 20 "test" amino acids during continuous bathing of the olfactory mucosa with water only (control) to those during each of the eight "adapting" amino acid regimes. Both the adapting and test amino acids were adjusted in concentrations to provide approximately equal response magnitudes in the unadapted state. Under all eight adapting regimes, the test EOG responses were reduced from those obtained in the unadapted state, but substantial quantitative differences resulted, depending upon the molecular structure of the adapting stimulus. Analyses of the patterns of EOG responses to the test stimuli identified and characterized the respective "transduction processes," a term used to describe membrane events initiated by a particular subset of amino acid stimuli that are intricately linked to the origin of the olfactory receptor potential. Only when the stimulus compounds interact with different transduction processes are the stimuli assumed to bind to different membrane "sites." Four relatively independent L-alpha-amino acid transduction processes (and thus at least four binding sites) identified in this report include: (a) the A process for aspartic and glutamic acids; (b) the B process for arginine and lysine; (c) the SCN process for glycine, alanine, serine, glutamine, and possibly cysteine; (d) the LCN process for methionine, ethionine, valine, norvaline, leucine, norleucine, glutamic acid-gamma-methyl ester, histidine, phenylalanine, and also

  3. Ocean acidification-induced food quality deterioration constrains trophic transfer.

    PubMed

    Rossoll, Dennis; Bermúdez, Rafael; Hauss, Helena; Schulz, Kai G; Riebesell, Ulf; Sommer, Ulrich; Winder, Monika

    2012-01-01

    Our present understanding of ocean acidification (OA) impacts on marine organisms caused by rapidly rising atmospheric carbon dioxide (CO(2)) concentration is almost entirely limited to single species responses. OA consequences for food web interactions are, however, still unknown. Indirect OA effects can be expected for consumers by changing the nutritional quality of their prey. We used a laboratory experiment to test potential OA effects on algal fatty acid (FA) composition and resulting copepod growth. We show that elevated CO(2) significantly changed the FA concentration and composition of the diatom Thalassiosira pseudonana, which constrained growth and reproduction of the copepod Acartia tonsa. A significant decline in both total FAs (28.1 to 17.4 fg cell(-1)) and the ratio of long-chain polyunsaturated to saturated fatty acids (PUFA:SFA) of food algae cultured under elevated (750 µatm) compared to present day (380 µatm) pCO(2) was directly translated to copepods. The proportion of total essential FAs declined almost tenfold in copepods and the contribution of saturated fatty acids (SFAs) tripled at high CO(2). This rapid and reversible CO(2)-dependent shift in FA concentration and composition caused a decrease in both copepod somatic growth and egg production from 34 to 5 eggs female(-1) day(-1). Because the diatom-copepod link supports some of the most productive ecosystems in the world, our study demonstrates that OA can have far-reaching consequences for ocean food webs by changing the nutritional quality of essential macromolecules in primary producers that cascade up the food web.

  4. Constrained sampling method for analytic continuation

    NASA Astrophysics Data System (ADS)

    Sandvik, Anders W.

    2016-12-01

    A method for analytic continuation of imaginary-time correlation functions (here obtained in quantum Monte Carlo simulations) to real-frequency spectral functions is proposed. Stochastically sampling a spectrum parametrized by a large number of δ functions, treated as a statistical-mechanics problem, it avoids distortions caused by (as demonstrated here) configurational entropy in previous sampling methods. The key development is the suppression of entropy by constraining the spectral weight to within identifiable optimal bounds and imposing a set number of peaks. As a test case, the dynamic structure factor of the S =1 /2 Heisenberg chain is computed. Very good agreement is found with Bethe ansatz results in the ground state (including a sharp edge) and with exact diagonalization of small systems at elevated temperatures.

  5. Disappearance and Creation of Constrained Amorphous Phase

    NASA Astrophysics Data System (ADS)

    Cebe, Peggy; Lu, Sharon X.

    1997-03-01

    We report observation of the disappearance and recreation of rigid, or constrained, amorphous phase by sequential thermal annealing. Tempera- ture modulated differential scanning calorimetry (MDSC) is used to study the glass transition and lower melting endotherm after annealing. Cold crystallization of poly(phenylene sulfide), PPS, at a temperature just above Tg creates an initial large fraction of rigid amorphous phase (RAP). Brief, rapid annealing to a higher temperature causes RAP almost to disappear completely. Subsequent reannealing at the original lower temperature restores RAP to its original value. At the same time that RAP is being removed, Tg decreases; when RAP is restored, Tg also returns to its initial value. The crystal fraction remains unaffected by the annealing sequence.

  6. Printer model inversion by constrained optimization

    NASA Astrophysics Data System (ADS)

    Cholewo, Tomasz J.

    1999-12-01

    This paper describes a novel method for finding colorant amounts for which a printer will produce a requested color appearance based on constrained optimization. An error function defines the gamut mapping method and black replacement method. The constraints limit the feasible solution region to the device gamut and prevent exceeding the maximum total area coverage. Colorant values corresponding to in-gamut colors are found with precision limited only by the accuracy of the device model. Out-of- gamut colors are mapped to colors within the boundary of the device gamut. This general approach, used in conjunction with different types of color difference equations, can perform a wide range of out-of-gamut mappings such as chroma clipping or for finding colors on gamut boundary having specified properties. We present an application of this method to the creation of PostScript color rendering dictionaries and ICC profiles.

  7. Constrained Aerothermodynamic Design of Hypersonic Vehicles

    NASA Technical Reports Server (NTRS)

    Gally, Tom; Campbell, Dick

    2002-01-01

    An investigation was conducted into possible methods of incorporating a hypersonic design capability with aerothermodynamic constraints into the CDISC aerodynamic design tool. The work was divided into two distinct phases: develop relations between surface curvature and hypersonic pressure coefficient which are compatible with CDISC's direct-iterative design method; and explore and implement possible methods of constraining the heat transfer rate over all or portions of the design surface. The main problem in implementing this method has been the weak relationship between surface shape and pressure coefficient at the stagnation point and the need to design around the surface blunt leading edge where there is a slope singularity. The final results show that some success has been achieved, but further improvements are needed.

  8. Constrained Nonnegative Matrix Factorization for Image Representation.

    PubMed

    Liu, Haifeng; Wu, Zhaohui; Li, Xuelong; Cai, Deng; Huang, Thomas S

    2012-07-01

    Nonnegative matrix factorization (NMF) is a popular technique for finding parts-based, linear representations of nonnegative data. It has been successfully applied in a wide range of applications such as pattern recognition, information retrieval, and computer vision. However, NMF is essentially an unsupervised method and cannot make use of label information. In this paper, we propose a novel semi-supervised matrix decomposition method, called Constrained Nonnegative Matrix Factorization (CNMF), which incorporates the label information as additional constraints. Specifically, we show how explicitly combining label information improves the discriminating power of the resulting matrix decomposition. We explore the proposed CNMF method with two cost function formulations and provide the corresponding update solutions for the optimization problems. Empirical experiments demonstrate the effectiveness of our novel algorithm in comparison to the state-of-the-art approaches through a set of evaluations based on real-world applications.

  9. Remote gaming on resource-constrained devices

    NASA Astrophysics Data System (ADS)

    Reza, Waazim; Kalva, Hari; Kaufman, Richard

    2010-08-01

    Games have become important applications on mobile devices. A mobile gaming approach known as remote gaming is being developed to support games on low cost mobile devices. In the remote gaming approach, the responsibility of rendering a game and advancing the game play is put on remote servers instead of the resource constrained mobile devices. The games rendered on the servers are encoded as video and streamed to mobile devices. Mobile devices gather user input and stream the commands back to the servers to advance game play. With this solution, mobile devices with video playback and network connectivity can become game consoles. In this paper we present the design and development of such a system and evaluate the performance and design considerations to maximize the end user gaming experience.

  10. Constraining the Interior Earth Objects population

    NASA Astrophysics Data System (ADS)

    Fuentes, Cesar; Trilling, David E.; Knight, Matthew M.; Mommert, Michael; Hechenleitner, Federico

    2016-10-01

    Interior Earth Objects (IEOs) are among the least known populations in the Solar Sytem. Ground-based surveys are extremely inefficient in surveying them as most of the time IEOs are located inside the orbit of the Earth. We present observational constraints to the IEO population from STEREO (Solar TErrestrial RElations Observatory). This is the first result of searching through the archival STEREO data. Although after analyzing a year's worth of data we found no new IEOs, we observed hundreds of known asteroids. Our survey efficiency is computed with known and implanted synthetic objects, yielding a limiting magnitude of V~14.5. We constrain different IEO population models, yielding an upper limit for the total number of IEOs in line with previous estimates.

  11. The asymptotics of large constrained graphs

    NASA Astrophysics Data System (ADS)

    Radin, Charles; Ren, Kui; Sadun, Lorenzo

    2014-05-01

    We show, through local estimates and simulation, that if one constrains simple graphs by their densities ɛ of edges and τ of triangles, then asymptotically (in the number of vertices) for over 95% of the possible range of those densities there is a well-defined typical graph, and it has a very simple structure: the vertices are decomposed into two subsets V1 and V2 of fixed relative size c and 1 - c, and there are well-defined probabilities of edges, gjk, between vj ∈ Vj, and vk ∈ Vk. Furthermore the four parameters c, g11, g22 and g12 are smooth functions of (ɛ, τ) except at two smooth ‘phase transition’ curves.

  12. How alive is constrained SUSY really?

    DOE PAGES

    Bechtle, Philip; Desch, Klaus; Dreiner, Herbert K.; ...

    2016-05-31

    Constrained supersymmetric models like the CMSSM might look less attractive nowadays because of fine tuning arguments. They also might look less probable in terms of Bayesian statistics. The question how well the model under study describes the data, however, is answered by frequentist p-values. Thus, for the first time, we calculate a p-value for a supersymmetric model by performing dedicated global toy fits. We combine constraints from low-energy and astrophysical observables, Higgs boson mass and rate measurements as well as the non-observation of new physics in searches for supersymmetry at the LHC. Furthermore, using the framework Fittino, we perform globalmore » fits of the CMSSM to the toy data and find that this model is excluded at the 90% confidence level.« less

  13. How alive is constrained SUSY really?

    SciTech Connect

    Bechtle, Philip; Desch, Klaus; Dreiner, Herbert K.; Hamer, Matthias; Kramer, Michael; O'Leary, Ben; Porod, Werner; Sarrazin, Bjorn; Stefaniak, Tim; Uhlenbrock, Mathias; Wienemann, Peter

    2016-05-31

    Constrained supersymmetric models like the CMSSM might look less attractive nowadays because of fine tuning arguments. They also might look less probable in terms of Bayesian statistics. The question how well the model under study describes the data, however, is answered by frequentist p-values. Thus, for the first time, we calculate a p-value for a supersymmetric model by performing dedicated global toy fits. We combine constraints from low-energy and astrophysical observables, Higgs boson mass and rate measurements as well as the non-observation of new physics in searches for supersymmetry at the LHC. Furthermore, using the framework Fittino, we perform global fits of the CMSSM to the toy data and find that this model is excluded at the 90% confidence level.

  14. Spatially constrained propulsion in jumping archer fish

    NASA Astrophysics Data System (ADS)

    Mendelson, Leah; Techet, Alexandra

    2016-11-01

    Archer fish jump multiple body lengths out of the water for prey capture with impressive accuracy. Their remarkable aim is facilitated by jumping from a stationary position directly below the free surface. As a result of this starting position, rapid acceleration to a velocity sufficient for reaching the target occurs with only a body length to travel before the fish leaves the water. Three-dimensional measurements of jumping kinematics and volumetric velocimetry using Synthetic Aperture PIV highlight multiple strategies for such spatially constrained acceleration. Archer fish rapidly extend fins at jump onset to increase added mass forces and modulate their swimming kinematics to minimize wasted energy when the body is partially out of the water. Volumetric measurements also enable assessment of efficiency during a jump, which is crucial to understanding jumping's role as an energetically viable hunting strategy for the fish.

  15. Sampling Motif-Constrained Ensembles of Networks

    NASA Astrophysics Data System (ADS)

    Fischer, Rico; Leitão, Jorge C.; Peixoto, Tiago P.; Altmann, Eduardo G.

    2015-10-01

    The statistical significance of network properties is conditioned on null models which satisfy specified properties but that are otherwise random. Exponential random graph models are a principled theoretical framework to generate such constrained ensembles, but which often fail in practice, either due to model inconsistency or due to the impossibility to sample networks from them. These problems affect the important case of networks with prescribed clustering coefficient or number of small connected subgraphs (motifs). In this Letter we use the Wang-Landau method to obtain a multicanonical sampling that overcomes both these problems. We sample, in polynomial time, networks with arbitrary degree sequences from ensembles with imposed motifs counts. Applying this method to social networks, we investigate the relation between transitivity and homophily, and we quantify the correlation between different types of motifs, finding that single motifs can explain up to 60% of the variation of motif profiles.

  16. Fluctuation theorem for constrained equilibrium systems.

    PubMed

    Gilbert, Thomas; Dorfman, J Robert

    2006-02-01

    We discuss the fluctuation properties of equilibrium chaotic systems with constraints such as isokinetic and Nosé-Hoover thermostats. Although the dynamics of these systems does not typically preserve phase-space volumes, the average phase-space contraction rate vanishes, so that the stationary states are smooth. Nevertheless, finite-time averages of the phase-space contraction rate have nontrivial fluctuations which we show satisfy a simple version of the Gallavotti-Cohen fluctuation theorem, complementary to the usual fluctuation theorem for nonequilibrium stationary states and appropriate to constrained equilibrium states. Moreover, we show that these fluctuations are distributed according to a Gaussian curve for long enough times. Three different systems are considered here: namely, (i) a fluid composed of particles interacting with Lennard-Jones potentials, (ii) a harmonic oscillator with Nosé-Hoover thermostatting, and (iii) a simple hyperbolic two-dimensional map.

  17. Fluctuation theorem for constrained equilibrium systems

    NASA Astrophysics Data System (ADS)

    Gilbert, Thomas; Dorfman, J. Robert

    2006-02-01

    We discuss the fluctuation properties of equilibrium chaotic systems with constraints such as isokinetic and Nosé-Hoover thermostats. Although the dynamics of these systems does not typically preserve phase-space volumes, the average phase-space contraction rate vanishes, so that the stationary states are smooth. Nevertheless, finite-time averages of the phase-space contraction rate have nontrivial fluctuations which we show satisfy a simple version of the Gallavotti-Cohen fluctuation theorem, complementary to the usual fluctuation theorem for nonequilibrium stationary states and appropriate to constrained equilibrium states. Moreover, we show that these fluctuations are distributed according to a Gaussian curve for long enough times. Three different systems are considered here: namely, (i) a fluid composed of particles interacting with Lennard-Jones potentials, (ii) a harmonic oscillator with Nosé-Hoover thermostatting, and (iii) a simple hyperbolic two-dimensional map.

  18. Statistical mechanics of budget-constrained auctions

    NASA Astrophysics Data System (ADS)

    Altarelli, F.; Braunstein, A.; Realpe-Gomez, J.; Zecchina, R.

    2009-07-01

    Finding the optimal assignment in budget-constrained auctions is a combinatorial optimization problem with many important applications, a notable example being in the sale of advertisement space by search engines (in this context the problem is often referred to as the off-line AdWords problem). On the basis of the cavity method of statistical mechanics, we introduce a message-passing algorithm that is capable of solving efficiently random instances of the problem extracted from a natural distribution, and we derive from its properties the phase diagram of the problem. As the control parameter (average value of the budgets) is varied, we find two phase transitions delimiting a region in which long-range correlations arise.

  19. Perceived visual speed constrained by image segmentation

    NASA Technical Reports Server (NTRS)

    Verghese, P.; Stone, L. S.

    1996-01-01

    Little is known about how or where the visual system parses the visual scene into objects or surfaces. However, it is generally assumed that the segmentation and grouping of pieces of the image into discrete entities is due to 'later' processing stages, after the 'early' processing of the visual image by local mechanisms selective for attributes such as colour, orientation, depth, and motion. Speed perception is also thought to be mediated by early mechanisms tuned for speed. Here we show that manipulating the way in which an image is parsed changes the way in which local speed information is processed. Manipulations that cause multiple stimuli to appear as parts of a single patch degrade speed discrimination, whereas manipulations that perceptually divide a single large stimulus into parts improve discrimination. These results indicate that processes as early as speed perception may be constrained by the parsing of the visual image into discrete entities.

  20. Constrained sampling method for analytic continuation.

    PubMed

    Sandvik, Anders W

    2016-12-01

    A method for analytic continuation of imaginary-time correlation functions (here obtained in quantum Monte Carlo simulations) to real-frequency spectral functions is proposed. Stochastically sampling a spectrum parametrized by a large number of δ functions, treated as a statistical-mechanics problem, it avoids distortions caused by (as demonstrated here) configurational entropy in previous sampling methods. The key development is the suppression of entropy by constraining the spectral weight to within identifiable optimal bounds and imposing a set number of peaks. As a test case, the dynamic structure factor of the S=1/2 Heisenberg chain is computed. Very good agreement is found with Bethe ansatz results in the ground state (including a sharp edge) and with exact diagonalization of small systems at elevated temperatures.

  1. Constrained fits with non-Gaussian distributions

    NASA Astrophysics Data System (ADS)

    Frühwirth, R.; Cencic, O.

    2016-10-01

    Non-normally distributed data are ubiquitous in many areas of science, including high-energy physics. We present a general formalism for constrained fits, also called data reconciliation, with data that are not normally distributed. It is based on Bayesian reasoning and implemented via MCMC sampling. We show how systems of both linear and non-linear constraints can be efficiently treated. We also show how the fit can be made robust against outlying observations. The method is demonstrated on a couple of examples ranging from material flow analysis to the combination of non-normal measurements. Finally, we discuss possible applications in the field of event reconstruction, such as vertex fitting and kinematic fitting with non-normal track errors.

  2. Explaining evolution via constrained persistent perfect phylogeny.

    PubMed

    Bonizzoni, Paola; Carrieri, Anna Paola; Della Vedova, Gianluca; Trucco, Gabriella

    2014-01-01

    The perfect phylogeny is an often used model in phylogenetics since it provides an efficient basic procedure for representing the evolution of genomic binary characters in several frameworks, such as for example in haplotype inference. The model, which is conceptually the simplest, is based on the infinite sites assumption, that is no character can mutate more than once in the whole tree. A main open problem regarding the model is finding generalizations that retain the computational tractability of the original model but are more flexible in modeling biological data when the infinite site assumption is violated because of e.g. back mutations. A special case of back mutations that has been considered in the study of the evolution of protein domains (where a domain is acquired and then lost) is persistency, that is the fact that a character is allowed to return back to the ancestral state. In this model characters can be gained and lost at most once. In this paper we consider the computational problem of explaining binary data by the Persistent Perfect Phylogeny model (referred as PPP) and for this purpose we investigate the problem of reconstructing an evolution where some constraints are imposed on the paths of the tree. We define a natural generalization of the PPP problem obtained by requiring that for some pairs (character, species), neither the species nor any of its ancestors can have the character. In other words, some characters cannot be persistent for some species. This new problem is called Constrained PPP (CPPP). Based on a graph formulation of the CPPP problem, we are able to provide a polynomial time solution for the CPPP problem for matrices whose conflict graph has no edges. Using this result, we develop a parameterized algorithm for solving the CPPP problem where the parameter is the number of characters. A preliminary experimental analysis shows that the constrained persistent perfect phylogeny model allows to explain efficiently data that do not

  3. Constraining Paleoearthquake Slip Distributions with Coral Microatolls

    NASA Astrophysics Data System (ADS)

    Lindsay, A.; McCloskey, J.; nic Bhloscaidh, M.; Murphy, S.

    2014-12-01

    Key to understanding the threat posed by large megathrust earthquakes is identifying where the potential for these destructive events exists. Studying extended sequences of earthquakes, Slip Deficit and Stress Evolution modelling techniques may hold the key to locating areas of concern. However, as well as using recent instrumentally constrained slip distributions they require the production of high resolution source models for pre-instrumental events. One place we can attempt this longer term modelling is along the Sunda Trench with its record of large megathrust earthquakes dating back centuries. Coral microatolls populating the intertidal areas of the Sumatran Forearc act as long-term geodetic recorders of tectonic activity. Repeated cycles of stress accumulation and release alter relative sea levels around these islands. Growth of corals, controlled by the level of the lowest tide, exploit interseismic rises in sea level. In turn, they experience die-offs when coseismic drops in sea level lead to subaerially exposure. Examination of coral stratigraphy reveals a history of displacements from which information of past earthquakes can be inferred. We have developed a Genetic Algorithm Slip Estimator (GASE) to rapidly produce high resolution slip distributions from coral displacement data. GASE recombines information held in populations of randomly generated slip distributions, to create superior models, satisfying observed displacements. Non-unique solutions require multiple iterations of the algorithm, producing a suite of models from which an ensemble slip distribution is drawn. Systematic testing of the algorithm demonstrates its ability to reliably estimate both known synthetic and instrumentally constrained slip distributions based on surface displacements. We will present high-resolution source models satisfying published displacement data for a number recent and paleoearthquakes along the Sunda trench, including the great 1797 and 1833 events.

  4. A Path Algorithm for Constrained Estimation

    PubMed Central

    Zhou, Hua; Lange, Kenneth

    2013-01-01

    Many least-square problems involve affine equality and inequality constraints. Although there are a variety of methods for solving such problems, most statisticians find constrained estimation challenging. The current article proposes a new path-following algorithm for quadratic programming that replaces hard constraints by what are called exact penalties. Similar penalties arise in l1 regularization in model selection. In the regularization setting, penalties encapsulate prior knowledge, and penalized parameter estimates represent a trade-off between the observed data and the prior knowledge. Classical penalty methods of optimization, such as the quadratic penalty method, solve a sequence of unconstrained problems that put greater and greater stress on meeting the constraints. In the limit as the penalty constant tends to ∞, one recovers the constrained solution. In the exact penalty method, squared penalties!are replaced by absolute value penalties, and the solution is recovered for a finite value of the penalty constant. The exact path-following method starts at the unconstrained solution and follows the solution path as the penalty constant increases. In the process, the solution path hits, slides along, and exits from the various constraints. Path following in Lasso penalized regression, in contrast, starts with a large value of the penalty constant and works its way downward. In both settings, inspection of the entire solution path is revealing. Just as with the Lasso and generalized Lasso, it is possible to plot the effective degrees of freedom along the solution path. For a strictly convex quadratic program, the exact penalty algorithm can be framed entirely in terms of the sweep operator of regression analysis. A few well-chosen examples illustrate the mechanics and potential of path following. This article has supplementary materials available online. PMID:24039382

  5. Newton's method for large bound-constrained optimization problems.

    SciTech Connect

    Lin, C.-J.; More, J. J.; Mathematics and Computer Science

    1999-01-01

    We analyze a trust region version of Newton's method for bound-constrained problems. Our approach relies on the geometry of the feasible set, not on the particular representation in terms of constraints. The convergence theory holds for linearly constrained problems and yields global and superlinear convergence without assuming either strict complementarity or linear independence of the active constraints. We also show that the convergence theory leads to an efficient implementation for large bound-constrained problems.

  6. Asynchronous parallel generating set search for linearly-constrained optimization.

    SciTech Connect

    Lewis, Robert Michael; Griffin, Joshua D.; Kolda, Tamara Gibson

    2006-08-01

    Generating set search (GSS) is a family of direct search methods that encompasses generalized pattern search and related methods. We describe an algorithm for asynchronous linearly-constrained GSS, which has some complexities that make it different from both the asynchronous bound-constrained case as well as the synchronous linearly-constrained case. The algorithm has been implemented in the APPSPACK software framework and we present results from an extensive numerical study using CUTEr test problems. We discuss the results, both positive and negative, and conclude that GSS is a reliable method for solving small-to-medium sized linearly-constrained optimization problems without derivatives.

