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Sample records for non-conservative aminoacid substitutions

  1. A 20-state empirical amino-acid substitution model for green plant chloroplasts.

    PubMed

    Cox, Cymon J; Foster, Peter G

    2013-08-01

    We introduce a new empirical amino-acid substitution model intended for use with for green plant (Viridiplantae) chloroplast protein data, which we call gcpREV (green chloroplast reversible model). Relative exchange rates and base composition frequencies among amino-acids were calculated using a Markov-chain Monte Carlo analysis on a combined data set of 34 proteins sampled among 27 taxa of green plants. The gcpREV model is a better fit than the commonly-used cpREV model to five previously published chloroplast protein test data sets of green plants, but is not a better fit to test data consisting mostly of non-green plant chloroplasts. Consequently, our analyses suggest a degree of specificity of the new model to green plant chloroplast data. The new model is implemented in the software P4, and model description files are available for other popular phylogenetic analysis software. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Molecular Evolution of a Pervasive Natural Amino-Acid Substitution in Drosophila cryptochrome

    PubMed Central

    Pegoraro, Mirko; Noreen, Shumaila; Bhutani, Supriya; Tsolou, Avgi; Schmid, Ralf; Kyriacou, Charalambos P.; Tauber, Eran

    2014-01-01

    Genetic variations in circadian clock genes may serve as molecular adaptations, allowing populations to adapt to local environments. Here, we carried out a survey of genetic variation in Drosophila cryptochrome (cry), the fly’s dedicated circadian photoreceptor. An initial screen of 10 European cry alleles revealed substantial variation, including seven non-synonymous changes. The SNP frequency spectra and the excessive linkage disequilibrium in this locus suggested that this variation is maintained by natural selection. We focused on a non-conservative SNP involving a leucine - histidine replacement (L232H) and found that this polymorphism is common, with both alleles at intermediate frequencies across 27 populations surveyed in Europe, irrespective of latitude. Remarkably, we were able to reproduce this natural observation in the laboratory using replicate population cages where the minor allele frequency was initially set to 10%. Within 20 generations, the two allelic variants converged to approximately equal frequencies. Further experiments using congenic strains, showed that this SNP has a phenotypic impact, with variants showing significantly different eclosion profiles. At the long term, these phase differences in eclosion may contribute to genetic differentiation among individuals, and shape the evolution of wild populations. PMID:24475129

  3. Amino-acid substitutions in the IKAP gene product significantly increase risk for bronchial asthma in children.

    PubMed

    Takeoka, S; Unoki, M; Onouchi, Y; Doi, S; Fujiwara, H; Miyatake, A; Fujita, K; Inoue, I; Nakamura, Y; Tamari, M

    2001-01-01

    The complex etiology of bronchial asthma (BA), one of the most common inflammatory diseases throughout the world, involves a combination of various genetic and environmental factors. A number of investigators have undertaken linkage and association studies to shed light on the genetic background of BA, but the genetic aspects of this disease are still poorly understood. In the course of a project to screen the entire human genome for single nucleotide polymorphisms (SNPs) that might represent useful markers for large-scale association analyses of common diseases and pharmacogenetic traits, we identified six SNPs within the gene encoding I-kappaB-associated protein (IKAP), a regulator of the NF-kappaB signal pathway. Most of these SNPs were in linkage disequilibrium with each other. We observed a strong allelic association between BA in childhood and two of the SNP sites, T3214A (Cys1072Ser) and C3473T (Pro1158Leu); P = 0.000004 for T3214A and P = 0.0009 for C3473T. T3214A was also associated with BA in adult patients (P = 0.000002), but C3473T was not (P = 0.056). To confirm the above results, we compared estimated frequencies of haplotypes of the six SNPs between BA patients and controls. We found a strong association between BA in childhood and a specific haplotype, TGAAAT, that involved two amino-acid substitutions (819T, 2295G, 2446A, 2490A, 3214A, and 3473T; P = 0.00004, odds ratio, 2.94; 95% confidence interval [CI], 2.48-3.4). On the other hand, haplotype TACGTC, which differed from the TGAAAT haplotype in the last five nucleotides, was inversely correlated with the BA phenotype (P = 0.002; odds ratio, 9.83; 95% CI, 8.35-11.31). These results indicated that specific variants of the IKAP gene, or a variant in linkage disequilibrium with the TGAAAT haplotype, might be associated with mechanisms responsible for early-onset BA.

  4. Structural and Functional Characteristics of Oxysterol 7α-Hydroxylase with Amino-Acid Substitution R486C and Their Relation to the Appearance of Neurodegenerative Diseases

    NASA Astrophysics Data System (ADS)

    Dichenko, Ya. V.; Yantsevich, A. V.; Usanov, S. A.

    2015-03-01

    The influence of the amino-acid substitution Arg486Cys on the conformational stability of recombinant cytochrome P450 7B1 (CYP7B1, oxysterol 7α-hydroxylase) was studied. The single base change was shown to decrease the free energy of the transition of the heme-protein from its native state to a denatured one, which pointed to a lower thermodynamic stability for the mutant form of the enzyme. This could be the cause of the metabolic disruption of neurosteroids and, as a consequence, the appearance of neurodegenerative diseases.

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

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

  6. Application of laser fluorimetry for determining the influence of a single amino-acid substitution on the individual photophysical parameters of a fluorescent form of a fluorescent protein mRFP1

    SciTech Connect

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

    2009-03-31

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

  7. A Single Amino-Acid Substitution in the Sodium Transporter HKT1 Associated with Plant Salt Tolerance.

    PubMed

    Ali, Akhtar; Raddatz, Natalia; Aman, Rashid; Kim, Songmi; Park, Hyeong Cheol; Jan, Masood; Baek, Dongwon; Khan, Irfan Ullah; Oh, Dong-Ha; Lee, Sang Yeol; Bressan, Ray A; Lee, Keun Woo; Maggio, Albino; Pardo, Jose M; Bohnert, Hans J; Yun, Dae-Jin

    2016-07-01

    A crucial prerequisite for plant growth and survival is the maintenance of potassium uptake, especially when high sodium surrounds the root zone. The Arabidopsis HIGH-AFFINITY K(+) TRANSPORTER1 (HKT1), and its homologs in other salt-sensitive dicots, contributes to salinity tolerance by removing Na(+) from the transpiration stream. However, TsHKT1;2, one of three HKT1 copies in Thellungiella salsuginea, a halophytic Arabidopsis relative, acts as a K(+) transporter in the presence of Na(+) in yeast (Saccharomyces cerevisiae). Amino-acid sequence comparisons indicated differences between TsHKT1;2 and most other published HKT1 sequences with respect to an Asp residue (D207) in the second pore-loop domain. Two additional T salsuginea and most other HKT1 sequences contain Asn (n) in this position. Wild-type TsHKT1;2 and altered AtHKT1 (AtHKT1(N-D)) complemented K(+)-uptake deficiency of yeast cells. Mutant hkt1-1 plants complemented with both AtHKT1(N) (-) (D) and TsHKT1;2 showed higher tolerance to salt stress than lines complemented by the wild-type AtHKT1 Electrophysiological analysis in Xenopus laevis oocytes confirmed the functional properties of these transporters and the differential selectivity for Na(+) and K(+) based on the n/d variance in the pore region. This change also dictated inward-rectification for Na(+) transport. Thus, the introduction of Asp, replacing Asn, in HKT1-type transporters established altered cation selectivity and uptake dynamics. We describe one way, based on a single change in a crucial protein that enabled some crucifer species to acquire improved salt tolerance, which over evolutionary time may have resulted in further changes that ultimately facilitated colonization of saline habitats.

  8. A Single Amino-Acid Substitution in the Sodium Transporter HKT1 Associated with Plant Salt Tolerance1[OPEN

    PubMed Central

    Ali, Akhtar; Aman, Rashid; Park, Hyeong Cheol; Jan, Masood; Baek, Dongwon; Khan, Irfan Ullah; Oh, Dong-Ha; Lee, Sang Yeol; Bressan, Ray A.; Lee, Keun Woo; Maggio, Albino; Yun, Dae-Jin

    2016-01-01

    A crucial prerequisite for plant growth and survival is the maintenance of potassium uptake, especially when high sodium surrounds the root zone. The Arabidopsis HIGH-AFFINITY K+ TRANSPORTER1 (HKT1), and its homologs in other salt-sensitive dicots, contributes to salinity tolerance by removing Na+ from the transpiration stream. However, TsHKT1;2, one of three HKT1 copies in Thellungiella salsuginea, a halophytic Arabidopsis relative, acts as a K+ transporter in the presence of Na+ in yeast (Saccharomyces cerevisiae). Amino-acid sequence comparisons indicated differences between TsHKT1;2 and most other published HKT1 sequences with respect to an Asp residue (D207) in the second pore-loop domain. Two additional T. salsuginea and most other HKT1 sequences contain Asn (n) in this position. Wild-type TsHKT1;2 and altered AtHKT1 (AtHKT1N-D) complemented K+-uptake deficiency of yeast cells. Mutant hkt1-1 plants complemented with both AtHKT1N-D and TsHKT1;2 showed higher tolerance to salt stress than lines complemented by the wild-type AtHKT1. Electrophysiological analysis in Xenopus laevis oocytes confirmed the functional properties of these transporters and the differential selectivity for Na+ and K+ based on the n/d variance in the pore region. This change also dictated inward-rectification for Na+ transport. Thus, the introduction of Asp, replacing Asn, in HKT1-type transporters established altered cation selectivity and uptake dynamics. We describe one way, based on a single change in a crucial protein that enabled some crucifer species to acquire improved salt tolerance, which over evolutionary time may have resulted in further changes that ultimately facilitated colonization of saline habitats. PMID:27208305

  9. The potential impact of a single amino-acid substitution on the efficacy of equine influenza vaccines.

    PubMed

    Yamanaka, T; Cullinane, A; Gildea, S; Bannai, H; Nemoto, M; Tsujimura, K; Kondo, T; Matsumura, T

    2015-07-01

    The protection induced by an equine influenza (EI) vaccine strain depends on its antigenic relatedness to the challenge virus. Although the World Organisation for Animal Health (OIE) recommend that both Florida sublineage clade 1 (Fc1) and clade 2 (Fc2) viruses should be included in EI vaccines, Japanese EI vaccines have not, thus far, been updated to include a Fc2 virus. To evaluate the efficacy of antibodies raised against Japanese EI vaccine strains in the neutralisation of recent Fc2 viruses. Antigenic analysis. Virus neutralisation tests were performed using antisera from experimentally infected horses and from horses that had received a primary course of the currently available vaccines. Antiserum raised against the Japanese EI vaccine strain, A/equine/La Plata/1993, exhibited poor cross-neutralising activity against the Fc2 viruses isolated recently in Ireland and the UK, which have the substitution of alanine to valine at position 144 in antigenic site A of the haemagglutinin gene. In contrast, the antiserum exhibited good cross-neutralising activity against the Fc2 viruses without the substitution. This finding was supported in experiments with antisera collected from vaccinated horses. This suggests that the efficacy of the Japanese EI vaccine for some of the recent Fc2 viruses is suboptimal and that vaccines should be updated in accordance with the OIE recommendations. © 2014 EVJ Ltd.

  10. Natural and non-natural amino-acid side-chain substitutions: affinity and diffraction studies of meditope–Fab complexes

    PubMed Central

    Bzymek, Krzysztof P.; Avery, Kendra A.; Ma, Yuelong; Horne, David A.; Williams, John C.

    2016-01-01

    Herein, multiple crystal structures of meditope peptide derivatives incorporating natural and unnatural amino acids bound to the cetuximab Fab domain are presented. The affinity of each derivative was determined by surface plasmon resonance and correlated to the atomic structure. Overall, it was observed that the hydrophobic residues in the meditope peptide, Phe3, Leu5 and Leu10, could accommodate a number of moderate substitutions, but these invariably reduced the overall affinity and half-life of the interaction. In one case, the substitution of Phe3 by histidine led to a change in the rotamer conformation, in which the imidazole ring flipped to a solvent-exposed position. Based on this observation, Phe3 was substituted by diphenylalanine and it was found that the phenyl rings in this variant mimic the superposition of the Phe3 and His3 structures, producing a moderate increase, of 1.4-fold, in the half-life of the complex. In addition, it was observed that substitution of Leu5 by tyrosine and glutamate strongly reduced the affinity, whereas the substitution of Leu5 by diphenyl­alanine moderately reduced the half-life (by approximately fivefold). Finally, it was observed that substitution of Arg8 and Arg9 by citrulline dramatically reduced the overall affinity, presumably owing to lost electrostatic interactions. Taken together, these studies provide insight into the meditope–cetuximab interaction at the atomic level. PMID:27834791

  11. A single amino-acid substitution toggles chloride dependence of the alpha-amylase paralog amyrel in Drosophila melanogaster and Drosophila virilis species.

    PubMed

    Claisse, Gaëlle; Feller, Georges; Bonneau, Magalie; Da Lage, Jean-Luc

    2016-08-01

    In animals, most α-amylases are chloride-dependent enzymes. A chloride ion is required for allosteric activation and is coordinated by one asparagine and two arginine side chains. Whereas the asparagine and one arginine are strictly conserved, the main chloride binding arginine is replaced by a glutamine in some rare instances, resulting in the loss of chloride binding and activation. Amyrel is a distant paralogue of α-amylase in Diptera, which was not characterized biochemically to date. Amyrel shows both substitutions depending on the species. In Drosophila melanogaster, an arginine is present in the sequence but in Drosophila virilis, a glutamine occurs at this position. We have investigated basic enzymological parameters and the dependence to chloride of Amyrel of both species, produced in yeast, and in mutants substituting arginine to glutamine or glutamine to arginine. We found that the amylolytic activity of Amyrel is about thirty times weaker than the classical Drosophila α-amylase, and that the substitution of the arginine by a glutamine in D. melanogaster suppressed the chloride-dependence but was detrimental to activity. In contrast, changing the glutamine into an arginine rendered D. virilis Amyrel chloride-dependent, and interestingly, significantly increased its catalytic efficiency. These results show that the chloride ion is not mandatory for Amyrel but stimulates the reaction rate. The possible phylogenetic origin of the arginine/glutamine substitution is also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. PET with radiolabeled aminoacid.

    PubMed

    Crippa, F; Alessi, A; Serafini, G L

    2012-04-01

    Since the clinical introduction of FDG, neuroimaging has been the first area of PET application in oncology. Later, while FDG-PET became progressively a key imaging modality in the management of the majority of malignancies outside the brain, its neuro-oncologic indications faced some limitations because of the unfavourable characteristics of FDG as brain tumor-seeking agent. PET applications in neuro-oncology have received new effectiveness by the advent of positron-emission labelled amino acids, so that it has been coined the term "Amino acid PET" to differentiate this imaging tool from FDG-PET. Radiolabeled amino acids are a very interesting class of PET tracers with great diagnostic potential in neuro-oncology because of their low uptake in normal brain and, conversely, high uptake in most brain tumors including low-grade gliomas. The present article surveys the results obtained using L-[methyl-11C]Methionine (MET), that has been the ancestor of PET amino acid tracers and is still the most popular amino acid imaging modality in oncology, and stresses the important role that this diagnostic modality can play in the evaluation of brain tumors. However, the use of MET is restricted to PET centers with an in-house cyclotron and radiochemistry facility, because of the short half-life (20 min) of 11C. The promising results of MET have stimulated the development of 18F-labelled aminoacid tracers, particularly O-(2-18F-fluoeoethyl1)-L-tyrosine (FET), that has the same properties of MET and, thanks to the longer half-life of 18F (about 110 min), allows a distribution strategy from a production tracer site to user satellite PET centers. Considering a more widespread use of Amino acid PET, together with the recent development of integrated PET-MRI imaging systems, and the oncoming clinical validation of other interesting PET tracers, i.e. FMISO or 18F-FAZA for hypoxia imaging and FLT for tumor proliferation imaging, it can be reasonably expected that metabolic imaging

  13. The amino-acid mutational spectrum of human genetic disease.

    PubMed

    Vitkup, Dennis; Sander, Chris; Church, George M

    2003-01-01

    Nonsynonymous mutations in the coding regions of human genes are responsible for phenotypic differences between humans and for susceptibility to genetic disease. Computational methods were recently used to predict deleterious effects of nonsynonymous human mutations and polymorphisms. Here we focus on understanding the amino-acid mutation spectrum of human genetic disease. We compare the disease spectrum to the spectra of mutual amino-acid mutation frequencies, non-disease polymorphisms in human genes, and substitutions fixed between species. We find that the disease spectrum correlates well with the amino-acid mutation frequencies based on the genetic code. Normalized by the mutation frequencies, the spectrum can be rationalized in terms of chemical similarities between amino acids. The disease spectrum is almost identical for membrane and non-membrane proteins. Mutations at arginine and glycine residues are together responsible for about 30% of genetic diseases, whereas random mutations at tryptophan and cysteine have the highest probability of causing disease. The overall disease spectrum mainly reflects the mutability of the genetic code. We corroborate earlier results that the probability of a nonsynonymous mutation causing a genetic disease increases monotonically with an increase in the degree of evolutionary conservation of the mutation site and a decrease in the solvent-accessibility of the site; opposite trends are observed for non-disease polymorphisms. We estimate that the rate of nonsynonymous mutations with a negative impact on human health is less than one per diploid genome per generation.

  14. Promotion of gallbladder emptying by intravenous aminoacids.

    PubMed

    Zoli, G; Ballinger, A; Healy, J; O'Donnell, L J; Clark, M; Farthing, M J

    1993-05-15

    Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.

  15. Radiation reaction as a non-conservative force

    NASA Astrophysics Data System (ADS)

    Aashish, Sandeep; Haque, Asrarul

    2016-09-01

    We study a system of a finite size charged particle interacting with a radiation field by exploiting Hamilton’s principle for a non-conservative system recently introduced by Galley [1]. This formulation leads to the equation of motion of the charged particle that turns out to be the same as that obtained by Jackson [2]. We show that the radiation reaction stems from the non-conservative part of the effective action for a charged particle. We notice that a charge interacting with a radiation field modeled as a heat bath affords a way to justify that the radiation reaction is a non-conservative force. The topic is suitable for graduate courses on advanced electrodynamics and classical theory of fields.

  16. Amino-acid contamination of aqueous hydrochloric acid.

    NASA Technical Reports Server (NTRS)

    Wolman, Y.; Miller, S. L.

    1971-01-01

    Considerable amino-acid contamination in commercially available analytical grade hydrochloric acid (37% HCl) was found. One bottle contained 8,300 nmol of amino-acids per liter. A bottle from another supplier contained 6,700 nmol per liter. The contaminants were mostly protein amino-acids and several unknowns. Data on the volatility of the amino-acids during HCl distillation were also obtained.

  17. Amino-acid contamination of aqueous hydrochloric acid.

    NASA Technical Reports Server (NTRS)

    Wolman, Y.; Miller, S. L.

    1971-01-01

    Considerable amino-acid contamination in commercially available analytical grade hydrochloric acid (37% HCl) was found. One bottle contained 8,300 nmol of amino-acids per liter. A bottle from another supplier contained 6,700 nmol per liter. The contaminants were mostly protein amino-acids and several unknowns. Data on the volatility of the amino-acids during HCl distillation were also obtained.

  18. Free Amino-acid Concentrations in Fetal Fluids

    PubMed Central

    Cockburn, F.; Robins, S. P.; Forfar, J. O.

    1970-01-01

    The pattern of free amino-acid concentrations in maternal venous plasma, fetal umbilical arterial plasma, fetal urine, and amniotic fluid at 15 to 20 weeks' gestation has been determined. Free amino-acid concentrations were greater in fetal plasma than in maternal plasma, amniotic fluid, or fetal urine. The ratios of amino-acid concentrations in fetal umbilical arterial plasma and urine indicate that the fetal kidney can effectively conserve amino-acids, possibly reaching an adult level of competence in this respect. There was little correlation between amino-acid concentrations in the fluids analysed with the exception of that between amniotic fluid and fetal urine. PMID:5472758

  19. Human splanchnic amino-acid metabolism.

    PubMed

    Neis, Evelien P J G; Sabrkhany, S; Hundscheid, I; Schellekens, D; Lenaerts, K; Olde Damink, S W; Blaak, E E; Dejong, C H C; Rensen, Sander S

    2017-01-01

    Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery. The difference between arterial and venous concentrations of 21 amino acids was determined using liquid chromatography as a measure of amino-acid metabolism across a given organ. Whereas glutamine was significantly taken up by the small intestine (121.0 ± 23.8 µmol/L; P < 0.0001), citrulline was released (-36.1 ± 4.6 µmol/L; P < 0.0001). This, however, was not seen for the colon. Interestingly, the liver showed a small, but a significant uptake of citrulline from the circulation (4.8 ± 1.6 µmol/L; P = 0.0138) next to many other amino acids. The kidneys showed a marked release of serine and alanine into the circulation (-58.0 ± 4.4 µmol/L and -61.8 ± 5.2 µmol/L, P < 0.0001), and a smaller, but statistically significant release of tyrosine (-12.0 ± 1.3 µmol/L, P < 0.0001). The spleen only released taurine (-9.6 ± 3.3 µmol/L; P = 0.0078). Simultaneous blood sampling in different veins provides unique qualitative and quantitative information on integrative amino-acid physiology, and reveals that the well-known intestinal glutamine-citrulline pathway appears to be functional in the small intestine but not in the colon.