  7. Resource Management in Constrained Dynamic Situations

    NASA Astrophysics Data System (ADS)

    Seok, Jinwoo

    Resource management is considered in this dissertation for systems with limited resources, possibly combined with other system constraints, in unpredictably dynamic environments. Resources may represent fuel, power, capabilities, energy, and so on. Resource management is important for many practical systems; usually, resources are limited, and their use must be optimized. Furthermore, systems are often constrained, and constraints must be satisfied for safe operation. Simplistic resource management can result in poor use of resources and failure of the system. Furthermore, many real-world situations involve dynamic environments. Many traditional problems are formulated based on the assumptions of given probabilities or perfect knowledge of future events. However, in many cases, the future is completely unknown, and information on or probabilities about future events are not available. In other words, we operate in unpredictably dynamic situations. Thus, a method is needed to handle dynamic situations without knowledge of the future, but few formal methods have been developed to address them. Thus, the goal is to design resource management methods for constrained systems, with limited resources, in unpredictably dynamic environments. To this end, resource management is organized hierarchically into two levels: 1) planning, and 2) control. In the planning level, the set of tasks to be performed is scheduled based on limited resources to maximize resource usage in unpredictably dynamic environments. In the control level, the system controller is designed to follow the schedule by considering all the system constraints for safe and efficient operation. Consequently, this dissertation is mainly divided into two parts: 1) planning level design, based on finite state machines, and 2) control level methods, based on model predictive control. We define a recomposable restricted finite state machine to handle limited resource situations and unpredictably dynamic environments

  8. Eulerian Formulation of Spatially Constrained Elastic Rods

    NASA Astrophysics Data System (ADS)

    Huynen, Alexandre

    Slender elastic rods are ubiquitous in nature and technology. For a vast majority of applications, the rod deflection is restricted by an external constraint and a significant part of the elastic body is in contact with a stiff constraining surface. The research work presented in this doctoral dissertation formulates a computational model for the solution of elastic rods constrained inside or around frictionless tube-like surfaces. The segmentation strategy adopted to cope with this complex class of problems consists in sequencing the global problem into, comparatively simpler, elementary problems either in continuous contact with the constraint or contact-free between their extremities. Within the conventional Lagrangian formulation of elastic rods, this approach is however associated with two major drawbacks. First, the boundary conditions specifying the locations of the rod centerline at both extremities of each elementary problem lead to the establishment of isoperimetric constraints, i.e., integral constraints on the unknown length of the rod. Second, the assessment of the unilateral contact condition requires, in principle, the comparison of two curves parametrized by distinct curvilinear coordinates, viz. the rod centerline and the constraint axis. Both conspire to burden the computations associated with the method. To streamline the solution along the elementary problems and rationalize the assessment of the unilateral contact condition, the rod governing equations are reformulated within the Eulerian framework of the constraint. The methodical exploration of both types of elementary problems leads to specific formulations of the rod governing equations that stress the profound connection between the mechanics of the rod and the geometry of the constraint surface. The proposed Eulerian reformulation, which restates the rod local equilibrium in terms of the curvilinear coordinate associated with the constraint axis, describes the rod deformed configuration

  9. A General Framework of Dynamic Constrained Multiobjective Evolutionary Algorithms for Constrained Optimization.

    PubMed

    Zeng, Sanyou; Jiao, Ruwang; Li, Changhe; Li, Xi; Alkasassbeh, Jawdat S

    2017-09-01

    A novel multiobjective technique is proposed for solving constrained optimization problems (COPs) in this paper. The method highlights three different perspectives: 1) a COP is converted into an equivalent dynamic constrained multiobjective optimization problem (DCMOP) with three objectives: a) the original objective; b) a constraint-violation objective; and c) a niche-count objective; 2) a method of gradually reducing the constraint boundary aims to handle the constraint difficulty; and 3) a method of gradually reducing the niche size aims to handle the multimodal difficulty. A general framework of the design of dynamic constrained multiobjective evolutionary algorithms is proposed for solving DCMOPs. Three popular types of multiobjective evolutionary algorithms, i.e., Pareto ranking-based, decomposition-based, and hype-volume indicator-based, are employed to instantiate the framework. The three instantiations are tested on two benchmark suites. Experimental results show that they perform better than or competitive to a set of state-of-the-art constraint optimizers, especially on problems with a large number of dimensions.

  10. Brain amino acid requirements and toxicity: the example of leucine.

    PubMed

    Yudkoff, Marc; Daikhin, Yevgeny; Nissim, Ilana; Horyn, Oksana; Luhovyy, Bohdan; Luhovyy, Bogdan; Lazarow, Adam; Nissim, Itzhak

    2005-06-01

    Glutamic acid is an important excitatory neurotransmitter of the brain. Two key goals of brain amino acid handling are to maintain a very low intrasynaptic concentration of glutamic acid and also to provide the system with precursors from which to synthesize glutamate. The intrasynaptic glutamate level must be kept low to maximize the signal-to-noise ratio upon the release of glutamate from nerve terminals and to minimize the risk of excitotoxicity consequent to excessive glutamatergic stimulation of susceptible neurons. The brain must also provide neurons with a constant supply of glutamate, which both neurons and glia robustly oxidize. The branched-chain amino acids (BCAAs), particularly leucine, play an important role in this regard. Leucine enters the brain from the blood more rapidly than any other amino acid. Astrocytes, which are in close approximation to brain capillaries, probably are the initial site of metabolism of leucine. A mitochondrial branched-chain aminotransferase is very active in these cells. Indeed, from 30 to 50% of all alpha-amino groups of brain glutamate and glutamine are derived from leucine alone. Astrocytes release the cognate ketoacid [alpha-ketoisocaproate (KIC)] to neurons, which have a cytosolic branched-chain aminotransferase that reaminates the KIC to leucine, in the process consuming glutamate and providing a mechanism for the "buffering" of glutamate if concentrations become excessive. In maple syrup urine disease, or a congenital deficiency of branched-chain ketoacid dehydrogenase, the brain concentration of KIC and other branched-chain ketoacids can increase 10- to 20-fold. This leads to a depletion of glutamate and a consequent reduction in the concentration of brain glutamine, aspartate, alanine, and other amino acids. The result is a compromise of energy metabolism because of a failure of the malate-aspartate shuttle and a diminished rate of protein synthesis.

  11. Explaining evolution via constrained persistent perfect phylogeny

    PubMed Central

    2014-01-01

    Background The perfect phylogeny is an often used model in phylogenetics since it provides an efficient basic procedure for representing the evolution of genomic binary characters in several frameworks, such as for example in haplotype inference. The model, which is conceptually the simplest, is based on the infinite sites assumption, that is no character can mutate more than once in the whole tree. A main open problem regarding the model is finding generalizations that retain the computational tractability of the original model but are more flexible in modeling biological data when the infinite site assumption is violated because of e.g. back mutations. A special case of back mutations that has been considered in the study of the evolution of protein domains (where a domain is acquired and then lost) is persistency, that is the fact that a character is allowed to return back to the ancestral state. In this model characters can be gained and lost at most once. In this paper we consider the computational problem of explaining binary data by the Persistent Perfect Phylogeny model (referred as PPP) and for this purpose we investigate the problem of reconstructing an evolution where some constraints are imposed on the paths of the tree. Results We define a natural generalization of the PPP problem obtained by requiring that for some pairs (character, species), neither the species nor any of its ancestors can have the character. In other words, some characters cannot be persistent for some species. This new problem is called Constrained PPP (CPPP). Based on a graph formulation of the CPPP problem, we are able to provide a polynomial time solution for the CPPP problem for matrices whose conflict graph has no edges. Using this result, we develop a parameterized algorithm for solving the CPPP problem where the parameter is the number of characters. Conclusions A preliminary experimental analysis shows that the constrained persistent perfect phylogeny model allows to

  12. Constraining electromagnetic core-mantle coupling

    NASA Astrophysics Data System (ADS)

    Wicht, J.; Jault, D.

    1999-02-01

    Electromagnetic core-mantle coupling is one candidate for explaining length of day (LOD) variations on decadal time scales. This coupling has traditionally been calculated from models of core surface flow /U-->, but core flow inversions are not unique. Unfortunately, the main torque contribution depends on the toroidal part /∇×r-->Φ of the vector field (U-->Br), which is left undetermined by the radial induction equation that links core flows to magnetic field data under the frozen-flux hypothesis. (Br is the radial magnetic field at the core surface.) We have developed a new method that bypasses flow inversions. Using the vector field (U-->Br) directly, we estimate its toroidal part by imposing that (U-->Br) vanishes where Br=0. The calculation of the electromagnetic torque is also hindered by the uncertainty in the conductivity structure of the lower mantle. However, we conclude that the conductivity of the lower mantle has to be much larger than current estimates derived from diamond anvil cell experiments to make the electromagnetic torque significant. The region beneath Africa and the mid-Atlantic (where there is the most significant (Br=0) curve apart from the magnetic equator) is particularly important. Here, the field Φ is relatively well constrained, and this is the single region that contributes most to the torque. Following Holme [Holme, R., 1998a. Electromagnetic core-mantle coupling 1: explaining decadal changes in the length of day. Geophys. J. Int. (132) 167-180.], we show nevertheless that small changes to Φ suffice to recover the torque ΓLOD required to explain LOD variations provided that the lower mantle conductivity is high enough. We find a value similar to Holme [Holme, R., 1998b. Electromagnetic core-mantle coupling 2: probing deep mantle conductance. In: Gunis, M., Wysession, M.E., Knittel, E., Buffett, B.A. (Eds.), The Core-Mantle Boundary Region. AGU, pp. 139-151.] for the minimum conductance (108 S). However, we were not able to

  13. Sequential unconstrained minimization algorithms for constrained optimization

    NASA Astrophysics Data System (ADS)

    Byrne, Charles

    2008-02-01

    The problem of minimizing a function f(x):RJ → R, subject to constraints on the vector variable x, occurs frequently in inverse problems. Even without constraints, finding a minimizer of f(x) may require iterative methods. We consider here a general class of iterative algorithms that find a solution to the constrained minimization problem as the limit of a sequence of vectors, each solving an unconstrained minimization problem. Our sequential unconstrained minimization algorithm (SUMMA) is an iterative procedure for constrained minimization. At the kth step we minimize the function G_k(x)=f(x)+g_k(x), to obtain xk. The auxiliary functions gk(x):D ⊆ RJ → R+ are nonnegative on the set D, each xk is assumed to lie within D, and the objective is to minimize the continuous function f:RJ → R over x in the set C=\\overline D , the closure of D. We assume that such minimizers exist, and denote one such by \\hat x . We assume that the functions gk(x) satisfy the inequalities 0\\leq g_k(x)\\leq G_{k-1}(x)-G_{k-1}(x^{k-1}), for k = 2, 3, .... Using this assumption, we show that the sequence {f(xk)} is decreasing and converges to f({\\hat x}) . If the restriction of f(x) to D has bounded level sets, which happens if \\hat x is unique and f(x) is closed, proper and convex, then the sequence {xk} is bounded, and f(x^*)=f({\\hat x}) , for any cluster point x*. Therefore, if \\hat x is unique, x^*={\\hat x} and \\{x^k\\}\\rightarrow {\\hat x} . When \\hat x is not unique, convergence can still be obtained, in particular cases. The SUMMA includes, as particular cases, the well-known barrier- and penalty-function methods, the simultaneous multiplicative algebraic reconstruction technique (SMART), the proximal minimization algorithm of Censor and Zenios, the entropic proximal methods of Teboulle, as well as certain cases of gradient descent and the Newton-Raphson method. The proof techniques used for SUMMA can be extended to obtain related results for the induced proximal

  14. Grape Composition under Abiotic Constrains: Water Stress and Salinity.

    PubMed

    Mirás-Avalos, José M; Intrigliolo, Diego S

    2017-01-01

    Water stress and increasing soil salt concentration represent the most common abiotic constrains that exert a negative impact on Mediterranean vineyards performance. However, several studies have proven that deficit irrigation strategies are able to improve grape composition. In contrast, irrigation with saline waters negatively affected yield and grape composition, although the magnitude of these effects depended on the cultivar, rootstock, phenological stage when water was applied, as well as on the salt concentration in the irrigation water. In this context, agronomic practices that minimize these effects on berry composition and, consequently, on wine quality must be achieved. In this paper, we briefly reviewed the main findings obtained regarding the effects of deficit irrigation strategies, as well as irrigation with saline water, on the berry composition of both red and white cultivars, as well as on the final wine. A meta-analysis was performed using published data for red and white varieties; a general liner model accounting for the effects of cultivar, rootstock, and midday stem water potential was able to explain up to 90% of the variability in the dataset, depending on the selected variable. In both red and white cultivars, berry weight, must titratable acidity and pH were fairly well simulated, whereas the goodness-of-fit for wine attributes was better for white cultivars.

  15. Constrained de novo sequencing of conotoxins.

    PubMed

    Bhatia, Swapnil; Kil, Yong J; Ueberheide, Beatrix; Chait, Brian T; Tayo, Lemmuel; Cruz, Lourdes; Lu, Bingwen; Yates, John R; Bern, Marshall

    2012-08-03

    De novo peptide sequencing by mass spectrometry (MS) can determine the amino acid sequence of an unknown peptide without reference to a protein database. MS-based de novo sequencing assumes special importance in focused studies of families of biologically active peptides and proteins, such as hormones, toxins, and antibodies, for which amino acid sequences may be difficult to obtain through genomic methods. These protein families often exhibit sequence homology or characteristic amino acid content; yet, current de novo sequencing approaches do not take advantage of this prior knowledge and, hence, search an unnecessarily large space of possible sequences. Here, we describe an algorithm for de novo sequencing that incorporates sequence constraints into the core graph algorithm and thereby reduces the search space by many orders of magnitude. We demonstrate our algorithm in a study of cysteine-rich toxins from two cone snail species (Conus textile and Conus stercusmuscarum) and report 13 de novo and about 60 total toxins.

  16. Constrained De Novo Sequencing of Conotoxins

    PubMed Central

    Bhatia, Swapnil; Kil, Yong J.; Ueberheide, Beatrix; Chait, Brian T.; Tayo, Lemmuel; Cruz, Lourdes; Lu, Bingwen; Yates, John R.; Bern, Marshall

    2012-01-01

    De novo peptide sequencing by mass spectrometry (MS) can determine the amino acid sequence of an unknown peptide without reference to a protein database. MS-based de novo sequencing assumes special importance in focused studies of families of biologically active peptides and proteins, such as hormones, toxins, and antibodies, for which amino acid sequences may be difficult to obtain through genomic methods. These protein families often exhibit sequence homology or characteristic amino acid content, yet current de novo sequencing approaches do not take advantage of this prior knowledge and hence search an unnecessarily large space of possible sequences. Here, we describe an algorithm for de novo sequencing that incorporates sequence constraints into the core graph algorithm, and thereby reduces the search space by many orders of magnitude. We demonstrate our algorithm in a study of cysteine-rich toxins from two cone snail species (Conus textile and Conus stercusmuscarum), and report 13 de novo and about 60 total toxins. PMID:22709442

  17. Comparison between constrained and non-constrained Cobb techniques for the assessment of thoracic kyphosis and lumbar lordosis

    PubMed Central

    Pinel-Giroux, Fanny-Maud; de Guise, Jacques A.; Labelle, Hubert

    2007-01-01

    Sagittal curvatures of the spine can be assessed using the constrained or non-constrained Cobb techniques. However, there is no study that specifically compares these two techniques. The objective of this study is to assess the reproducibility and clinical relevance of the non-constrained Cobb technique (non-constrained limit vertebrae) compared to the constrained Cobb technique (constrained limit vertebrae). Standing sagittal radiographs of the spine of ten adolescents with idiopathic scoliosis, ten adolescents with spondylolisthesis and ten normal adolescents were selected. Thoracic kyphosis (TK) and lumbar lordosis (LL) were measured twice by three observers using both constrained and non-constrained Cobb techniques. Pearson’s correlation coefficients, as well as intra- and inter-observer intra-class correlation coefficients (ICC) were calculated. Inter-observer ICCs were similar for TK and LL with both techniques, ranging from 0.84 to 0.89. Intra-observer ICCs for both techniques were between 0.74 and 0.92 for TK, while they were between 0.87 and 0.97 for LL. The two techniques were highly correlated for the measurement of the TK (r = 0.96) and LL (r = 0.94). Computer-assisted assessment of the sagittal profile using the non-constrained Cobb technique provides excellent reproducibility. As opposed to the constrained Cobb technique, the non-constrained Cobb technique takes into account the variability in the level of transition between the TK and LL. However, adequate use of this technique requires accurate identification of the limit vertebrae in the thoracolumbar spine. Consequently, a computer-assisted technique is recommended when using the non-constrained Cobb technique. PMID:17426991

  18. Constraining inflation with future galaxy redshift surveys

    SciTech Connect

    Huang, Zhiqi; Vernizzi, Filippo; Verde, Licia E-mail: liciaverde@icc.ub.edu

    2012-04-01

    With future galaxy surveys, a huge number of Fourier modes of the distribution of the large scale structures in the Universe will become available. These modes are complementary to those of the CMB and can be used to set constraints on models of the early universe, such as inflation. Using a MCMC analysis, we compare the power of the CMB with that of the combination of CMB and galaxy survey data, to constrain the power spectrum of primordial fluctuations generated during inflation. We base our analysis on the Planck satellite and a spectroscopic redshift survey with configuration parameters close to those of the Euclid mission as examples. We first consider models of slow-roll inflation, and show that the inclusion of large scale structure data improves the constraints by nearly halving the error bars on the scalar spectral index and its running. If we attempt to reconstruct the inflationary single-field potential, a similar conclusion can be reached on the parameters characterizing the potential. We then study models with features in the power spectrum. In particular, we consider ringing features produced by a break in the potential and oscillations such as in axion monodromy. Adding large scale structures improves the constraints on features by more than a factor of two. In axion monodromy we show that there are oscillations with small amplitude and frequency in momentum space that are undetected by CMB alone but can be measured by including galaxy surveys in the analysis.

  19. Constraining the Evolution of ZZ Ceti

    NASA Technical Reports Server (NTRS)

    Mukadam, Anjum S.; Kepler, S. O.; Winget, D. E.; Nather, R. E.; Kilic, M.; Mullally, F.; vonHippel, T.; Kleinman, S. J.; Nitta, A.; Guzik, J. A.

    2003-01-01

    We report our analysis of the stability of pulsation periods in the DAV star (pulsating hydrogen atmosphere white dwarf) ZZ Ceti, also called R548. On the basis of observations that span 31 years, we conclude that the period 213.13 s observed in ZZ Ceti drifts at a rate dP/dt 5 (5.5 plus or minus 1.9) x 10(exp -15) ss(sup -1), after correcting for proper motion. Our results are consistent with previous P values for this mode and an improvement over them because of the larger time base. The characteristic stability timescale implied for the pulsation period is |P||P(raised dot)|greater than or equal to 1.2 Gyr, comparable to the theoretical cooling timescale for the star. Our current stability limit for the period 213.13 s is only slightly less than the present measurement for another DAV, G117-B15A, for the period 215.2 s, establishing this mode in ZZ Ceti as the second most stable optical clock known, comparable to atomic clocks and more stable than most pulsars. Constraining the cooling rate of ZZ Ceti aids theoretical evolutionary models and white dwarf cosmochronology. The drift rate of this clock is small enough that we can set interesting limits on reflex motion due to planetary companions.

  20. Constrained Markovian Dynamics of Random Graphs

    NASA Astrophysics Data System (ADS)

    Coolen, A. C. C.; de Martino, A.; Annibale, A.

    2009-09-01

    We introduce a statistical mechanics formalism for the study of constrained graph evolution as a Markovian stochastic process, in analogy with that available for spin systems, deriving its basic properties and highlighting the role of the `mobility' (the number of allowed moves for any given graph). As an application of the general theory we analyze the properties of degree-preserving Markov chains based on elementary edge switchings. We give an exact yet simple formula for the mobility in terms of the graph's adjacency matrix and its spectrum. This formula allows us to define acceptance probabilities for edge switchings, such that the Markov chains become controlled Glauber-type detailed balance processes, designed to evolve to any required invariant measure (representing the asymptotic frequencies with which the allowed graphs are visited during the process). As a corollary we also derive a condition in terms of simple degree statistics, sufficient to guarantee that, in the limit where the number of nodes diverges, even for state-independent acceptance probabilities of proposed moves the invariant measure of the process will be uniform. We test our theory on synthetic graphs and on realistic larger graphs as studied in cellular biology, showing explicitly that, for instances where the simple edge swap dynamics fails to converge to the uniform measure, a suitably modified Markov chain instead generates the correct phase space sampling.

  1. Constraining Simulated Photosynthesis with Fluorescence Observations

    NASA Astrophysics Data System (ADS)

    Baker, I. T.; Berry, J. A.; Lee, J.; Frankenberg, C.; Denning, S.

    2012-12-01

    The measurement of chlorophyll fluorescence from satellites is an emerging technology. To date, most applications have compared fluorescence to light use efficiency models of Gross Primary Productivity (GPP). A close correspondence between fluorescence and GPP has been found in these comparisons. Here, we 'go the other way' and calculate fluorescence using an enzyme kinetic photosynthesis model (the Simple Biosphere Model; SiB), and compare to spectral retrievals. We utilize multiple representations for model phenology as a sensitivity test, obtaining leaf area index (LAI) and fraction of photosynthetically active radiation absorbed (fPAR) from both MODIS-derived products as well as a prognostic model of LAI/fPAR based on growing season index (PGSI). We find that bidirectional reflectance distribution function (BRDF), canopy radiative transfer, and leaf-to-canopy scaling all contribute to variability in simulated fluorescence. We use our results to evaluate discrepancies between light use efficiency and enzyme kinetic models across latitudinal, vegetation and climatological gradients. Satellite retrievals of fluorescence will provide insight into photosynthetic process and constrain simulations of the carbon cycle across multiple spatiotemporal scales.

  2. Constraining the oblateness of Kepler planets

    SciTech Connect

    Zhu, Wei; Huang, Chelsea X.; Zhou, George; Lin, D. N. C.

    2014-11-20

    We use Kepler short-cadence light curves to constrain the oblateness of planet candidates in the Kepler sample. The transits of rapidly rotating planets that are deformed in shape will lead to distortions in the ingress and egress of their light curves. We report the first tentative detection of an oblate planet outside the solar system, measuring an oblateness of 0.22{sub −0.11}{sup +0.11} for the 18 M{sub J} mass brown dwarf Kepler 39b (KOI 423.01). We also provide constraints on the oblateness of the planets (candidates) HAT-P-7b, KOI 686.01, and KOI 197.01 to be <0.067, <0.251, and <0.186, respectively. Using the Q' values from Jupiter and Saturn, we expect tidal synchronization for the spins of HAT-P-7b, KOI 686.01, and KOI 197.01, and for their rotational oblateness signatures to be undetectable in the current data. The potentially large oblateness of KOI 423.01 (Kepler 39b) suggests that the Q' value of the brown dwarf needs to be two orders of magnitude larger than that of the solar system gas giants to avoid being tidally spun down.

  3. Proximity Navigation of Highly Constrained Spacecraft

    NASA Technical Reports Server (NTRS)

    Scarritt, S.; Swartwout, M.

    2007-01-01

    Bandit is a 3-kg automated spacecraft in development at Washington University in St. Louis. Bandit's primary mission is to demonstrate proximity navigation, including docking, around a 25-kg student-built host spacecraft. However, because of extreme constraints in mass, power and volume, traditional sensing and actuation methods are not available. In particular, Bandit carries only 8 fixed-magnitude cold-gas thrusters to control its 6 DOF motion. Bandit lacks true inertial sensing, and the ability to sense position relative to the host has error bounds that approach the size of the Bandit itself. Some of the navigation problems are addressed through an extremely robust, error-tolerant soft dock. In addition, we have identified a control methodology that performs well in this constrained environment: behavior-based velocity potential functions, which use a minimum-seeking method similar to Lyapunov functions. We have also adapted the discrete Kalman filter for use on Bandit for position estimation and have developed a similar measurement vs. propagation weighting algorithm for attitude estimation. This paper provides an overview of Bandit and describes the control and estimation approach. Results using our 6DOF flight simulator are provided, demonstrating that these methods show promise for flight use.

  4. Optimization of input-constrained systems

    NASA Astrophysics Data System (ADS)

    Malki, Suleyman; Spaanenburg, Lambert

    2009-05-01

    The computational demands of algorithms are rapidly growing. The naive implementation uses extended doubleprecision floating-point numbers and has therefore extreme difficulties in maintaining real-time performance. For fixedpoint numbers, the value representation pushes in two directions (value range and step size) to set the applicationdependent word size. In the general case, checking all combinations of all different values on all system inputs will easily become computationally infeasible. Checking corner cases only helps to reduce the combinatorial explosion, as still checking for accuracy and precision to limit word size remains a considerable effort. A range of evolutionary techniques have been tried where the sheer size of the problem withstands an extensive search. When the value range can be limited, the problem becomes tractable and a constructive approach becomes feasible. We propose an approach that is reminiscent of the Quine-Mc.Cluskey logic minimization procedure. Next to the conjunctive search as popular in Boolean minimization, we investigate the disjunctive approach that starts from a presumed minimal word size. To eliminate the occurrence of anomalies, this still has to be checked for larger word sizes. The procedure has initially been implemented using Java and Matlab. We have applied the above procedure to feed-forward and to cellular neural networks (CNN) as typical examples of input-constrained systems. In the case of hole-filling by means of a CNN, we find that the 1461 different coefficient sets can be reduced to 360, each giving robust behaviour on 7-bits internal words.

  5. Scheduling Aircraft Landings under Constrained Position Shifting

    NASA Technical Reports Server (NTRS)

    Balakrishnan, Hamsa; Chandran, Bala

    2006-01-01

    Optimal scheduling of airport runway operations can play an important role in improving the safety and efficiency of the National Airspace System (NAS). Methods that compute the optimal landing sequence and landing times of aircraft must accommodate practical issues that affect the implementation of the schedule. One such practical consideration, known as Constrained Position Shifting (CPS), is the restriction that each aircraft must land within a pre-specified number of positions of its place in the First-Come-First-Served (FCFS) sequence. We consider the problem of scheduling landings of aircraft in a CPS environment in order to maximize runway throughput (minimize the completion time of the landing sequence), subject to operational constraints such as FAA-specified minimum inter-arrival spacing restrictions, precedence relationships among aircraft that arise either from airline preferences or air traffic control procedures that prevent overtaking, and time windows (representing possible control actions) during which each aircraft landing can occur. We present a Dynamic Programming-based approach that scales linearly in the number of aircraft, and describe our computational experience with a prototype implementation on realistic data for Denver International Airport.

  6. Joint Chance-Constrained Dynamic Programming

    NASA Technical Reports Server (NTRS)

    Ono, Masahiro; Kuwata, Yoshiaki; Balaram, J. Bob

    2012-01-01

    This paper presents a novel dynamic programming algorithm with a joint chance constraint, which explicitly bounds the risk of failure in order to maintain the state within a specified feasible region. A joint chance constraint cannot be handled by existing constrained dynamic programming approaches since their application is limited to constraints in the same form as the cost function, that is, an expectation over a sum of one-stage costs. We overcome this challenge by reformulating the joint chance constraint into a constraint on an expectation over a sum of indicator functions, which can be incorporated into the cost function by dualizing the optimization problem. As a result, the primal variables can be optimized by a standard dynamic programming, while the dual variable is optimized by a root-finding algorithm that converges exponentially. Error bounds on the primal and dual objective values are rigorously derived. We demonstrate the algorithm on a path planning problem, as well as an optimal control problem for Mars entry, descent and landing. The simulations are conducted using a real terrain data of Mars, with four million discrete states at each time step.

  7. Distributed Constrained Optimization with Semicoordinate Transformations

    NASA Technical Reports Server (NTRS)

    Macready, William; Wolpert, David

    2006-01-01

    Recent work has shown how information theory extends conventional full-rationality game theory to allow bounded rational agents. The associated mathematical framework can be used to solve constrained optimization problems. This is done by translating the problem into an iterated game, where each agent controls a different variable of the problem, so that the joint probability distribution across the agents moves gives an expected value of the objective function. The dynamics of the agents is designed to minimize a Lagrangian function of that joint distribution. Here we illustrate how the updating of the Lagrange parameters in the Lagrangian is a form of automated annealing, which focuses the joint distribution more and more tightly about the joint moves that optimize the objective function. We then investigate the use of "semicoordinate" variable transformations. These separate the joint state of the agents from the variables of the optimization problem, with the two connected by an onto mapping. We present experiments illustrating the ability of such transformations to facilitate optimization. We focus on the special kind of transformation in which the statistically independent states of the agents induces a mixture distribution over the optimization variables. Computer experiment illustrate this for &sat constraint satisfaction problems and for unconstrained minimization of NK functions.

  8. Constrained Graph Optimization: Interdiction and Preservation Problems

    SciTech Connect

    Schild, Aaron V

    2012-07-30

    The maximum flow, shortest path, and maximum matching problems are a set of basic graph problems that are critical in theoretical computer science and applications. Constrained graph optimization, a variation of these basic graph problems involving modification of the underlying graph, is equally important but sometimes significantly harder. In particular, one can explore these optimization problems with additional cost constraints. In the preservation case, the optimizer has a budget to preserve vertices or edges of a graph, preventing them from being deleted. The optimizer wants to find the best set of preserved edges/vertices in which the cost constraints are satisfied and the basic graph problems are optimized. For example, in shortest path preservation, the optimizer wants to find a set of edges/vertices within which the shortest path between two predetermined points is smallest. In interdiction problems, one deletes vertices or edges from the graph with a particular cost in order to impede the basic graph problems as much as possible (for example, delete edges/vertices to maximize the shortest path between two predetermined vertices). Applications of preservation problems include optimal road maintenance, power grid maintenance, and job scheduling, while interdiction problems are related to drug trafficking prevention, network stability assessment, and counterterrorism. Computational hardness results are presented, along with heuristic methods for approximating solutions to the matching interdiction problem. Also, efficient algorithms are presented for special cases of graphs, including on planar graphs. The graphs in many of the listed applications are planar, so these algorithms have important practical implications.

  9. Flexible constrained de Finetti reductions and applications

    NASA Astrophysics Data System (ADS)

    Lancien, Cécilia; Winter, Andreas

    2017-09-01

    De Finetti theorems show how sufficiently exchangeable states are well-approximated by convex combinations of independent identically distributed states. Recently, it was shown that in many quantum information applications, a more relaxed de Finetti reduction (i.e., only a matrix inequality between the symmetric state and one of the de Finetti forms) is enough and that it leads to more concise and elegant arguments. Here we show several uses and general flexible applicability of a constrained de Finetti reduction in quantum information theory, which was recently discovered by Duan, Severini, and Winter. In particular, we show that the technique can accommodate other symmetries commuting with the permutation action and permutation-invariant linear constraints. We then demonstrate that, in some cases, it is also fruitful with convex constraints, in particular separability in a bipartite setting. This is a constraint particularly interesting in the context of the complexity class QMA(2) of interactive quantum Merlin-Arthur games with unentangled provers, and our results relate to the soundness gap amplification of QMA(2) protocols by parallel repetition. It is also relevant for the regularization of certain entropic channel parameters. As an aside, we present an alternative way of attacking this problem, relying on an entanglement measure theory rather than the de Finetti approach. Finally, we explore an extension to infinite-dimensional systems, which usually pose inherent problems to de Finetti techniques in the quantum case.

  10. Pairwise constrained concept factorization for data representation.

    PubMed

    He, Yangcheng; Lu, Hongtao; Huang, Lei; Xie, Saining

    2014-04-01

    Concept factorization (CF) is a variant of non-negative matrix factorization (NMF). In CF, each concept is represented by a linear combination of data points, and each data point is represented by a linear combination of concepts. More specifically, each concept is represented by more than one data point with different weights, and each data point carries various weights called membership to represent their degrees belonging to that concept. However, CF is actually an unsupervised method without making use of prior information of the data. In this paper, we propose a novel semi-supervised concept factorization method, called Pairwise Constrained Concept Factorization (PCCF), which incorporates pairwise constraints into the CF framework. We expect that data points which have pairwise must-link constraints should have the same class label as much as possible, while data points with pairwise cannot-link constraints will have different class labels as much as possible. Due to the incorporation of the pairwise constraints, the learning quality of the CF has been significantly enhanced. Experimental results show the effectiveness of our proposed novel method in comparison to the state-of-the-art algorithms on several real world applications.

  11. Joint Chance-Constrained Dynamic Programming

    NASA Technical Reports Server (NTRS)

    Ono, Masahiro; Kuwata, Yoshiaki; Balaram, J. Bob

    2012-01-01

    This paper presents a novel dynamic programming algorithm with a joint chance constraint, which explicitly bounds the risk of failure in order to maintain the state within a specified feasible region. A joint chance constraint cannot be handled by existing constrained dynamic programming approaches since their application is limited to constraints in the same form as the cost function, that is, an expectation over a sum of one-stage costs. We overcome this challenge by reformulating the joint chance constraint into a constraint on an expectation over a sum of indicator functions, which can be incorporated into the cost function by dualizing the optimization problem. As a result, the primal variables can be optimized by a standard dynamic programming, while the dual variable is optimized by a root-finding algorithm that converges exponentially. Error bounds on the primal and dual objective values are rigorously derived. We demonstrate the algorithm on a path planning problem, as well as an optimal control problem for Mars entry, descent and landing. The simulations are conducted using a real terrain data of Mars, with four million discrete states at each time step.

  12. Pressure compensated transducer system with constrained diaphragm

    NASA Astrophysics Data System (ADS)

    Percy, Joseph L.

    1992-08-01

    An acoustic source apparatus has an acoustic transducer that is enclosed in a substantially rigid and watertight enclosure to resist the pressure of water on the transducer and to seal the transducer from the water. The enclosure has an opening through which acoustic signals pass and over which is placed a resilient, expandable and substantially water-impermeable diaphragm. A net stiffens and strengthens the diaphragm as well as constrains the diaphragm from overexpansion or from migrating due to buoyancy forces. Pressurized gas, regulated at slightly above ambient pressure, is supplied to the enclosure and the diaphragm to compensate for underwater ambient pressures. Gas pressure regulated at above ambient pressure is used to selectively tune the pressure levels within the enclosure and diaphragm so that diaphragm resonance can be achieved. Controls are used to selectively fill, as well as vent the enclosure and diaphragm during system descent and ascent, respectively. A signal link is used to activate these controls and to provide the driving force for the acoustic transducer.

  13. Computational studies of spatially constrained DNA

    SciTech Connect

    Olson, W.K.; Westcott, T.P.; Liu, Guo-Hua

    1996-12-31

    Closed loops of double stranded DNA are ubiquitous in nature, occurring in systems ranging from plasmids, bacterial chromosomes, and many viral genomes, which form single closed loops, to eukaryotic chromosomes and other linear DNAs, which appear to be organized into topologically constrained domains by DNA-binding proteins. The topological constraints in the latter systems are determined by the spacing of the bound proteins along the contour of the double helix along with the imposed turns and twists of DNA in the intermolecular complexes. As long as the duplex remains unbroken, the linking number Lk, or number of times the two strands of the DNA wrap around one another, is conserved. If one of the strands is nicked and later re-sealed, the change in overall folding that accompanies DNA-protein interactions leads to a change in Lk. The supercoiling brought about by such protein action, in turn, determines a number of key biological events, including replication, transcription, and recombination. 51 refs., 5 figs., 1 tab.

  14. Constrained Sypersymmetric Flipped SU (5) GUT Phenomenology

    SciTech Connect

    Ellis, John; Mustafayev, Azar; Olive, Keith A.; /Minnesota U., Theor. Phys. Inst. /Minnesota U. /Stanford U., Phys. Dept. /SLAC

    2011-08-12

    We explore the phenomenology of the minimal supersymmetric flipped SU(5) GUT model (CFSU(5)), whose soft supersymmetry-breaking (SSB) mass parameters are constrained to be universal at some input scale, Min, above the GUT scale, M{sub GUT}. We analyze the parameter space of CFSU(5) assuming that the lightest supersymmetric particle (LSP) provides the cosmological cold dark matter, paying careful attention to the matching of parameters at the GUT scale. We first display some specific examples of the evolutions of the SSB parameters that exhibit some generic features. Specifically, we note that the relationship between the masses of the lightest neutralino {chi} and the lighter stau {tilde {tau}}{sub 1} is sensitive to M{sub in}, as is the relationship between m{sub {chi}} and the masses of the heavier Higgs bosons A,H. For these reasons, prominent features in generic (m{sub 1/2}, m{sub 0}) planes such as coannihilation strips and rapid-annihilation funnels are also sensitive to Min, as we illustrate for several cases with tan {beta} = 10 and 55. However, these features do not necessarily disappear at large Min, unlike the case in the minimal conventional SU(5) GUT. Our results are relatively insensitive to neutrino masses.

  15. Constrained spheroids for prolonged hepatocyte culture.

    PubMed

    Tong, Wen Hao; Fang, Yu; Yan, Jie; Hong, Xin; Hari Singh, Nisha; Wang, Shu Rui; Nugraha, Bramasta; Xia, Lei; Fong, Eliza Li Shan; Iliescu, Ciprian; Yu, Hanry

    2016-02-01

    Liver-specific functions in primary hepatocytes can be maintained over extended duration in vitro using spheroid culture. However, the undesired loss of cells over time is still a major unaddressed problem, which consequently generates large variations in downstream assays such as drug screening. In static culture, the turbulence generated by medium change can cause spheroids to detach from the culture substrate. Under perfusion, the momentum generated by Stokes force similarly results in spheroid detachment. To overcome this problem, we developed a Constrained Spheroids (CS) culture system that immobilizes spheroids between a glass coverslip and an ultra-thin porous Parylene C membrane, both surface-modified with poly(ethylene glycol) and galactose ligands for optimum spheroid formation and maintenance. In this configuration, cell loss was minimized even when perfusion was introduced. When compared to the standard collagen sandwich model, hepatocytes cultured as CS under perfusion exhibited significantly enhanced hepatocyte functions such as urea secretion, and CYP1A1 and CYP3A2 metabolic activity. We propose the use of the CS culture as an improved culture platform to current hepatocyte spheroid-based culture systems.

  16. Optimization of constrained density functional theory

    NASA Astrophysics Data System (ADS)

    O'Regan, David D.; Teobaldi, Gilberto

    2016-07-01

    Constrained density functional theory (cDFT) is a versatile electronic structure method that enables ground-state calculations to be performed subject to physical constraints. It thereby broadens their applicability and utility. Automated Lagrange multiplier optimization is necessary for multiple constraints to be applied efficiently in cDFT, for it to be used in tandem with geometry optimization, or with molecular dynamics. In order to facilitate this, we comprehensively develop the connection between cDFT energy derivatives and response functions, providing a rigorous assessment of the uniqueness and character of cDFT stationary points while accounting for electronic interactions and screening. In particular, we provide a nonperturbative proof that stable stationary points of linear density constraints occur only at energy maxima with respect to their Lagrange multipliers. We show that multiple solutions, hysteresis, and energy discontinuities may occur in cDFT. Expressions are derived, in terms of convenient by-products of cDFT optimization, for quantities such as the dielectric function and a condition number quantifying ill definition in multiple constraint cDFT.

  17. Constrained tricritical phenomena in two dimensions.

    PubMed

    Deng, Youjin; Heringa, Jouke R; Blöte, Henk W J

    2005-03-01

    We investigate several tricritical models on the square lattice by means of Monte Carlo simulations. These include the Blume-Capel model, Baxter's hard-square model, and the q=1 , 3, and 4 Potts models with vacancies. We use a combination of the Wolff and geometric cluster methods, which conserves the total number of vacancies or lattice-gas particles and suppresses critical slowing down. Several quantities are sampled, such as the specific heat C and the structure factor C(s) , which accounts for the large-scale spatial inhomogeneity of the energy fluctuations. We find that the constraint strongly modifies some of the critical singularities. For instance, the specific heat C reaches a finite value at tricriticality, while C(s) remains divergent as in the unconstrained system. We are able to explain these observed constrained phenomena on the basis of the Fisher renormalization mechanism generalized to include a subleading relevant thermal scaling field. In this context, we find that, under the constraint, the leading thermal exponent y(t1) is renormalized to 2- y(t1) , while the subleading exponent y(t2) remains unchanged.

  18. Constraining Amazonian Methane Emission from Wetlands

    NASA Astrophysics Data System (ADS)

    Boesch, Hartmut; Parker, Robert; Webb, Alex; Wilson, Chris; Chipperfield, Martyn; Gloor, Emanuel; Feng, Liang; Palmer, Paul

    2017-04-01

    The Amazon Basin contains large wetland ecosystems which are important sources of methane (CH4). Spaceborne observations provide detailed information about the spatio-temporal distributions of atmospheric methane over the Amazon Basin which will provide a strong constrain on the underlying emissions and their year to year variations. Methane observations from space are available from the Japanese GOSAT instrument since 2009. We use the proxy retrieval method which provides much greater coverage over the Amazon region compared to so-called Full-Physics methods due to their lower sensitivity to thin clouds. Validation of GOSAT retrieval over the Amazon using the ground-based TCCON network is currently not possible due to a lack of data and we have used routine aircraft profiles to show that GOSAT columns are sufficiently accurate for estimating surface flux for the region. Using a variational flux inverse system together with the 3-D atmospheric chemical transport model TOMCAT, we infer surface fluxes for the Amazon region from GOSAT observations which are used to analyse the spatial distribution of methane wetlands emissions as well as annual variations in emissions with a focus on periods 2011/2012 and 2013/14 which are characterized by large variations in rainfall.

  19. Constraining Cosmological Models with Different Observations

    NASA Astrophysics Data System (ADS)

    Wei, J. J.

    2016-07-01

    With the observations of Type Ia supernovae (SNe Ia), scientists discovered that the Universe is experiencing an accelerated expansion, and then revealed the existence of dark energy in 1998. Since the amazing discovery, cosmology has became a hot topic in the physical research field. Cosmology is a subject that strongly depends on the astronomical observations. Therefore, constraining different cosmological models with all kinds of observations is one of the most important research works in the modern cosmology. The goal of this thesis is to investigate cosmology using the latest observations. The observations include SNe Ia, Type Ic Super Luminous supernovae (SLSN Ic), Gamma-ray bursts (GRBs), angular diameter distance of galaxy cluster, strong gravitational lensing, and age measurements of old passive galaxies, etc. In Chapter 1, we briefly review the research background of cosmology, and introduce some cosmological models. Then we summarize the progress on cosmology from all kinds of observations in more details. In Chapter 2, we present the results of our studies on the supernova cosmology. The main difficulty with the use of SNe Ia as standard candles is that one must optimize three or four nuisance parameters characterizing SN luminosities simultaneously with the parameters of an expansion model of the Universe. We have confirmed that one should optimize all of the parameters by carrying out the method of maximum likelihood estimation in any situation where the parameters include an unknown intrinsic dispersion. The commonly used method, which estimates the dispersion by requiring the reduced χ^{2} to equal unity, does not take into account all possible variances among the parameters. We carry out such a comparison of the standard ΛCDM cosmology and the R_{h}=ct Universe using the SN Legacy Survey sample of 252 SN events, and show that each model fits its individually reduced data very well. Moreover, it is quite evident that SLSNe Ic may be useful

  20. NUCLEI SEGMENTATION VIA SPARSITY CONSTRAINED CONVOLUTIONAL REGRESSION

    PubMed Central

    Zhou, Yin; Chang, Hang; Barner, Kenneth E.; Parvin, Bahram

    2017-01-01

    Automated profiling of nuclear architecture, in histology sections, can potentially help predict the clinical outcomes. However, the task is challenging as a result of nuclear pleomorphism and cellular states (e.g., cell fate, cell cycle), which are compounded by the batch effect (e.g., variations in fixation and staining). Present methods, for nuclear segmentation, are based on human-designed features that may not effectively capture intrinsic nuclear architecture. In this paper, we propose a novel approach, called sparsity constrained convolutional regression (SCCR), for nuclei segmentation. Specifically, given raw image patches and the corresponding annotated binary masks, our algorithm jointly learns a bank of convolutional filters and a sparse linear regressor, where the former is used for feature extraction, and the latter aims to produce a likelihood for each pixel being nuclear region or background. During classification, the pixel label is simply determined by a thresholding operation applied on the likelihood map. The method has been evaluated using the benchmark dataset collected from The Cancer Genome Atlas (TCGA). Experimental results demonstrate that our method outperforms traditional nuclei segmentation algorithms and is able to achieve competitive performance compared to the state-of-the-art algorithm built upon human-designed features with biological prior knowledge. PMID:28101301

  1. Founder niche constrains evolutionary adaptive radiation.

    PubMed

    Flohr, Régis C E; Blom, Carsten J; Rainey, Paul B; Beaumont, Hubertus J E

    2013-12-17

    Adaptive radiation of a lineage into a range of organisms with different niches underpins the evolution of life's diversity. Although the role of the environment in shaping adaptive radiation is well established, theory predicts that the evolvability and niche of the founding ancestor are also of importance. Direct demonstration of a causal link requires resolving the independent effects of these additional factors. Here, we accomplish this using experimental bacterial populations and demonstrate how the dynamics of adaptive radiation are constrained by the niche of the founder. We manipulated the propensity of the founder to undergo adaptive radiation and resolved the underlying causal changes in both its evolvability and niche. Evolvability did not change, but the propensity for adaptive radiation was altered by changes in the position and breadth of the niche of the founder. These observations provide direct empirical evidence for a link between the niche of organisms and their propensity for adaptive radiation. This general mechanism may have rendered the evolutionary dynamics of extant adaptive radiations dependent on chance events that determined their founding ancestors.

  2. Constrained Subjective Assessment of Student Learning

    NASA Astrophysics Data System (ADS)

    Saliu, Sokol

    2005-09-01

    Student learning is a complex incremental cognitive process; assessment needs to parallel this, reporting the results in similar terms. Application of fuzzy sets and logic to the criterion-referenced assessment of student learning is considered here. The constrained qualitative assessment (CQA) system was designed, and then applied in assessing a past course in microcomputer system design (MSD). CQA criteria were articulated in fuzzy terms and sets, and the assessment procedure was cast as a fuzzy inference rule base. An interactive graphic interface provided for transparent assessment, student "backwash," and support to the teacher when compiling the tests. Grade intervals, obtained from a departmental poll, were used to compile a fuzzy "grade" set. Assessment results were compared to those of a former standard method and to those of a modified version of it (but with fewer criteria). The three methods yielded similar results, supporting the application of CQA. The method improved assessment reliability by means of the consensus embedded in the fuzzy grade set, and improved assessment validity by integrating fuzzy criteria into the assessment procedure.

  3. String theory origin of constrained multiplets

    NASA Astrophysics Data System (ADS)

    Kallosh, Renata; Vercnocke, Bert; Wrase, Timm

    2016-09-01

    We study the non-linearly realized spontaneously broken supersymmetry of the (anti-)D3-brane action in type IIB string theory. The worldvolume fields are one vector A μ , three complex scalars ϕ i and four 4d fermions λ 0, λ i. These transform, in addition to the more familiar {N}=4 linear supersymmetry, also under 16 spontaneously broken, non-linearly realized supersymmetries. We argue that the worldvolume fields can be packaged into the following constrained 4d non-linear {N}=1 multiplets: four chiral multiplets S, Y i that satisfy S 2 = SY i =0 and contain the worldvolume fermions λ 0 and λ i ; and four chiral multiplets W α , H i that satisfy S{W}_{α }=S{overline{D}}_{overset{\\cdotp }{α }}{overline{H}}^{overline{imath}}=0 and contain the vector A μ and the scalars ϕ i . We also discuss how placing an anti-D3-brane on top of intersecting O7-planes can lead to an orthogonal multiplet Φ that satisfies S(Φ -overline{Φ})=0 , which is particularly interesting for inflationary cosmology.

  4. Steroselective synthesis and application of L-( sup 15 N) amino acids

    SciTech Connect

    Unkefer, C.J. ); Lodwig, S.N. . Div. of Science)

    1991-01-01

    We have developed two general approaches to the stereoselective synthesis of {sup 15}N- and {sup 13}C-labeled amino acids. First, labeled serine, biosynthesized using the methylotrophic bacterium M. extorquens AM1, serves as a chiral precursor for the synthesis of other amino acids. For example, pyridoxal phosphate enzymes can be used for the conversion of L-({alpha}-{sup 15}N)serine to L-({alpha}-{sup 15}N)tyrosine, L-({alpha}-{sup 15}N)tryptophan, and L-({alpha}-{sup 15}N)cysteine. In the second approach, developed by Oppolzer and Tamura, an electrophilic amination'' reagent, 1-chloro-1-nitrosocyclohexane, was used to convert chiral enolates into L-{alpha}-amino acids. We prepared 1-chloro-1-({sup 15}N) nitrosocyclohexane and used it to aminate chiral enolates to produce L-({alpha}-{sup 15}N)amino acids. The stereoselectivity of this scheme using the Oppolzer sultam chiral auxiliary is remarkable, producing enantiomer ratios of 200 to 1. 22 refs., 4 figs.

  5. T Cell Determinants Incorporating [beta]-Amino Acid Residues Are Protease Resistant and Remain Immunogenic In Vivo

    SciTech Connect

    Webb, Andrew I.; Dunstone, Michelle A.; Williamson, Nicholas A.; Price, Jason D.; Kauwe, Andreade; Chen, Weisan; Oakley, Aaron; Perlmutter, Patrick; McCluskey, James; Aguilar, Marie-Isabel; Rossjohn, Jamie; Purcell, Anthony W.

    2010-07-20

    A major hurdle in designing successful epitope-based vaccines resides in the delivery, stability, and immunogenicity of the peptide immunogen. The short-lived nature of unmodified peptide-based vaccines in vivo limits their therapeutic application in the immunotherapy of cancers and chronic viral infections as well as their use in generating prophylactic immunity. The incorporation of {beta}-amino acids into peptides decreases proteolysis, yet its potential application in the rational design of T cell mimotopes is poorly understood. To address this, we have replaced each residue of the SIINFEKL epitope individually with the corresponding {beta}-amino acid and examined the resultant efficacy of these mimotopes. Some analogs displayed similar MHC binding and superior protease stability compared with the native epitope. Importantly, these analogs were able to generate cross-reactive CTLs in vivo that were capable of lysing tumor cells that expressed the unmodified epitope as a surrogate tumor Ag. Structural analysis of peptides in which anchor residues were substituted with {beta}-amino acids revealed the basis for enhanced MHC binding and retention of immunogenicity observed for these analogs and paves the way for future vaccine design using {beta}-amino acids. We conclude that the rational incorporation of {beta}-amino acids into T cell determinants is a powerful alternative to the traditional homologous substitution of randomly chosen naturally occurring {alpha}-amino acids, and these mimotopes may prove particularly useful for inclusion in epitope-based vaccines.

  6. The Pendulum: From Constrained Fall to the Concept of Potential

    ERIC Educational Resources Information Center

    Bevilacqua, Fabio; Falomo, Lidia; Fregonese, Lucio; Giannetto, Enrico; Giudice, Franco; Mascheretti, Paolo

    2006-01-01

    Kuhn underlined the relevance of Galileo's gestalt switch in the interpretation of a swinging body from constrained fall to time metre. But the new interpretation did not eliminate the older one. The constrained fall, both in the motion of pendulums and along inclined planes, led Galileo to the law of free fall. Experimenting with physical…

  7. Constrained spectral clustering under a local proximity structure assumption

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri; Xu, Qianjun; des Jardins, Marie

    2005-01-01

    This work focuses on incorporating pairwise constraints into a spectral clustering algorithm. A new constrained spectral clustering method is proposed, as well as an active constraint acquisition technique and a heuristic for parameter selection. We demonstrate that our constrained spectral clustering method, CSC, works well when the data exhibits what we term local proximity structure.