  20. Optimality of the genetic code with respect to protein stability and amino-acid frequencies

    PubMed Central

    Gilis, Dimitri; Massar, Serge; Cerf, Nicolas J; Rooman, Marianne

    2001-01-01

    Background The genetic code is known to be efficient in limiting the effect of mistranslation errors. A misread codon often codes for the same amino acid or one with similar biochemical properties, so the structure and function of the coded protein remain relatively unaltered. Previous studies have attempted to address this question quantitatively, by estimating the fraction of randomly generated codes that do better than the genetic code in respect of overall robustness. We extended these results by investigating the role of amino-acid frequencies in the optimality of the genetic code. Results We found that taking the amino-acid frequency into account decreases the fraction of random codes that beat the natural code. This effect is particularly pronounced when more refined measures of the amino-acid substitution cost are used than hydrophobicity. To show this, we devised a new cost function by evaluating in silico the change in folding free energy caused by all possible point mutations in a set of protein structures. With this function, which measures protein stability while being unrelated to the code's structure, we estimated that around two random codes in a billion (109) are fitter than the natural code. When alternative codes are restricted to those that interchange biosynthetically related amino acids, the genetic code appears even more optimal. Conclusions These results lead us to discuss the role of amino-acid frequencies and other parameters in the genetic code's evolution, in an attempt to propose a tentative picture of primitive life. PMID:11737948

  1. Parity Non-Conservation in Proton-Proton Elastic Scattering

    SciTech Connect

    V.R. Brown; B.F. Gibson; J.A. Carlson; R. Schiavilla

    2002-06-01

    The parity non-conserving longitudinal asymmetry in proton-proton (pp) elastic scattering is calculated in the lab-energy range 0-350 MeV using contemporary, realistic strong-interaction potentials combined with a weak-interaction potential comprised of rho- and omega-meson exchanges as exemplified by the DDH model. Values for the rho- and omega-meson coupling constants, h{sup rho rho}{sub rho} and h{sup rho rho}{sub omega}, are determined from comparison with the measured asymmetries at 13.6 MeV, 45 MeV, and 221 MeV.

  2. Helicity non-conserving form factor of the proton

    SciTech Connect

    Voutier, E.; Furget, C.; Knox, S.

    1994-04-01

    The study of the hadron structure in the high Q{sup 2} range contributes to the understanding of the mechanisms responsible for the confinement of quarks and gluons. Among the numerous experimental candidates sensitive to these mechanisms, the helicity non-conserving form factor of the proton is a privileged observable since it is controlled by non-perturbative effects. The authors investigate here the feasibility of high Q{sup 2} measurements of this form factor by means of the recoil polarization method in the context of the CEBAF 8 GeV facility. For that purpose, they discuss the development of a high energy proton polarimeter, based on the H({rvec p},pp) elastic scattering, to be placed at the focal plane of a new hadron spectrometer. It is shown that this experimental method significantly improves the knowledge of the helicity non-conserving form factor of the proton up to 10 GeV{sup 2}/c{sup 2}.

  3. Non-conservative perturbations of homoclinic snaking scenarios

    NASA Astrophysics Data System (ADS)

    Knobloch, Jürgen; Vielitz, Martin

    2016-01-01

    Homoclinic snaking refers to the continuation of homoclinic orbits to an equilibrium E near a heteroclinic cycle connecting E and a periodic orbit P. Typically homoclinic snaking appears in one-parameter families of reversible, conservative systems. Here we discuss perturbations of this scenario which are both non-reversible and non-conservative. We treat this problem analytically in the spirit of the work [3]. The continuation of homoclinic orbits happens with respect to both the original continuation parameter μ and the perturbation parameter λ. The continuation curves are parametrised by the dwelling time L of the homoclinic orbit near P. It turns out that λ (L) tends to zero while the μ vs. L diagram displays isolas or criss-cross snaking curves in a neighbourhood of the original snakes-and-ladder structure. In the course of our studies we adapt both Fenichel coordinates near P and the analysis of Shilnikov problems near P to the present situation.

  4. Non-conservative optical forces and Brownian vortexes

    NASA Astrophysics Data System (ADS)

    Sun, Bo

    Optical manipulation using optical tweezers has been widely adopted in physics, chemical engineering and biology. While most applications and fundamental studies of optical trapping have focused on optical forces resulting from intensity gradients, we have also explored the role of radiation pressure, which is directed by phase gradients in beams of light. Interestingly, radiation pressure turns out to be a non-conservative force and drives trapped objects out of thermodynamic equilibrium with their surrounding media. We have demonstrated the resulting nonequilibrium effects experimentally by tracking the thermally driven motions of optically trapped colloidal spheres using holographic video microscopy. Rather than undergoing equilibrium thermal fluctuations, as has been assumed for more than a quarter century, a sphere in an optical tweezer enters into a stochastic steady-state characterized by closed loops in its probability current density. These toroidal vortexes constitute a bias in the particle's otherwise random thermal fluctuations arising at least indirectly from a solenoidal component in the optical force. This surprising effect is a particular manifestation of a more general class of noise-driven machines that we call Brownian vortexes. This previously unrecognized class of stochastic heat engines operates on qualitatively different principles from such extensively studied nonequilibrium systems as thermal ratchets and Brownian motors. Among its interesting properties, a Brownian vortex can reverse its direction with changes in temperature or equivalent control parameters.

  5. Non-conservative evolution in Algols: where is the matter?

    NASA Astrophysics Data System (ADS)

    Deschamps, R.; Braun, K.; Jorissen, A.; Siess, L.; Baes, M.; Camps, P.

    2015-05-01

    Context. There is indirect evidence of non-conservative evolutions in Algols. However, the systemic mass-loss rate is poorly constrained by observations and generally set as a free parameter in binary-star evolution simulations. Moreover, systemic mass loss may lead to observational signatures that still need to be found. Aims: Within the "hotspot" ejection mechanism, some of the material that is initially transferred from the companion star via an accretion stream is expelled from the system due to the radiative energy released on the gainer's surface by the impacting material. The objective of this paper is to retrieve observable quantities from this process and to compare them with observations. Methods: We investigate the impact of the outflowing gas and the possible presence of dust grains on the spectral energy distribution (SED). We used the 1D plasma code Cloudy and compared the results with the 3D Monte-Carlo radiative transfer code Skirt for dusty simulations. The circumbinary mass-distribution and binary parameters were computed with state-of-the-art binary calculations done with the Binstar evolution code. Results: The outflowing material reduces the continuum flux level of the stellar SED in the optical and UV. Because of the time-dependence of this effect, it may help to distinguish between different ejection mechanisms. If present, dust leads to observable infrared excesses, even with low dust-to-gas ratios, and traces the cold material at large distances from the star. By searching for this dust emission in the WISE catalogue, we found a small number of Algols showing infrared excesses, among which the two rather surprising objects SX Aur and CZ Vel. We find that some binary B[e] stars show the same strong Balmer continuum as we predict with our models. However, direct evidence of systemic mass loss is probably not observable in genuine Algols, since these systems no longer eject mass through the hotspot mechanism. Furthermore, owing to its high

  6. Synthesis of magnetite nanoparticles in the presence of aminoacids

    NASA Astrophysics Data System (ADS)

    Marinescu, Gabriela; Patron, Luminita; Culita, Daniela C.; Neagoe, Cristian; Lepadatu, Costinel I.; Balint, Ioan; Bessais, Lotfi; Cizmas, Corneliu Bazil

    2006-12-01

    A new synthesis route to prepare magnetite nanoparticles in only one step is described. The precipitation of magnetite is performed in the presence of aminoacid solution. The experimental protocol is original and the nanomagnetites are characterized by XRD, FTIR, TEM and SQUID magnetometry. A theoretical study of the consistent experimental results was performed using QSPR (Quantitative Structure Property Relationsheep). According with these studies the synthesized nanoparticles seem to be organized into a core-shell system, where the inner-core is formed from unit cells of magnetite. A way to control the self-assembly and the physical properties of the synthesized nanoparticles consists in their correlation with descriptors representing the aminoacid chemical structures. Using quantum chemical as well as the other simplest original descriptors it was found a relationship between the used aminoacids and the magnetization, nanoparticles diameter, magnetite core diameter and the (Fe3O4)8 cells in each nanoparticle core.

  7. The amino-acid sequence of alpha A- and beta-chains from the major hemoglobin component of American flamingo (Phoenicopterus ruber ruber).

    PubMed

    Godovac-Zimmermann, J; Braunitzer, G

    1984-04-01

    The complete amino-acid sequence of alpha A- and beta-chains from the major hemoglobin component (HbA) of American Flamingo ( Phoenicopterus ruber ruber) is presented. The minor component (HbD) with alpha D-chains was detected in similar amounts (25%) as in chicken and pheasant hemoglobins. The comparison of American Flamingo and Greylag Goose (Anser anser) hemoglobins shows that alpha A-chains differ by 22 exchanges and beta-chains by only 4 exchanges. Two substitutions modify alpha 1 beta 1-contacts. Amino-acid replacements between American Flamingo and other bird hemoglobins are discussed.

  8. Computational prediction of the tolerance to amino-acid deletion in green-fluorescent protein

    PubMed Central

    Jackson, Eleisha L.; Spielman, Stephanie J.

    2017-01-01

    Proteins evolve through two primary mechanisms: substitution, where mutations alter a protein’s amino-acid sequence, and insertions and deletions (indels), where amino acids are either added to or removed from the sequence. Protein structure has been shown to influence the rate at which substitutions accumulate across sites in proteins, but whether structure similarly constrains the occurrence of indels has not been rigorously studied. Here, we investigate the extent to which structural properties known to covary with protein evolutionary rates might also predict protein tolerance to indels. Specifically, we analyze a publicly available dataset of single—amino-acid deletion mutations in enhanced green fluorescent protein (eGFP) to assess how well the functional effect of deletions can be predicted from protein structure. We find that weighted contact number (WCN), which measures how densely packed a residue is within the protein’s three-dimensional structure, provides the best single predictor for whether eGFP will tolerate a given deletion. We additionally find that using protein design to explicitly model deletions results in improved predictions of functional status when combined with other structural predictors. Our work suggests that structure plays fundamental role in constraining deletions at sites in proteins, and further that similar biophysical constraints influence both substitutions and deletions. This study therefore provides a solid foundation for future work to examine how protein structure influences tolerance of more complex indel events, such as insertions or large deletions. PMID:28369116

  9. Purification of a marsupial insulin: amino-acid sequence of insulin from the eastern grey kangaroo Macropus giganteus.

    PubMed

    Treacy, G B; Shaw, D C; Griffiths, M E; Jeffrey, P D

    1989-03-24

    Insulin has been purified from kangaroo pancreas by acidic ethanol extraction, diethyl ether precipitation and gel filtration. The amino-acid sequence of this, the first marsupial insulin to be studied, is reported. It differs from human insulin by only four amino-acid substitutions, all in regions of the molecule previously known to be variable. However, it should be noted that one of these, asparagine for threonine at A8, has not been reported before. Computer comparisons of all 43 insulin sequences reported to date with kangaroo insulin show it to be most closely related to a group of mammalian insulins (dog, pig, cow, human) known to be of high biological potency. The measurement of blood glucose lowering in the rabbit by kangaroo insulin is consistent with this conclusion. Comparisons of amino-acid sequences of other proteins with their kangaroo counterparts show a greater difference, in line with the time of divergence of marsupials. The limited differences observed in insulin and cytochrome c suggest that their structures need to be closely conserved in order to maintain function.

  10. A Fiber Optic Colorimeter For Liquid Phase Chromatography Of Aminoacids

    NASA Astrophysics Data System (ADS)

    Donati, S.; Tambosso, T.

    1989-01-01

    Liquid phase chromatography is a well known technique routinely used in analytical chemistry for assays and measurements of aminoacids 1,2. Basically, the solution is pumped at high pressure in a long capillary tube (the chromatographic column) to fraction out the constituents, is mixed to a suitable reactant (usually ninhydrine) so as to develop a spectral absorbance, and is finally analyzed in a flow cell by a colorimeter. With ninhydrine, the reaction product is DIDA (diketo-hydrindilidene-diketolhydrin diamine) which exhibits absorbance peaks at 440 nm (blue) and 570 nm (yellow) in a proportion dependent on the specific aminoacid (Fig. 1), while the amplitude of peaks is proportional to the aminoacid concentration in view of Lambert-Beer law. Besides the two measurement channels of absorbance, either of which or the sum of which is taken as the output signal, a third channel at the wavelength 690 nm at which DIDA is transparent (Ar = 0), is used internally as the reference to the first two. Thus, the colorimeter is actually a spectrophotometer with two fixed-wavelength channels, each referenced in wavelength. In this paper, we report on the design and engineering of a colorimeter aimed to medium/high performances, high reliability and low cost. Use of fiber optics as the beamsplitter of the optical channels is shown to give substantial advantages.

  11. A new comment on the computation of non-conservative products using Roe-type path conservative schemes

    NASA Astrophysics Data System (ADS)

    Chalons, Christophe; Coquel, Frédéric

    2017-04-01

    We are interested in the numerical approximation of the discontinuous solutions of non-conservative hyperbolic systems. We more precisely consider a non-conservative formulation of the usual gas dynamics equations and show how to slightly modify the so-called Roe-type path-conservative schemes to properly capture the underlying shock discontinuities. Numerical evidences are proposed. The present note follows a first comment on the computation of non-conservative products in [1].

  12. An uncertainty inclusive un-mixing model to identify tracer non-conservativeness

    NASA Astrophysics Data System (ADS)

    Sherriff, Sophie; Rowan, John; Franks, Stewart; Fenton, Owen; Jordan, Phil; hUallacháin, Daire Ó.

    2015-04-01

    Sediment fingerprinting is being increasingly recognised as an essential tool for catchment soil and water management. Selected physico-chemical properties (tracers) of soils and river sediments are used in a statistically-based 'un-mixing' model to apportion sediment delivered to the catchment outlet (target) to its upstream sediment sources. Development of uncertainty-inclusive approaches, taking into account uncertainties in the sampling, measurement and statistical un-mixing, are improving the robustness of results. However, methodological challenges remain including issues of particle size and organic matter selectivity and non-conservative behaviour of tracers - relating to biogeochemical transformations along the transport pathway. This study builds on our earlier uncertainty-inclusive approach (FR2000) to detect and assess the impact of tracer non-conservativeness using synthetic data before applying these lessons to new field data from Ireland. Un-mixing was conducted on 'pristine' and 'corrupted' synthetic datasets containing three to fifty tracers (in the corrupted dataset one target tracer value was manually corrupted to replicate non-conservative behaviour). Additionally, a smaller corrupted dataset was un-mixed using a permutation version of the algorithm. Field data was collected in an 11 km2 river catchment in Ireland. Source samples were collected from topsoils, subsoils, channel banks, open field drains, damaged road verges and farm tracks. Target samples were collected using time integrated suspended sediment samplers at the catchment outlet at 6-12 week intervals from July 2012 to June 2013. Samples were dried (<40°C), sieved (125 µm) and analysed for mineral magnetic susceptibility, anhysteretic remanence and iso-thermal remanence, and geochemical elements Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn (following microwave-assisted acid digestion). Discriminant analysis was used to reduce the number of tracer numbers before un-mixing. Tracer non-conservativeness

  13. Review on hydroxylamine, a precursor to amino-acids

    NASA Astrophysics Data System (ADS)

    Lemaire, Jean Louis

    2015-08-01

    Does life on earth come from interstellar space (IS)?It has been recently demonstrated that part of the terrestrial water is of IS origin [Cleeves et al. Science 2014]. This raises the question whether materials like amino-acids or their pre-biotic molecular precursors could have been formed and brought to earth in the same way than water. Another question is whether these molecules were formed in the gas phase or through reactions on the surface/volume of ice-covered grains. This may then have occurred in the vicinity of proto-stellar cores or deep into a pristine dense molecular clouds at very low temperatures.As far as bio-related molecules are concerned, chemistry with nitrogen-bearing molecules (like NH3 and NO) is involved. I review recent experimental work showing that hydroxylamine (NH2OH) could be formed either by surface or by volume reactions in conditions close to those prevailing in dense media. They use either electron-UV irradiation of water-ammonia ices [Zheng & Kaiser JCPA 2010] or successive hydrogenation of solid nitric oxide[Congiu, Fedoseev & al. ApJL.2012] or the simple oxidation of ammonia [He, Vidali, Lemaire & Garrod, ApJ, 2015] or the reaction of ammonia with hydroxyl radicals in a rare gas matrix [Zins & Krim, 2014, 69th ISMS]. A step further, the synthesis of the simplest amino-acids, glycine (NH2CH2COOH) and L- or D-alanine (NH2CH3CHCOOH) has already been obtained via reactions in the gas phase involving NH2OH+ [Blagojevic & al. MNRAS 2003].In addition to several earlier models demonstrating that the formation of all these molecules is possible in the gas phase, a new recent three-phase gas-grain chemical kinetics model of hot cores [Garrod ApJ 2013] shows that the results of ammonia oxidation we obtain are plausible by surface/volume reactions.Although none of the aforementioned molecules (except glycine in a sample of cometary origin) has been yet detected in the IS, they all are considered by many observers and modelers as likely

  14. Statistical Mechanics of Colloidal Particles in Non-Conservative Force Fields

    NASA Astrophysics Data System (ADS)

    Wakil Moyses, Henrique

    Systems that are in mechanical equilibrium but are driven away from thermodynamic equilibrium present directed motion when in a thermal bath. This thesis explores this motion when systems are out of thermodynamic equilibrium due to the presence of non-conservative force fields. The first system we explored are Brownian vortexes. These are stochastic machines that use static non-conservative force fields to bias random thermal fluctuations into steadily circulating currents. The archetype for this class of systems is a colloidal sphere in an optical tweezer. Trapped near the focus of a strongly converging beam of light, the particle is displaced by random thermal kicks into the nonconservative part of the optical force field arising from radiation pressure, which then biases its diffusion. Assuming the particle remains localized within the trap, its time-averaged trajectory traces out a toroidal vortex. Unlike trivial Brownian vortexes, such as the biased Brownian pendulum, which circulate preferentially in the direction of the bias, the general Brownian vortex can change direction and even topology in response to temperature changes. In this thesis we introduce a theory based on a perturbative expansion of the Fokker-Planck equation for weak non-conservative driving. We show that the first-order solution takes the form of a modified Boltzmann relation and accounts for the rich phenomenology observed in experiments on micrometer-scale colloidal spheres in optical tweezers. Another system we explore are colloidal Janus particles composed of an optically absorbing and transparent faces. When illuminated by a defocused optical tweezer these particles swim vigorously, without requiring any chemical fuel. Most surprisingly, these optically activated colloidal swimmers circulate back and forth through the beam of light, tracing out regular sinuous patterns. In this thesis we propose a model for this class of light-activated swimmers in which a combination of radiation

  15. Family number non-conservation induced by the supersymmetric mixing of scalar leptons

    SciTech Connect

    Levine, M.J.S.

    1987-08-01

    The most egregious aspect of (N = 1) supersymmetric theories is that each particle state is accompanied by a 'super-partner', a state with identical quantum numbers save that it differs in spin by one half unit. For the leptons these are scalars and are called ''sleptons'', or scalar leptons. These consist of the charged sleptons (selectron, smuon, stau) and the scalar neutrinos ('sneutrinos'). We examine a model of supersymmetry with soft breaking terms in the electroweak sector. Explicit mixing among the scalar leptons results in a number of effects, principally non-conservation of lepton family number. Comparison with experiment permits us to place constraints upon the model. 49 refs., 12 figs.

  16. Hyperfine Structure, Scalar-pseudoscalar Interaction and Parity Non-Conservation Effect in Some Heavy Atoms and Ions

    NASA Astrophysics Data System (ADS)

    Khetselius, O. Yu.; Florko, T. A.; Nikola, L. V.; Svinarenko, A. A.; Serga, I. N.; Tkach, T. B.; Mischenko, E. V.

    2010-05-01

    The hyperfine structure parameters, scalar-pseudoscalar interaction constants and parity non-conservation effect in some heavy atomic systems are calculated and treated within the combined QED perturbation theory formalism and relativistic nuclear mean-field theory.

  17. Activation of α-secretase by curcumin-aminoacid conjugates.

    PubMed

    Narasingappa, Ramesh B; Narasingapa, Ramesh B; Javagal, Manjunatha R; Jargaval, Manjunatha R; Pullabhatla, Srinivas; Htoo, Htut Htut; Rao, Jagannatha K S; Hernandez, Jean-François; Govitrapong, Piyarat; Vincent, Bruno

    2012-08-10

    The extracellular senile plaques observed in Alzheimer's disease (AD) patients are mainly composed of amyloid peptides produced from the β-amyloid precursor protein (βAPP) by β- and γ-secretases. A third non-amyloidogenic α-secretase activity performed by the disintegrins ADAM10 and ADAM17 occurs in the middle of the amyloid-β peptide Aβ and liberates the large sAPPα neuroprotective fragment. Since the activation of α-secretase recently emerged as a promising therapeutic approach to treat AD, the identification of natural compounds able to trigger this cleavage is highly required. Here we describe new curcumin-based modified compounds as α-secretase activators. We established that the aminoacid conjugates curcumin-isoleucine, curcumin-phenylalanine and curcumin-valine promote the constitutive α-secretase activity and increase ADAM10 immunoreactivity. Strickingly, experiments carried out under conditions mimicking the PKC/muscarinic receptor-regulated pathway display different patterns of activation by these compounds. Altogether, our data identified new lead natural compounds for the future development of powerful and stable α-secretase activators and established that some of these molecules are able to discriminate between the constitutive and regulated α-secretase pathways.

  18. Evolution of wealth in a non-conservative economy driven by local Nash equilibria

    PubMed Central

    Degond, Pierre; Liu, Jian-Guo; Ringhofer, Christian

    2014-01-01

    We develop a model for the evolution of wealth in a non-conservative economic environment, extending a theory developed in Degond et al. (2014 J. Stat. Phys. 154, 751–780 (doi:10.1007/s10955-013-0888-4)). The model considers a system of rational agents interacting in a game-theoretical framework. This evolution drives the dynamics of the agents in both wealth and economic configuration variables. The cost function is chosen to represent a risk-averse strategy of each agent. That is, the agent is more likely to interact with the market, the more predictable the market, and therefore the smaller its individual risk. This yields a kinetic equation for an effective single particle agent density with a Nash equilibrium serving as the local thermodynamic equilibrium. We consider a regime of scale separation where the large-scale dynamics is given by a hydrodynamic closure with this local equilibrium. A class of generalized collision invariants is developed to overcome the difficulty of the non-conservative property in the hydrodynamic closure derivation of the large-scale dynamics for the evolution of wealth distribution. The result is a system of gas dynamics-type equations for the density and average wealth of the agents on large scales. We recover the inverse Gamma distribution, which has been previously considered in the literature, as a local equilibrium for particular choices of the cost function. PMID:25288808

  19. Novel insights from non-conserved microRNAs in plants

    PubMed Central

    Qin, Zhengrui; Li, Chunlian; Mao, Long; Wu, Liang

    2014-01-01

    Plant microRNAs (miRNAs), a class of small non-coding regulatory RNAs, are canonically 20–24 nucleotides in length and bind to complementary target RNA sequences, guiding target attenuation via mRNA degradation or translation inhibition. Of the annotated miRNA families, evolutionarily conserved families have been well known to extensively regulate analogous targets and play critical roles in plant development and adaptation to adverse environments. By contrast, majority of these families that are merely present in a specific lineage or in a few closely related species have not been well functionally explored until recently. The fast-growing progresses being made in the actions of non-conserved miRNAs nowadays in diverse plant species may represent a highly promising research field in future. This review thereby summarizes the emerging advances in our understanding of the biogenesis, associated effectors, modes to targets, and biological functions of plant non-conserved miRNAs. In addition, it outlines the regulatory units recently discovered between conserved miRNAs and their alternative targets. PMID:25389431

  20. Hamiltonian formulation of the spin-orbit model with time-varying non-conservative forces

    NASA Astrophysics Data System (ADS)

    Gkolias, Ioannis; Efthymiopoulos, Christos; Pucacco, Giuseppe; Celletti, Alessandra

    2017-10-01

    In a realistic scenario, the evolution of the rotational dynamics of a celestial or artificial body is subject to dissipative effects. Time-varying non-conservative forces can be due to, for example, a variation of the moments of inertia or to tidal interactions. In this work, we consider a simplified model describing the rotational dynamics, known as the spin-orbit problem, where we assume that the orbital motion is provided by a fixed Keplerian ellipse. We consider different examples in which a non-conservative force acts on the model and we propose an analytical method, which reduces the system to a Hamiltonian framework. In particular, we compute a time parametrisation in a series form, which allows us to transform the original system into a Hamiltonian one. We also provide applications of our method to study the rotational motion of a body with time-varying moments of inertia, e.g. an artificial satellite with flexible components, as well as subject to a tidal torque depending linearly on the velocity.

  1. Spectroscopy with Laser-cooled Francium and Progress on Atomic Parity Non-conservation

    NASA Astrophysics Data System (ADS)

    Zhang, Jiehang

    Francium, the heaviest alkali, possesses a unique combination of structural simplicity and great sensitivity to effects such as atomic parity non-conservation (APNC). We report in this thesis our progress towards measuring weak-interaction physics in a low energy system: the francium atom. We have built a new generation of high-efficiency laser cooling and trapping facility at TRIUMF national laboratory in Canada. We constructed a precision science chamber and demonstrate francium atom transfer into the precision trap, where the electromagnetic field environments can be exquisitely controlled such that weak-interaction studies via optical and microwave excitations can take place. We perform laser spectroscopy measurements of the hyperfine structure and isotope shifts in a chain of francium isotopes near the neutron closed shell (N = 126), including both ground and isomeric nuclear states. These measurements provide a basis for benchmarking state of the art atomic theory, as well as future nuclear structure calculations in Fr, necessary for interpreting the weak-interaction studies. These developments lay important foundations for precision parity non-conservation measurements with francium.

  2. Evolution of wealth in a non-conservative economy driven by local Nash equilibria.

    PubMed

    Degond, Pierre; Liu, Jian-Guo; Ringhofer, Christian

    2014-11-13

    We develop a model for the evolution of wealth in a non-conservative economic environment, extending a theory developed in Degond et al. (2014 J. Stat. Phys. 154, 751-780 (doi:10.1007/s10955-013-0888-4)). The model considers a system of rational agents interacting in a game-theoretical framework. This evolution drives the dynamics of the agents in both wealth and economic configuration variables. The cost function is chosen to represent a risk-averse strategy of each agent. That is, the agent is more likely to interact with the market, the more predictable the market, and therefore the smaller its individual risk. This yields a kinetic equation for an effective single particle agent density with a Nash equilibrium serving as the local thermodynamic equilibrium. We consider a regime of scale separation where the large-scale dynamics is given by a hydrodynamic closure with this local equilibrium. A class of generalized collision invariants is developed to overcome the difficulty of the non-conservative property in the hydrodynamic closure derivation of the large-scale dynamics for the evolution of wealth distribution. The result is a system of gas dynamics-type equations for the density and average wealth of the agents on large scales. We recover the inverse Gamma distribution, which has been previously considered in the literature, as a local equilibrium for particular choices of the cost function.

  3. Bidimensional nano-optomechanics and topological backaction in a non-conservative radiation force field.

    PubMed

    Gloppe, A; Verlot, P; Dupont-Ferrier, E; Siria, A; Poncharal, P; Bachelier, G; Vincent, P; Arcizet, O

    2014-11-01

    Optomechanics, which explores the fundamental coupling between light and mechanical motion, has made important advances in manipulating macroscopic mechanical oscillators down to the quantum level. However, dynamical effects related to the vectorial nature of the optomechanical interaction remain to be investigated. Here we study a nanowire with subwavelength dimensions coupled strongly to a tightly focused beam of light, enabling an ultrasensitive readout of the nanoresonator dynamics. We determine experimentally the vectorial structure of the optomechanical interaction and demonstrate that a bidimensional dynamical backaction governs the nanowire dynamics. Moreover, the spatial topology of the optomechanical interaction is responsible for novel canonical signatures of strong coupling between mechanical modes, which leads to a topological instability that underlies the non-conservative nature of the optomechanical interaction. These results have a universal character and illustrate the increased sensitivity of nanomechanical devices towards spatially varying interactions, opening fundamental perspectives in nanomechanics, optomechanics, ultrasensitive scanning force microscopy and nano-optics.

  4. Power flow and energy balance of non-conservatively coupled structures, II: Experimental verification of theory

    NASA Astrophysics Data System (ADS)

    Sun, J. C.; Chow, L. C.; Lalor, N.; Richards, E. J.

    1987-01-01

    A series of experiments has been carried out on a thick plate bolted to a thin plate in an L shape to verify the theory presented in the first of these two companion papers. The ratio of energy stored in the plates was measured with and without different gaskets between the joint, and the results are compared with those calculated from the energy balance equations for non-conservatively coupled structures [1]. The theory presented in Part I has also been applied to the estimation of the effective loss factors due to air pumping of two plates bolted in parallel. In both cases, agreement between measured and calculated results is found to be good.

  5. The FrPNC experiment at TRIUMF: Atomic parity non-conservation in francium

    NASA Astrophysics Data System (ADS)

    Aubin, S.; Gomez, E.; Behr, J. A.; Pearson, M. R.; Sheng, D.; Zhang, J.; Collister, R.; Melconian, D.; Flambaum, V. V.; Sprouse, G. D.; Orozco, L. A.; Gwinner, G.

    2012-09-01

    The FrPNC collaboration has begun the construction of an on-line laser cooling and trapping apparatus at TRIUMF to measure atomic parity non-conservation (PNC) and the nuclear anapole moment in a string of artificially produced francium isotopes. Atomic PNC experiments provide unique high precision tests of the electroweak sector of the Standard Model at very low energies. Furthermore, precision measurements of spin-dependent atomic PNC can determine nuclear anapole moments and probe the weak force within the nucleus. Francium is an excellent candidate for precision measurements of atomic PNC due to its simple electronic structure and enhanced parity violation: both the optical PNC and anapole moment signals are expected to be over an order of magnitude larger than in cesium.

  6. The conservative and non-conservative properties of DOM in the Beaufort Sea

    NASA Astrophysics Data System (ADS)

    Osburn, C.; Stedmon, C.; Vincent, W.

    2004-12-01

    The Beaufort Sea is strongly influenced by the Mackenzie River, which annually discharges large amounts of dissolved organic matter (DOM) to the western Arctic Ocean. We have evidence from water samples collected in 2002 that DOM from the Mackenzie River may be consumed such that DOM behaves non-conservatively up to a salinity of 20 in the Beaufort Sea. Experimental evidence showed that Mackenzie River DOM is highly susceptible to photochemical degradation and we have calculated rates of DOM oxidation and photobleaching. These rates provide upper estimates on the turnover of terrigenous organic carbon in the Beaufort Sea. A possible mechanism is presented that suggests residence time in the surface waters of the Beaufort Gyre as the mechanism by which Mackenzie River DOM may be removed.

  7. Non-Conservative Variational Approximation for Nonlinear Schrodinger Equations and its Applications

    NASA Astrophysics Data System (ADS)

    Rossi, Julia M.

    Recently, Galley [Phys. Rev. Lett. 110, 174301 (2013)] proposed an initial value problem formulation of Hamilton's principle applied to non-conservative systems. Here, we explore this formulation for complex partial differential equations of the nonlinear Schrodinger (NLS) type, using the non-conservative variational approximation (NCVA) outlined by Galley. We compare the formalism of the NCVA to two variational techniques used in dissipative systems; namely, the perturbed variational approximation and a generalization of the so-called Kantorovitch method. We showcase the relevance of the NCVA method by exploring test case examples within the NLS setting including combinations of linear and density dependent loss and gain. We also present an example applied to exciton-polariton condensates that intrinsically feature loss and a spatially dependent gain term. We also study a variant of the NLS used in optical systems called the Lugiato-Lefever (LL) model applied to (i) spontaneous temporal symmetry breaking instability in a coherently-driven optical Kerr resonator observed experimentally by Xu and Coen in Opt. Lett. 39, 3492 (2014) and (ii) temporal tweezing of cavity solitons in a passive loop of optical fiber pumped by a continuous-wave laser beam observed experimentally by Jang, Erkintalo, Coen, and Murdoch in Nat. Commun. 6, 7370 (2015). For application (i) we perform a detailed stability analysis and analyze the temporal bifurcation structure of stationary symmetric configurations and the emerging asymmetric states as a function of the pump power. For intermediate pump powers a pitchfork loop is responsible for the destabilization of symmetric states towards stationary asymmetric ones while at large pump powers we find the emergence of periodic asymmetric solutions via a Hopf bifurcation. For application (ii) we study the existence and dynamics of cavity solitons through phase-modulation of the holding beam. We find parametric regions for the manipulation of

  8. Non-conservative oscillations of a tool for deep hole honing

    NASA Astrophysics Data System (ADS)

    Gouskov, Alexander M.; Voronov, Sergey A.; Butcher, Eric A.; Sinha, S. C.

    2006-09-01

    The dynamics of a rotating tool, commonly employed in deep hole honing, is considered. A mathematical model of the process including a dynamic representation of tool, workpiece surface and honing stones interaction is suggested and analyzed. It is shown that interaction forces are non-conservative. The honing tool is modeled as a rotating continuous slender beam with a mandrel attached at an intermediate cross-section. The transverse oscillations of tool shaft cause variation in expansion pressure and change the interaction forces on the surface of the workpiece. The interaction forces are nonlinear and non-conservative in the general case including delayed functions. The expansion pressure of stones turns out to be a critical parameter in a honing process. Since the removal of stock increases linearly with pressure, the productivity can be improved by increasing expansion pressure, but in certain conditions may cause dynamic instability of the tool shaft. On the other hand, the lower expansion pressure and feed rates increase accuracy. Another source of shaft instability is due to the asymmetry of the tool that leads to discrepancy of the system stiffness in the transverse directions. As a result, under certain conditions unstable parametric vibrations may occur. Needless to say, the dynamic behavior of the tool can considerably influence the machined surface formation. In this study a model of honing surface formation is introduced and integrated into the model of process simulation. The system response is studied for different parameters in a non-dimensional form. Thus it is possible to analyze a set of real processes by applying the similarity conditions. The variation in the machined surface having various initial discrepancies from ideal cylinder is also analyzed.

  9. The effect of aminoacids on the crystal growth of calcium carbonate

    NASA Astrophysics Data System (ADS)

    Manoli, F.; Kanakis, J.; Malkaj, P.; Dalas, E.

    2002-03-01

    The kinetics of vaterite (CaCO 3) crystallization on calcite in the presence of the aminoacids alanine, glycine, lysine as well as on lysine, polyglycine, polytyrosine and polymethionine was investigated by the constant composition method. The presence of the above mentioned aminoacids stabilizes this calcium carbonate polymorph. The number of ions forming the critical nucleus, the surface energy as well as the apparent growth order for the forming phase was estimated.

  10. Parameters of proteome evolution from histograms of amino-acid sequence identities of paralogous proteins

    PubMed Central

    Axelsen, Jacob Bock; Yan, Koon-Kiu; Maslov, Sergei

    2007-01-01

    Background The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic parameters of these three basic processes is contained in the proteome-wide distribution of sequence identities of pairs of paralogous proteins. Results We introduce a simple mathematical framework based on a stochastic birth-and-death model that allows one to extract some of this information and apply it to the set of all pairs of paralogous proteins in H. pylori, E. coli, S. cerevisiae, C. elegans, D. melanogaster, and H. sapiens. It was found that the histogram of sequence identities p generated by an all-to-all alignment of all protein sequences encoded in a genome is well fitted with a power-law form ~ p-γ with the value of the exponent γ around 4 for the majority of organisms used in this study. This implies that the intra-protein variability of substitution rates is best described by the Gamma-distribution with the exponent α ≈ 0.33. Different features of the shape of such histograms allow us to quantify the ratio between the genome-wide average deletion/duplication rates and the amino-acid substitution rate. Conclusion We separately measure the short-term ("raw") duplication and deletion rates rdup∗, rdel∗ which include gene copies that will be removed soon after the duplication event and their dramatically reduced long-term counterparts rdup, rdel. High deletion rate among recently duplicated proteins is consistent with a scenario in which they didn't have enough time to significantly change their functional roles and thus are to a large degree disposable. Systematic trends of each of the four duplication/deletion rates with the total number of genes in the genome were analyzed. All but the deletion rate of recent duplicates rdel∗ were shown to systematically increase with Ngenes. Abnormally flat shapes

  11. Noether's theorem for non-conservative Hamilton system based on El-Nabulsi dynamical model extended by periodic laws

    NASA Astrophysics Data System (ADS)

    Long, Zi-Xuan; Zhang, Yi

    2014-11-01

    This paper focuses on the Noether symmetries and the conserved quantities for both holonomic and nonholonomic systems based on a new non-conservative dynamical model introduced by El-Nabulsi. First, the El-Nabulsi dynamical model which is based on a fractional integral extended by periodic laws is introduced, and El-Nabulsi—Hamilton's canonical equations for non-conservative Hamilton system with holonomic or nonholonomic constraints are established. Second, the definitions and criteria of El-Nabulsi—Noether symmetrical transformations and quasi-symmetrical transformations are presented in terms of the invariance of El-Nabulsi—Hamilton action under the infinitesimal transformations of the group. Finally, Noether's theorems for the non-conservative Hamilton system under the El-Nabulsi dynamical system are established, which reveal the relationship between the Noether symmetry and the conserved quantity of the system.

  12. Interspecific comparison of the period gene of Drosophila reveals large blocks of non-conserved coding DNA.

    PubMed Central

    Colot, H V; Hall, J C; Rosbash, M

    1988-01-01

    We have cloned and sequenced the coding region of the period (per) gene from Drosophila pseudoobscura and D. virilis. A comparison with that of D. melanogaster reveals that the conceptual translation products consist of interspersed blocks of conserved and non-conserved amino acid sequence. The non-conserved portion, comprising approximately 33% of the protein sequence, includes the perfect Thr-Gly repeat of D. melanogaster, which is absent from the D. pseudoobscura and D. virilis proteins. Based on these observations and cross-species transformation experiments, we suggest that the interspecific variability in the per primary amino acid sequence contributes to the control of species-specific behaviors. PMID:3208754

  13. Evidence of a non-conservative mass transfer for XTE J0929-314

    NASA Astrophysics Data System (ADS)

    Marino, A.; Di Salvo, T.; Gambino, A. F.; Iaria, R.; Burderi, L.; Matranga, M.; Sanna, A.; Riggio, A.

    2017-07-01

    Context. In 1998 the first accreting millisecond pulsar, SAX J1808.4-3658, was discovered and to date 18 systems showing coherent, high frequency (>100 Hz) pulsations in low-mass X-ray binaries are known. Since their discovery, this class of sources has shown interesting and sometimes puzzling behaviours. In particular, apart from a few exceptions, they are all transient with very long X-ray quiescent periods implying a quite low averaged mass accretion rate onto the neutron star. Among these sources, XTE J0929-314 has been detected in outburst just once in about 15 years of continuous monitoring of the X-ray sky. Aims: We aim to demonstrate that a conservative mass transfer in this system will result in an X-ray luminosity that is higher than the observed, long-term averaged X-ray luminosity. Methods: Under the hypothesis of a conservative mass transfer driven by gravitational radiation, as expected for this system given the short orbital period of about 43.6 min and the low-mass of the companion implied by the mass function derived from timing techniques, we calculate the expected mass transfer rate in this system and predict the long-term averaged X-ray luminosity. This is compared with the averaged, over 15 years, X-ray flux observed from the system, and a lower limit of the distance to the source is inferred. Results: This distance is shown to be >7.4 kpc in the direction of the Galactic anticentre, implying a large height, >1.8 kpc, of the source with respect to the Galactic plane, placing the source in an empty region of the Galaxy. We suggest that the inferred value of the distance is unlikely. Conclusions: This problem can be solved if we hypothesize that the source is undergoing a non-conservative mass transfer, in which most of the mass transferred from the companion star is ejected from the system, probably because of the (rotating magnetic dipole) radiation pressure of the pulsar. If confirmed by future observations, this may be another piece of

  14. Characterization of yeast EF-1 alpha: non-conservation of post-translational modifications.

    PubMed

    Cavallius, J; Zoll, W; Chakraburtty, K; Merrick, W C

    1993-04-21

    Elongation factor 1 alpha (EF-1 alpha) is an abundant cellular protein and its amino-acid sequence has been inferred from numerous organisms, including bacteria, archaebacteria, plants and animals. In large measure, it would appear that the overall structure has probably been maintained given the 33% identity and 56% similarity of Escherichia coli EF-Tu with human EF-1 alpha. Chemical sequencing of EF-Tu and EF-1 alpha has revealed that these proteins are post-translationally modified. In order to assess the possible function of these modifications, we have chemically sequenced the EF-1 alpha from the lower eukaryote Saccharomyces cerevisiae (yeast). To our surprise, the methylation pattern of yeast EF-1 alpha was quite different from either rabbit or brine shrimp EF-1 alpha with only the trimethyllysine at position 79 conserved although the yeast protein is 81% identical to rabbit EF-1 alpha. A dimethyllysine was observed at position 316 which corresponds to a trimethyllysine in brine shrimp and rabbit EF-1 alpha. The other positions in yeast EF-1 alpha which were methylated were unrelated to the other six possible positions for modification observed in brine shrimp or rabbit EF-1 alpha. In addition, the unique glyceryl-phosphorylethanolamine observed in mammalian EF-1 alpha and suspected in brine shrimp EF-1 alpha was not found in yeast EF-1 alpha.