  8. Regularized Partial and/or Constrained Redundancy Analysis

    ERIC Educational Resources Information Center

    Takane, Yoshio; Jung, Sunho

    2008-01-01

    Methods of incorporating a ridge type of regularization into partial redundancy analysis (PRA), constrained redundancy analysis (CRA), and partial and constrained redundancy analysis (PCRA) were discussed. The usefulness of ridge estimation in reducing mean square error (MSE) has been recognized in multiple regression analysis for some time,…

  9. Regularized Partial and/or Constrained Redundancy Analysis

    ERIC Educational Resources Information Center

    Takane, Yoshio; Jung, Sunho

    2008-01-01

    Methods of incorporating a ridge type of regularization into partial redundancy analysis (PRA), constrained redundancy analysis (CRA), and partial and constrained redundancy analysis (PCRA) were discussed. The usefulness of ridge estimation in reducing mean square error (MSE) has been recognized in multiple regression analysis for some time,…

  10. The Pendulum: From Constrained Fall to the Concept of Potential

    ERIC Educational Resources Information Center

    Bevilacqua, Fabio; Falomo, Lidia; Fregonese, Lucio; Giannetto, Enrico; Giudice, Franco; Mascheretti, Paolo

    2006-01-01

    Kuhn underlined the relevance of Galileo's gestalt switch in the interpretation of a swinging body from constrained fall to time metre. But the new interpretation did not eliminate the older one. The constrained fall, both in the motion of pendulums and along inclined planes, led Galileo to the law of free fall. Experimenting with physical…

  11. Probability Statements Extraction with Constrained Conditional Random Fields.

    PubMed

    Deleris, Léa A; Jochim, Charles

    2016-01-01

    This paper investigates how to extract probability statements from academic medical papers. In previous work we have explored traditional classification methods which led to numerous false negatives. This current work focuses on constraining classification output obtained from a Conditional Random Field (CRF) model to allow for domain knowledge constraints. Our experimental results indicate constraining leads to a significant improvement in performance.

  12. Smooth Constrained Heuristic Optimization of a Combinatorial Chemical Space

    DTIC Science & Technology

    2015-05-01

    ARL-TR-7294•MAY 2015 US Army Research Laboratory Smooth ConstrainedHeuristic Optimization of a Combinatorial Chemical Space by Berend Christopher...7294•MAY 2015 US Army Research Laboratory Smooth ConstrainedHeuristic Optimization of a Combinatorial Chemical Space by Berend Christopher...

  13. Analogues of arginine vasopressin modified in position 2 and 3 with conformationally constrained dipeptide fragments.

    PubMed

    Łempicka, Elzbieta; Derdowska, Izabela; Kowalczyk, Wioleta; Dawidowska, Olga; Prahl, Adam; Janecki, Marcin; Jasiński, Tomasz; Trzeciak, Henryk I; Lammek, Bernard

    2005-02-01

    This study describes the synthesis and some pharmacological properties of ten new analogues of arginine vasopressin (AVP) containing a conformationally constrained dipeptide fragment in the N-terminal part of their molecules. Amino acid residues in positions 2 and 3 of AVP and some of its agonistic analogues were replaced with -Phe-Phe and D-Phe-D-Phe, dipeptides having a -CH2-CH2- link bridging two nitrogens. All the new peptides were tested for vasopressor and antidiuretic activities. Four peptides with pA2 values ranging from 5.96 to 7.21 turned out to be weak or moderately potent V1a antagonists. The results supplied new information about the structure-activity relationship of AVP analogues. As some of these were unexpected, they point to the need for caution when extrapolating previously known effects of modifications to analogues having conformationally constrained fragments in their molecules.

  14. The constrained reinitialization equation for level set methods

    NASA Astrophysics Data System (ADS)

    Hartmann, Daniel; Meinke, Matthias; Schröder, Wolfgang

    2010-03-01

    Based on the constrained reinitialization scheme [D. Hartmann, M. Meinke, W. Schröder, Differential equation based constrained reinitialization for level set methods, J. Comput. Phys. 227 (2008) 6821-6845] a new constrained reinitialization equation incorporating a forcing term is introduced. Two formulations for high-order constrained reinitialization (HCR) are presented combining the simplicity and generality of the original reinitialization equation [M. Sussman, P. Smereka, S. Osher, A level set approach for computing solutions to incompressible two-phase flow, J. Comput. Phys. 114 (1994) 146-159] in terms of high-order standard discretization and the accuracy of the constrained reinitialization scheme in terms of interface displacement. The novel HCR schemes represent simple extensions of standard implementations of the original reinitialization equation. The results evidence the significantly increased accuracy and robustness of the novel schemes.

  15. Constraining the Evolution of Poor Clusters

    NASA Astrophysics Data System (ADS)

    Broming, Emma J.; Fuse, C. R.

    2012-01-01

    There currently exists no method by which to quantify the evolutionary state of poor clusters (PCs). Research by Broming & Fuse (2010) demonstrated that the evolution of Hickson compact groups (HCGs) are constrained by the correlation between the X-ray luminosities of point sources and diffuse gas. The current investigation adopts an analogous approach to understanding PCs. Plionis et al. (2009) proposed a theory to define the evolution of poor clusters. The theory asserts that cannibalism of galaxies causes a cluster to become more spherical, develop increased velocity dispersion and increased X-ray temperature and gas luminosity. Data used to quantify the evolution of the poor clusters were compiled across multiple wavelengths. The sample includes 162 objects from the WBL catalogue (White et al. 1999), 30 poor clusters in the Chandra X-ray Observatory archive, and 15 Abell poor clusters observed with BAX (Sadat et al. 2004). Preliminary results indicate that the cluster velocity dispersion and X-ray gas and point source luminosities can be used to highlight a weak correlation. An evolutionary trend was observed for multiple correlations detailed herein. The current study is a continuation of the work by Broming & Fuse examining point sources and their properties to determine the evolutionary stage of compact groups, poor clusters, and their proposed remnants, isolated ellipticals and fossil groups. Preliminary data suggests that compact groups and their high-mass counterpart, poor clusters, evolve along tracks identified in the X-ray gas - X-ray point source relation. While compact groups likely evolve into isolated elliptical galaxies, fossil groups display properties that suggest they are the remains of fully coalesced poor clusters.

  16. Constraining Cosmic Evolution of Type Ia Supernovae

    SciTech Connect

    Foley, Ryan J.; Filippenko, Alexei V.; Aguilera, C.; Becker, A.C.; Blondin, S.; Challis, P.; Clocchiatti, A.; Covarrubias, R.; Davis, T.M.; Garnavich, P.M.; Jha, S.; Kirshner, R.P.; Krisciunas, K.; Leibundgut, B.; Li, W.; Matheson, T.; Miceli, A.; Miknaitis, G.; Pignata, G.; Rest, A.; Riess, A.G.; /UC, Berkeley, Astron. Dept. /Cerro-Tololo InterAmerican Obs. /Washington U., Seattle, Astron. Dept. /Harvard-Smithsonian Ctr. Astrophys. /Chile U., Catolica /Bohr Inst. /Notre Dame U. /KIPAC, Menlo Park /Texas A-M /European Southern Observ. /NOAO, Tucson /Fermilab /Chile U., Santiago /Harvard U., Phys. Dept. /Baltimore, Space Telescope Sci. /Johns Hopkins U. /Res. Sch. Astron. Astrophys., Weston Creek /Stockholm U. /Hawaii U. /Illinois U., Urbana, Astron. Dept.

    2008-02-13

    We present the first large-scale effort of creating composite spectra of high-redshift type Ia supernovae (SNe Ia) and comparing them to low-redshift counterparts. Through the ESSENCE project, we have obtained 107 spectra of 88 high-redshift SNe Ia with excellent light-curve information. In addition, we have obtained 397 spectra of low-redshift SNe through a multiple-decade effort at Lick and Keck Observatories, and we have used 45 ultraviolet spectra obtained by HST/IUE. The low-redshift spectra act as a control sample when comparing to the ESSENCE spectra. In all instances, the ESSENCE and Lick composite spectra appear very similar. The addition of galaxy light to the Lick composite spectra allows a nearly perfect match of the overall spectral-energy distribution with the ESSENCE composite spectra, indicating that the high-redshift SNe are more contaminated with host-galaxy light than their low-redshift counterparts. This is caused by observing objects at all redshifts with similar slit widths, which corresponds to different projected distances. After correcting for the galaxy-light contamination, subtle differences in the spectra remain. We have estimated the systematic errors when using current spectral templates for K-corrections to be {approx}0.02 mag. The variance in the composite spectra give an estimate of the intrinsic variance in low-redshift maximum-light SN spectra of {approx}3% in the optical and growing toward the ultraviolet. The difference between the maximum-light low and high-redshift spectra constrain SN evolution between our samples to be < 10% in the rest-frame optical.

  17. Quasi-optical constrained lens amplifiers

    NASA Astrophysics Data System (ADS)

    Schoenberg, Jon S.

    1995-09-01

    A major goal in the field of quasi-optics is to increase the power available from solid state sources by combining the power of individual devices in free space, as demonstrated with grid oscillators and grid amplifiers. Grid amplifiers and most amplifier arrays require a plane wave feed, provided by a far field source or at the beam waist of a dielectric lens pair. These feed approaches add considerable loss and size, which is usually greater than the quasi-optical amplifier gain. In addition, grid amplifiers require external polarizers for stability, further increasing size and complexity. This thesis describes using constrained lens theory in the design of quasi optical amplifier arrays with a focal point feed, improving the power coupling between the feed and the amplifier for increased gain. Feed and aperture arrays of elements, input/output isolation and stability, amplifier circuitry, delay lines and bias distribution are all contained on a single planar substrate, making monolithic circuit integration possible. Measured results of X band transmission lenses and a low noise receive lens are presented, including absolute power gain up to 13 dB, noise figure as low as 1.7 dB, beam scanning to +/-30 deg, beam forming and beam switching of multiple sources, and multiple level quasi-optical power combining. The design and performance of millimeter wave power combining amplifier arrays is described, including a Ka Band hybrid array with 1 watt output power, and a V Band 36 element monolithic array with a 5 dB on/off ratio.

  18. Mars, Moon, Mercury: Magnetometry Constrains Planetary Evolution

    NASA Astrophysics Data System (ADS)

    Connerney, John E. P.

    2015-04-01

    We have long appreciated that magnetic measurements obtained about a magnetized planet are of great value in probing the deep interior. The existence of a substantial planetary magnetic field implies dynamo action requiring an electrically conducting, fluid core in convective motion and a source of energy to maintain it. Application of the well-known Lowe's spectrum may in some cases identify the dynamo outer radius; where secular variation can be measured, the outer radius can be estimated using the frozen flux approximation. Magnetic induction may be used to probe the electrical conductivity of the mantle and crust. These are useful constraints that together with gravity and/or other observables we may infer the state of the interior and gain insight into planetary evolution. But only recently has it become clear that space magnetometry can do much more, particularly about a planet that once sustained a dynamo that has since disappeared. Mars is the best example of this class: the Mars Global Surveyor spacecraft globally mapped a remanent crustal field left behind after the demise of the dynamo. This map is a magnetic record of the planet's evolution. I will argue that this map may be interpreted to constrain the era of dynamo activity within Mars; to establish the reversal history of the Mars dynamo; to infer the magnetization intensity of Mars crustal rock and the depth of the magnetized crustal layer; and to establish that plate tectonics is not unique to planet Earth, as has so often been claimed. The Lunar magnetic record is in contrast one of weakly magnetized and scattered sources, not easily interpreted as yet in terms of the interior. Magnetometry about Mercury is more difficult to interpret owing to the relatively weak field and proximity to the sun, but MESSENGER (and ultimately Beppi Columbo) may yet map crustal anomalies (induced and/or remanent).

  19. The cost-constrained traveling salesman problem

    SciTech Connect

    Sokkappa, P.R.

    1990-10-01

    The Cost-Constrained Traveling Salesman Problem (CCTSP) is a variant of the well-known Traveling Salesman Problem (TSP). In the TSP, the goal is to find a tour of a given set of cities such that the total cost of the tour is minimized. In the CCTSP, each city is given a value, and a fixed cost-constraint is specified. The objective is to find a subtour of the cities that achieves maximum value without exceeding the cost-constraint. Thus, unlike the TSP, the CCTSP requires both selection and sequencing. As a consequence, most results for the TSP cannot be extended to the CCTSP. We show that the CCTSP is NP-hard and that no K-approximation algorithm or fully polynomial approximation scheme exists, unless P = NP. We also show that several special cases are polynomially solvable. Algorithms for the CCTSP, which outperform previous methods, are developed in three areas: upper bounding methods, exact algorithms, and heuristics. We found that a bounding strategy based on the knapsack problem performs better, both in speed and in the quality of the bounds, than methods based on the assignment problem. Likewise, we found that a branch-and-bound approach using the knapsack bound was superior to a method based on a common branch-and-bound method for the TSP. In our study of heuristic algorithms, we found that, when selecting modes for inclusion in the subtour, it is important to consider the neighborhood'' of the nodes. A node with low value that brings the subtour near many other nodes may be more desirable than an isolated node of high value. We found two types of repetition to be desirable: repetitions based on randomization in the subtour buildings process, and repetitions encouraging the inclusion of different subsets of the nodes. By varying the number and type of repetitions, we can adjust the computation time required by our method to obtain algorithms that outperform previous methods.

  20. Motor Demands Constrain Cognitive Rule Structures

    PubMed Central

    Collins, Anne Gabrielle Eva; Frank, Michael Joshua

    2016-01-01

    Study of human executive function focuses on our ability to represent cognitive rules independently of stimulus or response modality. However, recent findings suggest that executive functions cannot be modularized separately from perceptual and motor systems, and that they instead scaffold on top of motor action selection. Here we investigate whether patterns of motor demands influence how participants choose to implement abstract rule structures. In a learning task that requires integrating two stimulus dimensions for determining appropriate responses, subjects typically structure the problem hierarchically, using one dimension to cue the task-set and the other to cue the response given the task-set. However, the choice of which dimension to use at each level can be arbitrary. We hypothesized that the specific structure subjects adopt would be constrained by the motor patterns afforded within each rule. Across four independent data-sets, we show that subjects create rule structures that afford motor clustering, preferring structures in which adjacent motor actions are valid within each task-set. In a fifth data-set using instructed rules, this bias was strong enough to counteract the well-known task switch-cost when instructions were incongruent with motor clustering. Computational simulations confirm that observed biases can be explained by leveraging overlap in cortical motor representations to improve outcome prediction and hence infer the structure to be learned. These results highlight the importance of sensorimotor constraints in abstract rule formation and shed light on why humans have strong biases to invent structure even when it does not exist. PMID:26966909

  1. Ductile failure of a constrained metal foil

    NASA Astrophysics Data System (ADS)

    Varias, A. G.; Suo, Z.; Shih, C. F.

    A METAL foil bonded between stiff ceramic blocks may fail in a variety of ways, including de-adhesion of interfaces, cracking in the ceramics and ductile rupture of the metal. If the interface bond is strong enough to allow the foil to undergo substantial plastic deformation dimples are usually present on fracture surfaces and the nominal fracture energy is enhanced. Ductile fracture mechanisms responsible for such morphology include (i) growth of near-tip voids nucleated at second-phase particles and or interface pores, (ii) cavitation and (iii) interfacial debonding at the site of maximum stress which develops at distances of several foil thicknesses ahead of the crack tip. For a crack in a low to moderately hardening bulk metal, it is known that the maximum mean stress which develops at a distance of several crack openings ahead of the tip does not exceed about three times the yield stress. In contrast, the maximum mean stress that develops at several foil thicknesses ahead of the crack tip in a constrained metal foil can increase continuously with the applied load. Mean stress and interfacial traction of about four to six times the yield of the metal foil can trigger cavitation and/or interfacial debonding. The mechanical fields which bear on the competition between failure mechanisms are obtained by a large deformation finite element analysis. Effort is made to formulate predictive criteria indicating, for a given material system, which one of the several mechanisms operates and the relevant parameters that govern the nominal fracture work. The shielding of the crack tip in the context of ductile adhesive joints, due to the non-proportional deformation in a region of the order of the foil thickness, is also discussed.

  2. Constraining the source of mantle plumes

    NASA Astrophysics Data System (ADS)

    Cagney, N.; Crameri, F.; Newsome, W. H.; Lithgow-Bertelloni, C.; Cotel, A.; Hart, S. R.; Whitehead, J. A.

    2016-02-01

    In order to link the geochemical signature of hot spot basalts to Earth's deep interior, it is first necessary to understand how plumes sample different regions of the mantle. Here, we investigate the relative amounts of deep and shallow mantle material that are entrained by an ascending plume and constrain its source region. The plumes are generated in a viscous syrup using an isolated heater for a range of Rayleigh numbers. The velocity fields are measured using stereoscopic Particle-Image Velocimetry, and the concept of the 'vortex ring bubble' is used to provide an objective definition of the plume geometry. Using this plume geometry, the plume composition can be analysed in terms of the proportion of material that has been entrained from different depths. We show that the plume composition can be well described using a simple empirical relationship, which depends only on a single parameter, the sampling coefficient, sc. High-sc plumes are composed of material which originated from very deep in the fluid domain, while low-sc plumes contain material entrained from a range of depths. The analysis is also used to show that the geometry of the plume can be described using a similarity solution, in agreement with previous studies. Finally, numerical simulations are used to vary both the Rayleigh number and viscosity contrast independently. The simulations allow us to predict the value of the sampling coefficient for mantle plumes; we find that as a plume reaches the lithosphere, 90% of its composition has been derived from the lowermost 260-750 km in the mantle, and negligible amounts are derived from the shallow half of the lower mantle. This result implies that isotope geochemistry cannot provide direct information about this unsampled region, and that the various known geochemical reservoirs must lie in the deepest few hundred kilometres of the mantle.

  3. Laterally constrained inversion for CSAMT data interpretation

    NASA Astrophysics Data System (ADS)

    Wang, Ruo; Yin, Changchun; Wang, Miaoyue; Di, Qingyun

    2015-10-01

    Laterally constrained inversion (LCI) has been successfully applied to the inversion of dc resistivity, TEM and airborne EM data. However, it hasn't been yet applied to the interpretation of controlled-source audio-frequency magnetotelluric (CSAMT) data. In this paper, we apply the LCI method for CSAMT data inversion by preconditioning the Jacobian matrix. We apply a weighting matrix to Jacobian to balance the sensitivity of model parameters, so that the resolution with respect to different model parameters becomes more uniform. Numerical experiments confirm that this can improve the convergence of the inversion. We first invert a synthetic dataset with and without noise to investigate the effect of LCI applications to CSAMT data, for the noise free data, the results show that the LCI method can recover the true model better compared to the traditional single-station inversion; and for the noisy data, the true model is recovered even with a noise level of 8%, indicating that LCI inversions are to some extent noise insensitive. Then, we re-invert two CSAMT datasets collected respectively in a watershed and a coal mine area in Northern China and compare our results with those from previous inversions. The comparison with the previous inversion in a coal mine shows that LCI method delivers smoother layer interfaces that well correlate to seismic data, while comparison with a global searching algorithm of simulated annealing (SA) in a watershed shows that though both methods deliver very similar good results, however, LCI algorithm presented in this paper runs much faster. The inversion results for the coal mine CSAMT survey show that a conductive water-bearing zone that was not revealed by the previous inversions has been identified by the LCI. This further demonstrates that the method presented in this paper works for CSAMT data inversion.

  4. Constrained Inversion of Enceladus Interaction Observations

    NASA Astrophysics Data System (ADS)

    Herbert, Floyd; Khurana, K. K.

    2007-10-01

    Many detailed and sophisticated ab initio calculations of the electrodynamic interaction of Enceladus' plume with Saturn's corotating magnetospheric plasma flow have been computed. So far, however, all such calculations have been forward models, that assume the properties of the plume and compute perturbations to the magnetic (and in some cases, flow velocity) field. As a complement to the forward calculations, work reported here explores the inverse approach, of using simplified physical models of the interaction for computationally inverting the observed magnetic field perturbations of the interaction, in order to determine the cross-B-field conductivity distribution near Enceladus, and from that, the neutral gas distribution. Direct inversion of magnetic field observations to current systems is, of course, impossible, but adding the additional constraint of the interaction physics greatly reduces the non-uniqueness of the computed result. This approach was successfully used by Herbert (JGR 90:8241, 1985) to constrain the atmospheric distribution on Io and the Io torus mass density at the time of the Voyager encounter. Work so far has derived the expected result that there is a cone-shaped region of enhanced cross-field conductivity south of Enceladus, through which currents are driven by the motional electric field. That is, near Enceladus' south pole the cross-field currents are localized, but more widely spread at greater distance. This cross-field conductivity is presumably both pickup and collisional (Pedersen and Hall). Due to enforcement of current conservation, Alfven-wing-like currents north of the main part of the interaction region seem to close partly around Enceladus (assumed insulating) and also to continue northward with attenuated intensity, as though there were a tenuous global exosphere on Enceladus providing additional cross-field conductivity. FH thanks the NASA Outer Planets Research, Planetary Atmospheres, and Geospace Science Programs for

  5. Extraterrestrial Amino Acids Identified in Metal-Rich CH and CB Carbonaceous Chondrites from Antarctica

    NASA Technical Reports Server (NTRS)

    Burton, Aaron S.; Elsila, Jamie E.; Hein, Jason E.; Glavin, Daniel P.; Dworkin, Jason P.

    2013-01-01

    Carbonaceous chondrites contain numerous indigenous organic compounds and could have been an important source of prebiotic compounds required for the origin of life on Earth or elsewhere. Extraterrestrial amino acids have been reported in five of the eight groups of carbonaceous chondrites and are most abundant in CI, CM, and CR chondritesbut are also present in the more thermally altered CV and CO chondrites. We report the abundance, distribution, and enantiomeric and isotopic compositions of simple primary amino acids in six metal-rich CH and CB carbonaceous chondrites that have not previously been investigated for amino acids: Allan Hills (ALH) 85085 (CH3), Pecora Escarpment(PCA) 91467 (CH3), Patuxent Range (PAT) 91546 (CH3), MacAlpine Hills (MAC) 02675(CBb), Miller Range (MIL) 05082 (CB), and Miller Range (MIL) 07411 (CB). Amino acid abundances and carbon isotopic values were obtained by using both liquid chromatography time-of-flight mass spectrometry and fluorescence, and gas chromatography isotope ratiomass spectrometry. The (delta D, delta C-13, delta N-15) ratios of multiple amino acids fall outside of the terrestrial range and support their extraterrestrial origin. Extracts of CH chondrites were found to be particularly rich in amino acids (1316 parts per million, ppm) while CB chondrite extracts had much lower abundances (0.22 ppm). The amino acid distributions of the CH and CB chondrites were distinct from the distributions observed in type 2 and 3 CM and CR chondrites and contained elevated levels of beta-, gamma-, and delta-amino acids compared to the corresponding alpha-amino acids, providing evidence that multiple amino acid formation mechanisms were important in CH and CB chondrites.

  6. Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown.

    PubMed Central

    Hershko, A; Heller, H; Eytan, E; Kaklij, G; Rose, I A

    1984-01-01

    Previous studies suggest that the conjugation of ubiquitin to NH2 groups of proteins is required for protein breakdown. We now show that the selective modification of NH2-terminal alpha-NH2 groups of globin and lysozyme prevents their degradation by the ubiquitin proteolytic system from reticulocytes. The conjugation by ubiquitin of epsilon-NH2 groups of lysine residues, usually seen in multiples, was also inhibited in alpha-NH2-blocked proteins. Naturally occurring N alpha-acetylated proteins are not degraded by the ubiquitin system at a significant rate, while their nonacetylated counterparts from other species are good substrates. This suggests that one function of N alpha-acetylation of cellular proteins is to prevent their degradation by the ubiquitin system. alpha-NH2-blocked proteins can have their activity as substrates for degradation increased by incorporation of alpha-NH2 groups through the introduction of polyalanine side chains. Proteins in which most epsilon-NH2 groups are blocked but the alpha-NH2 group is free are degraded by the ubiquitin system, but at a reduced rate. It is therefore suggested that the exposure of a free NH2 terminus of proteins is required for degradation and probably initiates the formation of ubiquitin conjugates committed for degradation. Images PMID:6095265

  7. Therapeutic Agents in Acne Vulgaris: Part II. D-Alpha Amino Benzyl Penicillin, Erythromycin and Sulfadimethoxine.

    PubMed

    Stewart, W D; Maddin, S; Nelson, A J; Danto, J L

    1965-06-26

    A total of 379 patients with pustular and cystic acne vulgaris were selected for study in three groups. Each group was assigned one of the following medications: benzyl penicillin, erythromycin, sulfadimethoxine, or placebo; these were to be compared with tetracycline, a medication whose effectiveness was previously demonstrated in this type of acne. The study revealed a larger number of favourable responses to tetracycline and erythromycin than to sulfadimethoxine. Sulfadimethoxine, however, produced a greater number of favourable responses than did the benzyl penicillin or the placebo; the last-named had equivalent results.

  8. Depolarizing actions of gamma-aminobutyric acid and related compounds on rat superior cervical ganglia in vitro.

    PubMed

    Bowery, N G; Brown, D A

    1974-02-01

    1 Potential changes in rat superior cervical ganglia were recorded in vitro with surface electrodes.2 gamma-aminobutyric acid (GABA) produced a transient, low-amplitude ganglion depolarization at rest, and a transient hyperpolarization in ganglia depolarized by carbachol. Depolarization was not prevented by preganglionic denervation. The log dose-response curve for depolarization was sigmoid with a mean ED(50) of 12.5 muM.3 The ganglion was depolarized in similar manner by the following compounds (mean molar potencies relative to GABA (=1) in brackets): 3-aminopropane sulphonic acid (3.4), gamma-amino-beta-hydroxybutyric acid (0.27), beta-guanidino-propionic acid (0.12), guanidinoacetic acid (0.057), delta-aminovaleric acid (0.048), beta-alanine (0.01), 2,4-diaminobutyric acid, gamma-guanidinobutyric acid, taurine and N-methyl-GABA (all <0.01). The following compounds did not depolarize the ganglion at 10 mM concentrations: alpha- and beta-amino-n-butyric acids, alpha-amino-iso-butyric acid, glycine and glutamic acid.4 Depolarization declined in the continued presence of GABA. Ganglia thus ;desensitized' to GABA showed a diminished response to other amino acids but not to carbachol.5 The effect of GABA was not antagonized by hyoscine and hexamethonium in combination, in concentrations sufficient to block responses to carbachol.6 Responses to GABA were blocked more readily than those to carbachol by bicuculline (IC(50), 14 muM) and picrotoxin (IC(50), 37 muM). Strychnine (IC(50), 73 muM) was a relatively weak and less selective GABA-antagonist.7 It is concluded that sympathetic ganglion cells possess receptors for GABA and related amino acids which are (a) different from the acetylcholine receptors and (b) similar to GABA receptors in the central nervous system.

  9. How We Can Constrain Aerosol Type Globally

    NASA Technical Reports Server (NTRS)

    Kahn, Ralph

    2016-01-01

    In addition to aerosol number concentration, aerosol size and composition are essential attributes needed to adequately represent aerosol-cloud interactions (ACI) in models. As the nature of ACI varies enormously with environmental conditions, global-scale constraints on particle properties are indicated. And although advanced satellite remote-sensing instruments can provide categorical aerosol-type classification globally, detailed particle microphysical properties are unobtainable from space with currently available or planned technologies. For the foreseeable future, only in situ measurements can constrain particle properties at the level-of-detail required for ACI, as well as to reduce uncertainties in regional-to-global-scale direct aerosol radiative forcing (DARF). The limitation of in situ measurements for this application is sampling. However, there is a simplifying factor: for a given aerosol source, in a given season, particle microphysical properties tend to be repeatable, even if the amount varies from day-to-day and year-to-year, because the physical nature of the particles is determined primarily by the regional environment. So, if the PDFs of particle properties from major aerosol sources can be adequately characterized, they can be used to add the missing microphysical detail the better sampled satellite aerosol-type maps. This calls for Systematic Aircraft Measurements to Characterize Aerosol Air Masses (SAM-CAAM). We are defining a relatively modest and readily deployable, operational aircraft payload capable of measuring key aerosol absorption, scattering, and chemical properties in situ, and a program for characterizing statistically these properties for the major aerosol air mass types, at a level-of-detail unobtainable from space. It is aimed at: (1) enhancing satellite aerosol-type retrieval products with better aerosol climatology assumptions, and (2) improving the translation between satellite-retrieved aerosol optical properties and

  10. Constraining duty cycles through a Bayesian technique

    NASA Astrophysics Data System (ADS)

    Romano, P.; Guidorzi, C.; Segreto, A.; Ducci, L.; Vercellone, S.

    2014-12-01

    The duty cycle (DC) of astrophysical sources is generally defined as the fraction of time during which the sources are active. It is used to both characterize their central engine and to plan further observing campaigns to study them. However, DCs are generally not provided with statistical uncertainties, since the standard approach is to perform Monte Carlo bootstrap simulations to evaluate them, which can be quite time consuming for a large sample of sources. As an alternative, considerably less time-consuming approach, we derived the theoretical expectation value for the DC and its error for sources whose state is one of two possible, mutually exclusive states, inactive (off) or flaring (on), as based on a finite set of independent observational data points. Following a Bayesian approach, we derived the analytical expression for the posterior, the conjugated distribution adopted as prior, and the expectation value and variance. We applied our method to the specific case of the inactivity duty cycle (IDC) for supergiant fast X-ray transients, a subclass of flaring high mass X-ray binaries characterized by large dynamical ranges. We also studied IDC as a function of the number of observations in the sample. Finally, we compare the results with the theoretical expectations. We found excellent agreement with our findings based on the standard bootstrap method. Our Bayesian treatment can be applied to all sets of independent observations of two-state sources, such as active galactic nuclei, X-ray binaries, etc. In addition to being far less time consuming than bootstrap methods, the additional strength of this approach becomes obvious when considering a well-populated class of sources (Nsrc ≥ 50) for which the prior can be fully characterized by fitting the distribution of the observed DCs for all sources in the class, so that, through the prior, one can further constrain the DC of a new source by exploiting the information acquired on the DC distribution derived

  11. Folding of Small Proteins Using Constrained Molecular Dynamics

    PubMed Central

    Balaraman, Gouthaman S.; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

    2011-01-01

    The focus of this paper is to examine whether conformational search using constrained molecular dynamics (MD) method is more enhanced and enriched towards “native-like” structures compared to all-atom MD for the protein folding as a model problem. Constrained MD methods provide an alternate MD tool for protein structure prediction and structure refinement. It is computationally expensive to perform all-atom simulations of protein folding because the processes occur on a timescale of microseconds. Compared to the all-atom MD simulation, constrained MD methods have the advantage that stable dynamics can be achieved for larger time steps and the number of degrees of freedom is an order of magnitude smaller, leading to a decrease in computational cost. We have developed a generalized constrained MD method that allows the user to “freeze and thaw” torsional degrees of freedom as fit for the problem studied. We have used this method to perform all-torsion constrained MD in implicit solvent coupled with the replica exchange method to study folding of small proteins with various secondary structural motifs such as, α-helix (polyalanine, WALP16), β-turn (1E0Q), and a mixed motif protein (Trp-cage). We demonstrate that constrained MD replica exchange method exhibits a wider conformational search than all-atom MD with increased enrichment of near native structures. “Hierarchical” constrained MD simulations, where the partially formed helical regions in the initial stretch of the all-torsion folding simulation trajectory of Trp-cage were frozen, showed a better sampling of near native structures than all-torsion constrained MD simulations. This is in agreement with the zipping-and-assembly folding model put forth by Dill and coworkers for folding proteins. The use of hierarchical “freeze and thaw” clustering schemes in constrained MD simulation can be used to sample conformations that contribute significantly to folding of proteins. PMID:21591767

  12. Detection and characterization of carrier-mediated cationic amino acid transport in lysosomes of normal and cystinotic human fibroblasts. Role in therapeutic cystine removal

    SciTech Connect

    Pisoni, R.L.; Thoene, J.G.; Christensen, H.N.

    1985-04-25

    The discovery of a trans-stimulation property associated with lysine exodus from lysosomes of human fibroblasts has enabled us to characterize a system mediating the transport of cationic amino acids across the lysosomal membrane of human fibroblasts. The cationic amino acids arginine, lysine, ornithine, diaminobutyrate, histidine, 2-aminoethylcysteine, and the mixed disulfide of cysteine and cysteamine all caused trans-stimulation of the exodus of radiolabeled lysine from the lysosomal fraction of human fibroblasts at pH 6.5. In contrast, neutral and acidic amino acids did not affect the rate of lysine exodus. Trans-stimulation of lysine exodus was observed over the pH range from 5.5 to 7.6, was specific for the L-isomer of the cationic amino acid, and was intolerant to methylation of the alpha-amino group of the amino acid. The lysosomotropic amine, chloroquine, greatly retarded lysine exodus, whereas the presence of sodium ion was without effect. The specificity and lack of Na+ dependence of this lysosomal transport system is similar to that of System y+ present on the plasma membrane of human fibroblasts. An important mechanism by which cysteamine treatment of cystinosis allows cystine escape from lysosomes may be the ability of the mixed disulfide of cysteine and cysteamine formed by sulfhydryl-disulfide exchange to migrate by this newly discovered system mediating cationic amino acid transport.

  13. The mechanism of MIO-based aminomutases in beta-amino acid biosynthesis.

    PubMed

    Christianson, Carl V; Montavon, Timothy J; Festin, Grace M; Cooke, Heather A; Shen, Ben; Bruner, Steven D

    2007-12-26

    Beta-amino acids are widely used building blocks in both natural and synthetic compounds. Aromatic beta-amino acids can be biosynthesized directly from proteinogenic alpha-amino acids by the action of MIO (4-methylideneimidazole-5-one)-based aminomutase enzymes. The uncommon cofactor MIO plays a role in both ammonia lyases and 2,3-aminomutases; however, the precise mechanism of the cofactor has not been resolved. Here we provide evidence that the electrophilic cofactor uses covalent catalysis through the substrate amine to direct the elimination and subsequent readdition of ammonia. A mechanism-based inhibitor was synthesized and the X-ray cocomplex structure was determined to 2.0 A resolution. The inhibitor halts the chemistry of the reverse reaction, providing a stable complex that establishes the mode of substrate binding and the importance of tyrosine 63 in the chemistry. The proposed mechanism is consistent with the biochemistry of aminomutases and ammonia lyases and provides strong support for an amine-adduct mechanism of catalysis for this enzyme class.

  14. Binding of flexible and constrained ligands to the Grb2 SH2 domain: structural effects of ligand preorganization

    PubMed Central

    Clements, John H.; DeLorbe, John E.; Benfield, Aaron P.; Martin, Stephen F.

    2010-01-01

    Structures of the Grb2 SH2 domain complexed with a series of pseudopeptides containing flexible (benzyl succinate) and constrained (aryl cyclopropanedicarboxylate) replacements of the phosphotyrosine (pY) residue in tripeptides derived from Ac-pYXN-NH2 (where X = V, I, E and Q) were elucidated by X-ray crystallography. Complexes of flexible/constrained pairs having the same pY + 1 amino acid were analyzed in order to ascertain what structural differences might be attributed to constraining the phosphotyrosine replacement. In this context, a given structural dissimilarity between complexes was considered to be significant if it was greater than the corresponding difference in complexes coexisting within the same asymmetric unit. The backbone atoms of the domain generally adopt a similar conformation and orientation relative to the ligands in the complexes of each flexible/constrained pair, although there are some significant differences in the relative orientations of several loop regions, most notably in the BC loop that forms part of the binding pocket for the phosphate group in the tyrosine replacements. These variations are greater in the set of complexes of constrained ligands than in the set of complexes of flexible ligands. The constrained ligands make more direct polar contacts to the domain than their flexible counterparts, whereas the more flexible ligand of each pair makes more single-water-mediated contacts to the domain; there was no correlation between the total number of protein–ligand contacts and whether the phosphotyrosine replacement of the ligand was preorganized. The observed differences in hydrophobic interactions between the complexes of each flexible/constrained ligand pair were generally similar to those observed upon comparing such contacts in coexisting complexes. The average adjusted B factors of the backbone atoms of the domain and loop regions are significantly greater in the complexes of constrained ligands than in the complexes of

  15. Constrained reduced-order models based on proper orthogonal decomposition

    DOE PAGES

    Reddy, Sohail R.; Freno, Brian Andrew; Cizmas, Paul G. A.; ...

    2017-04-09

    A novel approach is presented to constrain reduced-order models (ROM) based on proper orthogonal decomposition (POD). The Karush–Kuhn–Tucker (KKT) conditions were applied to the traditional reduced-order model to constrain the solution to user-defined bounds. The constrained reduced-order model (C-ROM) was applied and validated against the analytical solution to the first-order wave equation. C-ROM was also applied to the analysis of fluidized beds. Lastly, it was shown that the ROM and C-ROM produced accurate results and that C-ROM was less sensitive to error propagation through time than the ROM.

  16. Onomatopoeia characters extraction from comic images using constrained Delaunay triangulation

    NASA Astrophysics Data System (ADS)

    Liu, Xiangping; Shoji, Kenji; Mori, Hiroshi; Toyama, Fubito

    2014-02-01

    A method for extracting onomatopoeia characters from comic images was developed based on stroke width feature of characters, since they nearly have a constant stroke width in a number of cases. An image was segmented with a constrained Delaunay triangulation. Connected component grouping was performed based on the triangles generated by the constrained Delaunay triangulation. Stroke width calculation of the connected components was conducted based on the altitude of the triangles generated with the constrained Delaunay triangulation. The experimental results proved the effectiveness of the proposed method.

  17. Residual flexibility test method for verification of constrained structural models

    NASA Technical Reports Server (NTRS)

    Admire, John R.; Tinker, Michael L.; Ivey, Edward W.

    1992-01-01

    A method is presented for deriving constrained modes and frequencies from a model correlated to a set of free-free test modes and a set of measured residual flexibilities. The method involves a simple modification of the MacNeal and Rubin component mode representation to allow verification of a constrained structural model. Results for two spaceflight structures show quick convergence of constrained modes using an easily measurable set of free-free modes plus the residual flexibility matrix or its boundary partition. This paper further validates the residual flexibility approach as an alternative test/analysis method when fixed-base testing proves impractical.

  18. Quantum dynamics by the constrained adiabatic trajectory method

    SciTech Connect

    Leclerc, A.; Jolicard, G.; Guerin, S.; Killingbeck, J. P.

    2011-03-15

    We develop the constrained adiabatic trajectory method (CATM), which allows one to solve the time-dependent Schroedinger equation constraining the dynamics to a single Floquet eigenstate, as if it were adiabatic. This constrained Floquet state (CFS) is determined from the Hamiltonian modified by an artificial time-dependent absorbing potential whose forms are derived according to the initial conditions. The main advantage of this technique for practical implementation is that the CFS is easy to determine even for large systems since its corresponding eigenvalue is well isolated from the others through its imaginary part. The properties and limitations of the CATM are explored through simple examples.

  19. Stereochemically constrained complex organic molecules extracted from olivine crystal matrix

    NASA Astrophysics Data System (ADS)

    Gerasimenko, I.; Freund, F. T.; Imanaka, H.; Rodgers, R.

    2011-12-01

    Paradoxically, the dense solid state of magmatic minerals is a medium, in which organic synthesis can take place. The reason is that gas-fluid components such as H2O, CO/CO2/N2 and H2S are omnipresent in terrestrial magmatic environments. Any silicate mineral that crystallizes from such magmas will incorporate small quantities of the fluid-phase components in the form of structurally incompatible low-z impurities. During cooling the solute species undergo a redox conversion, resulting in chemically reduced low-z elements. To the extent that these low-z impurities are diffusively mobile, they will exsolve to the surface and/or to major structural defects inside the crystal matrix such as dislocations. Dislocations provide a 3-D structured environment, where the low-z impurities will tend to form stereochemically constrained polyatomic Cn-H-O-N-S entities, which we call organic protomolecules. In Nature, during weathering, such protomolecules will be released into the environment in the form of complex organic molecules. In our study we crush samples under clean conditions as a way to expose Cn-H-O-N-S entities at the fracture surfaces. We conduct identical experiments with selected large olivine single crystals, mm-sized olivine from peridiotite nodules from the San Carlos Volcanic Field, Arizona, and the vesiculated basalt that had carried the nodules upward in the volcanic conduit. We Soxhlet-extract the crushed powders with water, THF and ethyl acetate. The extracts are analyzed at the FTICR-MS facility at Florida State University using ultrahigh resolution Mass Spectrometry techniques capable of determining the chemical composition of the organic molecules up to 600 amu and more. So far we have found several analog sequences of oxygen-rich aliphatic hydrocarbons, families with up to 34 carbon atoms, probably poly-carboxylic acids, and some families containing sulfur.

  20. Constraining Anthropogenic and Biogenic Emissions Using Chemical Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Spencer, Kathleen M.

    Numerous gas-phase anthropogenic and biogenic compounds are emitted into the atmosphere. These gases undergo oxidation to form other gas-phase species and particulate matter. Whether directly or indirectly, primary pollutants, secondary gas-phase products, and particulate matter all pose health and environmental risks. In this work, ambient measurements conducted using chemical ionization mass spectrometry are used as a tool for investigating regional air quality. Ambient measurements of peroxynitric acid (HO2NO2) were conducted in Mexico City. A method of inferring the rate of ozone production, PO3, is developed based on observations of HO2NO 2, NO, and NO2. Comparison of this observationally based PO3 to a highly constrained photochemical box model indicates that regulations aimed at reducing ozone levels in Mexico City by reducing NOx concentrations may be effective at higher NO x levels than predicted using accepted photochemistry. Measurements of SO2 and particulate sulfate were conducted over the Los Angeles basin in 2008 and are compared to measurements made in 2002. A large decrease in SO2 concentration and a change in spatial distribution are observed. Nevertheless, only a modest reduction in sulfate concentration is observed at ground sites within the basin. Possible explanations for these trends are investigated. Two techniques, single and triple quadrupole chemical ionization mass spectrometry, were used to quantify ambient concentrations of biogenic oxidation products, hydroxyacetone and glycolaldehyde. The use of these techniques demonstrates the advantage of triple quadrupole mass spectrometry for separation of mass analogues, provided the collision-induced daughter ions are sufficiently distinct. Enhancement ratios of hydroxyacetone and glycolaldehyde in Californian biomass burning plumes are presented as are concentrations of these compounds at a rural ground site downwind of Sacramento.

  1. CONDORR--CONstrained Dynamics of Rigid Residues: a molecular dynamics program for constrained molecules.

    PubMed

    York, William S; Yi, Xiaobing

    2004-08-01

    A computer program CONDORR (CONstrained Dynamics of Rigid Residues) was developed for molecular dynamics simulations of large and/or constrained molecular systems, particularly carbohydrates. CONDORR efficiently calculates molecular trajectories on the basis of 2D or 3D potential energy maps, and can generate such maps based on a simple force field. The simulations involve three translational and three rotational degrees of freedom for each rigid, asymmetrical residue in the model. Total energy and angular momentum are conserved when no stochastic or external forces are applied to the model, if the time step is kept sufficiently short. Application of Langevin dynamics allows longer time steps, providing efficient exploration of conformational space. The utility of CONDORR was demonstrated by application to a constrained polysaccharide model and to the calculation of residual dipolar couplings for a disaccharide. [Figure: see text]. Molecular models (bottom) are created by cloning rigid residue archetypes (top) and joining them together. As defined here, the archetypes AX, HM and BG respectively correspond to an alpha-D-Xyl p residue, a hydroxymethyl group, and a beta-D-Glc p residue lacking O6, H6a and H6b. Each archetype contains atoms (indicated by boxes) that can be shared with other archetypes to form a linked structure. For example, the glycosidic link between the two D-Glc p residues is established by specifying that O1 of the nonreducing beta-D-Glc p (BG) residue (2) is identical to O4 of the reducing Glc p (BG) residue (1). The coordinates of the two residues are adjusted so as to superimpose these two (nominally distinct) atoms. Flexible hydroxymethyl (HM) groups (3 and 4) are treated as separate residues, and the torsional angles (normally indicated by the symbol omega) that define their geometric relationships to the pyranosyl rings of the BG residues are specified as psi3 and psi4, respectively. The torsional angles phi3 and phi4, defined solely to

  2. Inhibitors of metalloendopeptidase EC 3.4.24.15 and EC 3.4.24.16 stabilized against proteolysis by the incorporation of beta-amino acids.

    PubMed

    Steer, David; Lew, Rebecca; Perlmutter, Patrick; Smith, A Ian; Aguilar, Marie-Isabel

    2002-09-03

    The enzyme EC 3.4.24.15 (EP 24.15) is a zinc metalloendopeptidase whose precise function in vivo remains unknown but is thought to participate in the regulated metabolism of a number of specific neuropeptides. The lack of stable and selective inhibitors has hindered the determination of the exact function of EP 24.15. Of the limited number of EP 24.15 inhibitors that have been developed, N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (CFP) is the most widely studied. CFP is a potent and specific inhibitor, but it is unstable in vivo due to cleavage between the alanine and tyrosine residues by the enzyme neprilysin (EP 24.11). This cleavage by EP 24.11 generates a potent inhibitor of angiotensin converting enzyme, thereby limiting the use of CFP for in vivo studies. To develop specific inhibitors of EP 24.15 that are resistant to in vitro and potentially in vivo proteolysis by EP 24.11, this study incorporated beta-amino acids replacing the Ala-Tyr scissile alpha-amino acids of CFP. Both C2 and C3 substituted beta-amino acids were synthesized and substituted at the EP 24.11 scissile Ala-Tyr bond. Significant EP 24.15 inhibitory activity was observed with some of the beta-amino acid containing analogues. Moreover, binding to EP 24.11 was eliminated, thus rendering all analogues containing beta-amino acids resistant to degradation by EP 24.11. Selective inhibition of either EP 24.15 or EP 24.16 was also observed with some analogues. The results demonstrated the use of beta-amino acids in the design of inhibitors of EP 24.15 and EP 24.16 with K(i)'s in the low micromolar range. At the same time, these analogues were resistant to cleavage by the related metalloendopeptidase EP 24.11, in contrast to the alpha-amino acid based parent peptide. This study has therefore clearly shown the potential of beta-amino acids in the design of stable enzyme inhibitors and their use in generating molecules with selectivity between closely related enzymes.

  3. Mantle Convection Models Constrained by Seismic Tomography

    NASA Astrophysics Data System (ADS)

    Durbin, C. J.; Shahnas, M.; Peltier, W. R.; Woodhouse, J. H.

    2011-12-01

    Perovskite-post-Perovskite transition (Murakami et al., 2004, Science) that appears to define the D" layer at the base of the mantle. In this initial phase of what will be a longer term project we are assuming that the internal mantle viscosity structure is spherically symmetric and compatible with the recent inferences of Peltier and Drummond (2010, Geophys. Res. Lett.) based upon glacial isostatic adjustment and Earth rotation constraints. The internal density structure inferred from the tomography model is assimilated into the convection model by continuously "nudging" the modification to the input density structure predicted by the convection model back towards the tomographic constraint at the long wavelengths that the tomography specifically resolves, leaving the shorter wavelength structure free to evolve, essentially "slaved" to the large scale structure. We focus upon the ability of the nudged model to explain observed plate velocities, including both their poloidal (divergence related) and toroidal (strike slip fault related) components. The true plate velocity field is then used as an additional field towards which the tomographically constrained solution is nudged.

  4. Constrained transcription factor spacing is prevalent and important for transcriptional control of mouse blood cells.

    PubMed

    Ng, Felicia S L; Schütte, Judith; Ruau, David; Diamanti, Evangelia; Hannah, Rebecca; Kinston, Sarah J; Göttgens, Berthold

    2014-12-16

    Combinatorial transcription factor (TF) binding is essential for cell-type-specific gene regulation. However, much remains to be learned about the mechanisms of TF interactions, including to what extent constrained spacing and orientation of interacting TFs are critical for regulatory element activity. To examine the relative prevalence of the 'enhanceosome' versus the 'TF collective' model of combinatorial TF binding, a comprehensive analysis of TF binding site sequences in large scale datasets is necessary. We developed a motif-pair discovery pipeline to identify motif co-occurrences with preferential distance(s) between motifs in TF-bound regions. Utilizing a compendium of 289 mouse haematopoietic TF ChIP-seq datasets, we demonstrate that haematopoietic-related motif-pairs commonly occur with highly conserved constrained spacing and orientation between motifs. Furthermore, motif clustering revealed specific associations for both heterotypic and homotypic motif-pairs with particular haematopoietic cell types. We also showed that disrupting the spacing between motif-pairs significantly affects transcriptional activity in a well-known motif-pair-E-box and GATA, and in two previously unknown motif-pairs with constrained spacing-Ets and Homeobox as well as Ets and E-box. In this study, we provide evidence for widespread sequence-specific TF pair interaction with DNA that conforms to the 'enhanceosome' model, and furthermore identify associations between specific haematopoietic cell-types and motif-pairs. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Is oil consumption constrained by industrial structure? Evidence from China

    NASA Astrophysics Data System (ADS)

    Jia, Y. Q.; Duan, H. M.

    2017-08-01

    This paper examines whether oil consumption is constrained by output value, applying a cointegration test and an ECM to the primary, secondary, and tertiary sectors in China during 1985-2013. The empirical results indicate that oil consumption in China is constrained by the industrial structure both in the short run and in the long run. Regardless of the time horizon considered, the oil consumption constraint is the lowest for the primary sector as well as the highest for the tertiary sector. This is because the long-term industrial structure formation and the technological level of each sector underlines the existence of long run equilibrium and short run fluctuations of output value and oil consumption, with the latter being constrained by adjustments in industrial structure. In order to decrease the constraining effect of output value on oil consumption, the government should take some measures to improve the utilization rate, reducing the intensity of oil consumption, and secure the supply of oil.

  6. A Constrained Spline Estimator of a Hazard Function.

    ERIC Educational Resources Information Center

    Bloxom, Bruce

    1985-01-01

    A constrained quadratic spline is proposed as an estimator of the hazard function of a random variable. A maximum penalized likelihood procedure is used to fit the estimator to a sample of psychological response times. (Author/LMO)

  7. Vibration control through passive constrained layer damping and active control

    NASA Astrophysics Data System (ADS)

    Lam, Margaretha J.; Inman, Daniel J.; Saunders, William R.

    1997-05-01

    To add damping to systems, viscoelastic materials (VEM) are added to structures. In order to enhance the damping effects of the VEM, a constraining layer is attached. When this constraining layer is an active element, the treatment is called active constrained layer damping (ACLD). Recently, the investigation of ACLD treatments has shown it to be an effective method of vibration suppression. In this paper, the treatment of a beam with a separate active element and passive constrained layer (PCLD) element is investigated. A Ritz- Galerkin approach is used to obtain discretized equations of motion. The damping is modeled using the GHM method and the system is analyzed in the time domain. By optimizing on the performance and control effort for both the active and passive case, it is shown that this treatment is capable of lower control effort with more inherent damping, and is therefore a better approach to damp vibration.

  8. Thin-shell wormholes constrained by cosmological observations

    NASA Astrophysics Data System (ADS)

    Wang, Deng; Meng, Xin-He

    2017-09-01

    We investigate the thin-shell wormholes constrained by cosmological observations for the first time in the literature. Without loss of generality, we study the thin-shell wormholes in ωCDM model and analyze their stability under perturbations preserving the symmetry. Firstly, we constrain the ωCDM model using a combination of Union 2.1 SNe Ia data, the latest H(z) data and CMB data. Secondly, we use the constrained dark energy equation of state (EoS) ω which lies in [ - 1 . 05 , - 0 . 89 ] to investigate thin-shell wormholes generated by various black hole spacetimes. We find that the stable Schwarzschild and Reinssner-Nordström thin-shell wormholes constrained by cosmological observations do not exist. In addition, the method we developed can be applied in exploring the stable thin-shell wormholes from any black hole spacetime in the framework of any cosmological theory.