  15. Non-conservative extension of Keplerian integrals and a new class of integrable system

    NASA Astrophysics Data System (ADS)

    Roa, Javier

    2016-12-01

    The invariance of the Lagrangian under time translations and rotations in Kepler's problem yields the conservation laws related to the energy and angular momentum. Noether's theorem reveals that these same symmetries furnish generalized forms of the first integrals in a special non-conservative case, which approximates various physical models. The system is perturbed by a biparametric acceleration with components along the tangential and normal directions. A similarity transformation reduces the biparametric disturbance to a simpler uniparametric forcing along the velocity vector. The solvability conditions of this new problem are discussed, and closed-form solutions for the integrable cases are provided. Thanks to the conservation of a generalized energy, the orbits are classified as elliptic, parabolic, and hyperbolic. Keplerian orbits appear naturally as particular solutions to the problem. After characterizing the orbits independently, a unified form of the solution is built based on the Weierstrass elliptic functions. The new trajectories involve fundamental curves such as cardioids and logarithmic, sinusoidal, and Cotes' spirals. These orbits can represent the motion of particles perturbed by solar radiation pressure, of spacecraft with continuous-thrust propulsion, and some instances of Schwarzschild geodesics. Finally, the problem is connected with other known integrable systems in celestial mechanics.

  16. Neutralizer for TRIUMF's experiment for measurements of parity non-conservation in francium

    NASA Astrophysics Data System (ADS)

    Gorelov, Alexandre; Behr, J. A.; Kalita, M. R.; Pearson, M. R.; Tandecki, M.,; L, D.; Aubin, S.; Collister, R.; Dehart, A. C.; Gwinner, G.; Gomez, E.; Orozco, L. A.; Z, J.

    2016-09-01

    The experiment at TRIUMF for measurements of parity non-conservation (PNC) effects in magneto-optically trapped (MOT) isotopes of francium to test the Standard Model at low energies underwent significant development. In particular, we have overhauled the design of the neutralizer, which catches ionized atoms from the ISAC radioactive beam facility and releases them in neutral form for trapping. We have adopted the design idea, proposed by group of researchers from State University of New York, Stony Brook. It assumed sequential collecting of radioactive species on cold foil, transport them to capture cell and release during short time heating of the foil. We have modified original electric connections to the foil, the way of mounting foil and replaced yttrium foil by zirconium one, more robust. Such modifications allowed us to ensure an operation of the neutralizer through more than 500,000 cycles (this makes possible continuous taking of data during 2 months) with the release about 10% of embedded atoms per cycle. This work is supported by the DOE and NSF (USA), CONACYT (Mexico) and NSERC (Canada). TRIUMF receives federal funding via a contribution agreement with the National Research Council of Canada.

  17. Self-organized criticality occurs in non-conservative neuronal networks during `up' states

    NASA Astrophysics Data System (ADS)

    Millman, Daniel; Mihalas, Stefan; Kirkwood, Alfredo; Niebur, Ernst

    2010-10-01

    During sleep, under anaesthesia and in vitro, cortical neurons in sensory, motor, association and executive areas fluctuate between so-called up and down states, which are characterized by distinct membrane potentials and spike rates. Another phenomenon observed in preparations similar to those that exhibit up and down states-such as anaesthetized rats, brain slices and cultures devoid of sensory input, as well as awake monkey cortex-is self-organized criticality (SOC). SOC is characterized by activity `avalanches' with a branching parameter near unity and size distribution that obeys a power law with a critical exponent of about -3/2. Recent work has demonstrated SOC in conservative neuronal network models, but critical behaviour breaks down when biologically realistic `leaky' neurons are introduced. Here, we report robust SOC behaviour in networks of non-conservative leaky integrate-and-fire neurons with short-term synaptic depression. We show analytically and numerically that these networks typically have two stable activity levels, corresponding to up and down states, that the networks switch spontaneously between these states and that up states are critical and down states are subcritical.

  18. Non-Conservative Instability of Non-uniform Beams Resting on an Elastic Foundation

    NASA Astrophysics Data System (ADS)

    Lee, S. Y.; Yang, C. C.

    1994-01-01

    The influence of a Winkler elastic foundation and the slenderness ratio on the non-conservative instability of cantilever non-uniform beams of rectangular cross-section with constant height and linearly varied breadth (T1), constant breadth and linearly varied height (T2) and double taper (T3), subjected to an end concentrated follower force is investigated. It is found that without the elastic foundation the critical flutter load of the non-uniform beam decreases as the taper ratio of the beam is increased. However, when the elastic foundation modulus is greater than a critical value, the critical flutter load of the taper beams is always greater than that of uniform beams. Within the domain considered, when the taper ratio of the beam lies in a certain range, several critical turning points, including a jump phenomenon, may exist for the critical flutter load. The jump mechanism and the influence of the elastic foundation modulus and the slenderness ratio on the jump phenomenon of Timoshenko beams is explored.

  19. How Does Krein Signature Determine Veering and Crossing of Eigencurves of Non-Conservative Rotating Continua?

    NASA Astrophysics Data System (ADS)

    Kirillov, Oleg N.

    2010-09-01

    Frequency loci crossing and veering phenomena are closely related to wave propagation and instabilities in fluids and structures. In engineering applications the crossings of the eigencurves are typically observed in gyroscopic or potential systems in the presence of symmetries, such as rotational or spherical one. The examples are perfect solids of revolution that serve for modeling turbine wheels, disk and drum brakes, tires, clutches, paper calenders and other rotating machinery. We consider an axi-symmetric flexible rotor perturbed by dissipative, conservative, and non-conservative positional forces originated at the contact with the anisotropic stator. The Campbell diagram of the unperturbed system is a mesh-like structure in the frequency-speed plane with double eigenfrequencies at the nodes. Computing sensitivities of the doublets we find that at every particular node the unfolding of the mesh into the branches of complex eigenvalues in the first approximation is generically determined by only four 2×2 sub-blocks of the perturbing matrix. Selection of the unstable modes that cause self-excited vibrations in the subcritical speed range, is governed by the exceptional points at the corners of the singular eigenvalue surfaces—`double coffee filter' and `viaduct'—which are sharply associated with the crossings of the unperturbed Campbell diagram with the definite symplectic (Krein) signature. A model of a rotating shaft with two degrees of freedom and a continuous model of a rotating circular string passing through the eyelet are studied in detail.

  20. Monte Carlo simulation of non-conservative positron transport in pure argon

    NASA Astrophysics Data System (ADS)

    Šuvakov, M.; Petrović, Z. Lj; Marler, J. P.; Buckman, S. J.; Robson, R. E.; Malović, G.

    2008-05-01

    The main aim of this paper is to apply modern phenomenology and accurate Monte Carlo simulation techniques to obtain the same level of understanding of positron transport as has been achieved for electrons. To this end, a reasonably complete set of cross sections for low energy positron scattering in argon has been used to calculate transport coefficients of low energy positrons in pure argon gas subject to an electrostatic field. We have analyzed the main features of these coefficients and have compared the calculated values with those for electrons in the same gas. The particular focus is on the influence of the non-conservative nature of positronium formation. This effect is substantial, generally speaking much larger than any comparable effects in electron transport due to attachment and/or ionization. As a result several new phenomena have been observed, such as negative differential conductivity (NDC) in the bulk drift velocity, but with no indication of any NDC for the flux drift velocity. In addition, there is a drastic effect on the bulk longitudinal diffusion coefficient for positrons, which is reduced to almost zero, in contrast to the other components of the diffusion tensor, which have normal values. It is found that the best way of explaining these kinetic phenomena is by sampling real space distributions which reveal drastic modification of the usual Gaussian profile due to pronounced spatial differentiation of the positrons by energy.

  1. Self-organized criticality occurs in non-conservative neuronal networks during Up states.

    PubMed

    Millman, Daniel; Mihalas, Stefan; Kirkwood, Alfredo; Niebur, Ernst

    2010-10-01

    During sleep, under anesthesia and in vitro, cortical neurons in sensory, motor, association and executive areas fluctuate between Up and Down states (UDS) characterized by distinct membrane potentials and spike rates [1, 2, 3, 4, 5]. Another phenomenon observed in preparations similar to those that exhibit UDS, such as anesthetized rats [6], brain slices and cultures devoid of sensory input [7], as well as awake monkey cortex [8] is self-organized criticality (SOC). This is characterized by activity "avalanches" whose size distributions obey a power law with critical exponent of about [Formula: see text] and branching parameter near unity. Recent work has demonstrated SOC in conservative neuronal network models [9, 10], however critical behavior breaks down when biologically realistic non-conservatism is introduced [9]. We here report robust SOC behavior in networks of non-conservative leaky integrate-and-fire neurons with short-term synaptic depression. We show analytically and numerically that these networks typically have 2 stable activity levels corresponding to Up and Down states, that the networks switch spontaneously between them, and that Up states are critical and Down states are subcritical.

  2. Amino-acid transporters in T-cell activation and differentiation.

    PubMed

    Ren, W; Liu, G; Yin, J; Tan, B; Wu, G; Bazer, F W; Peng, Y; Yin, Y

    2017-03-02

    T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yielded surprising findings in the importance of amino-acid transporters for T-cell development, homeostasis, activation, differentiation and memory. In this review, we present current information on amino-acid transporters, such as LAT1 (l-leucine transporter), ASCT2 (l-glutamine transporter) and GAT-1 (γ-aminobutyric acid transporter-1), which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells. Mechanically, the influence of amino-acid transporters on T-cell fate decision may largely depend on the mechanistic target of rapamycin complex 1 (mTORC1) signaling. These discoveries remarkably demonstrate the role of amino-acid transporters in T-cell fate determination, and strongly indicate that manipulation of the amino-acid transporter-mTORC1 axis could ameliorate many inflammatory or autoimmune diseases associated with T-cell-based immune responses.

  3. Differential D-glucose requirements of the general amino-acid permease and protein synthesis in Saccharomyces cerevisiae var. ellipsoideus.

    PubMed

    Iglesias, R; Ferreras, J M; Muñoz, R; Arias, F J; Rojo, M A; Girbés, T

    1990-01-01

    The dependence of the general aminoacid permease and protein synthesis on the availability of D-glucose as energy source was studied. Stimulation by the sugar was immediate once added to the cell suspensions and seems to be mediated by energy derived directly from glycolysis. The general aminoacid permease was saturated linearly with D-glucose whereas protein synthesis was saturated sigmoidealy requiring much higher concentration of the sugar than the general aminoacid permease.

  4. Non-conservative behavior of fluorescent dissolved organic matter (FDOM) within a subterranean estuary

    NASA Astrophysics Data System (ADS)

    Suryaputra, I. G. N. A.; Santos, I. R.; Huettel, M.; Burnett, W. C.; Dittmar, T.

    2015-11-01

    The role of submarine groundwater discharge (SGD) in releasing fluorescent dissolved organic matter (FDOM) to the coastal ocean and the possibility of using FDOM as a proxy for dissolved organic carbon (DOC) was investigated in a subterranean estuary in the northeastern Gulf of Mexico (Turkey Point, Florida). FDOM was continuously monitored for three weeks in shallow beach groundwater and in the adjacent coastal ocean. Radon (222Rn) was used as a natural groundwater tracer. FDOM and DOC correlated in groundwater and seawater samples, implying that FDOM may be a proxy of DOC in waters influenced by SGD. A mixing model using salinity as a seawater tracer revealed FDOM production in the high salinity region of the subterranean estuary. This production was probably a result of infiltration and transformation of labile marine organic matter in the beach sediments. The non-conservative FDOM behavior in this subterranean estuary differs from most surface estuaries where FDOM typically behaves conservatively. At the study site, fresh and saline SGD delivered about 1800 mg d-1 of FDOM (quinine equivalents) to the coastal ocean per meter of shoreline. About 11% of this input was related to fresh SGD, while 89% were related to saline SGD resulting from FDOM production within the shallow aquifer. If these fluxes are representative of the Florida Gulf Coast, SGD-derived FDOM fluxes would be equivalent to at least 18% of the potential regional riverine FDOM inputs. To reduce uncertainties related to the scarcity of FDOM data, further investigations of river and groundwater FDOM inputs in Florida and elsewhere are necessary.

  5. Multi-scale coarse-graining of non-conservative interactions in molecular liquids

    SciTech Connect

    Izvekov, Sergei Rice, Betsy M.

    2014-03-14

    A new bottom-up procedure for constructing non-conservative (dissipative and stochastic) interactions for dissipative particle dynamics (DPD) models is described and applied to perform hierarchical coarse-graining of a polar molecular liquid (nitromethane). The distant-dependent radial and shear frictions in functional-free form are derived consistently with a chosen form for conservative interactions by matching two-body force-velocity and three-body velocity-velocity correlations along the microscopic trajectories of the centroids of Voronoi cells (clusters), which represent the dissipative particles within the DPD description. The Voronoi tessellation is achieved by application of the K-means clustering algorithm at regular time intervals. Consistently with a notion of many-body DPD, the conservative interactions are determined through the multi-scale coarse-graining (MS-CG) method, which naturally implements a pairwise decomposition of the microscopic free energy. A hierarchy of MS-CG/DPD models starting with one molecule per Voronoi cell and up to 64 molecules per cell is derived. The radial contribution to the friction appears to be dominant for all models. As the Voronoi cell sizes increase, the dissipative forces rapidly become confined to the first coordination shell. For Voronoi cells of two and more molecules the time dependence of the velocity autocorrelation function becomes monotonic and well reproduced by the respective MS-CG/DPD models. A comparative analysis of force and velocity correlations in the atomistic and CG ensembles indicates Markovian behavior with as low as two molecules per dissipative particle. The models with one and two molecules per Voronoi cell yield transport properties (diffusion and shear viscosity) that are in good agreement with the atomistic data. The coarser models produce slower dynamics that can be appreciably attributed to unaccounted dissipation introduced by regular Voronoi re-partitioning as well as by larger

  6. Atomic parity non-conservation: the francium anapole project of the FrPNC collaboration at TRIUMF

    NASA Astrophysics Data System (ADS)

    Aubin, S.; Behr, J. A.; Collister, R.; Flambaum, V. V.; Gomez, E.; Gwinner, G.; Jackson, K. P.; Melconian, D.; Orozco, L. A.; Pearson, M. R.; Sheng, D.; Sprouse, G. D.; Tandecki, M.; Zhang, J.; Zhao, Y.

    2013-03-01

    We present a method for measuring the nuclear anapole in a string of francium isotopes. The anapole is a parity non-conserving electromagnetic moment that enables parity-forbidden transitions between ground state hyperfine levels of an atom. The experiment is run by the FrPNC collaboration and relies on a beam of artificially-produced francium from the ISAC facility at TRIUMF.

  7. Effects of a Non-Conservative Sequence on the Properties of β-glucuronidase from Aspergillus terreus Li-20

    PubMed Central

    Liu, Yanli; Huangfu, Jie; Qi, Feng; Kaleem, Imdad; E, Wenwen; Li, Chun

    2012-01-01

    We cloned the β-glucuronidase gene (AtGUS) from Aspergillus terreus Li-20 encoding 657 amino acids (aa), which can transform glycyrrhizin into glycyrrhetinic acid monoglucuronide (GAMG) and glycyrrhetinic acid (GA). Based on sequence alignment, the C-terminal non-conservative sequence showed low identity with those of other species; thus, the partial sequence AtGUS(-3t) (1–592 aa) was amplified to determine the effects of the non-conservative sequence on the enzymatic properties. AtGUS and AtGUS(-3t) were expressed in E. coli BL21, producing AtGUS-E and AtGUS(-3t)-E, respectively. At the similar optimum temperature (55°C) and pH (AtGUS-E, 6.6; AtGUS(-3t)-E, 7.0) conditions, the thermal stability of AtGUS(-3t)-E was enhanced at 65°C, and the metal ions Co2+, Ca2+ and Ni2+ showed opposite effects on AtGUS-E and AtGUS(-3t)-E, respectively. Furthermore, Km of AtGUS(-3t)-E (1.95 mM) was just nearly one-seventh that of AtGUS-E (12.9 mM), whereas the catalytic efficiency of AtGUS(-3t)-E was 3.2 fold higher than that of AtGUS-E (7.16 vs. 2.24 mM s−1), revealing that the truncation of non-conservative sequence can significantly improve the catalytic efficiency of AtGUS. Conformational analysis illustrated significant difference in the secondary structure between AtGUS-E and AtGUS(-3t)-E by circular dichroism (CD). The results showed that the truncation of the non-conservative sequence could preferably alter and influence the stability and catalytic efficiency of enzyme. PMID:22347419

  8. Flow path functioning identified from fundamental dynamics in sub-hourly, non-conservative stream chemistry

    NASA Astrophysics Data System (ADS)

    Chappell, N. A.; Jones, T.

    2013-12-01

    Within upland streams, concentration & load of many solutes (e.g. H+, DOC) varies very rapidly through storm periods. The shape & features of concentration or load chemographs are an expression of the fundamental dynamics in hydrologic & biogeochemical delivery mechanisms integrated at basin scales. If storm-period chemographs are grossly under-sampled so that time-series does not represent the true chemograph shape, then numerical descriptors of this shape or of the dynamic relationship between controlling variables (e.g. rainfall) & the chemograph will be distorted from true values (Littlewood 1992 IH Rpt 117; Littlewood & Croke 2013 Hydrol Res). Distortions of these dynamic response characteristics or DRCs (model parameters) can then lead to misinterpretation of hydrologic & biogeochemical processes via errors in relative contributions of identified flow paths, rates of propagation along these paths etc. A transfer function (TF) approach can be used to illustrate minimum sampling intensities needed to avoid these errors. Given 15-min observations, CAPTAIN-RIV identification routines for continuous-time TFs give Time Constants (TCs) of only 2 hrs for fast components of responses of rainfall to H+ load in Llyn Brianne streams (Chappell et al 2013 BHS). Given that Time Series Analysis dictates a sampling intensity five times finer than the TC, sampling at 24 min intervals or shorter was needed & achieved in this example. Considerable work is now focused on modeling of chemically-conservative river constituents (namely chloride & water isotopes) to help determine differences in residence times, storage & other DRCs of rainfall-streamflow & associated solute paths (Hrachowitz et al 2013 Hydrol Earth Syst Sci). Comparatively little modeling has focused on high frequency (i.e. sub-hourly), non-conservative river solutes (e.g. H+, DOC). Modeling of these basin-integrated variables should be considered complementary to that for conservative solutes, given: (1) their

  9. Excess of non-conservative amino acid changes in marine bacterioplankton lineages with reduced genomes.

    PubMed

    Luo, Haiwei; Huang, Yongjie; Stepanauskas, Ramunas; Tang, Jijun

    2017-06-12

    Surface ocean waters are dominated by planktonic bacterial lineages with highly reduced genomes. The best examples are the cyanobacterial genus Prochlorococcus, the alphaproteobacterial clade SAR11 and the gammaproteobacterial clade SAR86, which together represent over 50% of the cells in surface oceans. Several studies have identified signatures of selection on these lineages in today's ocean and have postulated selection as the primary force throughout their evolutionary history. However, massive loss of genomic DNA in these lineages often occurred in the distant past, and the selective pressures underlying these ancient events have not been assessed. Here, we probe ancient selective pressures by computing %GC-corrected rates of conservative and radical nonsynonymous nucleotide substitutions. Surprisingly, we found an excess of radical changes in several of these lineages in comparison to their relatives with larger genomes. Furthermore, analyses of allelic genome sequences of several populations within these lineages consistently supported that radical replacements are more likely to be deleterious than conservative changes. Our results suggest coincidence of massive genomic DNA losses and increased power of genetic drift, but we also suggest that additional evidence independent of the nucleotide substitution analyses is needed to support a primary role of genetic drift driving ancient genome reduction of marine bacterioplankton lineages.

  10. Substitute Solutions.

    ERIC Educational Resources Information Center

    Jones, Kevin R.; Hawkins, Amber

    2000-01-01

    In summer 1999, a group of Park City, Utah, school administrators, personnel directors, human-resource specialists, and substitute teacher coordinators brainstormed on improving the recruitment, training, and retention of substitute teachers. Providing effective preservice and on-the-job training and professional recognition are key suggestions.…

  11. [Bone substitutes].