  9. FXR agonist activity of conformationally constrained analogs of GW 4064

    SciTech Connect

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Navas, III, Frank; Parks, Derek J.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce

    2010-09-27

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  10. Constrained Adaptive Beamforming for Improved Contrast in Breast Ultrasound

    DTIC Science & Technology

    2006-06-01

    have led us to utilize a recently proposed method, Spatial Processing Optimized and Constrained ( SPOC ). In initial simulations this method not only...6 Summary of First Year Progress……………………………………6 Conventional Beamformer Optimization………….…………….….7 SPOC Progress...and hundreds of papers published in this area, only the SPOC (Spatial Processing Optimized and Constrained) algorithm could be readily modified to meet

  11. Constrained Adaptive Beamforming for Improved Contrast in Breast Ultrasound

    DTIC Science & Technology

    2008-06-01

    us to modify the Spatial Processing Optimized and Constrained algorithm ( SPOC ) to yield the Time-Domain Optimized Near-field Estimator (TONE). In...beamformers - Improvement and evaluation of adaptive imaging algorithms based loosely on SPOC - Invention and testing of the basic TONE algorithm...named the Time-domain Optimized Near-Filed Estimator, or TONE. The novel ABF was developed from Spatial Processing: Optimized and Constrained ( SPOC

  12. Constrained Fisher Scoring for a Mixture of Factor Analyzers

    DTIC Science & Technology

    2016-09-01

    ARL-TR-7836• SEP 2016 US Army Research Laboratory Constrained Fisher Scoring for a Mixture of Factor Analyzers by Gene T Whipps, Emre Ertin, and...TR-7836• SEP 2016 US Army Research Laboratory Constrained Fisher Scoring for a Mixture of Factor Analyzers by Gene T Whipps Sensors and Electron... Research Laboratory Sensors and Electron Devices Directorate ATTN: RDRL-SES-A Adelphi, MD 20783 primary author’s email: <gene.t.whipps.civ@mail.mil>. This

  13. Constrained minimization of smooth functions using a genetic algorithm

    NASA Technical Reports Server (NTRS)

    Moerder, Daniel D.; Pamadi, Bandu N.

    1994-01-01

    The use of genetic algorithms for minimization of differentiable functions that are subject to differentiable constraints is considered. A technique is demonstrated for converting the solution of the necessary conditions for a constrained minimum into an unconstrained function minimization. This technique is extended as a global constrained optimization algorithm. The theory is applied to calculating minimum-fuel ascent control settings for an energy state model of an aerospace plane.

  14. Geometric constrained variational calculus. II: The second variation (Part I)

    NASA Astrophysics Data System (ADS)

    Massa, Enrico; Bruno, Danilo; Luria, Gianvittorio; Pagani, Enrico

    2016-10-01

    Within the geometrical framework developed in [Geometric constrained variational calculus. I: Piecewise smooth extremals, Int. J. Geom. Methods Mod. Phys. 12 (2015) 1550061], the problem of minimality for constrained calculus of variations is analyzed among the class of differentiable curves. A fully covariant representation of the second variation of the action functional, based on a suitable gauge transformation of the Lagrangian, is explicitly worked out. Both necessary and sufficient conditions for minimality are proved, and reinterpreted in terms of Jacobi fields.

  15. Constraining compartmental models using multiple voltage recordings and genetic algorithms.

    PubMed

    Keren, Naomi; Peled, Noam; Korngreen, Alon

    2005-12-01

    Compartmental models with many nonlinearly and nonhomogeneous distributions of voltage-gated conductances are routinely used to investigate the physiology of complex neurons. However, the number of loosely constrained parameters makes manually constructing the desired model a daunting if not impossible task. Recently, progress has been made using automated parameter search methods, such as genetic algorithms (GAs). However, these methods have been applied to somatically recorded action potentials using relatively simple target functions. Using a genetic minimization algorithm and a reduced compartmental model based on a previously published model of layer 5 neocortical pyramidal neurons we compared the efficacy of five cost functions (based on the waveform of the membrane potential, the interspike interval, trajectory density, and their combinations) to constrain the model. When the model was constrained using somatic recordings only, a combined cost function was found to be the most effective. This combined cost function was then applied to investigate the contribution of dendritic and axonal recordings to the ability of the GA to constrain the model. The more recording locations from the dendrite and the axon that were added to the data set the better was the genetic minimization algorithm able to constrain the compartmental model. Based on these simulations we propose an experimental scheme that, in combination with a genetic minimization algorithm, may be used to constrain compartmental models of neurons.

  16. Glycotargeting: the preparation of glyco-amino acids and derivatives from unprotected reducing sugars.

    PubMed

    Monsigny, M; Quétard, C; Bourgerie, S; Delay, D; Pichon, C; Midoux, P; Mayer, R; Roche, A C

    1998-02-01

    Lectins are present on the surface of many cells. Many lectins actively recycle from membrane to endosomes and efficiently take up glycoconjugates in a sugar-dependent manner. On this basis, glycoconjugates, specially those obtained by chemical means, are good candidates as carriers of drugs, oligonucleotides or genes. In this paper, we present a panel of methods suitable to transform unprotected reducing oligosaccharides into glycosynthons designed to be easily linked to therapeutic agents. All the glycosynthons presented here are glycosylamines or derivatives, mainly glyco-amino acids or glycopeptides. Glycosylamines are easy to obtain, but they are very labile in slightly acidic or neutral medium; they must be stabilized, by acylation for instance. The coupling efficiency of a reducing sugar with ammonia as well as an alkylamine or an arylamine is higher at high temperature, however, because of the Amadori rearrangement, special conditions have to be selected to prepare the expected glycosylamine derivative with a high yield. Glycosylamines are easily acylated by N-protected amino acids, or by halogeno acids which can then be transformed into amino acids. Alternatively, unprotected reducing oligosaccharides may very efficiently be transformed into N-glycosyl-amino acids and then protected by N-acylation. With a glutamyl derivative having both the alpha-amino and the gamma-carboxylic groups free, the coupling and the acylation, which is intramolecular, are roughly quantitative. N-oligosaccharyl-amino acid derivatives are interesting glycosynthons, because their sugar moiety bears the specificity towards membrane lectins while the amino acid part has the capacity to easily substitute a therapeutic agent.

  17. Studies on renal adaptation to altered dietary amino acid intake: tissue taurine responses in nursing and adult rats.

    PubMed

    Chesney, R W; Lippincott, S; Gusowski, N; Padilla, M; Zelikovic, I

    1986-10-01

    This study examines the effect of a low sulfur amino acid diet (LTD) and a high taurine diet (HTD), compared with a normal diet, on the plasma, urine, muscle, brain and renal cortex levels of taurine in immature and adult rats. Milk taurine from lactating dams reflected the taurine content of the diet, being low in LTD-fed and high in HTD-fed animals. Nursing pups (7, 14 and 21 d old) often had plasma, urine and tissue--renal cortex, heart, skeletal muscle--levels of taurine related to dietary exposure, a situation also found in adult animals. These diets did not influence the urinary excretion of the sulfur-containing alpha-amino acids methionine and cystine but a sulfur aminoaciduria of immaturity was evident. By contrast, the content of taurine in brain was constant regardless of dietary intake of sulfur amino acids. An age-related decline in brain taurine content was found--as noted by others--but this too was influenced by diet. This dual finding of brain taurine constancy despite wide differences in sulfur amino acid intake and changes in the renal handling of taurine as influenced by diet suggest that the renal adaptive response serves to maintain the stability of brain taurine content.

  18. SNAT2 amino acid transporter is regulated by amino acids of the SLC6 gamma-aminobutyric acid transporter subfamily in neocortical neurons and may play no role in delivering glutamine for glutamatergic transmission.

    PubMed

    Grewal, Sukhjeevan; Defamie, Norah; Zhang, Xiong; De Gois, Stéphanie; Shawki, Ali; Mackenzie, Bryan; Chen, Chu; Varoqui, Hélène; Erickson, Jeffrey D

    2009-04-24

    System A transporters SNAT1 and SNAT2 mediate uptake of neutral alpha-amino acids (e.g. glutamine, alanine, and proline) and are expressed in central neurons. We tested the hypothesis that SNAT2 is required to support neurotransmitter glutamate synthesis by examining spontaneous excitatory activity after inducing or repressing SNAT2 expression for prolonged periods. We stimulated de novo synthesis of SNAT2 mRNA and increased SNAT2 mRNA stability and total SNAT2 protein and functional activity, whereas SNAT1 expression was unaffected. Increased endogenous SNAT2 expression did not affect spontaneous excitatory action-potential frequency over control. Long term glutamine exposure strongly repressed SNAT2 expression but increased excitatory action-potential frequency. Quantal size was not altered following SNAT2 induction or repression. These results suggest that spontaneous glutamatergic transmission in pyramidal neurons does not rely on SNAT2. To our surprise, repression of SNAT2 activity was not limited to System A substrates. Taurine, gamma-aminobutyric acid, and beta-alanine (substrates of the SLC6 gamma-aminobutyric acid transporter family) repressed SNAT2 expression more potently (10x) than did System A substrates; however, the responses to System A substrates were more rapid. Since ATF4 (activating transcription factor 4) and CCAAT/enhancer-binding protein are known to bind to an amino acid response element within the SNAT2 promoter and mediate induction of SNAT2 in peripheral cell lines, we tested whether either factor was similarly induced by amino acid deprivation in neurons. We found that glutamine and taurine repressed the induction of both transcription factors. Our data revealed that SNAT2 expression is constitutively low in neurons under physiological conditions but potently induced, together with the taurine transporter TauT, in response to depletion of neutral amino acids.

  19. Soil phosphorus constrains biodiversity across European grasslands.

    PubMed

    Ceulemans, Tobias; Stevens, Carly J; Duchateau, Luc; Jacquemyn, Hans; Gowing, David J G; Merckx, Roel; Wallace, Hilary; van Rooijen, Nils; Goethem, Thomas; Bobbink, Roland; Dorland, Edu; Gaudnik, Cassandre; Alard, Didier; Corcket, Emmanuel; Muller, Serge; Dise, Nancy B; Dupré, Cecilia; Diekmann, Martin; Honnay, Olivier

    2014-12-01

    Nutrient pollution presents a serious threat to biodiversity conservation. In terrestrial ecosystems, the deleterious effects of nitrogen pollution are increasingly understood and several mitigating environmental policies have been developed. Compared to nitrogen, the effects of increased phosphorus have received far less attention, although some studies have indicated that phosphorus pollution may be detrimental for biodiversity as well. On the basis of a dataset covering 501 grassland plots throughout Europe, we demonstrate that, independent of the level of atmospheric nitrogen deposition and soil acidity, plant species richness was consistently negatively related to soil phosphorus. We also identified thresholds in soil phosphorus above which biodiversity appears to remain at a constant low level. Our results indicate that nutrient management policies biased toward reducing nitrogen pollution will fail to preserve biodiversity. As soil phosphorus is known to be extremely persistent and we found no evidence for a critical threshold below which no environmental harm is expected, we suggest that agro-environmental schemes should include grasslands that are permanently free from phosphorus fertilization. © 2014 John Wiley & Sons Ltd.

  20. Reduced amino acid transport in skeletal muscle caused by a circulating factor during endotoxemia.

    PubMed Central

    Warner, B W; Hasselgren, P O; James, J H; Hummel, R P; Rigel, D F; Fischer, J E

    1990-01-01

    The present study was designed to determine whether reduced amino acid uptake in skeletal muscle during endotoxemia is due to associated hypotension or is caused by a factor present in plasma. Three series of experiments were performed. In the first series of experiments, mean arterial pressure (MAP), heart rate, and amino acid uptake in incubated soleus muscles were measured after intravenous injection of endotoxin (1 mg/kg) in male Sprague-Dawley rats (40 to 60 g). Amino acid transport was measured by determining intracellular uptake of [3H]-alpha-amino-isobutyric acid (AIB) during 2 hours of incubation. In the second series of experiments, hypotension was induced by bleeding and muscle amino acid uptake was measured. In the third series of experiments, whole plasma or a low molecular weight fraction (less than 10,000 d) of plasma from endotoxin-injected rats was added in vitro to incubated muscles and amino acid uptake was determined. One hour after injection of endotoxin, MAP was reduced from 80 +/- 2 mmHg to 54 +/- 4 mmHg (p less than 0.05). AIB uptake was reduced by 20% (p less than 0.05) 2 hours after endotoxin injection. When MAP was maintained at 50 mmHg for 1 hour by bleeding, no changes in muscle AIB uptake were noted. When plasma obtained from rats 2 hours after endotoxin injection was added to incubated soleus muscles, AIB uptake was reduced by 22%. This effect was duplicated by a fraction of endotoxic plasma containing substances with a molecular weight less than 10,000 d. The present results suggest that reduced muscle amino acid uptake during endotoxemia is not due to associated hypotension, but may be caused by a circulating factor(s) with a molecular weight less than 10,000 d. PMID:2178567

  1. Constraining condensed-phase formation kinetics of secondary organic aerosol components from isoprene epoxydiols

    NASA Astrophysics Data System (ADS)

    Riedel, T. P.; Lin, Y.-H.; Zhang, Z.; Chu, K.; Thornton, J. A.; Vizuete, W.; Gold, A.; Surratt, J. D.

    2016-02-01

    Isomeric epoxydiols from isoprene photooxidation (IEPOX) have been shown to produce substantial amounts of secondary organic aerosol (SOA) mass and are therefore considered a major isoprene-derived SOA precursor. Heterogeneous reactions of IEPOX on atmospheric aerosols form various aerosol-phase components or "tracers" that contribute to the SOA mass burden. A limited number of the reaction rate constants for these acid-catalyzed aqueous-phase tracer formation reactions have been constrained through bulk laboratory measurements. We have designed a chemical box model with multiple experimental constraints to explicitly simulate gas- and aqueous-phase reactions during chamber experiments of SOA growth from IEPOX uptake onto acidic sulfate aerosol. The model is constrained by measurements of the IEPOX reactive uptake coefficient, IEPOX and aerosol chamber wall losses, chamber-measured aerosol mass and surface area concentrations, aerosol thermodynamic model calculations, and offline filter-based measurements of SOA tracers. By requiring the model output to match the SOA growth and offline filter measurements collected during the chamber experiments, we derive estimates of the tracer formation reaction rate constants that have not yet been measured or estimated for bulk solutions.

  2. SENSE Phase-Constrained Magnitude Reconstruction With Iterative Phase Refinement

    PubMed Central

    Lew, Calvin; Pineda, Angel R.; Clayton, David; Spielman, Dan; Chan, Frandics; Bammer, Roland

    2012-01-01

    Conventional sensitivity encoding (SENSE) reconstruction is based on equations in the complex domain. However, for many MRI applications only the magnitude is relevant. If there exists an estimate of the underlying phase information, a magnitude-only phase-constrained reconstruction can help to improve the conditioning of the SENSE reconstruction problem. Consequently, this reduces g-factor-related noise enhancement. In previous attempts at phase-constrained SENSE reconstruction, image quality was hampered by strong aliasing artifacts resulting from inadequate phase estimates and high sensitivity to phase errors. If a full-resolution phase image is used, a significant reduction in aliasing errors and better noise properties compared to SENSE can be obtained. An iterative scheme that improves the phase estimate to better approximate the phase is presented. The mathematical framework of the new approach is provided together with comparisons of conventional SENSE, phase-constrained SENSE, and the new phase-refinement method. Both theory and experimental verification demonstrate significantly better noise performance at high reduction factors, i.e., close to the theoretical limit. For applications that need only magnitude data, an iterative phase-constrained SENSE reconstruction can provide substantial SNR improvement over SENSE reconstruction and less artifacts than phase-constrained SENSE. PMID:17969127

  3. Constrained Source Space MR Spectroscopy: Multiple Voxels, No Gradient Readout.

    PubMed

    Landheer, K; Sahgal, A; Das, S; Graham, S J

    2015-08-01

    Our goal was to develop a novel technique for measuring a small number of localized spectra simultaneously and in a time-efficient manner. Using appropriate radiofrequency pulses, the magnetization from multiple voxels is excited simultaneously and then separated (reconstructed) by using the individual coil-sensitivity profiles from a multichannel receiver coil. Because no gradients are used for k-space encoding, constrained source space MR spectroscopy provides a time advantage over conventional spectroscopic imaging and an improved signal-to-noise ratio per square root of unit time over single-voxel spectroscopy applied at each successive location. In the present work, we considered prototype application of constrained source space MR spectroscopy for 2 voxels. Experimental data from healthy volunteers and simulation results showed that constrained source space MR spectroscopy is effective at extracting 2 independent spectra even in the challenging scenario of the voxels being closely spaced. Also, from 6 patients with various types of brain cancer we obtained 2-voxel constrained source space MR spectroscopy data, which showed spectra of clinical quality in half the time required to perform successive single-voxel MR spectroscopy. Constrained source space MR spectroscopy provides clinical quality spectra and could be used to probe multiple voxels simultaneously in combination with Hadamard encoding for further scan-time reductions. © 2015 by American Journal of Neuroradiology.

  4. The 1.9 A Structure of the Branched-Chain Amino-Acid Transaminase (IlvE) from Mycobacterium tuberculosis

    SciTech Connect

    Tremblay, L.; Blanchard, J

    2009-01-01

    Unlike mammals, bacteria encode enzymes that synthesize branched-chain amino acids. The pyridoxal 5'-phosphate-dependent transaminase performs the final biosynthetic step in these pathways, converting keto acid precursors into {alpha}-amino acids. The branched-chain amino-acid transaminase from Mycobacterium tuberculosis (MtIlvE) has been crystallized and its structure has been solved at 1.9 {angstrom} resolution. The MtIlvE monomer is composed of two domains that interact to form the active site. The biologically active form of IlvE is a homodimer in which each monomer contributes a substrate-specificity loop to the partner molecule. Additional substrate selectivity may be imparted by a conserved N-terminal Phe30 residue, which has previously been observed to shield the active site in the type IV fold homodimer. The active site of MtIlvE contains density corresponding to bound PMP, which is likely to be a consequence of the presence of tryptone in the crystallization medium. Additionally, two cysteine residues are positioned at the dimer interface for disulfide-bond formation under oxidative conditions. It is unknown whether they are involved in any regulatory activities analogous to those of the human mitochondrial branched-chain amino-acid transaminase.

  5. Constraining Effects of Brine Leakage from Carbon Sequestration Sites

    NASA Astrophysics Data System (ADS)

    Wunsch, A.; Navarre-Sitchler, A. K.; McCray, J. E.

    2011-12-01

    Research has shown that pressure build up associated with injection of CO2 into a deep saline aquifer has the potential to promote brine leakage into overlying formations. In order to understand and quantify chemical changes in an underground source of drinking water (USDW) invaded by deep saline brines, we analyzed over 90,000 brine geochemical data entries from the NETL NATCARB brine database to identify potential brine constituents of concern. Using a variety of statistical methods and EPA regulatory levels or standards (RLS) we narrowed the list of brine constituents of potential concern to USDWs to TDS, thallium, chloride, sulfate and arsenic. Somewhat surprisingly, the distribution of reported pH had a fairly narrow distribution around a median value of 7.4, with over 78% of values complying with EPA recommended secondary standard for drinking water acidity. The pH distribution implies that unlike pure CO2 leakage, far-field brine leakage (i.e., brine not in contact with CO2) is not expected to bear a low-pH signature, thus suggesting use of other means of geochemical monitoring for brine leakage, such as electrical conductivity. Geochemical mixing models of brine and dilute water were used to constrain mixing ratios where RLS values are exceeded for the TDS, thallium and chloride. TDS and chloride exceed the EPA secondary standards at a brine/USDW mixing ratio of 0.012 and 0.459, respectively. The thallium maximum contaminant level (MCL) is exceeded at a brine/USDW mixing ratio of 0.3753, smaller than the chloride mixing ratio. However, sorption and/or desorption processes may alter thallium concentrations along a leakage pathway resulting in lower concentrations in the aquifer than predicted by simple mixing models. While leakage into USDWs has received considerable attention, brine contamination of groundwater used for irrigation of agricultural crops is also an important area of research. Our calculations suggest that almost all crops grown in the United

  6. Using extracellular action potential recordings to constrain compartmental models.

    PubMed

    Gold, Carl; Henze, Darrell A; Koch, Christof

    2007-08-01

    We investigate the use of extracellular action potential (EAP) recordings for biophysically faithful compartmental models. We ask whether constraining a model to fit the EAP is superior to matching the intracellular action potential (IAP). In agreement with previous studies, we find that the IAP method under-constrains the parameters. As a result, significantly different sets of parameters can have virtually identical IAP's. In contrast, the EAP method results in a much tighter constraint. We find that the distinguishing characteristics of the waveform--but not its amplitude-resulting from the distribution of active conductances are fairly invariant to changes of electrode position and detailed cellular morphology. Based on these results, we conclude that EAP recordings are an excellent source of data for the purpose of constraining compartmental models.

  7. Undulatory buckling of a rod constrained by an elastic matrix

    NASA Astrophysics Data System (ADS)

    Liu, Jia; Su, Tianxiang; Lopez-Pamies, Oscar; Reis, Pedro; Bertoldi, Katia

    2012-02-01

    Elastic instabilities of rods constrained by an elastic matrix and subjected to axial compression have long been recognized as essential for structural applications in the context of failure mitigation and, more recently, towards exploitation of functionality. Relevant fields for this class of problems include drilling, biomedical instrumentation and root growth in plants. We explore the two possible scenarios observed when, above a threshold load, compression is applied to a rod constrained by a matrix: i) the rod can develop a planar oscillatory solution (sinusoidal buckling) or ii) it can take the configuration of a helix (helical buckling). We identify the principal parameters of this system, perform a systematic parametric study and rationalize the phase diagram through a hybrid of theoretical and numerical analyses. Particular attention is devoted to the effect of the mechanical properties of the constraining matrix which is found to have a critical influence on this buckling scenario.

  8. Residual flexibility test method for verification of constrained structural models

    NASA Technical Reports Server (NTRS)

    Admire, John R.; Tinker, Michael L.; Ivey, Edward W.

    1994-01-01

    A method is described for deriving constrained modes and frequencies from a reduced model based on a subset of the free-free modes plus the residual effects of neglected modes. The method involves a simple modification of the MacNeal and Rubin component mode representation to allow development of a verified constrained (fixed-base) structural model. Results for two spaceflight structures having translational boundary degrees of freedom show quick convergence of constrained modes using a measureable number of free-free modes plus the boundary partition of the residual flexibility matrix. This paper presents the free-free residual flexibility approach as an alternative test/analysis method when fixed-base testing proves impractical.

  9. Value, Cost, and Sharing: Open Issues in Constrained Clustering

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.

    2006-01-01

    Clustering is an important tool for data mining, since it can identify major patterns or trends without any supervision (labeled data). Over the past five years, semi-supervised (constrained) clustering methods have become very popular. These methods began with incorporating pairwise constraints and have developed into more general methods that can learn appropriate distance metrics. However, several important open questions have arisen about which constraints are most useful, how they can be actively acquired, and when and how they should be propagated to neighboring points. This position paper describes these open questions and suggests future directions for constrained clustering research.

  10. Augmented Lagrangian method for constrained nuclear density functional theory

    NASA Astrophysics Data System (ADS)

    Staszczak, A.; Stoitsov, M.; Baran, A.; Nazarewicz, W.

    2010-10-01

    The augmented Lagrangiam method (ALM), widely used in quantum chemistry constrained optimization problems, is applied in the context of the nuclear Density Functional Theory (DFT) in the self-consistent constrained Skyrme Hartree-Fock-Bogoliubov (CHFB) variant. The ALM allows precise calculations of multi-dimensional energy surfaces in the space of collective coordinates that are needed to, e.g., determine fission pathways and saddle points; it improves the accuracy of computed derivatives with respect to collective variables that are used to determine collective inertia; and is well adapted to supercomputer applications.

  11. Constraining dark energy with Sunyaev-Zel'dovich cluster surveys.

    PubMed

    Weller, Jochen; Battye, Richard A; Kneissl, Rüdiger

    2002-06-10

    We discuss the prospects of constraining the properties of a dark energy component, with particular reference to a time varying equation of state, using future cluster surveys selected by their Sunyaev-Zel'dovich effect. We compute the number of clusters expected for a given set of cosmological parameters and propogate the errors expected from a variety of surveys. In the short term they will constrain dark energy in conjunction with future observations of type Ia supernovae, but may in time do so in their own right.

  12. Value, Cost, and Sharing: Open Issues in Constrained Clustering

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.

    2006-01-01

    Clustering is an important tool for data mining, since it can identify major patterns or trends without any supervision (labeled data). Over the past five years, semi-supervised (constrained) clustering methods have become very popular. These methods began with incorporating pairwise constraints and have developed into more general methods that can learn appropriate distance metrics. However, several important open questions have arisen about which constraints are most useful, how they can be actively acquired, and when and how they should be propagated to neighboring points. This position paper describes these open questions and suggests future directions for constrained clustering research.