    PubMed

    Jordana, Fabienne; Le Visage, Catherine; Weiss, Pierre

    2017-01-01

    Bone substitutes, used to fill a defect after a surgery or a trauma, provide a mechanical support and might induce bone healing. They constitute an alternative to autogenous bone grafts, the 'gold standard' which remains the reference despite its risk of postoperative complications. The clinician choice of a bone substitute is based on the required bone volume, the handling (injectability, malleability) and mechanical properties (setting time, viscosity, resorbability among others) of the material. Bone substitutes are commonly used in orthopedic surgery, neurosurgery, stomatology and dental applications. Their use increases steadily, with the recent clinical development of injectable forms. In addition, novel technologies by subtractive or additive techniques allow today the production of controlled architecture materials. Here, we present a bone substitutes classification according to their origin (natural or synthetic) and chemical composition, and the most common use of these substitutes. © 2017 médecine/sciences – Inserm.

  12. Skin Substitutes

    PubMed Central

    Howe, Nicole; Cohen, George

    2014-01-01

    In a relatively short timespan, a wealth of new skin substitutes made of synthetic and biologically derived materials have arisen for the purpose of wound healing of various etiologies. This review article focuses on providing an overview of skin substitutes including their indications, contraindications, benefits, and limitations. The result of this overview was an appreciation of the vast array of options available for clinicians, many of which did not exist a short time ago. Yet, despite the rapid expansion this field has undergone, no ideal skin substitute is currently available. More research in the field of skin substitutes and wound healing is required not only for the development of new products made of increasingly complex biomolecular material, but also to compare the existing skin substitutes. PMID:25371771

  13. Isolation and amino-acid sequence determination of monkey insulin and proinsulin.

    PubMed

    Naithani, V K; Steffens, G J; Tager, H S; Buse, G; Rubenstein, A H; Steiner, D F

    1984-05-01

    Insulin has been isolated and purified from rhesus monkey pancreas by means of acid-ethanol extraction, gel filtration and ion exchange chromatography. The complete amino-acid sequence of the hormone has been determined by amino-acid analysis of the oxidized A- and B-chains, by end group determination, by the identification of the C-terminal residues (AsnA21 and ThrB30) by carboxypeptidase A digestion and by Edman degradation of the S-carboxymethylated A- and B-chains. The 51-residue monkey insulin was shown to be identical to human insulin. From the known insulin and C-peptide sequence the primary sequence of monkey proinsulin has been proposed.

  14. A new efficient formulation of the HLLEM Riemann solver for general conservative and non-conservative hyperbolic systems

    NASA Astrophysics Data System (ADS)

    Dumbser, Michael; Balsara, Dinshaw S.

    2016-01-01

    In this paper a new, simple and universal formulation of the HLLEM Riemann solver (RS) is proposed that works for general conservative and non-conservative systems of hyperbolic equations. For non-conservative PDE, a path-conservative formulation of the HLLEM RS is presented for the first time in this paper. The HLLEM Riemann solver is built on top of a novel and very robust path-conservative HLL method. It thus naturally inherits the positivity properties and the entropy enforcement of the underlying HLL scheme. However, with just the slight additional cost of evaluating eigenvectors and eigenvalues of intermediate characteristic fields, we can represent linearly degenerate intermediate waves with a minimum of smearing. For conservative systems, our paper provides the easiest and most seamless path for taking a pre-existing HLL RS and quickly and effortlessly converting it to a RS that provides improved results, comparable with those of an HLLC, HLLD, Osher or Roe-type RS. This is done with minimal additional computational complexity, making our variant of the HLLEM RS also a very fast RS that can accurately represent linearly degenerate discontinuities. Our present HLLEM RS also transparently extends these advantages to non-conservative systems. For shallow water-type systems, the resulting method is proven to be well-balanced. Several test problems are presented for shallow water-type equations and two-phase flow models, as well as for gas dynamics with real equation of state, magnetohydrodynamics (MHD & RMHD), and nonlinear elasticity. Since our new formulation accommodates multiple intermediate waves and has a broader applicability than the original HLLEM method, it could alternatively be called the HLLI Riemann solver, where the ;I; stands for the intermediate characteristic fields that can be accounted for.

  15. A new efficient formulation of the HLLEM Riemann solver for general conservative and non-conservative hyperbolic systems

    SciTech Connect

    Dumbser, Michael; Balsara, Dinshaw S.

    2016-01-01

    In this paper a new, simple and universal formulation of the HLLEM Riemann solver (RS) is proposed that works for general conservative and non-conservative systems of hyperbolic equations. For non-conservative PDE, a path-conservative formulation of the HLLEM RS is presented for the first time in this paper. The HLLEM Riemann solver is built on top of a novel and very robust path-conservative HLL method. It thus naturally inherits the positivity properties and the entropy enforcement of the underlying HLL scheme. However, with just the slight additional cost of evaluating eigenvectors and eigenvalues of intermediate characteristic fields, we can represent linearly degenerate intermediate waves with a minimum of smearing. For conservative systems, our paper provides the easiest and most seamless path for taking a pre-existing HLL RS and quickly and effortlessly converting it to a RS that provides improved results, comparable with those of an HLLC, HLLD, Osher or Roe-type RS. This is done with minimal additional computational complexity, making our variant of the HLLEM RS also a very fast RS that can accurately represent linearly degenerate discontinuities. Our present HLLEM RS also transparently extends these advantages to non-conservative systems. For shallow water-type systems, the resulting method is proven to be well-balanced. Several test problems are presented for shallow water-type equations and two-phase flow models, as well as for gas dynamics with real equation of state, magnetohydrodynamics (MHD & RMHD), and nonlinear elasticity. Since our new formulation accommodates multiple intermediate waves and has a broader applicability than the original HLLEM method, it could alternatively be called the HLLI Riemann solver, where the “I” stands for the intermediate characteristic fields that can be accounted for. -- Highlights: •New simple and general path-conservative formulation of the HLLEM Riemann solver. •Application to general conservative and non-conservative

  16. Sensitivity test of a blue-detuned dipole trap designed for parity non-conservation measurements in Fr

    NASA Astrophysics Data System (ADS)

    Sheng, D.; Zhang, J.; Orozco, L. A.

    2012-04-01

    A dynamic blue-detuned optical dipole trap with stable 87Rb atoms produces a differential ac Stark shift of 18 Hz in the ground state hyperfine transition, and it preserves the ground state hyperfine superpositions for a long coherence time of 180 ms. The trapped atoms undergoing microwave Rabi oscillations are sensitive to a small signal, artificially generated with a second microwave source, phase locked to the first allowing a simple and effective method for determining signal-to-noise ratio limits through interference techniques. This provides an excellent means of calibrating sensitivity in experiments such as our ongoing Fr parity non-conservation measurement.

  17. ACTIONS OF AMINO-ACIDS ON THE ISOLATED HEMISECTED SPINAL CORD OF THE TOAD

    PubMed Central

    Curtis, D R; Phillis, J W; Watkins, J C

    1997-01-01

    The actions of a series of amino-acids related to γ-aminobutyric acid and glutamic acid have been determined upon the isolated and sagittally hemisected spinal cord of the toad, Bufo marinus. Slow and fast components of the ventral root reflex responses following dorsal root stimulation were depressed by γ-aminobutyric acid and by a series of neutral amino-acids having a similar structure. The relative depressant potencies of the members of this series were determined by comparison of the concentrations of each required to cause the same reduction in the electrically integrated slow components of these reflex responses. Glutamic acid and closely related substances facilitated reflex responses in low concentrations and depressed these responses in high concentrations. The actions of these substances resulted in the depolarization of motoneurones which was recorded as a negative potential in the ventral root. The relative potencies of the substances were estimated from the concentrations of each required to produce negative potentials of the same magnitude. Several amino-acids not previously tested proved to have remarkably strong actions on this preparation. 3-Aminopropanesulphonic acid was the most potent depressant tested; homocysteic acid and n-methylaspartic acid were the most powerful excitatory substances. The d forms of optically active depressants or excitants were always stronger than the corresponding l forms where both enantiomorphs were available. Points of similarity and dissimilarity between these results and those of related investigations are discussed. PMID:9142407

  18. Combined use of bile acids and aminoacids to improve permeation properties of acyclovir.

    PubMed

    Cirri, M; Maestrelli, F; Mennini, N; Mura, P

    2015-07-25

    The aim of this work was to develop a topical formulation with improved permeation properties of acyclovir. Ursodeoxycholic (UDC) and dehydrocholic (DHC) acids were tested as potential enhancers, alone or in combination with different aminoacids. Equimolar binary and ternary systems of acyclovir with cholic acids and basic, hydrophilic or hydrophobic aminoacids were prepared by co-grinding in a high vibrational micromill. Differential scanning calorimetry (DSC) was used to characterize the solid state of these systems, while their permeation properties were evaluated in vitro through a lipophilic artificial membrane. UDC was more than 2 times more effective than DHC in improving drug AUC and permeation rate. As for the ternary systems drug-UDC-aminoacid, only the combined use of l-lysine with UDC acid produced an evident synergistic effect in enhancing drug permeation properties, enabling an almost 3 and 8 times AUC increase compared to the binary UDC system or the pure drug, respectively. The best systems were selected for the development of topical cream formulations, adequately characterized and tested for in vitro drug permeation properties and stability on storage. The better performance revealed by acyclovir-UDC-l-lysine was mainly attributed to the formation of a more permeable activated system induced by the multicomponent co-grinding process.

  19. Fermentation of Agave tequilana juice by Kloeckera africana: influence of amino-acid supplementations.

    PubMed

    Valle-Rodríguez, Juan Octavio; Hernández-Cortés, Guillermo; Córdova, Jesús; Estarrón-Espinosa, Mirna; Díaz-Montaño, Dulce María

    2012-02-01

    This study aimed to improve the fermentation efficiency of Kloeckera africana K1, in tequila fermentations. We investigated organic and inorganic nitrogen source requirements in continuous K. africana fermentations fed with Agave tequilana juice. The addition of a mixture of 20 amino-acids greatly improved the fermentation efficiency of this yeast, increasing the consumption of reducing sugars and production of ethanol, compared with fermentations supplemented with ammonium sulfate. The preference of K. africana for each of the 20 amino-acids was further determined in batch fermentations and we found that asparagine supplementation increased K. africana biomass production, reducing sugar consumption and ethanol production (by 30, 36.7 and 45%, respectively) over fermentations supplemented with ammonium sulfate. Therefore, asparagine appears to overcome K. africana nutritional limitation in Agave juice. Surprisingly, K. africana produced a high concentration of ethanol. This contrasts to poor ethanol productivities reported for other non-Saccharomyces yeasts indicating a relatively high ethanol tolerance for the K. africana K1 strain. Kloeckera spp. strains are known to synthesize a wide variety of volatile compounds and we have shown that amino-acid supplements influenced the synthesis by K. africana of important metabolites involved in the bouquet of tequila. The findings of this study have revealed important nutritional limitations of non-Saccharomyces yeasts fermenting Agave tequilana juice, and have highlighted the potential of K. africana in tequila production processes.

  20. High order space-time adaptive ADER-WENO finite volume schemes for non-conservative hyperbolic systems

    NASA Astrophysics Data System (ADS)

    Dumbser, Michael; Hidalgo, Arturo; Zanotti, Olindo

    2014-01-01

    We present a class of high order finite volume schemes for the solution of non-conservative hyperbolic systems that combines the one-step ADER-WENO finite volume approach with space-time adaptive mesh refinement (AMR). The resulting algorithm, which is particularly well suited for the treatment of material interfaces in compressible multi-phase flows, is based on: (i) high order of accuracy in space obtained through WENO reconstruction, (ii) a high order one-step time discretization via a local space-time discontinuous Galerkin predictor method, and (iii) the use of a path conservative scheme for handling the non-conservative terms of the equations. The AMR property with time accurate local time stepping, which has been treated according to a 'cell-by-cell' strategy, strongly relies on the high order one-step time discretization, which naturally allows a high order accurate and consistent computation of the jump terms at interfaces between elements using different time steps. The new scheme has been successfully validated on some test problems for the Baer-Nunziato model of compressible multiphase flows.

  1. The behavioural homing response of adult chum salmon Oncorhynchus keta to amino-acid profiles.

    PubMed

    Chen, E Y; Leonard, J B K; Ueda, H

    2016-11-21

    Adult chum salmon Oncorhynchus keta homing behaviour in a two-choice test tank (Y-maze) was monitored using a passive integrated transponder (PIT)-tag system in response to river-specific dissolved free amino-acid (DFAA) profiles and revealed that the majority of O. keta showed a preference for artificial natal-stream water and tended to stay in this maze arm for a longer period; natal-stream water was chosen over a nearby tributary's water, but not when the O. keta were presented with a non-tributary water. The results demonstrate the ability of O. keta to discriminate artificial stream waters containing natural levels of DFAA.

  2. Reduced Acid Dissociation of Amino-Acids at the Surface of Water

    PubMed Central

    2017-01-01

    We use surface-specific intensity vibrational sum-frequency generation and attenuated total reflection spectroscopy to probe the ionization state of the amino-acids l-alanine and l-proline at the air/water surface and in the bulk. The ionization state is determined by probing the vibrational signatures of the carboxylic acid group, representing the nondissociated acid form, and the carboxylate anion group, representing the dissociated form, over a wide range of pH values. We find that the carboxylic acid group deprotonates at a significantly higher pH at the surface than in the bulk. PMID:28177623

  3. Amino-Acid Sequence of NADP-Specific Glutamate Dehydrogenase of Neurospora crassa

    PubMed Central

    Wootton, John C.; Chambers, Geoffrey K.; Holder, Anthony A.; Baron, Andrew J.; Taylor, John G.; Fincham, John R. S.; Blumenthal, Kenneth M.; Moon, Kenneth; Smith, Emil L.

    1974-01-01

    A tentative primary structure of the NADP-specific glutamate dehydrogenase [L-glutamate: NADP oxidoreductase (deaminating), EC 1.4.1.4] from Neurospora crassa has been determined. The proposed sequence contains 452 amino-acid residues in each of the identical subunits of the hexameric enzyme. Comparison of the sequence with that of the bovine liver enzyme reveals considerable homology in the amino-terminal portion of the chain, including the vicinity of the reactive lysine, with only shorter stretches of homology within the carboxyl-terminal regions. The significance of this distribution of homologous regions is discussed. PMID:4155068

  4. Reduced Acid Dissociation of Amino-Acids at the Surface of Water.

    PubMed

    Strazdaite, Simona; Meister, Konrad; Bakker, Huib J

    2017-03-15

    We use surface-specific intensity vibrational sum-frequency generation and attenuated total reflection spectroscopy to probe the ionization state of the amino-acids l-alanine and l-proline at the air/water surface and in the bulk. The ionization state is determined by probing the vibrational signatures of the carboxylic acid group, representing the nondissociated acid form, and the carboxylate anion group, representing the dissociated form, over a wide range of pH values. We find that the carboxylic acid group deprotonates at a significantly higher pH at the surface than in the bulk.

  5. Theory of Metastable State Relaxation for Non-Critical Binary Systems with Non-Conserved Order Parameter

    NASA Technical Reports Server (NTRS)

    Izmailov, Alexander; Myerson, Allan S.

    1993-01-01

    A new mathematical ansatz for a solution of the time-dependent Ginzburg-Landau non-linear partial differential equation is developed for non-critical systems such as non-critical binary solutions (solute + solvent) described by the non-conserved scalar order parameter. It is demonstrated that in such systems metastability initiates heterogeneous solute redistribution which results in formation of the non-equilibrium singly-periodic spatial solute structure. It is found how the time-dependent period of this structure evolves in time. In addition, the critical radius r(sub c) for solute embryo of the new solute rich phase together with the metastable state lifetime t(sub c) are determined analytically and analyzed.

  6. Theory of Metastable State Relaxation for Non-Critical Binary Systems with Non-Conserved Order Parameter

    NASA Technical Reports Server (NTRS)

    Izmailov, Alexander; Myerson, Allan S.

    1993-01-01

    A new mathematical ansatz for a solution of the time-dependent Ginzburg-Landau non-linear partial differential equation is developed for non-critical systems such as non-critical binary solutions (solute + solvent) described by the non-conserved scalar order parameter. It is demonstrated that in such systems metastability initiates heterogeneous solute redistribution which results in formation of the non-equilibrium singly-periodic spatial solute structure. It is found how the time-dependent period of this structure evolves in time. In addition, the critical radius r(sub c) for solute embryo of the new solute rich phase together with the metastable state lifetime t(sub c) are determined analytically and analyzed.

  7. Solvent substitution

    SciTech Connect

    Not Available

    1990-01-01

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

  8. An improved GRACE monthly gravity field solution by modeling the non-conservative acceleration and attitude observation errors

    NASA Astrophysics Data System (ADS)

    Chen, Qiujie; Shen, Yunzhong; Chen, Wu; Zhang, Xingfu; Hsu, Houze

    2016-06-01

    The main contribution of this study is to improve the GRACE gravity field solution by taking errors of non-conservative acceleration and attitude observations into account. Unlike previous studies, the errors of the attitude and non-conservative acceleration data, and gravity field parameters, as well as accelerometer biases are estimated by means of weighted least squares adjustment. Then we compute a new time series of monthly gravity field models complete to degree and order 60 covering the period Jan. 2003 to Dec. 2012 from the twin GRACE satellites' data. The derived GRACE solution (called Tongji-GRACE02) is compared in terms of geoid degree variances and temporal mass changes with the other GRACE solutions, namely CSR RL05, GFZ RL05a, and JPL RL05. The results show that (1) the global mass signals of Tongji-GRACE02 are generally consistent with those of CSR RL05, GFZ RL05a, and JPL RL05; (2) compared to CSR RL05, the noise of Tongji-GRACE02 is reduced by about 21 % over ocean when only using 300 km Gaussian smoothing, and 60 % or more over deserts (Australia, Kalahari, Karakum and Thar) without using Gaussian smoothing and decorrelation filtering; and (3) for all examples, the noise reductions are more significant than signal reductions, no matter whether smoothing and filtering are applied or not. The comparison with GLDAS data supports that the signals of Tongji-GRACE02 over St. Lawrence River basin are close to those from CSR RL05, GFZ RL05a and JPL RL05, while the GLDAS result shows the best agreement with the Tongji-GRACE02 result.

  9. Structural and Functional Perturbation of Giardia lamblia Triosephosphate Isomerase by Modification of a Non-Catalytic, Non-Conserved Region

    PubMed Central

    Hernández-Alcántara, Gloria; Torres-Larios, Alfredo; Enríquez-Flores, Sergio; García-Torres, Itzhel; Castillo-Villanueva, Adriana; Méndez, Sara T.; de la Mora-de la Mora, Ignacio; Gómez-Manzo, Saúl; Torres-Arroyo, Angélica; López-Velázquez, Gabriel; Reyes-Vivas, Horacio; Oria-Hernández, Jesús

    2013-01-01

    Background We have previously proposed triosephosphate isomerase of Giardia lamblia (GlTIM) as a target for rational drug design against giardiasis, one of the most common parasitic infections in humans. Since the enzyme exists in the parasite and the host, selective inhibition is a major challenge because essential regions that could be considered molecular targets are highly conserved. Previous biochemical evidence showed that chemical modification of the non-conserved non-catalytic cysteine 222 (C222) inactivates specifically GlTIM. The inactivation correlates with the physicochemical properties of the modifying agent: addition of a non-polar, small chemical group at C222 reduces the enzyme activity by one half, whereas negatively charged, large chemical groups cause full inactivation. Results In this work we used mutagenesis to extend our understanding of the functional and structural effects triggered by modification of C222. To this end, six GlTIM C222 mutants with side chains having diverse physicochemical characteristics were characterized. We found that the polarity, charge and volume of the side chain in the mutant amino acid differentially alter the activity, the affinity, the stability and the structure of the enzyme. The data show that mutagenesis of C222 mimics the effects of chemical modification. The crystallographic structure of C222D GlTIM shows the disruptive effects of introducing a negative charge at position 222: the mutation perturbs loop 7, a region of the enzyme whose interactions with the catalytic loop 6 are essential for TIM stability, ligand binding and catalysis. The amino acid sequence of TIM in phylogenetic diverse groups indicates that C222 and its surrounding residues are poorly conserved, supporting the proposal that this region is a good target for specific drug design. Conclusions The results demonstrate that it is possible to inhibit species-specifically a ubiquitous, structurally highly conserved enzyme by modification of a

  10. Unexpected additional mode of energization of amino-acid transport into Ehrlich cells.

    PubMed Central

    Garcia-Sancho, J; Sanchez, A; Handlogten, M E; Christensen, H N

    1977-01-01

    Ehrlich cells treated with dinitrophenol and iodoacetate rapidly recover their 30-sec uptake of 2-(methyl-amino)-isobutyrate on treatment with 0.1 mM phenazine methosulfate + 20 mM sodium ascorbate before they begin to recover from the severely depressed ATP levels and alkali-ion gradients. Addition of 10 mM pyruvate also restores uptake of methylaminoisobutyrate before the alkali-ion gradients rise. This restoration is prevented by rotenone, but rotenone does not handicap restoration by phenazine methosulfate/ascorbate. Na+-independent uptake of 2-aminonorbornane-2-carboxylate by Ehrlich cells is affected the same way. Quinacrine almost completely suppresses uptake of methylaminoisobutyrate within the 30-sec uptake test, even when ATP levels are sustained by pyruvate and alkali-ion gradients are not depressed. Ouabain prevents restoration of both Na+-dependent and Na+-independent amino-acid transport by phenazine methosulfate/ascorbate or pyruvate. We interpret these results to indicate that amino-acid transport can be energized not only by known means, but also by reducing equivalents, which presumably reach the plasma membrane in the form of NADH from the mitochondria when the source of energy is pyruvate. In support of this hypothesis, the distribution of methylaminoisobutyrate between plasma membrane vesicles and their supporting media was influenced in the predictable way by NADH, quinacrine, and an uncoupling agent, proceeding on the assumption that more of the vesicles had the everted rather than the natural orientation. PMID:266189

  11. Exploring the evolution of standard amino-acid alphabet: when genomics meets thermodynamics.

    PubMed

    Zhang, Hong-Yu

    2007-08-03

    One of the most intriguing aspects of life is that despite the diversified apparent shapes, similar building blocks and infrastructures, such as standard amino acids and canonical genetic codes, are shared by most life on Earth. Thus, it is challenging to explore: why nature just selects these building blocks and strategies from numerous candidates to construct life? Was this deterministic or fortuitous? Thanks to the rapid progress in genomics, bioinformatics and synthetic biology, more and more basic principles underlying life design and construction were disclosed in the past decade. However, since the origin of early life is substantially a chemical process, to understand the enigma of life origin, chemists' efforts can not be neglected. In this paper, we focus on the evolution of standard amino-acid alphabet and indicate that chemistry, especially thermodynamics, is indeed critical to understanding the forming mechanisms of amino-acid alphabet. It is revealed that nature prefers low free energy and thus ubiquitous (cheap) small amino acids when beginning to build life, which is compatible with many recent findings from genomics and bioinformatics.

  12. Aminoacids as non-traditional plasticizers of maltodextrins fast-dissolving films.

    PubMed

    Selmin, Francesca; Franceschini, Ilaria; Cupone, Irma E; Minghetti, Paola; Cilurzo, Francesco

    2015-01-22

    This study explored the effect of aminoacids as non-traditional plasticizers of maltodextrins fast dissolving films. 5% w/w glycine and proline decreased the glass transition temperature (Tg) of maltodextrins from 102.6±2.0°C to 73.1±1.4°C and 76.1±0.7°C, respectively; meanwhile the binary mixture made with lysine had a Tg value of 83.6±2.2°C. At the same time, all aminoacids increased the ΔCp values. The shift of the thermal data were due to profound effect on the hydrogen bonding as evidenced by ATR-FTIR spectra since the OH stretching and scissoring bands decreased of about 15-26 cm(-1). A linear relationship was found (R(2)=0.9334) between HOH scissoring wavenumbers and Tg values. The addition of glycine and proline resulted effective in reducing the elastic modulus (about 50%) and tensile strength (about three times) and, therefore, can be used to increase the film ductility.

  13. Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals.

    PubMed

    Kimura, Tetsuya; Nada, Shigeyuki; Takegahara, Noriko; Okuno, Tatsusada; Nojima, Satoshi; Kang, Sujin; Ito, Daisuke; Morimoto, Keiko; Hosokawa, Takashi; Hayama, Yoshitomo; Mitsui, Yuichi; Sakurai, Natsuki; Sarashina-Kida, Hana; Nishide, Masayuki; Maeda, Yohei; Takamatsu, Hyota; Okuzaki, Daisuke; Yamada, Masaki; Okada, Masato; Kumanogoh, Atsushi

    2016-10-12

    Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H(+)-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization. Lamtor1 deficiency, amino-acid starvation, or inhibition of v-ATPase and mTOR result in defective M2 polarization and enhanced M1 polarization. Furthermore, we identified liver X receptor (LXR) as the downstream target of Lamtor1 and mTORC1. Production of 25-hydroxycholesterol is dependent on Lamtor1 and mTORC1. Our findings demonstrate that Lamtor1 plays an essential role in M2 polarization, coupling immunity and metabolism.

  14. Regulation of aspartate-derived amino-acid metabolism in Zygosaccharomyces rouxii compared to Saccharomyces cerevisiae.

    PubMed

    van der Sluis C; Smit; Hartmans; ter Schure EG; Tramper; Wijffels

    2000-07-01

    To elucidate the growth inhibitory effect of threonine, the regulation of the aspartate-derived amino-acid metabolism in Zygosaccharomyces rouxii, an important yeast for the flavor development in soy sauce, was investigated. It was shown that threonine inhibited the growth of Z. rouxii by blocking the methionine synthesis. It seemed that threonine blocked this synthesis by inhibiting the conversion of aspartate. In addition, it was shown that the growth of Z. rouxii, unlike that of Saccharomyces cerevisiae, was not inhibited by the herbicide sulfometuron methyl (SMM). From enzyme assays, it was concluded that the acetohydroxy acid synthase in Z. rouxii, unlike that in S. cerevisiae, was not sensitive to SMM. Furthermore, the enzyme assays demonstrated that the activity of threonine deaminase in Z. rouxii, like in S. cerevisiae, was strongly inhibited by isoleucine and stimulated by valine. From this work, it is clear that the aspartate-derived amino-acid metabolism in Z. rouxii only partly resembles that in S. cerevisiae.

  15. Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals

    PubMed Central

    Kimura, Tetsuya; Nada, Shigeyuki; Takegahara, Noriko; Okuno, Tatsusada; Nojima, Satoshi; Kang, Sujin; Ito, Daisuke; Morimoto, Keiko; Hosokawa, Takashi; Hayama, Yoshitomo; Mitsui, Yuichi; Sakurai, Natsuki; Sarashina-Kida, Hana; Nishide, Masayuki; Maeda, Yohei; Takamatsu, Hyota; Okuzaki, Daisuke; Yamada, Masaki; Okada, Masato; Kumanogoh, Atsushi

    2016-01-01

    Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H+-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization. Lamtor1 deficiency, amino-acid starvation, or inhibition of v-ATPase and mTOR result in defective M2 polarization and enhanced M1 polarization. Furthermore, we identified liver X receptor (LXR) as the downstream target of Lamtor1 and mTORC1. Production of 25-hydroxycholesterol is dependent on Lamtor1 and mTORC1. Our findings demonstrate that Lamtor1 plays an essential role in M2 polarization, coupling immunity and metabolism. PMID:27731330

  16. Exploring the evolution of standard amino-acid alphabet: When genomics meets thermodynamics

    SciTech Connect

    Zhang, Hong-Yu . E-mail: zhanghy@sdut.edu.cn

    2007-08-03

    One of the most intriguing aspects of life is that despite the diversified apparent shapes, similar building blocks and infrastructures, such as standard amino acids and canonical genetic codes, are shared by most life on Earth. Thus, it is challenging to explore: why nature just selects these building blocks and strategies from numerous candidates to construct life? Was this deterministic or fortuitous? Thanks to the rapid progress in genomics, bioinformatics and synthetic biology, more and more basic principles underlying life design and construction were disclosed in the past decade. However, since the origin of early life is substantially a chemical process, to understand the enigma of life origin, chemists' efforts can not be neglected. In this paper, we focus on the evolution of standard amino-acid alphabet and indicate that chemistry, especially thermodynamics, is indeed critical to understanding the forming mechanisms of amino-acid alphabet. It is revealed that nature prefers low free energy and thus ubiquitous (cheap) small amino acids when beginning to build life, which is compatible with many recent findings from genomics and bioinformatics.

  17. Selective charging of tRNA isoacceptors induced by amino-acid starvation

    PubMed Central

    Dittmar, Kimberly A; Sørensen, Michael A; Elf, Johan; Ehrenberg, Måns; Pan, Tao

    2005-01-01

    Aminoacylated (charged) transfer RNA isoacceptors read different messenger RNA codons for the same amino acid. The concentration of an isoacceptor and its charged fraction are principal determinants of the translation rate of its codons. A recent theoretical model predicts that amino-acid starvation results in ‘selective charging' where the charging levels of some tRNA isoacceptors will be low and those of others will remain high. Here, we developed a microarray for the analysis of charged fractions of tRNAs and measured charging for all Escherichia coli tRNAs before and during leucine, threonine or arginine starvation. Before starvation, most tRNAs were fully charged. During starvation, the isoacceptors in the leucine, threonine or arginine families showed selective charging when cells were starved for their cognate amino acid, directly confirming the theoretical prediction. Codons read by isoacceptors that retain high charging can be used for efficient translation of genes that are essential during amino-acid starvation. Selective charging can explain anomalous patterns of codon usage in the genes for different families of proteins. PMID:15678157

  18. Hydrophobicity, expressivity and aromaticity are the major trends of amino-acid usage in 999 Escherichia coli chromosome-encoded genes.

    PubMed Central

    Lobry, J R; Gautier, C

    1994-01-01

    Multivariate analysis of the amino-acid compositions of 999 chromosome-encoded proteins from Escherichia coli showed that three main factors influence the variability of amino-acid composition. The first factor was correlated with the global hydrophobicity of proteins, and it discriminated integral membrane proteins from the others. The second factor was correlated with gene expressivity, showing a bias in highly expressed genes towards amino-acids having abundant major tRNAs. Just as highly expressed genes have reduced codon diversity in protein coding sequences, so do they have a reduced diversity of amino-acid choice. This showed that translational constraints are important enough to affect the global amino-acid composition of proteins. The third factor was correlated with the aromaticity of proteins, showing that aromatic amino-acid content is highly variable. PMID:8065933

  19. Non-conservative characteristics of fluorescent tracers help to assess in-situ transport and attenuation of pesticides

    NASA Astrophysics Data System (ADS)

    Lange, Jens; Payraudeau, Sylvain; Imfeld, Gwenaël

    2016-04-01

    Traditionally, hydrological tracers are selected to behave as conservatively as possible, since most applications aim to investigate the transport of water or conservative solutes. Non-conservative tracer behavior is regarded as a limitation. However, the environmental behavior of organic pesticides is strictly non-conservative as their fate is affected by various processes, including sorption, photolysis and biochemical transformation in various environmental compartments. If tracers are used to study pesticides under these conditions, we believe that a paradigm shift is necessary: only a tracer that is affected by similar attenuation processes can realistically reproduce the overall behavior of a target pesticide. We present here two examples from two different environmental compartments: (i) agricultural soils and (ii) wetland systems. In both studies two organic fluorescent tracers (uranine, UR and sulforhodamine-B, SRB) and the salt tracer bromide (BR) were applied together with the chloroacetanilide herbicide S-metolachlor (S-MET). On an agricultural field, plot experiments were conducted under artificial and natural rainfall conditions. The use of BR overestimated both slow leaching and fast preferential transport of S-MET in the unsaturated zone, while UR/SRB were more realistic markers. Under artificial conditions, recovery rates of BR in a tile drain were twice as high as UR and one order of magnitude higher than SRB. Under natural conditions, BR concentrations in surface soils (0-1 cm) displayed larger variances during wetting and drying periods than UR, SRB and S-MET. BR also leached deeper (below 5 cm) than S-MET in the soil column. After 70 days, characteristic fluorescent peaks of UR and SRB gradually decreased in soil samples, while a new peak increased in another spectrum, which suggests the production of a potential transformation product. In two artificial wetland systems the impact of hydrological conditions (batch versus continuous-flow) on

  20. Purification of dirucotide, a synthetic 17-aminoacid peptide, by ion exchange centrifugal partition chromatography.

    PubMed

    Boudesocque, Leslie; Forni, Luciano; Martinez, Agathe; Nuzillard, Jean-Marc; Giraud, Matthieu; Renault, Jean-Hugues

    2017-09-01

    Dirucotide is a synthetic drug candidate for the treatment of multiple sclerosis. This 17-aminoacid peptide was successfully purified by ion exchange centrifugal partition chromatography. The optimized conditions involved the biphasic methyl tert-butyl ether/acetonitrile/n-butanol/water (2:1:2:5, v/v) solvent system in the descending mode, the di(2-ethylhexyl)phosphoric acid cation-exchanger with an exchanger (di(2-ethylhexyl)phosphoric acid)/dirucotide mole ratio of 100 and Ca(2+) ions in aqueous solution as displacer. Critical impurities were efficiently eliminated and dirucotide was recovered in high yield and purity (69% and 98%, respectively) and with a productivity of 2.29g per liter of stationary phase per hour. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A glial amino-acid transporter controls synapse strength and courtship in Drosophila.

    PubMed

    Grosjean, Yael; Grillet, Micheline; Augustin, Hrvoje; Ferveur, Jean-François; Featherstone, David E

    2008-01-01

    Mate choice is an evolutionarily critical decision that requires the detection of multiple sex-specific signals followed by central integration of these signals to direct appropriate behavior. The mechanisms controlling mate choice remain poorly understood. Here, we show that the glial amino-acid transporter genderblind controls whether Drosophila melanogaster males will attempt to mate with other males. Genderblind (gb) mutant males showed no alteration in heterosexual courtship or copulation, but were attracted to normally unappealing male species-specific chemosensory cues. As a result, genderblind mutant males courted and attempted to copulate with other Drosophila males. This homosexual behavior could be induced within hours using inducible RNAi, suggesting that genderblind controls nervous system function rather than its development. Consistent with this, and indicating that glial genderblind regulates ambient extracellular glutamate to suppress glutamatergic synapse strength in vivo, homosexual behavior could be turned on and off by altering glutamatergic transmission pharmacologically and/or genetically.

  2. Allosteric ACTion: the varied ACT domains regulating enzymes of amino-acid metabolism.

    PubMed

    Lang, Eric J M; Cross, Penelope J; Mittelstädt, Gerd; Jameson, Geoffrey B; Parker, Emily J

    2014-12-01

    Allosteric regulation of enzyme activity plays important metabolic roles. Here we review the allostery of enzymes of amino-acid metabolism conferred by a discrete domain known as the ACT domain. This domain of 60-70 residues has a βαββαβ topology leading to a four-stranded β4β1β3β2 antiparallel sheet with two antiparallel helices on one face. Extensive sequence variation requires a combined sequence/structure/function analysis for identification of the ACT domain. Common features include highly varied modes of self-association of ACT domains, ligand binding at domain interfaces, and transmittal of allosteric signals through conformational changes and/or the manipulation of quaternary equilibria. A recent example illustrates the relatively facile adoption of this versatile module of allostery by gene fusion.

  3. In vivo blockade of thalamic GABA(B) receptors increases excitatory amino-acid levels.

    PubMed

    Nyitrai, G; Emri, Z; Crunelli, V; Kékesi, K A; Dobolyi, A; Juhász, G

    1996-12-30

    The effect of intrathalamic application of GABA(B) receptor antagonists on the basal excitatory amino-acid levels was studied using microdialysis probes implanted in the dorsal lateral geniculate nucleus and in the ventrobasal complex. In both nuclei, continuous perfusion of the GABA(B) receptor antagonist 3-aminopropyl-(diethoxymethyl)-phosphinic acid (CGP 35348) produced an increase in the extracellular concentration of aspartate and (to a lesser extent) glutamate, but no change was observed in the level of taurine, the main amino acid involved in the regulation of brain osmolarity processes. In contrast, 3-amino-2-hydroxy-2-(4-chlorophenyl)-propanesulphonic acid (2-hydroxy-saclofen), another GABA(B) receptor antagonist, failed to affect the extracellular concentration of aspartate, glutamate and taurine. Thus, the basal level of excitatory amino acids in the thalamus in vivo is under the control of CGP 35348-sensitive GABA(B) receptors.

  4. Mapping out tractor beams: topological angular momentum and reduced axial flux; gradient versus non-conservative forces

    NASA Astrophysics Data System (ADS)

    Spalding, Gabriel C.; Dahl, Patrick M.; Démoré, Christine E.; Yang, Zhengi; Glynne-Jones, Peter; Melzer, Andreas; Cochran, Sandy; MacDonald, Michael P.

    2013-09-01

    We experimentally demonstrate continuous attraction of macroscopic targets (> 1 cm) towards the source, against a net momentum flux in the system. Use of a simple setup provides an easily understood illustration of the negative radiation pressure concept for tractor beam, and how these are distinct from the gradient force acting in conventional optical tweezers. Here, we map out regimes over which negative radiation forces dominate, and (favorably) compare the thresholds observed to those that emerge from simulations. Theoretical explorations of tractor beam action commonly invoke higher-order Bessel beams, and here we make clear that the reason for this is because of the reduction in axial momentum associated with such hollow-core beams, which allows effects associated with off-axis "skew" momentum to become dominant. Ultimately, there is interest in exploring the language used for describing such effects: radiation pressure versus gradient force (which we suggest might be better described in terms of non-conservative versus conservative forces), and "orbital" angular momentum (which we suggest might be more appropriately termed "topological" angular momentum).

  5. Evidence for non-conservative current-induced forces in the breaking of Au and Pt atomic chains

    PubMed Central

    Sabater, Carlos; Untiedt, Carlos

    2015-01-01

    Summary This experimental work aims at probing current-induced forces at the atomic scale. Specifically it addresses predictions in recent work regarding the appearance of run-away modes as a result of a combined effect of the non-conservative wind force and a ‘Berry force’. The systems we consider here are atomic chains of Au and Pt atoms, for which we investigate the distribution of break down voltage values. We observe two distinct modes of breaking for Au atomic chains. The breaking at high voltage appears to behave as expected for regular break down by thermal excitation due to Joule heating. However, there is a low-voltage breaking mode that has characteristics expected for the mechanism of current-induced forces. Although a full comparison would require more detailed information on the individual atomic configurations, the systems we consider are very similar to those considered in recent model calculations and the comparison between experiment and theory is very encouraging for the interpretation we propose. PMID:26734525

  6. Evidence for non-conservative current-induced forces in the breaking of Au and Pt atomic chains.

    PubMed

    Sabater, Carlos; Untiedt, Carlos; van Ruitenbeek, Jan M

    2015-01-01

    This experimental work aims at probing current-induced forces at the atomic scale. Specifically it addresses predictions in recent work regarding the appearance of run-away modes as a result of a combined effect of the non-conservative wind force and a 'Berry force'. The systems we consider here are atomic chains of Au and Pt atoms, for which we investigate the distribution of break down voltage values. We observe two distinct modes of breaking for Au atomic chains. The breaking at high voltage appears to behave as expected for regular break down by thermal excitation due to Joule heating. However, there is a low-voltage breaking mode that has characteristics expected for the mechanism of current-induced forces. Although a full comparison would require more detailed information on the individual atomic configurations, the systems we consider are very similar to those considered in recent model calculations and the comparison between experiment and theory is very encouraging for the interpretation we propose.

  7. Both conserved and non-conserved regions of Spo11 are essential for meiotic recombination initiation in yeast.

    PubMed

    Nag, Dilip K; Pata, Janice D; Sironi, Manuela; Flood, David R; Hart, Ashley M

    2006-10-01

    DNA double-strand breaks (DSBs) are the initiators of most meiotic recombination events. In Saccharomyces cerevisiae, at least ten genes are necessary for meiotic DSB formation. However, the molecular roles of these proteins are not clearly understood. The meiosis-specific Spo11 protein, which shows sequence similarity with a subunit of an archaeal topoisomerase, is believed to catalyze the meiotic DSB formation. Spo11 is also required for induction of meiotic DSBs at long inverted repeats and at large trinucleotide repeat tracts. Here we report the isolation and characterization of temperature-sensitive spo11-mutant alleles to better understand how Spo11 functions, and how meiotic DSBs are generated at various recombination hotspots. Analysis of mutation sites of isolated spo11-mutant alleles indicated that both N-terminal and C-terminal non-conserved residues of Spo11 are essential for the protein's function, possibly for interaction with other meiotic DSB enzymes. Several of the mutation sites within the conserved region are predicted to lie on the surface of the protein, suggesting that this region is required for activation of the meiotic initiation complex via protein-protein interaction. In addition to the conditional mutants, we isolated partially recombination-defective mutants; analysis of one of these mutants indicated that Ski8, as observed previously, interacts with Spo11 via the latter's C-terminal residues.

  8. Cytotoxicity and cellular uptake of ZnS:Mn nanocrystals biofunctionalized with chitosan and aminoacids

    NASA Astrophysics Data System (ADS)

    Sajimol Augustine, M.; Anas, Abdulaziz; Das, Ani V.; Sreekanth, S.; Jayalekshmi, S.