  13. Augmented Lagrangian Method for Constrained Nuclear Density Functiional Theory

    SciTech Connect

    Staszczak, A.; Stoitsov, Mario; Baran, Andrzej K; Nazarewicz, Witold

    2010-01-01

    The augmented Lagrangian method (ALM), widely used in quantum chemistry constrained optimization problems, is applied in the context of the nuclear Density Functional Theory (DFT) in the self-consistent constrained Skyrme Hartree-Fock-Bogoliubov (CHFB) variant. The ALM allows precise calculations of multidimensional energy surfaces in the space of collective coordinates that are needed to, e.g., determine fission pathways and saddle points; it improves accuracy of computed derivatives with respect to collective variables that are used to determine collective inertia and is well adapted to supercomputer applications.

  14. Constraining the scalar septet model through vector boson scattering

    NASA Astrophysics Data System (ADS)

    Harris, Mary-Jean; Logan, Heather E.

    2017-05-01

    The scalar septet model extends the standard model Higgs sector by an isospin septet with hypercharge chosen to preserve ρ ≡MW2/MZ2cos2θW=1 . In this paper we constrain the model at high septet masses using perturbative unitarity of longitudinal vector boson scattering amplitudes. We also apply the constraints from LHC searches for doubly-charged Higgs bosons produced in vector boson fusion, which constrain the model at lower septet masses. We point out some important differences between the septet model and extended Higgs models that preserve custodial symmetry in the scalar spectrum.

  15. A Novel Approach to Constraining Uncertain Stellar Evolution Models

    NASA Astrophysics Data System (ADS)

    Rosenfield, Philip; Girardi, Leo; Dalcanton, Julianne; Johnson, L. C.; Williams, Benjamin F.; Weisz, Daniel R.; Bressan, Alessandro; Fouesneau, Morgan

    2017-01-01

    Stellar evolution models are fundamental to nearly all studies in astrophysics. They are used to interpret spectral energy distributions of distant galaxies, to derive the star formation histories of nearby galaxies, and to understand fundamental parameters of exoplanets. Despite the success in using stellar evolution models, some important aspects of stellar evolution remain poorly constrained and their uncertainties rarely addressed. We present results using archival Hubble Space Telescope observations of 10 stellar clusters in the Magellanic Clouds to simultaneously constrain the values and uncertainties of the strength of core convective overshooting, metallicity, interstellar extinction, cluster distance, binary fraction, and age.

  16. A constrained EM algorithm for independent component analysis.

    PubMed

    Welling, M; Weber, M

    2001-03-01

    We introduce a novel way of performing independent component analysis using a constrained version of the expectation-maximization (EM) algorithm. The source distributions are modeled as D one-dimensional mixtures of gaussians. The observed data are modeled as linear mixtures of the sources with additive, isotropic noise. This generative model is fit to the data using constrained EM. The simpler "soft-switching" approach is introduced, which uses only one parameter to decide on the sub- or supergaussian nature of the sources. We explain how our approach relates to independent factor analysis.

  17. Constrained optimization for image restoration using nonlinear programming

    NASA Technical Reports Server (NTRS)

    Yeh, C.-L.; Chin, R. T.

    1985-01-01

    The constrained optimization problem for image restoration, utilizing incomplete information and partial constraints, is formulated using nonlinear proramming techniques. This method restores a distorted image by optimizing a chosen object function subject to available constraints. The penalty function method of nonlinear programming is used. Both linear or nonlinear object function, and linear or nonlinear constraint functions can be incorporated in the formulation. This formulation provides a generalized approach to solve constrained optimization problems for image restoration. Experiments using this scheme have been performed. The results are compared with those obtained from other restoration methods and the comparative study is presented.

  18. Constrained modes in control theory - Transmission zeros of uniform beams

    NASA Technical Reports Server (NTRS)

    Williams, T.

    1992-01-01

    Mathematical arguments are presented demonstrating that the well-established control system concept of the transmission zero is very closely related to the structural concept of the constrained mode. It is shown that the transmission zeros of a flexible structure form a set of constrained natural frequencies for it, with the constraints depending explicitly on the locations and the types of sensors and actuators used for control. Based on this formulation, an algorithm is derived and used to produce dimensionless plots of the zero of a uniform beam with a compatible sensor/actuator pair.

  19. A filter-based evolutionary algorithm for constrained optimization.

    SciTech Connect

    Clevenger, Lauren M.; Hart, William Eugene; Ferguson, Lauren Ann

    2004-02-01

    We introduce a filter-based evolutionary algorithm (FEA) for constrained optimization. The filter used by an FEA explicitly imposes the concept of dominance on a partially ordered solution set. We show that the algorithm is provably robust for both linear and nonlinear problems and constraints. FEAs use a finite pattern of mutation offsets, and our analysis is closely related to recent convergence results for pattern search methods. We discuss how properties of this pattern impact the ability of an FEA to converge to a constrained local optimum.

  20. Constrained optimization for image restoration using nonlinear programming

    NASA Technical Reports Server (NTRS)

    Yeh, C.-L.; Chin, R. T.

    1985-01-01

    The constrained optimization problem for image restoration, utilizing incomplete information and partial constraints, is formulated using nonlinear proramming techniques. This method restores a distorted image by optimizing a chosen object function subject to available constraints. The penalty function method of nonlinear programming is used. Both linear or nonlinear object function, and linear or nonlinear constraint functions can be incorporated in the formulation. This formulation provides a generalized approach to solve constrained optimization problems for image restoration. Experiments using this scheme have been performed. The results are compared with those obtained from other restoration methods and the comparative study is presented.

  1. A lexicographic approach to constrained MDP admission control

    NASA Astrophysics Data System (ADS)

    Panfili, Martina; Pietrabissa, Antonio; Oddi, Guido; Suraci, Vincenzo

    2016-02-01

    This paper proposes a reinforcement learning-based lexicographic approach to the call admission control problem in communication networks. The admission control problem is modelled as a multi-constrained Markov decision process. To overcome the problems of the standard approaches to the solution of constrained Markov decision processes, based on the linear programming formulation or on a Lagrangian approach, a multi-constraint lexicographic approach is defined, and an online implementation based on reinforcement learning techniques is proposed. Simulations validate the proposed approach.

  2. Fast Energy Minimization of large Polymers Using Constrained Optimization

    SciTech Connect

    Todd D. Plantenga

    1998-10-01

    A new computational technique is described that uses distance constraints to calculate empirical potential energy minima of partially rigid molecules. A constrained minimuzation algorithm that works entirely in Cartesian coordinates is used. The algorithm does not obey the constraints until convergence, a feature that reduces ill-conditioning and allows constrained local minima to be computed more quickly than unconstrained minima. Computational speedup exceeds the 3-fold factor commonly obtained in constained molecular dynamics simulations, where the constraints must be strictly obeyed at all times.

  3. Hypochlorous acid-mediated protein oxidation: how important are chloramine transfer reactions and protein tertiary structure?

    PubMed

    Pattison, David I; Hawkins, Clare L; Davies, Michael J

    2007-08-28

    Hypochlorous acid (HOCl) is a powerful oxidant generated from H2O2 and Cl- by the heme enzyme myeloperoxidase, which is released from activated leukocytes. HOCl possesses potent antibacterial properties, but excessive production can lead to host tissue damage that occurs in numerous human pathologies. As proteins and amino acids are highly abundant in vivo and react rapidly with HOCl, they are likely to be major targets for HOCl. In this study, two small globular proteins, lysozyme and insulin, have been oxidized with increasing excesses of HOCl to determine whether the pattern of HOCl-mediated amino acid consumption is consistent with reported kinetic data for isolated amino acids and model compounds. Identical experiments have been carried out with mixtures of N-acetyl amino acids (to prevent reaction at the alpha-amino groups) that mimic the protein composition to examine the role of protein structure on reactivity. The results indicate that tertiary structure facilitates secondary chlorine transfer reactions of chloramines formed on His and Lys side chains. In light of these data, second-order rate constants for reactions of Lys side chain and Gly chloramines with Trp side chains and disulfide bonds have been determined, together with those for further oxidation of Met sulfoxide by HOCl and His side chain chloramines. Computational kinetic models incorporating these additional rate constants closely predict the experimentally observed amino acid consumption. These studies provide insight into the roles of chloramine formation and three-dimensional structure on the reactions of HOCl with isolated proteins and demonstrate that kinetic models can predict the outcome of HOCl-mediated protein oxidation.

  4. 21 CFR 888.3210 - Finger joint metal/metal constrained cemented prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Finger joint metal/metal constrained cemented... metal/metal constrained cemented prosthesis. (a) Identification. A finger joint metal/metal constrained..., 1996 for any finger joint metal/metal constrained cemented prosthesis that was in...

  5. 21 CFR 888.3210 - Finger joint metal/metal constrained cemented prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Finger joint metal/metal constrained cemented... metal/metal constrained cemented prosthesis. (a) Identification. A finger joint metal/metal constrained..., 1996 for any finger joint metal/metal constrained cemented prosthesis that was in...

  6. 21 CFR 888.3210 - Finger joint metal/metal constrained cemented prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Finger joint metal/metal constrained cemented... metal/metal constrained cemented prosthesis. (a) Identification. A finger joint metal/metal constrained..., 1996 for any finger joint metal/metal constrained cemented prosthesis that was in...

  7. 21 CFR 888.3210 - Finger joint metal/metal constrained cemented prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Finger joint metal/metal constrained cemented... metal/metal constrained cemented prosthesis. (a) Identification. A finger joint metal/metal constrained..., 1996 for any finger joint metal/metal constrained cemented prosthesis that was in...

  8. 21 CFR 888.3300 - Hip joint metal constrained cemented or uncemented prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hip joint metal constrained cemented or uncemented... metal constrained cemented or uncemented prosthesis. (a) Identification. A hip joint metal constrained... Administration on or before December 26, 1996 for any hip joint metal constrained cemented or...

  9. 21 CFR 888.3210 - Finger joint metal/metal constrained cemented prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Finger joint metal/metal constrained cemented... metal/metal constrained cemented prosthesis. (a) Identification. A finger joint metal/metal constrained..., 1996 for any finger joint metal/metal constrained cemented prosthesis that was in...

  10. Effects of nitric oxide availability on responses of spinal wide dynamic range neurons to excitatory amino acids.

    PubMed

    Budai, D; Wilcox, G L; Larson, A A

    1995-05-04

    The role of nitric oxide (NO) in responses of spinal dorsal horn neurons to excitatory amino acids and to cutaneous mechanical stimuli was examined. Extracellular recordings were made from wide dynamic range neurons excited with iontophoretically applied excitatory amino acid agonists, N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) or kainic acid. Nitric oxide availability was decreased by iontrophoretic application of NO synthase inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) or L-N5-(1-iminoethyl)ornithine (L-NIO), or elevated by the NO donating compound, S-nitroso-N-penicillamine (SNAP). When cells were excited with successive application of NMDA and non-NMDA excitatory amino acid receptor agonists, application of NO synthase inhibitors led to a decrease in responses to NMDA in 60% of neurons. In more than a third of the cells tested, inhibition of NO synthase caused reciprocal changes in responses to glutamate receptor agonists: NMDA-evoked responses were significantly decreased whereas responses to the non-NMDA receptor agonists (AMPA or kainic acid) were increased. Application of the NO donating compound, S-nitroso-N-penicillamine, revealed an opposite tendency, increasing responses to NMDA in more than half of the neurons tested. In approximately 40% of the cells, reciprocal changes in responses to excitatory amino acid receptor agonists of NMDA versus non-NMDA types were observed after application of S-nitroso-N-penicillamine, such that the increase in NMDA responses was accompanied by decreases in the responses to kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Production of poly-gamma-glutamic acid by Bacillus subtilis and Bacillus licheniformis with different growth media.

    PubMed

    Kedia, Gopal; Hill, David; Hill, Robert; Radecka, Iza

    2010-09-01

    Poly gamma-glutamic acid is a naturally occurring homo-polyamide that is made of D- and L-glutamic acid units connected by amide linkages between alpha-amino and gamma-carboxylic groups. Many strains have been studied for the production of poly y-glutamic acid, B. licheniformis 9945a and B. subtilis natto are the two most widely studied strains due to their higher yield. Both of these strains require L-glutamic acid for poly gamma-glutamic acid production. This paper describes investigations on the biosynthesis of poly y-glutamic acid by B. licheniformis 9945a and B. subtilis natto in an automated pH-controlled fermenter. The effect of the growth media such as medium E, F, C and GS was investigated. Medium E produced poly gamma-glutamic acid both with and without MnSO4 in the medium when fermented by B. licheniformis. Presence of MnSO4 in the medium affected both the yield and biomass production. The yield was 12 g/l for the medium containing 2.46 mM MnSO4 whereas it was only 4-5 g/l for the medium without MnSO4 with molecular weight (Mw) of 321,000. Different media such as medium C, F and GS were used for production of poly gamma-glutamic acid by B. subtilis natto. The yield from GS medium was highest and it produced about 26-28 g/l with molecular weight (Mw) of 627,000.

  12. Constrained Adaptive Beamforming for Improved Contrast in Breast Ultrasound

    DTIC Science & Technology

    2005-06-01

    led us to utilize a recently proposed method, Spatial Processing Optimized and Constrained ( SPOC ). In initial simulations this method not only...6 Review of the Adaptive Beamforming Literature ................... 7 SPOC Progress...given the parameters of in vivo ultrasound imaging. SPOC Progress: Most of the Adaptive Beamforming algorithms previously described fail when applied to

  13. Applications of a Constrained Mechanics Methodology in Economics

    ERIC Educational Resources Information Center

    Janova, Jitka

    2011-01-01

    This paper presents instructive interdisciplinary applications of constrained mechanics calculus in economics on a level appropriate for undergraduate physics education. The aim of the paper is (i) to meet the demand for illustrative examples suitable for presenting the background of the highly expanding research field of econophysics even at the…

  14. A spatially constrained ecological classification: rationale, methodology and implementation

    Treesearch

    Franz Mora; Louis Iverson; Louis Iverson

    2002-01-01

    The theory, methodology and implementation for an ecological and spatially constrained classification are presented. Ecological and spatial relationships among several landscape variables are analyzed in order to define a new approach for a landscape classification. Using ecological and geostatistical analyses, several ecological and spatial weights are derived to...

  15. Extended Shadow Test Approach for Constrained Adaptive Testing. Research Report.

    ERIC Educational Resources Information Center

    Veldkamp, Bernard P.; Ariel, Adelaide

    Several methods have been developed for use on constrained adaptive testing. Item pool partitioning, multistage testing, and testlet-based adaptive testing are methods that perform well for specific cases of adaptive testing. The weighted deviation model and the Shadow Test approach can be more generally applied. These methods are based on…

  16. Constrained Hartree-Fock and quasi-spin projection

    NASA Astrophysics Data System (ADS)

    Cambiaggio, M. C.; Plastino, A.; Szybisz, L.

    1980-08-01

    The constrained Hartree-Fock approach of Elliott and Evans is studied in detail with reference to two quasi-spin models, and their predictions compared with those arising from a projection method. It is found that the new approach works fairly well, although limitations to its applicability are encountered.

  17. Extracting electron transfer coupling elements from constrained density functional theory

    NASA Astrophysics Data System (ADS)

    Wu, Qin; Van Voorhis, Troy

    2006-10-01

    Constrained density functional theory (DFT) is a useful tool for studying electron transfer (ET) reactions. It can straightforwardly construct the charge-localized diabatic states and give a direct measure of the inner-sphere reorganization energy. In this work, a method is presented for calculating the electronic coupling matrix element (Hab) based on constrained DFT. This method completely avoids the use of ground-state DFT energies because they are known to irrationally predict fractional electron transfer in many cases. Instead it makes use of the constrained DFT energies and the Kohn-Sham wave functions for the diabatic states in a careful way. Test calculations on the Zn2+ and the benzene-Cl atom systems show that the new prescription yields reasonable agreement with the standard generalized Mulliken-Hush method. We then proceed to produce the diabatic and adiabatic potential energy curves along the reaction pathway for intervalence ET in the tetrathiafulvalene-diquinone (Q-TTF-Q) anion. While the unconstrained DFT curve has no reaction barrier and gives Hab≈17kcal /mol, which qualitatively disagrees with experimental results, the Hab calculated from constrained DFT is about 3kcal /mol and the generated ground state has a barrier height of 1.70kcal/mol, successfully predicting (Q-TTF-Q)- to be a class II mixed-valence compound.

  18. How well can future CMB missions constrain cosmic inflation?

    SciTech Connect

    Martin, Jérôme; Vennin, Vincent; Ringeval, Christophe E-mail: christophe.ringeval@uclouvain.be

    2014-10-01

    We study how the next generation of Cosmic Microwave Background (CMB) measurement missions (such as EPIC, LiteBIRD, PRISM and COrE) will be able to constrain the inflationary landscape in the hardest to disambiguate situation in which inflation is simply described by single-field slow-roll scenarios. Considering the proposed PRISM and LiteBIRD satellite designs, we simulate mock data corresponding to five different fiducial models having values of the tensor-to-scalar ratio ranging from 10{sup -1} down to 10{sup -7}. We then compute the Bayesian evidences and complexities of all Encyclopædia Inflationaris models in order to assess the constraining power of PRISM alone and LiteBIRD complemented with the Planck 2013 data. Within slow-roll inflation, both designs have comparable constraining power and can rule out about three quarters of the inflationary scenarios, compared to one third for Planck 2013 data alone. However, we also show that PRISM can constrain the scalar running and has the capability to detect a violation of slow roll at second order. Finally, our results suggest that describing an inflationary model by its potential shape only, without specifying a reheating temperature, will no longer be possible given the accuracy level reached by the future CMB missions.

  19. Excision technique in constrained formulations of Einstein equations: collapse scenario

    NASA Astrophysics Data System (ADS)

    Cordero-Carrión, I.; Vasset, N.; Novak, J.; Jaramillo, J. L.

    2015-04-01

    We present a new excision technique used in constrained formulations of Einstein equations to deal with black hole in numerical simulations. We show the applicability of this scheme in several scenarios. In particular, we present the dynamical evolution of the collapse of a neutron star to a black hole, using the CoCoNuT code and this excision technique.

  20. Multiply-Constrained Semantic Search in the Remote Associates Test

    ERIC Educational Resources Information Center

    Smith, Kevin A.; Huber, David E.; Vul, Edward

    2013-01-01

    Many important problems require consideration of multiple constraints, such as choosing a job based on salary, location, and responsibilities. We used the Remote Associates Test to study how people solve such multiply-constrained problems by asking participants to make guesses as they came to mind. We evaluated how people generated these guesses…

  1. Constrained Quantum Mechanics: Chaos in Non-Planar Billiards

    ERIC Educational Resources Information Center

    Salazar, R.; Tellez, G.

    2012-01-01

    We illustrate some of the techniques to identify chaos signatures at the quantum level using as guiding examples some systems where a particle is constrained to move on a radial symmetric, but non-planar, surface. In particular, two systems are studied: the case of a cone with an arbitrary contour or "dunce hat billiard" and the rectangular…

  2. Reflections on How Color Term Acquisition Is Constrained

    ERIC Educational Resources Information Center

    Pitchford, Nicola J.

    2006-01-01

    Compared with object word learning, young children typically find learning color terms to be a difficult linguistic task. In this reflections article, I consider two questions that are fundamental to investigations into the developmental acquisition of color terms. First, I consider what constrains color term acquisition and how stable these…

  3. Constrained quantum mechanics: chaos in non-planar billiards

    NASA Astrophysics Data System (ADS)

    Salazar, R.; Téllez, G.

    2012-07-01

    We illustrate some of the techniques to identify chaos signatures at the quantum level using as guiding examples some systems where a particle is constrained to move on a radial symmetric, but non-planar, surface. In particular, two systems are studied: the case of a cone with an arbitrary contour or dunce hat billiard and the rectangular billiard with an inner Gaussian surface.

  4. Multiply-Constrained Semantic Search in the Remote Associates Test

    ERIC Educational Resources Information Center

    Smith, Kevin A.; Huber, David E.; Vul, Edward

    2013-01-01

    Many important problems require consideration of multiple constraints, such as choosing a job based on salary, location, and responsibilities. We used the Remote Associates Test to study how people solve such multiply-constrained problems by asking participants to make guesses as they came to mind. We evaluated how people generated these guesses…

  5. Constrained Transport vs. Divergence Cleanser Options in Astrophysical MHD Simulations

    NASA Astrophysics Data System (ADS)

    Lindner, Christopher C.; Fragile, P.

    2009-01-01

    In previous work, we presented results from global numerical simulations of the evolution of black hole accretion disks using the Cosmos++ GRMHD code. In those simulations we solved the magnetic induction equation using an advection-split form, which is known not to satisfy the divergence-free constraint. To minimize the build-up of divergence error, we used a hyperbolic cleanser function that simultaneously damped the error and propagated it off the grid. We have since found that this method produces qualitatively and quantitatively different behavior in high magnetic field regions than results published by other research groups, particularly in the evacuated funnels of black-hole accretion disks where Poynting-flux jets are reported to form. The main difference between our earlier work and that of our competitors is their use of constrained-transport schemes to preserve a divergence-free magnetic field. Therefore, to study these differences directly, we have implemented a constrained transport scheme into Cosmos++. Because Cosmos++ uses a zone-centered, finite-volume method, we can not use the traditional staggered-mesh constrained transport scheme of Evans & Hawley. Instead we must implement a more general scheme; we chose the Flux-CT scheme as described by Toth. Here we present comparisons of results using the divergence-cleanser and constrained transport options in Cosmos++.

  6. Testing a Constrained MPC Controller in a Process Control Laboratory

    ERIC Educational Resources Information Center

    Ricardez-Sandoval, Luis A.; Blankespoor, Wesley; Budman, Hector M.

    2010-01-01

    This paper describes an experiment performed by the fourth year chemical engineering students in the process control laboratory at the University of Waterloo. The objective of this experiment is to test the capabilities of a constrained Model Predictive Controller (MPC) to control the operation of a Double Pipe Heat Exchanger (DPHE) in real time.…

  7. Joint Force Interdependence for a Fiscally Constrained Future

    DTIC Science & Technology

    2013-03-01

    Army 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dr. Richard Meinhart ...Joint Force Interdependence For A Fiscally Constrained Future by Colonel Daniel P. Ray United States Army ...United States Army War College Class of 2013 DISTRIBUTION STATEMENT: A Approved for Public Release Distribution is Unlimited

  8. Improved Differential Evolution with Shrinking Space Technique for Constrained Optimization

    NASA Astrophysics Data System (ADS)

    Fu, Chunming; Xu, Yadong; Jiang, Chao; Han, Xu; Huang, Zhiliang

    2017-05-01

    Most of the current evolutionary algorithms for constrained optimization algorithm are low computational efficiency. In order to improve efficiency, an improved differential evolution with shrinking space technique and adaptive trade-off model, named ATMDE, is proposed to solve constrained optimization problems. The proposed ATMDE algorithm employs an improved differential evolution as the search optimizer to generate new offspring individuals into evolutionary population. For the constraints, the adaptive trade-off model as one of the most important constraint-handling techniques is employed to select better individuals to retain into the next population, which could effectively handle multiple constraints. Then the shrinking space technique is designed to shrink the search region according to feedback information in order to improve computational efficiency without losing accuracy. The improved DE algorithm introduces three different mutant strategies to generate different offspring into evolutionary population. Moreover, a new mutant strategy called "DE/rand/best/1" is constructed to generate new individuals according to the feasibility proportion of current population. Finally, the effectiveness of the proposed method is verified by a suite of benchmark functions and practical engineering problems. This research presents a constrained evolutionary algorithm with high efficiency and accuracy for constrained optimization problems.

  9. Information Retrieval by Constrained Spreading Activation in Semantic Networks.

    ERIC Educational Resources Information Center

    Cohen, Paul R.; Kjeldsen, Rick

    1987-01-01

    Describes GRANT, an expert system for finding sources of funding given research proposals. The architecture of GRANT and the implementation of constrained spreading activation (a modified search algorithm based on semantic memory) are described, and recall and precision rates are analyzed. (Author/LRW)

  10. Constrained Quantum Mechanics: Chaos in Non-Planar Billiards

    ERIC Educational Resources Information Center

    Salazar, R.; Tellez, G.

    2012-01-01

    We illustrate some of the techniques to identify chaos signatures at the quantum level using as guiding examples some systems where a particle is constrained to move on a radial symmetric, but non-planar, surface. In particular, two systems are studied: the case of a cone with an arbitrary contour or "dunce hat billiard" and the rectangular…

  11. Achieving Procurement Efficiencies in a Budget-Constrained Environment

    DTIC Science & Technology

    2015-05-13

    Copyright © 2015 Boeing. All rights reserved. . Corporate Contracts Darryl Scott Corporate Vice President, Contracts May 13, 2015 Naval...Budget-Constrained Environment T2012 Panel March 12, 2012 Copyright © 2012 Boeing. All rights reserved. Copyright © 2015 Boeing. All rights reserved...Corporate | Contracts Comparison of Commercial and Military Production Satellites Copyright © 2012 Boeing. All rights reserved. $407M ~58 mo

  12. Solution of a Complex Least Squares Problem with Constrained Phase.

    PubMed

    Bydder, Mark

    2010-12-30

    The least squares solution of a complex linear equation is in general a complex vector with independent real and imaginary parts. In certain applications in magnetic resonance imaging, a solution is desired such that each element has the same phase. A direct method for obtaining the least squares solution to the phase constrained problem is described.

  13. Bayesian Item Selection in Constrained Adaptive Testing Using Shadow Tests

    ERIC Educational Resources Information Center

    Veldkamp, Bernard P.