    2015-02-01

    Highly luminescent, manganese doped, zinc sulphide (ZnS:Mn) nanocrystals biofunctionalized with chitosan and various aminoacids such as L-citrulline, L-lysine, L-arginine, L-serine, L-histidine and glycine were synthesized by chemical capping co-precipitation method at room temperature, which is a simple and cost effective technique. The synthesized nanocrystals were structurally characterized by TEM, XRD, EDXS and FT-IR spectroscopy techniques. They possess high colloidal stability with strong orange red photoluminescence emission at 598 nm. The intensity of orange red emission has been observed to be maximum in L-citrulline capped ZnS:Mn nanocrystals in which the emission at 420 nm is effectively quenched by surface passivation due to capping. Taking into consideration the prospects of these highly luminescent, bio-compatible ZnS:Mn nanocrystals in bio-imaging applications, cytotoxicity studies were conducted to identify the capping combination which would accomplish minimum toxic effects. ZnS:Mn nanocrystals biofunctionalized with chitosan, L-citrulline, glycine, L-artginine, L-serine and L-histidine showed least toxicity up to 10 nM concentrations in mouse fibroblast L929 cells, which further confirms their cytocompatibility. Also the ZnS:Mn nanocrystals biofunctionalized with L-arginine showed maximum uptake in in vitro studies carried out in human embryonic kidney cells, HEK-293T, which shows the significant role of this particular amino acid in fetoplacental nutrition. The present study highlights the suitability of aminoacid conjugated ZnS:Mn nanocrystals, as promising candidates for biomedical applications.

  9. Vesicles from pH-regulated reversible gemini amino-acid surfactants as nanocapsules for delivery.

    PubMed

    Lv, Jing; Qiao, Weihong; Li, Zongshi

    2016-10-01

    Reversible transition from micelles to vesicles by regulating pH were realized by gemini amino-acid surfactants N,N'-dialkyl-N,N'-diacetate ethylenediamine. Measurement results of ζ-potential at different pH and DLS at varying solvents revealed that the protonation between H(+) and double NCH2COO(-) groups (generating NH(+)CH2COO(-)), expressed as pKa1 and pKa2, is the key driving force to control the aggregation behaviors of gemini surfactant molecule. Effect of pH on the bilayer structure was studied in detail by using steady-state fluorescence spectroscopy of hydrophobic pyrene and Coumarin 153 (C153) respectively and fluorescence resonance energy transfer (FRET) from C153 to Rhodamine 6G (R6G). Various pH-regulated and pH-reversible self-assemblies were obtained in one surfactant system. Vitamin D3 was encapsulated in vesicle bilayers to form nano-VD3-capsules as VD3 supplement agent for health care products. By using the electrostatic attraction between Ca(2+) and double -COO(-) groups, nano-VD3-capsules with Ca(2+) coated outermost layers were prepared as a formulation for VD3 and calcium co-supplement agent. DLS and TEM were performed to check stability and morphology of the nano-capsules. It is concluded that the pH-regulated gemini amino-acid surfactants can be used to construct colloidal systems for delivering hydrophobic drugs or nutritions without lipids at human physiological pH level. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Crystal structure of the novel amino-acid racemase isoleucine 2-epimerase from Lactobacillus buchneri.

    PubMed

    Hayashi, Junji; Mutaguchi, Yuta; Minemura, Yume; Nakagawa, Noriko; Yoneda, Kazunari; Ohmori, Taketo; Ohshima, Toshihisa; Sakuraba, Haruhiko

    2017-05-01

    Crystal structures of Lactobacillus buchneri isoleucine 2-epimerase, a novel branched-chain amino-acid racemase, were determined for the enzyme in the apo form, in complex with pyridoxal 5'-phosphate (PLP), in complex with N-(5'-phosphopyridoxyl)-L-isoleucine (PLP-L-Ile) and in complex with N-(5'-phosphopyridoxyl)-D-allo-isoleucine (PLP-D-allo-Ile) at resolutions of 2.77, 1.94, 2.65 and 2.12 Å, respectively. The enzyme assembled as a tetramer, with each subunit being composed of N-terminal, C-terminal and large PLP-binding domains. The active-site cavity in the apo structure was much more solvent-accessible than that in the PLP-bound structure. This indicates that a marked structural change occurs around the active site upon binding of PLP that provides a solvent-inaccessible environment for the enzymatic reaction. The main-chain coordinates of the L. buchneri isoleucine 2-epimerase monomer showed a notable similarity to those of α-amino-ℇ-caprolactam racemase from Achromobactor obae and γ-aminobutyrate aminotransferase from Escherichia coli. However, the amino-acid residues involved in substrate binding in those two enzymes are only partially conserved in L. buchneri isoleucine 2-epimerase, which may account for the differences in substrate recognition by the three enzymes. The structures bound with reaction-intermediate analogues (PLP-L-Ile and PLP-D-allo-Ile) and site-directed mutagenesis suggest that L-isoleucine epimerization proceeds through abstraction of the α-hydrogen of the substrate by Lys280, while Asp222 serves as the catalytic residue adding an α-hydrogen to the quinonoid intermediate to form D-allo-isoleucine.

  11. CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES: Properties of Parity Non-conserved and Parity Conserved States in Matrix Product Systems

    NASA Astrophysics Data System (ADS)

    Zhu, Jing-Min

    2010-08-01

    In terms of reflection transformation of a matrix product state (MPS), the parity of the MPS is defined. Based on the reflective parity non-conserved MPS pair we construct the even-parity state |Φerangle and the odd-parity state |Φorangle. It is interesting to find that the parity non-conserved reflective MPS pair have no long-range correlations; instead the even-parity state |Φerangle and the odd-parity state |Φorangle constructed from them have the same long-range correlations for the parity non-conserved block operators. Moreover, the entanglement between a block of n contiguous spins and the rest of the spin chain for the states |Φerangle and |Φorangle is larger than that for the reflective MPS pair except for n = 1, and the difference of them approaches 1 monotonically and asymptotically from 0 as n increases from 1. These characteristics indicate that MPS parity as a conserved physical quantity represents a kind of coherent collective quantum mode, and that the parity conserved MPSs contain more correlation, coherence, and entanglement than the parity non-conserved ones.

  12. Multicultural Challenges in Educational Policies within a Non-Conservative Scenario: The Case of the Emerging Reforms in Higher Education in Brazil

    ERIC Educational Resources Information Center

    Canen, Ana

    2005-01-01

    The article discusses the extent to which multiculturalism has had an impact in the emerging reforms in higher education in Brazil, against the backdrop of the rise of a new non-Conservative, Labour-oriented government whose political agenda is marked by a discursive stand against conservatism, neo-liberalism and neocolonialism. Building on a…

  13. [Classification of anticancer drugs with different mechanisms based on amino-acid consumption profiling in culture media].

    PubMed

    Han, Xiaofei; Wang, Longxing; Yang, Qianxu; Xiao, Hongbin

    2011-04-01

    An approach for quantitative determination of amino-acid consumption profiling in culture media by high performance liquid chromatography with fluorescence detection (HPLC-FLD) was developed and validated, using o-phthalic dicarboxaldehyde (OPA) as the derivatizing reagent and norvaline as the internal standard. Mobile phase A was 10 mmol/L Na2HPO4Na2B4O7 buffer (pH 7.95), and mobile phase B was acetonitrile-methanol-water (45:45:10, v/v/v). The linear elution program was 5% B at the start and 52% B at the end in 35 min. The 17 free amino-acids (FAAs) were separated satisfactorily in 33 min. Following HeLa cells incubation in conditioned medias of taxol (4 micromol/L) and mitomycin (75 micromol/L), respectively, with control for 24 h, the media 17 amino-acid consumption profilings were determined, and then analyzed by multivariate statistical analysis based on Matlab7.1 software platform. Relation analysis performed by partial least squares-discriminant analysis (PLS-DA) indicated that in comparison with the control group, the media amino-acid consumption profiling can distinguish the two anticancer drugs with different mechanisms, which provides a new perspective for the pre-classification of drug action mechanisms during the screening of new anticancer drugs. Meanwhile, the idea from the outer into the inner has convenient and economic characteristics.

  14. Influence of the Amino-Acid Sequence on the Inverse Temperature Transition of Elastin-Like Polymers

    PubMed Central

    Ribeiro, Artur; Arias, F. Javier; Reguera, Javier; Alonso, Matilde; Rodríguez-Cabello, J. Carlos

    2009-01-01

    Abstract This work explores the dependence of the inverse temperature transition of elastin-like polymers (ELPs) on the amino-acid sequence, i.e., the amino-acid arrangement along the macromolecule and the resulting linear distribution of the physical properties (mainly polarity) derived from it. The hypothesis of this work is that, in addition to mean polarity and molecular mass, the given amino-acid sequence, or its equivalent—the way in which polarity is arranged along the molecule—is also relevant for determining the transition temperature and the latent heat of that transition. To test this hypothesis, a set of linear and di- and triblock ELP copolymers were designed and produced as recombinant proteins. The absolute sequence control provided by recombinant technologies allows the effect of the amino-acid arrangement to be isolated while keeping the molecular mass or mean polarity under strict control. The selected block copolymers were made of two different ELPs: one exhibiting temperature and pH responsiveness, and one exhibiting temperature responsiveness only. By changing the arrangement and length of the blocks while keeping other parameters, such as the molecular mass or mean polarity, constant, we were able to show that the sequence plays a key role in the smart behavior of ELPs. PMID:19580769

  15. Cholecystokinin release and biliopancreatic secretion in response to selective perfusion of the duodenal loop with aminoacids in man.

    PubMed

    Colombel, J F; Sutton, A; Chayvialle, J A; Modigliani, R

    1988-09-01

    The aim of this study was to measure the role of the duodenal loop in biliopancreatic secretion in man by infusing various stimuli at the ampulla of Vater and collecting duodenal contents at the ligament of Treitz, above an occluding balloon. Perfusion at 10 ml/min of a first mixture of aminoacids - phenylalanine (47.2 mmol), methionine (38.2 mmol), tryptophan (11 mmol), valine (61.6 mmol) - increased cholecystokinin (CCK) plasma concentrations and duodenal bile salt output (p less than 0.005) as compared with a control electrolyte solution, but did not change pancreatic enzyme secretion significantly; duodenal infusion of another aminoacid mixture - arginine (32.4 mmol), histidine (14.1 mmol), leucine (36 mmol), isoleucine (21.5 mmol), lysine (31 mmol), threonine (23 mmol) - did not change CCK plasma concentrations, bile salt or pancreatic enzyme output. The respective role of duodenal distension and endogenous CCK was investigated by perfusing the first aminoacid solution and the control solution at 2, 5, and 10 ml/min. Changing the perfusion rate of control solution from 2 to 5 ml/min led to a significant increase (p less than 0.01) in pancreatic secretion with no further increase at 10 ml/min. Bile salt output was not influenced by the perfusion rate of control solution. During the perfusion of the aminoacid solution, despite a stepwise increase in CCK release, the only significant change in pancreatic secretion was an increase of lipase output (p less than 0.05) when the infusion rate was raised from 2 to 5 ml/min. Our results suggest that duodenal CCK release (1) depends on the nature of aminoacids (2) has predominant role in the regulation of pancreatic secretion at low perfusion rate but is less effective when superimposed on a mechanical stimulus caused by duodenal distension (3) is a major stimulus for gall bladder contraction which is not influenced by duodenal distension.

  16. Photochemical abiotic synthesis of amino-acid precursors from simulated planetary atmospheres by vacuum ultraviolet light

    NASA Astrophysics Data System (ADS)

    Takahashi, Jun-Ichi; Masuda, Hitomi; Kaneko, Takeo; Kobayashi, Kensei; Saito, Takeshi; Hosokawa, Teruo

    2005-07-01

    For the purpose of investigating the photon energy dependence of the photoinduced abiotic synthesis of organic molecules, gas mixtures that simulate typical planetary atmospheres, including a carbon source (CO or CH4), a nitrogen source (N2 or NH3), and H2O, were irradiated with synchrotron radiation through a vacuum-ultraviolet transmitting window. Three kinds of window material, fused silica, synthetic quartz, and MgF2, were used as a high-energy-cutting filter, whose absorption-edge energies are 6.4, 8.1, and 10.5 eV, respectively. Three types of gas mixture, Titan-type (CH4-N2-H2O), comet-type (CO-NH3-H2O), and primitive-Earth-type (CO-N2-H2O), were irradiated with vacuum-ultraviolet photons in the three energy ranges. After the irradiation, amino-acid formation yields in the acid-hydrolyzed solution of the product were measured with a high-performance liquid chromatograph method. From the Titan- and comet-type mixtures, amino acids were detected by irradiation with photons lower than 8.1 eV. For both mixtures, the averaged quantum yields of glycine generation in the photon energy region of 7-10.5 eV were of the order of 10-5, which was larger by about one order than that in the region 5-8 eV. On the other hand, from the primitive-Earth-type mixture, amino-acid formation was difficult to detect even with irradiation as high as 10.5 eV, even though amino acids were generated in comparable yields from the Titan- and comet-type mixtures by irradiation with soft x rays or proton beam, whose energies are much higher. These results suggest that the vacuum ultraviolet light is a more effective energy source for the generation of the precursors of bioorganic compounds in extraterrestrial environments than in primitive-Earth atmosphere.

  17. Substrate specificity and transport mechanism of amino-acid transceptor Slimfast from Aedes aegypti

    PubMed Central

    Boudko, Dmitri Y.; Tsujimoto, Hitoshi; Rodriguez, Stacy D.; Meleshkevitch, Ella A.; Price, David P.; Drake, Lisa L.; Hansen, Immo A.

    2015-01-01

    Anautogenous mosquitoes depend on vertebrate blood as nutrient source for their eggs. A highly efficient set of membrane transporters mediates the massive movement of nutrient amino acids between mosquito tissues after a blood meal. Here we report the characterization of the amino-acid transporter Slimfast (Slif) from the yellow-fever mosquito Aedes aegypti using codon-optimized heterologous expression. Slif is a well-known component of the target-of-rapamycin signalling pathway and fat body nutrient sensor, but its substrate specificity and transport mechanism were unknown. We found that Slif transports essential cationic and neutral amino acids with preference for arginine. It has an unusual dual-affinity mechanism with only the high affinity being Na+ dependent. Tissue-specific expression and blood meal-dependent regulation of Slif are consistent with conveyance of essential amino acids from gut to fat body. Slif represents a novel transport system and type of transceptor for sensing and transporting essential amino acids during mosquito reproduction. PMID:26449545

  18. Total nitrogen vs. amino-acid profile as indicator of protein content of beef.

    PubMed

    Hall, Nicolette G; Schönfeldt, Hettie C

    2013-10-01

    In most cited food composition studies and tables, the proximate system measures protein as total nitrogen (N) (determined by Kjeldahl or Dumas method) multiplied by a specific factor. A factor of 6.25 is used for determining total protein from total N (Jones, Munsey, & Walker, 1942). Although more expensive, it is considered more accurate to base protein content of foods on amino acid data (Greenfield & Southgate, 2003). A study on the nutrient composition of beef analysed the full amino-acid profile of fifteen retail cuts from three age groups and six fat codes, as well as determined total nitrogen content to determine proximate protein composition. For all cuts, the correlation coefficient of total amino acids to protein (N×6.25) was 0.635. This indicates a poor correlation for predicting actual protein content (as determined by total amino acid count), based on the nitrogen factor of 6.25. On average, the sum of amino acids per cut amounted to 91% of total determined protein (N×6.25) for the same cut.

  19. Extended longevity and survivorship during amino-acid starvation in a Drosophila Sir2 mutant heterozygote.

    PubMed

    Slade, Jennifer D; Staveley, Brian E

    2016-05-01

    The regulation of energy homeostasis is pivotal to survive periods of inadequate nutrition. A combination of intricate pathways and proteins are responsible for maximizing longevity during such conditions. The sirtuin deacetylase Sir2 is well conserved from single-celled yeast to mammals, and it controls a number of downstream targets that are active during periods of extreme stress. Overexpression of Sir2 has been established to enhance survival of a number of model organisms undergoing calorie restriction, during which insulin receptor signalling (IRS) is reduced, a condition that itself can enhance survivorship during starvation. Increased Sir2 expression and reduced IRS result in an increase in the activity of the transcription factor foxo, an advantageous activation during stress but lethal when overly active. We have found that a lowered gene dosage of Sir2, in mutant heterozygotes, can extend normal longevity and greatly augment survivorship during amino-acid starvation in Drosophila. Additionally, these mutants, in either heterozygous or homozygous form, do not appear to have any disadvantageous effects upon development or cell growth of the organism unlike IRS mutants. These results may advance the understanding of the biological response to starvation and allow for the development of a model organism to mimic the ability of individuals to tolerate nutrient deprivation.

  20. Partitioning of amino-acid analogues in a five-slab membrane model

    SciTech Connect

    Sengupta, D; Smith, Jeremy C; Ullmann, G. Matthias

    2008-09-01

    The positional preferences of the twenty amino-acid residues in a phospholipid bilayer are investigated by calculating the solvation free energy of the corresponding side chain analogues using a five-slab continuum electrostatic model. The side-chain analogues of the aromatic residues tryptophan and tyrosine are found to partition in the head-group region, due to compensation between the increase of the non-polar component of the solvation free energy at the boundary with the aqueous region and the decrease in the electrostatic component. The side chain analogue of phenylalanine differs from the other aromatic molecules by being able to partition in both the head-group region and the membrane core. This finding is consistent with experimental findings of the position of phenylalanine in membrane helices. Interestingly, the charged side-chain analogues of arginine and lysine are shown to prefer the head-group region in an orientation that allows the charged moiety to interact with the aqueous layer. The orientation adopted is similar to the 'snorkelling' effect seen in lysine and arginine residues in membrane helices. In contrast, the preference of the charged side-chain analogues of histidine (protonated) and aspartate (deprotonated) for the aqueous layer is shown to be due to a steep decrease in the electrostatic component of the solvation free energy at the boundary to the aqueous region. The calculations allow an understanding of the origins of side chain positioning in membranes and are thus useful in understanding membrane-protein:lipid thermodynamics.

  1. Structure and expression of the Drosophila ubiquitin-80-amino-acid fusion-protein gene.

    PubMed Central

    Barrio, R; del Arco, A; Cabrera, H L; Arribas, C

    1994-01-01

    In the fruitfly Drosophila, as in all eukaryotes examined so far, some ubiquitin-coding sequences appear fused to unrelated open reading frames. Two of these fusion genes have been previously described (the homologues of UBI1-UBI2 and UBI4 in yeast), and we report here the organization and expression of a third one, the DUb80 gene (the homologue of UBI3 in yeast). This gene encodes a ubiquitin monomer fused to an 80-amino-acid extension which is homologous with the ribosomal protein encoded by the UB13 gene. The 5' regulatory region of DUb80 shares common features with another ubiquitin fusion gene, DUb52, and with the ribosomal protein genes of Drosophila, Xenopus and mouse. We also find helix-loop-helix protein-binding sequences (E-boxes). The DUb80 gene is transcribed to a 0.9 kb mRNA which is particularly abundant under conditions of high protein synthesis, such as in ovaries and exponentially growing cells. Images Figure 3 Figure 4 PMID:8068011

  2. Cluster analysis identifies aminoacid compositional features that indicate Toxoplasma gondii adhesin proteins

    PubMed Central

    Arenas, Ailan F; Salcedo, Gladys E; Moncada, Diego M; Erazo, Diego A; Osorio, Juan F; Gomez-Marin, Jorge E

    2012-01-01

    Toxoplasma gondii invade host cells using a multi-step process that depends on the regulated secretion of adhesions. To identify key primary sequence features of adhesins in this parasite, we analyze the relative frequency of individual amino acids, their dipeptide frequencies, and the polarity, polarizability and Van der Waals volume of the individual amino acids by using cluster analysis. This method identified cysteine as a key amino acid in the Toxoplasma adhesin group. The best vector algorithm of non-concatenated features was for 2 attributes: the single amino acid relative frequency and the dipeptide frequency. Polarity, polarizability and Van der Waals volume were not good classificatory attributes. Single amino acid attributes clustered unambiguously 67 apicomplexan hypothetical adhesins. This algorithm was also useful for clustering hypothetical Toxoplasma target host receptors. All of the cluster performances had over 70% sensitivity and 80% specificity. Compositional aminoacid data can be useful for improving machine learning-based prediction software when homology and structural data are not sufficient. PMID:23144551

  3. The search for a deterministic origin for the presence of nonracemic amino-acids in meteorites: a computational approach.