    2010-01-01

    Application of Bayesian item selection criteria in computerized adaptive testing might result in improvement of bias and MSE of the ability estimates. The question remains how to apply Bayesian item selection criteria in the context of constrained adaptive testing, where large numbers of specifications have to be taken into account in the item…

  14. Hamiltonian dynamics and constrained variational calculus: continuous and discrete settings

    NASA Astrophysics Data System (ADS)

    de León, Manuel; Jiménez, Fernando; Martín de Diego, David

    2012-05-01

    The aim of this paper is to study the relationship between Hamiltonian dynamics and constrained variational calculus. We describe both using the notion of Lagrangian submanifolds of convenient symplectic manifolds and using the so-called Tulczyjew triples. The results are also extended to the case of discrete dynamics and nonholonomic mechanics. Interesting applications to the geometrical integration of Hamiltonian systems are obtained.

  15. Using Diagnostic Text Information to Constrain Situation Models

    ERIC Educational Resources Information Center

    Dutke, Stephan; Baadte, Christiane; Hahnel, Andrea; von Hecker, Ulrich; Rinck, Mike

    2010-01-01

    During reading, the model of the situation described by the text is continuously accommodated to new text input. The hypothesis was tested that readers are particularly sensitive to diagnostic text information that can be used to constrain their existing situation model. In 3 experiments, adult participants read narratives about social situations…

  16. Applications of a Constrained Mechanics Methodology in Economics

    ERIC Educational Resources Information Center

    Janova, Jitka

    2011-01-01

    This paper presents instructive interdisciplinary applications of constrained mechanics calculus in economics on a level appropriate for undergraduate physics education. The aim of the paper is (i) to meet the demand for illustrative examples suitable for presenting the background of the highly expanding research field of econophysics even at the…

  17. Constrained variational calculus for higher order classical field theories

    NASA Astrophysics Data System (ADS)

    Campos, Cédric M.; de León, Manuel; Martín de Diego, David

    2010-11-01

    We develop an intrinsic geometrical setting for higher order constrained field theories. As a main tool we use an appropriate generalization of the classical Skinner-Rusk formalism. Some examples of applications are studied, in particular to the geometrical description of optimal control theory for partial differential equations.

  18. Testing a Constrained MPC Controller in a Process Control Laboratory

    ERIC Educational Resources Information Center

    Ricardez-Sandoval, Luis A.; Blankespoor, Wesley; Budman, Hector M.

    2010-01-01

    This paper describes an experiment performed by the fourth year chemical engineering students in the process control laboratory at the University of Waterloo. The objective of this experiment is to test the capabilities of a constrained Model Predictive Controller (MPC) to control the operation of a Double Pipe Heat Exchanger (DPHE) in real time.…

  19. Constrained optimization schemes for geophysical inversion of seismic data

    NASA Astrophysics Data System (ADS)

    Sosa Aguirre, Uram Anibal

    Many experimental techniques in geophysics advance the understanding of Earth processes by estimating and interpreting Earth structure (e.g., velocity and/or density structure). These techniques use different types of geophysical data which can be collected and analyzed separately, sometimes resulting in inconsistent models of the Earth depending on data quality, methods and assumptions made. This dissertation presents two approaches for geophysical inversion of seismic data based on constrained optimization. In one approach we expand a one dimensional (1-D) joint inversion least-squares (LSQ) algorithm by introducing a constrained optimization methodology. Then we use the 1-D inversion results to produce 3-D Earth velocity structure models. In the second approach, we provide a unified constrained optimization framework for solving a 1-D inverse wave propagation problem. In Chapter 2 we present a constrained optimization framework for joint inversion. This framework characterizes 1-D Earth's structure by using seismic shear wave velocities as a model parameter. We create two geophysical synthetic data sets sensitive to shear velocities, namely receiver function and surface wave dispersion. We validate our approach by comparing our numerical results with a traditional unconstrained method, and also we test our approach robustness in the presence of noise. Chapter 3 extends this framework to include an interpolation technique for creating 3-D Earth velocity structure models of the Rio Grande Rift region. Chapter 5 introduces the joint inversion of multiple data sets by adding delay travel times information in a synthetic setup, and leave the posibility to include more data sets. Finally, in Chapter 4 we pose a 1-D inverse full-waveform propagation problem as a PDE-constrained optimization program, where we invert for the material properties in terms of shear wave velocities throughout the physical domain. We facilitate the implementation and comparison of different

  20. Constrained Laboratory vs. Unconstrained Steering-Induced Rollover Crash Tests.

    PubMed

    Kerrigan, Jason R; Toczyski, Jacek; Roberts, Carolyn; Zhang, Qi; Clauser, Mark

    2015-01-01

    The goal of this study was to evaluate how well an in-laboratory rollover crash test methodology that constrains vehicle motion can reproduce the dynamics of unconstrained full-scale steering-induced rollover crash tests in sand. Data from previously-published unconstrained steering-induced rollover crash tests using a full-size pickup and mid-sized sedan were analyzed to determine vehicle-to-ground impact conditions and kinematic response of the vehicles throughout the tests. Then, a pair of replicate vehicles were prepared to match the inertial properties of the steering-induced test vehicles and configured to record dynamic roof structure deformations and kinematic response. Both vehicles experienced greater increases in roll-axis angular velocities in the unconstrained tests than in the constrained tests; however, the increases that occurred during the trailing side roof interaction were nearly identical between tests for both vehicles. Both vehicles experienced linear accelerations in the constrained tests that were similar to those in the unconstrained tests, but the pickup, in particular, had accelerations that were matched in magnitude, timing, and duration very closely between the two test types. Deformations in the truck test were higher in the constrained than the unconstrained, and deformations in the sedan were greater in the unconstrained than the constrained as a result of constraints of the test fixture, and differences in impact velocity for the trailing side. The results of the current study suggest that in-laboratory rollover tests can be used to simulate the injury-causing portions of unconstrained rollover crashes. To date, such a demonstration has not yet been published in the open literature. This study did, however, show that road surface can affect vehicle response in a way that may not be able to be mimicked in the laboratory. Lastly, this study showed that configuring the in-laboratory tests to match the leading-side touchdown conditions

  1. The medium term outcome of the Omnifit constrained acetabular cup.

    PubMed

    Bigsby, Ewan; Whitehouse, Michael R; Bannister, Gordon C; Blom, Ashley W

    2012-01-01

    Recurrent dislocation requiring revision surgery occurs in approximately 4% of primary total hip arthroplasties (THAs). To reduce this risk, or to treat those patients who recurrently dislocate, a constrained acetabular component may be used, however there are concerns over the success of such components due to increased mechanical stresses. The purpose of this study was to analyse the survivorship and radiological results for the Omnifit constrained acetabular component, providing a longer patient reported outcome follow-up than previous studies. 117 patients (median age 82 years) underwent a THA with an Omnifit constrained acetabular component. Of these, 45 were primary replacements and 72 were revisions. Survivorship analysis was performed and patients were assessed both radiologically and functionally. At follow-up, 53 patients (45.3%) had died at a median time of 33 months from operation. The median overall follow-up was 7.0 (5.5-8.2) years. Survivors (median age 83 years) reported a median Oxford Hip Score (OHS) of 16.6 (0-48), 87.8% were satisfied with their surgery. 45 (91.8%) of the acetabular components were stable radiologically, 48 (96%) of the femoral components were stable (5 uncemented, 43 cemented) and two possibly unstable. Four of the 117 patients underwent further surgery. Only one required revision of the prosthesis and this was for a periprosthetic fracture. In the medium term the Omnifit constrained acetabular component prevents dislocation and does not cause excessive loosening of either the acetabular or femoral components in our patient population. Our results support the use of the Omnifit constrained acetabular component in elderly patients at risk of dislocation with low functional demand.

  2. Reaction of primary and secondary amines to form carbamic acid glucuronides.

    PubMed

    Schaefer, William H

    2006-12-01

    Glucuronidation is an important mechanism used by mammalian systems to clear and eliminate both endogenous and foreign chemicals. Many functional groups are susceptible to conjugation with glucuronic acid, including hydroxyls, phenols, carboxyls, activated carbons, thiols, amines, and selenium. Primary and secondary amines can also react with carbon dioxide (CO(2)) via a reversible reaction to form a carbamic acid. The carbamic acid is also a substrate for glucuronidation and results in a stable carbamate glucuronide metabolite. The detection and characterization of these products has been facilitated greatly by the advent of soft ionization mass spectrometry techniques and high field NMR instrumentation. The formation of carbamate glucuronide metabolites has been described for numerous pharmaceuticals and they have been identified in all of the species commonly used in drug metabolism studies (rat, dog, mouse, rabbit, guinea pig, and human). There has been no obvious species specificity for their formation and no preference for 1 degrees or 2 degrees amines. Many biological reactions have also been described in the literature that involve the reaction of CO(2) with amino groups of biomolecules. For example, CO(2) generated from cellular respiration is expired in part through the reversible formation of a carbamate between CO(2) and the alpha-amino groups of the alpha- and beta-chains of hemoglobin. Also, carbamic acid products of several amines, such as beta-N-methylamino-L-alanine (BMAA), ethylenediamine, and L-cysteine have been implicated in toxicity. Studies suggested that a significant portion of amino-compounds in biological samples (that naturally contain CO(2)/bicarbonate) can be present as a carbamic acid.

  3. MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks.

    PubMed

    Lippi, Giordano; Fernandes, Catarina C; Ewell, Laura A; John, Danielle; Romoli, Benedetto; Curia, Giulia; Taylor, Seth R; Frady, E Paxon; Jensen, Anne B; Liu, Jerry C; Chaabane, Melanie M; Belal, Cherine; Nathanson, Jason L; Zoli, Michele; Leutgeb, Jill K; Biagini, Giuseppe; Yeo, Gene W; Berg, Darwin K

    2016-12-21

    A critical feature of neural networks is that they balance excitation and inhibition to prevent pathological dysfunction. How this is achieved is largely unknown, although deficits in the balance contribute to many neurological disorders. We show here that a microRNA (miR-101) is a key orchestrator of this essential feature, shaping the developing network to constrain excitation in the adult. Transient early blockade of miR-101 induces long-lasting hyper-excitability and persistent memory deficits. Using target site blockers in vivo, we identify multiple developmental programs regulated in parallel by miR-101 to achieve balanced networks. Repression of one target, NKCC1, initiates the switch in γ-aminobutyric acid (GABA) signaling, limits early spontaneous activity, and constrains dendritic growth. Kif1a and Ank2 are targeted to prevent excessive synapse formation. Simultaneous de-repression of these three targets completely phenocopies major dysfunctions produced by miR-101 blockade. Our results provide new mechanistic insight into brain development and suggest novel candidates for therapeutic intervention.

  4. Synthesis and biological evaluation of flexible and conformationally constrained LpxC inhibitors.

    PubMed

    Löppenberg, Marius; Müller, Hannes; Pulina, Carla; Oddo, Alberto; Teese, Mark; Jose, Joachim; Holl, Ralph

    2013-09-28

    Inhibitors of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represent promising candidates for the development of antibiotics possessing a so far unexploited mechanism of action. In a chiral pool synthesis, starting from the D-mannose derived mannonolactone 4, conformationally constrained C-glycosidic as well as open chained hydroxamic acids with a defined stereochemistry were prepared. Diversity was introduced by performing C–C coupling reactions like the Sonogashira and Suzuki cross-coupling reactions. The biological evaluation of the synthesized compounds revealed that in the case of the C-glycosides a long, linear and rigid hydrophobic side chain is required for antibiotic activity against E. coli. The open chain derivatives show higher biological activity than the conformationally constrained C-glycosides. The morpholinomethyl substituted open chain derivative 43, being the most potent compound presented in this paper, inhibits LpxC with a Ki value of 0.35 μM and represents a promising lead structure.

  5. Bayesian methods for the analysis of inequality constrained contingency tables.

    PubMed

    Laudy, Olav; Hoijtink, Herbert

    2007-04-01

    A Bayesian methodology for the analysis of inequality constrained models for contingency tables is presented. The problem of interest lies in obtaining the estimates of functions of cell probabilities subject to inequality constraints, testing hypotheses and selection of the best model. Constraints on conditional cell probabilities and on local, global, continuation and cumulative odds ratios are discussed. A Gibbs sampler to obtain a discrete representation of the posterior distribution of the inequality constrained parameters is used. Using this discrete representation, the credibility regions of functions of cell probabilities can be constructed. Posterior model probabilities are used for model selection and hypotheses are tested using posterior predictive checks. The Bayesian methodology proposed is illustrated in two examples.

  6. Inadequacy of single-impulse transfers for path constrained rendezvous

    NASA Technical Reports Server (NTRS)

    Stern, S. A.; Soileau, K. M.

    1987-01-01

    The use of single-impulse techniques to maneuver from point to point about a large space structure (LSS) with an arbitrary geometrical configuration and spin is examined. Particular consideration is given to transfers with both endpoints on the forbidden zone surface. Clohessy-Wiltshire equations of relative motion are employed to solve path constrained rendezvous problems. External and internal transfers between arbitrary points are analyzed in terms of tangential departure and arrival conditions. It is observed that single-impulse techniques are inadequate for transferring about the exterior of any LSS; however, single-impulse transfers are applicable for transfers in the interior of LSSs. It is concluded that single-impulse transducers are not applicable for path constrained rendezvous guidance.

  7. Constraining the Noncommutative Spectral Action via Astrophysical Observations

    SciTech Connect

    Nelson, William; Ochoa, Joseph; Sakellariadou, Mairi

    2010-09-03

    The noncommutative spectral action extends our familiar notion of commutative spaces, using the data encoded in a spectral triple on an almost commutative space. Varying a rather simple action, one can derive all of the standard model of particle physics in this setting, in addition to a modified version of Einstein-Hilbert gravity. In this Letter we use observations of pulsar timings, assuming that no deviation from general relativity has been observed, to constrain the gravitational sector of this theory. While the bounds on the coupling constants remain rather weak, they are comparable to existing bounds on deviations from general relativity in other settings and are likely to be further constrained by future observations.

  8. Lilith: a tool for constraining new physics from Higgs measurements

    NASA Astrophysics Data System (ADS)

    Bernon, Jérémy; Dumont, Béranger

    2015-09-01

    The properties of the observed Higgs boson with mass around 125 GeV can be affected in a variety of ways by new physics beyond the Standard Model (SM). The wealth of experimental results, targeting the different combinations for the production and decay of a Higgs boson, makes it a non-trivial task to assess the patibility of a non-SM-like Higgs boson with all available results. In this paper we present Lilith, a new public tool for constraining new physics from signal strength measurements performed at the LHC and the Tevatron. Lilith is a Python library that can also be used in C and C++/ ROOT programs. The Higgs likelihood is based on experimental results stored in an easily extensible XML database, and is evaluated from the user input, given in XML format in terms of reduced couplings or signal strengths.The results of Lilith can be used to constrain a wide class of new physics scenarios.

  9. HYPR: constrained reconstruction for enhanced SNR in dynamic medical imaging

    NASA Astrophysics Data System (ADS)

    Mistretta, C.; Wieben, O.; Velikina, J.; Wu, Y.; Johnson, K.; Korosec, F.; Unal, O.; Chen, G.; Fain, S.; Christian, B.; Nalcioglu, O.; Kruger, R. A.; Block, W.; Samsonov, A.; Speidel, M.; Van Lysel, M.; Rowley, H.; Supanich, M.; Turski, P.; Wu, Yan; Holmes, J.; Kecskemeti, S.; Moran, C.; O'Halloran, R.; Keith, L.; Alexander, A.; Brodsky, E.; Lee, J. E.; Hall, T.; Zagzebski, J.

    2008-03-01

    During the last eight years our group has developed radial acquisitions with angular undersampling factors of several hundred that accelerate MRI in selected applications. As with all previous acceleration techniques, SNR typically falls as least as fast as the inverse square root of the undersampling factor. This limits the SNR available to support the small voxels that these methods can image over short time intervals in applications like time-resolved contrast-enhanced MR angiography (CE-MRA). Instead of processing each time interval independently, we have developed constrained reconstruction methods that exploit the significant correlation between temporal sampling points. A broad class of methods, termed HighlY Constrained Back PRojection (HYPR), generalizes this concept to other modalities and sampling dimensions.

  10. Functional coupling constrains craniofacial diversification in Lake Tanganyika cichlids

    PubMed Central

    Tsuboi, Masahito; Gonzalez-Voyer, Alejandro; Kolm, Niclas

    2015-01-01

    Functional coupling, where a single morphological trait performs multiple functions, is a universal feature of organismal design. Theory suggests that functional coupling may constrain the rate of phenotypic evolution, yet empirical tests of this hypothesis are rare. In fish, the evolutionary transition from guarding the eggs on a sandy/rocky substrate (i.e. substrate guarding) to mouthbrooding introduces a novel function to the craniofacial system and offers an ideal opportunity to test the functional coupling hypothesis. Using a combination of geometric morphometrics and a recently developed phylogenetic comparative method, we found that head morphology evolution was 43% faster in substrate guarding species than in mouthbrooding species. Furthermore, for species in which females were solely responsible for mouthbrooding the males had a higher rate of head morphology evolution than in those with bi-parental mouthbrooding. Our results support the hypothesis that adaptations resulting in functional coupling constrain phenotypic evolution. PMID:25948565

  11. Matter coupling in partially constrained vielbein formulation of massive gravity

    SciTech Connect

    Felice, Antonio De; Mukohyama, Shinji; Gümrükçüoğlu, A. Emir; Heisenberg, Lavinia E-mail: emir.gumrukcuoglu@nottingham.ac.uk E-mail: shinji.mukohyama@ipmu.jp

    2016-01-01

    We consider a linear effective vielbein matter coupling without introducing the Boulware-Deser ghost in ghost-free massive gravity. This is achieved in the partially constrained vielbein formulation. We first introduce the formalism and prove the absence of ghost at all scales. As next we investigate the cosmological application of this coupling in this new formulation. We show that even if the background evolution accords with the metric formulation, the perturbations display important different features in the partially constrained vielbein formulation. We study the cosmological perturbations of the two branches of solutions separately. The tensor perturbations coincide with those in the metric formulation. Concerning the vector and scalar perturbations, the requirement of absence of ghost and gradient instabilities yields slightly different allowed parameter space.

  12. CONMIN: A FORTRAN program for constrained function minimization: User's manual

    NASA Technical Reports Server (NTRS)

    Vanderplaats, G. N.

    1973-01-01

    CONMIN is a FORTRAN program, in subroutine form, for the solution of linear or nonlinear constrained optimization problems. The basic optimization algorithm is the Method of Feasible Directions. The user must provide a main calling program and an external routine to evaluate the objective and constraint functions and to provide gradient information. If analytic gradients of the objective or constraint functions are not available, this information is calculated by finite difference. While the program is intended primarily for efficient solution of constrained problems, unconstrained function minimization problems may also be solved, and the conjugate direction method of Fletcher and Reeves is used for this purpose. This manual describes the use of CONMIN and defines all necessary parameters. Sufficient information is provided so that the program can be used without special knowledge of optimization techniques. Sample problems are included to help the user become familiar with CONMIN and to make the program operational.

  13. Constraining new physics models with isotope shift spectroscopy

    NASA Astrophysics Data System (ADS)

    Frugiuele, Claudia; Fuchs, Elina; Perez, Gilad; Schlaffer, Matthias

    2017-07-01

    Isotope shifts of transition frequencies in atoms constrain generic long- and intermediate-range interactions. We focus on new physics scenarios that can be most strongly constrained by King linearity violation such as models with B -L vector bosons, the Higgs portal, and chameleon models. With the anticipated precision, King linearity violation has the potential to set the strongest laboratory bounds on these models in some regions of parameter space. Furthermore, we show that this method can probe the couplings relevant for the protophobic interpretation of the recently reported Be anomaly. We extend the formalism to include an arbitrary number of transitions and isotope pairs and fit the new physics coupling to the currently available isotope shift measurements.

  14. Colorimetric characterization of LCD based on constrained least squares

    NASA Astrophysics Data System (ADS)

    LI, Tong; Xie, Kai; Wang, Qiaojie; Yao, Luyang

    2017-01-01

    In order to improve the accuracy of colorimetric characterization of liquid crystal display, tone matrix model in color management modeling of display characterization is established by using constrained least squares for quadratic polynomial fitting, and find the relationship between the RGB color space to CIEXYZ color space; 51 sets of training samples were collected to solve the parameters, and the accuracy of color space mapping model was verified by 100 groups of random verification samples. The experimental results showed that, with the constrained least square method, the accuracy of color mapping was high, the maximum color difference of this model is 3.8895, the average color difference is 1.6689, which prove that the method has better optimization effect on the colorimetric characterization of liquid crystal display.

  15. Matter coupling in partially constrained vielbein formulation of massive gravity

    SciTech Connect

    Felice, Antonio De; Gümrükçüoğlu, A. Emir; Heisenberg, Lavinia; Mukohyama, Shinji

    2016-01-04

    We consider a linear effective vielbein matter coupling without introducing the Boulware-Deser ghost in ghost-free massive gravity. This is achieved in the partially constrained vielbein formulation. We first introduce the formalism and prove the absence of ghost at all scales. As next we investigate the cosmological application of this coupling in this new formulation. We show that even if the background evolution accords with the metric formulation, the perturbations display important different features in the partially constrained vielbein formulation. We study the cosmological perturbations of the two branches of solutions separately. The tensor perturbations coincide with those in the metric formulation. Concerning the vector and scalar perturbations, the requirement of absence of ghost and gradient instabilities yields slightly different allowed parameter space.

  16. Constraining the nuclear equation of state at subsaturation densities.

    PubMed

    Khan, E; Margueron, J; Vidaña, I

    2012-08-31

    Only one-third of the nucleons in 208Pb occupy the saturation density area. Consequently, nuclear observables related to the average properties of nuclei, such as masses or radii, constrain the equation of state not at the saturation density but rather around the so-called crossing density, localized close to the mean value of the density of nuclei: ρ is approximately equal to 0.11 fm(-3). This provides an explanation for the empirical fact that several equation of state quantities calculated with various functionals cross at a density significantly lower than the saturation one. The third derivative M of the energy per unit of volume at the crossing density is constrained by the giant monopole resonance measurements in an isotopic chain rather than the incompressibility at saturation density. The giant monopole resonance measurements provide M=1100±70 MeV (6% uncertainty), whose extrapolation gives K(∞)=230±40 MeV (17% uncertainty).

  17. Moving Forward to Constrain the Shear Viscosity of QCD Matter

    SciTech Connect

    Denicol, Gabriel; Monnai, Akihiko; Schenke, Björn

    2016-05-26

    In this work, we demonstrate that measurements of rapidity differential anisotropic flow in heavy-ion collisions can constrain the temperature dependence of the shear viscosity to entropy density ratio η/s of QCD matter. Comparing results from hydrodynamic calculations with experimental data from the RHIC, we find evidence for a small η/s ≈ 0.04 in the QCD crossover region and a strong temperature dependence in the hadronic phase. A temperature independent η/s is disfavored by the data. We further show that measurements of the event-by-event flow as a function of rapidity can be used to independently constrain the initial state fluctuations in three dimensions and the temperature dependent transport properties of QCD matter.

  18. Moving Forward to Constrain the Shear Viscosity of QCD Matter.

    PubMed

    Denicol, Gabriel; Monnai, Akihiko; Schenke, Björn

    2016-05-27

    We demonstrate that measurements of rapidity differential anisotropic flow in heavy-ion collisions can constrain the temperature dependence of the shear viscosity to entropy density ratio η/s of QCD matter. Comparing results from hydrodynamic calculations with experimental data from the RHIC, we find evidence for a small η/s≈0.04 in the QCD crossover region and a strong temperature dependence in the hadronic phase. A temperature independent η/s is disfavored by the data. We further show that measurements of the event-by-event flow as a function of rapidity can be used to independently constrain the initial state fluctuations in three dimensions and the temperature dependent transport properties of QCD matter.

  19. Functional coupling constrains craniofacial diversification in Lake Tanganyika cichlids.

    PubMed

    Tsuboi, Masahito; Gonzalez-Voyer, Alejandro; Kolm, Niclas

    2015-05-01

    Functional coupling, where a single morphological trait performs multiple functions, is a universal feature of organismal design. Theory suggests that functional coupling may constrain the rate of phenotypic evolution, yet empirical tests of this hypothesis are rare. In fish, the evolutionary transition from guarding the eggs on a sandy/rocky substrate (i.e. substrate guarding) to mouthbrooding introduces a novel function to the craniofacial system and offers an ideal opportunity to test the functional coupling hypothesis. Using a combination of geometric morphometrics and a recently developed phylogenetic comparative method, we found that head morphology evolution was 43% faster in substrate guarding species than in mouthbrooding species. Furthermore, for species in which females were solely responsible for mouthbrooding the males had a higher rate of head morphology evolution than in those with bi-parental mouthbrooding. Our results support the hypothesis that adaptations resulting in functional coupling constrain phenotypic evolution.

  20. A second-generation constrained reaction volume shock tube.

    PubMed

    Campbell, M F; Tulgestke, A M; Davidson, D F; Hanson, R K

    2014-05-01

    We have developed a shock tube that features a sliding gate valve in order to mechanically constrain the reactive test gas mixture to an area close to the shock tube endwall, separating it from a specially formulated non-reactive buffer gas mixture. This second-generation Constrained Reaction Volume (CRV) strategy enables near-constant-pressure shock tube test conditions for reactive experiments behind reflected shocks, thereby enabling improved modeling of the reactive flow field. Here we provide details of the design and operation of the new shock tube. In addition, we detail special buffer gas tailoring procedures, analyze the buffer/test gas interactions that occur on gate valve opening, and outline the size range of fuels that can be studied using the CRV technique in this facility. Finally, we present example low-temperature ignition delay time data to illustrate the CRV shock tube's performance.