    PubMed

    Vandenbussche, Sophie; Reisse, Jacques; Bartik, Kristin; Lievin, Jacques

    2011-05-01

    Amino-acid enantiomeric excesses (ee's) have been detected in different types of carbonaceous chondrites, all in favor of the L enantiomer. In this article, we discuss possible deterministic causes to the presence of these amino-acid ee's in meteorites and evaluate in particular enantioselective photolysis by circularly polarized light (CPL). The electronic circular dichroism spectra of a set of amino- and hydroxy-acids, all detected in chondritic matter but some with ee's and others without ee's, were calculated and compared. The spectra were calculated for the most stable conformation(s) of the considered molecules using quantum mechanical methods (density functional theory). Our results suggest that CPL photolysis in the gas phase was perhaps not at the origin of the presence of ee's in meteorites and that the search for another, but still unknown, deterministic cause must be seriously undertaken. Copyright © 2011 Wiley-Liss, Inc.

  4. Theoretical Studies of Interactions between O-Phosphorylated and Standard Amino-Acid Side-Chain Models in Water

    PubMed Central

    Wiśniewska, Marta; Sobolewski, Emil; Ołdziej, Stanisław; Liwo, Adam; Scheraga, Harold A.; Makowski, Mariusz

    2015-01-01

    Phosphorylation is a common post-translational modification of the amino-acid side chains (serine, tyrosine, and threonine) that contain hydroxyl groups. The transfer of the negatively charged phosphate group from an ATP molecule to such amino-acid side chains leads to changes in the local conformations of proteins and the pattern of interactions with other amino-acid side-chains. A convenient characteristic of the side chain–side chain interactions in the context of an aqueous environment is the potential of mean force (PMF) in water. A series of umbrella-sampling molecular dynamic (MD) simulations with the AMBER force field were carried out for pairs of O-phosphorylated serine (pSer), threonine (pThr), and tyrosine, (pTyr) with natural amino acids in a TIP3P water model as a solvent at 298 K. The weighted-histogram analysis method was used to calculate the four-dimensional potentials of mean force. The results demonstrate that the positions and depths of the contact minima and the positions and heights of the desolvation maxima, including their dependence on the relative orientation depend on the character of the interacting pairs. More distinct minima are observed for oppositely charged pairs such as, e.g., O-phosphorylated side-chains and positively charged ones, such as the side-chains of lysine and arginine. PMID:26100791

  5. Analysis of aminoacids pattern in receptor tyrosine kinase using Boolean association rule.

    PubMed

    Kalita, Pranjal; Kumar, Brindha Senthil; Krishnaswamy, Soundararajan; Nachimuthu, Senthil Kumar

    2012-01-01

    Cancers are characterized by unrestricted cell division and independency of growth factor and other external signal responsiveness. Eukaryotic parental cells of tumors, on the other hand, constitute tissues and other higher structures like organs and systems and are capable of performing various functions in a highly co-ordinated fashion. Hence, cancer cells may be considered as entities capable of incessant growth and cell division but lacking any evolutionarily advanced intracellular or intercellular regulation. Since receptor tyrosine kinases are highly altered and exist in deregulated/constitutively active forms in cancer cells - achieved through various epigenetic mechanisms - we hypothesize the functional RTKs in cancer cells to resemble their counterparts in more primitive species. Analysis of RTK sequences of various species and of cancer is, therefore, expected to prove this hypothesis. Association rule in data mining can reveal the hidden biological information. This study utilizes the Boolean association rule to mine the occurrence pattern of glycine, arginine and alanine in receptor tyrosine kinases (RTKs) of invertebrates, vertebrates and cancer related vertebrate RTKs based on protein sequence informations. The results reveal that vertebrate cancer RTKs resembles prokaryotes and invertebrate RTKs showing an increasing trend of glycine, alanine and decreasing trend in arginine composition. The aminoacid compositions of vertebrates: invertebrates: prokaryotes: vertebrate cancer with respect to Glycine (>=6.1) were 42.86: 50.0: 85.71: 100%, Alanine (>=6.2) were 10.72: 66.67: 85.71: 100%, whereas Arginine (>=5.9) were 21.43: 16.67: 14.29: 0%, respectively. In conclusion, results from this study supports our hypothesis that cancer cells may resemble lower organisms since functionally cancer cells are unresponsive to external signals and various regulatory mechanisms typically found in higher eukaryotes are largely absent.

  6. Improving amino-acid identification, fit and C(alpha) prediction using the Simplex method in automated model building.

    PubMed

    Romo, Tod D; Sacchettini, James C; Ioerger, Thomas R

    2006-11-01

    Automated methods for protein model building in X-ray crystallography typically use a two-phased approach that involves first modeling the protein backbone followed by building in the side chains. The latter phase requires the identification of the amino-acid side-chain type as well as fitting of the side-chain model into the observed electron density. While mistakes in identification of individual side chains are common for a number of reasons, sequence alignment can sometimes be used to correct errors by mapping fragments into the true (expected) amino-acid sequence and exploiting contiguity constraints among neighbors. However, side chains cannot always be confidently aligned; this depends on having sufficient accuracy in the initial calls. The recognition of amino-acid side-chains based on the surrounding pattern of electron density, whether by features, density correlation or free atoms, can be sensitive to inaccuracies in the coordinates of the predicted backbone C(alpha) atoms to which they are anchored. By incorporating a Nelder-Mead Simplex search into the side-chain identification and model-building routines of TEXTAL, it is demonstrated that this form of residue-by-residue rigid-body real-space refinement (in which the C(alpha) itself is allowed to shift) can improve the initial accuracy of side-chain selection by over 25% on average (from 25% average identity to 32% on a test set of five representative proteins, without corrections by sequence alignment). This improvement in amino-acid selection accuracy in TEXTAL is often sufficient to bring the pairwise amino-acid identity of chains in the model out of the so-called ;twilight zone' for sequence-alignment methods. When coupled with sequence alignment, use of the Simplex search yielded improvements in side-chain accuracy on average by over 13 percentage points (from 64 to 77%) and up to 38 percentage points (from 40 to 78%) in one case compared with using sequence alignment alone.

  7. [Coconut (Cocos nucifera L.) and the preparation of a milk substitute].

    PubMed

    Chitarra, M I; Campos, M A

    1975-01-01

    Coconut (Cocos nucifera, L.) is an abundant product in Brazil. The authors studied the use of the protein fraction to prepare "milk-substitute" beverages. The analyses were made on albumen, copra and cake. Protein coconut extraction was tried with water; NaCl solutions in different concentrations; HCl and NaOH solutions in different concentrations; HCl and NaOH solutions at different pH values. The extracted proteins were analysed for aminoacid composition and chemical score. The best results of protein extraction were obtained with NaCl 1 M solution using the ratio 100:75 (coconut:solution). The extracted proteins were coagulated with trichloroacetic acid and separated with water and analysed for aminoacid composition and solubility.

  8. Restoration of the contact surface in FORCE-type centred schemes II: Non-conservative one- and two-layer two-dimensional shallow water equations

    NASA Astrophysics Data System (ADS)

    Canestrelli, Alberto; Toro, Eleuterio F.

    2012-10-01

    Recently, a non-conservative well-balanced FORCE-type scheme has been proposed for solving multidimensional non-conservative equations such as the shallow water equations [4], the two-fluid flow model of Pitman and Le and the two- and three-dimensional Baer-Nunziato equations for compressible multiphase flows [17]. In the present paper the original scheme is first rewritten in a suitable form that allows easy manipulation of numerical fluxes. We then propose a modified scheme that provides a better resolution of contact waves for both one-layer and two-layer shallow water models. The improvement is particularly evident when an additional equation is solved for a passive solute. In this case, the original scheme does not satisfy the C-property for a uniformly distribute tracer, whereas the modified scheme provides a solution that is exact up to machine precision. Moreover, the modified scheme better resolves contact discontinuities, with an accuracy close to the one provided by a fully-upwind non-conservative ROE-type scheme accounting for the complete wave structure. When higher orders are achieved, the difference in accuracy between the various schemes is less pronounced. Moreover, the capability of the two-dimensional scheme to capture steady states is analyzed for both straight and meandering non-flat channels with non-zero friction, and for both one-layer and two-layer equations. Whereas the original first order FORCE scheme is able to correctly reproduce the longitudinal profile in the case of a straight channel even on a coarse mesh, when the channel is strongly meandering a modification of the scheme is necessary, otherwise a very refined mesh and a very high order of accuracy are needed, with a notable increase of computational time.

  9. Nucleophilic Aromatic Substitution.

    ERIC Educational Resources Information Center

    Avila, Walter B.; And Others

    1990-01-01

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

  10. Nucleophilic Aromatic Substitution.

    ERIC Educational Resources Information Center

    Avila, Walter B.; And Others

    1990-01-01

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

  11. Synthetic amphibian peptides and short amino-acids derivatives against planktonic cells and mature biofilm of Providencia stuartii clinical strains.

    PubMed

    Ostrowska, Kinga; Kamysz, Wojciech; Dawgul, Małgorzata; Różalski, Antoni

    2014-01-01

    Over the last decade, the growing number of multidrug resistant strains limits the use of many of the currently available chemotherapeutic agents. Furthermore, bacterial biofilm, due to its complex structure, constitutes an effective barrier to conventional antibiotics. The in vitro activities of naturally occurring peptide (Citropin 1.1), chemically engineered analogue (Pexiganan), newly-designed, short amino-acid derivatives (Pal-KK-NH2, Pal-KKK-NH2, Pal-RRR-NH2) and six clinically used antimicrobial agents (Gatifloxacin, Ampicilin, Cefotaxime, Ceftriaxone, Cefuroxime and Cefalexin) were investigated against planktonic cells and mature biofilm of multidrug-resistant Providencia stuartii strains, isolated from urological catheters. The MICs, MBCs values were determined by broth microdilution technique. Inhibition of biofilm formation by antimicrobial agents as well as biofilm susceptibility assay were tested using a surrogate model based on the Crystal Violet method. The antimicrobial activity of amino-acids derivatives and synthetic peptides was compared to that of clinically used antibiotics. For planktonic cells, MICs of peptides and antibiotics ranged between 1 and 256 μg/ml and 256 and ≥ 2048 μg/ml, respectively. The MBCs values of Pexiganan, Citropin 1.1 and amino-acids derivatives were between 16 and 256 μg/ml, 64 and 256 μg/ml and 16 and 512 μg/ml, respectively. For clinically used antibiotics the MBCs values were above 2048 μg/ml. All of the tested peptides and amino-acids derivatives, showed inhibitory activity against P. stuartii biofilm formation, in relation to their concentrations. Pexiganan and Citropin 1.1 in concentration range 32 and 256 μg/ml caused both strong and complete suppression of biofilm formation. None of the antibiotics caused complete inhibition of biofilm formation process. The biofilm susceptibility assay verified the extremely poor antibiofilm activity of conventional antibiotics compared to synthetic peptides. The

  12. Effects of hypotaurine, cysteamine and aminoacids solution on post-thaw microscopic and oxidative stress parameters of Angora goat semen.

    PubMed

    Bucak, Mustafa Numan; Tuncer, Pürhan Barbaros; Sariözkan, Serpil; Ulutaş, Pinar Alkim; Coyan, Kenan; Başpinar, Nuri; Ozkalp, Birol

    2009-12-01

    This study was conducted to determine the effects of cysteamine, hypotaurine and aminoacids solution (BME) on standard semen parameters, lipid peroxidation and antioxidant activities of Angora goat semen after the freeze-thawing process. Ejaculates collected from four Angora goats were evaluated and pooled at 37 degrees C. Semen samples, which were diluted with a Tris-based extender containing the antioxidants hypotaurine (5 mM) and cysteamine (5 mM), and an aminoacid solution (13%), and an extender containing no antioxidants (control), were cooled to 5 degrees C and frozen in 0.25-ml French straws in liquid nitrogen. Frozen straws were thawed individually at 37 degrees C for 20s in a water bath for evaluation. Supplementation with cysteamine, hypotaurine and BME caused significant (P<0.05) increases in sperm motility, and significant (P<0.05) decreases in total abnormality rates in comparison to the control group. While all in vitro treatments did not affect the acrosomal abnormality rates, hypotaurine and BME but not cysteamine significantly (P<0.05) increased the HOST results as compared to the control group. Supplementation with antioxidants and BME did not significantly affect MDA levels and CAT activity in comparison to the control group (P>0.05). The antioxidants hypotaurine and cysteamine decreased SOD activity when compared to the BME group and controls (P<0.001).

  13. Complexes of oxovanadium(IV), dioxovanadium(V) and dioxouranium(VI) with aminoacids in aqueous solution

    NASA Astrophysics Data System (ADS)

    Lagrange, P.; Schneider, M.; Lagrange, J.

    1998-11-01

    The equilibria between three oxocations (VO2+, VO2+ and UO22+) and several ?- aminoacids (glycine, serine, asparagine, lysine, aspartic acid and glutamic acid) are studied in aqueous solution. Stoichiometry and stability of the complexes formed are determined from a combination of potentiometric and spectroscopic measurements. Solution structures of the different complexes are proposed based on the thermodynamic results. The oxovanadium(IV) complexes appear less stable than the corresponding dioxouranium(VI) and dioxovanadium(V) complexes. VO2+ can be bound to only one ligand to form monodentate or chelate complexes. UO22+ and VO2+ cations may be chelated by one or two ligands. Les équilibres entre trois oxocations, VO2+, VO2+ et UO22+ et plusieurs α-aminoacides, glycine, sérine, asparagine, lysine et acides aspartique et glutamique, sont étudiés en solution aqueuse par potentiométrie couplée à la spectrophotométrie. Les complexes de VO2+ sont moins stables que les complexes de VO2+ et UO22+ de même stoechiométrie. VO2+ ne peut se lier qu'à un seul ligand pour former soit des complexes monodentés, soit des chélates. UO22+ et VO2+ peuvent être chélatés par un ou deux ligands. Des structures hypothétiques en solution sont proposées.

  14. In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

    PubMed Central

    Aguilera-Gomez, Angelica; van Oorschot, Marinke M; Veenendaal, Tineke; Rabouille, Catherine

    2016-01-01

    PARP catalysed ADP-ribosylation is a post-translational modification involved in several physiological and pathological processes, including cellular stress. In order to visualise both Poly-, and Mono-, ADP-ribosylation in vivo, we engineered specific fluorescent probes. Using them, we show that amino-acid starvation triggers an unprecedented display of mono-ADP-ribosylation that governs the formation of Sec body, a recently identified stress assembly that forms in Drosophila cells. We show that dPARP16 catalytic activity is necessary and sufficient for both amino-acid starvation induced mono-ADP-ribosylation and subsequent Sec body formation and cell survival. Importantly, dPARP16 catalyses the modification of Sec16, a key Sec body component, and we show that it is a critical event for the formation of this stress assembly. Taken together our findings establish a novel example for the role of mono-ADP-ribosylation in the formation of stress assemblies, and link this modification to a metabolic stress. DOI: http://dx.doi.org/10.7554/eLife.21475.001 PMID:27874829

  15. Comparison of the Amino-Acid Content in Pharmacopuncture Extracts Taken from a Scorpion's Body and from Its Tail

    PubMed Central

    Lee, Jin-Ho; Shin, Joon-Shik; Chi, Eun-Hya; Lee, In-Hee

    2013-01-01

    Objective: This study was conducted to investigate the amino-acid compositions of pharmacopuncture extracts taken from the body and from the tail of Buthus martensii Karsch, which are frequently prescribed in Oriental medicine. Methods: Amino acids in hot water and 70% ethanol extracts taken from the scorpion’s whole body and from its tail were screened by using high performance liquid chromatography (HPLC). The experiments were performed with linearity, precision and accuracy. Results: The results of the amino-acid-composition analysis showed that the Buthus martensii Karsch extracts contained various amino acids such as aspartic acid, histidine, alanine, tyrosine, and cystine. The amino-acid analysis showed that the hot water extract was more beneficial than the ethanol extract, except for histidine. The amino acids from the tail and the body of the scorpion were compared, and the concentration of aspartic acid in the extract from the scorpion’s tail was two times that found in the extract from its body. The results of validation experiments were all satisfactory. Conclusion: Studies on the ingredients in extracts from a scorpion other than buthotoxin may demonstrate that the antiepileptic efficacy, anticancer activity, antithrombotic action and analgesic effect are enhanced. Using only the tail of the scorpion when pharmacopuncture is dispensed may be beneficial because the extracts from the tail of the scorpion have higher potency than those from the whole body. PMID:25780666

  16. 132 A Novel Pathway of Proviral HIV-1 Latency Regulated by Aminoacid Starvation and HDAC4

    PubMed Central

    Poli, Guido; Vicenzi, Elisa; Schiaffino, Maria Vittoria; Van Lint, Carine

    2014-01-01

    An intrinsic property of all retroviruses is their capacity to establish a state of latent infection in addition to active viral replication. Both genetic and epigenetic factors contribute to silence the integrated provirus and are nowadays targets of experimental approaches aiming at reactivating virus expression in order to kill the infected cells either by immune-mediated mechanisms (such as CTL) or by pharmacological agents. We have recently uncovered an unsuspected pathway triggered by essential aminoacid starvation and involving the downregulation of HDAC4, a class II HDAC, leading to a significant uprising of latent HIV-1 infection in chronically infected cell lines, such as ACH-2 cells, expressing this enzyme, but not in similar cell lines, such as U1, negative for HDAC4 expression. Both pharmacological targeting of HDAC4 and siRNA-mediated downregulation of its expression gave the same result. A similar phenomenon was observed for heterologous transgenes, driven by different promoters, introduced for gene therapy purposes, but not for their endogenous counterparts. This observation suggests that the mTOR-independent pathway triggered by aminoacid starvation and involving HDAC4 modulation represents or contributes to an intracellular response to foreign nucleic acids (I. Palmisano et al., PNASPlus 2012). More recent results with a broader variety of HIV-1 latency models will be discussed.

  17. Crystal structures of Leishmania mexicana arginase complexed with α,α-disubstituted boronic amino-acid inhibitors.

    PubMed

    Hai, Yang; Christianson, David W

    2016-04-01

    Leishmania arginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiates de novo polyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections. To this end, two X-ray crystal structures of L. mexicana arginase complexed with α,α-disubstituted boronic amino-acid inhibitors based on the molecular scaffold of 2-(S)-amino-6-boronohexanoic acid are now reported. Structural comparisons with human and parasitic arginase complexes reveal interesting differences in the binding modes of the additional α-substituents, i.e. the D side chains, of these inhibitors. Subtle differences in the three-dimensional contours of the outer active-site rims among arginases from different species lead to different conformations of the D side chains and thus different inhibitor-affinity trends. The structures suggest that it is possible to maintain affinity while fine-tuning intermolecular interactions of the D side chain of α,α-disubstituted boronic amino-acid inhibitors in the search for isozyme-specific and species-specific arginase inhibitors.

  18. Theory of Metastable State Relaxation in a Gravitational Field for Non-Critical Binary Systems with Non-Conserved Order Parameter

    NASA Technical Reports Server (NTRS)

    Izmailov, Alexander F.; Myerson, Allan S.

    1993-01-01

    A new mathematical ansatz is developed for solution of the time-dependent Ginzburg-Landau nonlinear partial differential equation describing metastable state relaxation in binary (solute+solvent) non-critical solutions with non-conserved scalar order parameter in presence of a gravitational field. It has been demonstrated analytically that in such systems metastability initiates heterogeneous solute redistribution which results in the formation of a non-equilibrium singly-periodic spatial solute structure in the new solute-rich phase. The critical radius of nucleation and the induction time in these systems are gravity-dependent. It has also been proved that metastable state relaxation in vertical columns of supersaturated non-critical binary solutions leads to formation of the solute concentration gradient. Analytical expression for this concentration gradient is found and analysed. It is concluded that gravity can initiate phase separation (nucleation or spinodal decomposition).

  19. Rich stochastic dynamics of co-doped Er:Yb fluorescence upconversion nanoparticles in the presence of thermal, non-conservative, harmonic and optical forces

    NASA Astrophysics Data System (ADS)

    Nome, Rene A.; Sorbello, Cecilia; Jobbágy, Matías; Barja, Beatriz C.; Sanches, Vitor; Cruz, Joyce S.; Aguiar, Vinicius F.

    2017-03-01

    The stochastic dynamics of individual co-doped Er:Yb upconversion nanoparticles (UCNP) were investigated from experiments and simulations. The UCNP were characterized by high-resolution scanning electron microscopy, dynamic light scattering, and zeta potential measurements. Single UCNP measurements were performed by fluorescence upconversion micro-spectroscopy and optical trapping. The mean-square displacement (MSD) from single UCNP exhibited a time-dependent diffusion coefficient which was compared with Brownian dynamics simulations of a viscoelastic model of harmonically bound spheres. Experimental time-dependent two-dimensional trajectories of individual UCNP revealed correlated two-dimensional nanoparticle motion. The measurements were compared with stochastic trajectories calculated in the presence of a non-conservative rotational force field. Overall, the complex interplay of UCNP adhesion, thermal fluctuations and optical forces led to a rich stochastic behavior of these nanoparticles.

  20. Computational Identification of Amino-Acid Mutations that Further Improve the Activity of a Chalcone-Flavonone Isomerase from Glycine max.

    PubMed

    Yuan, Hui; Wu, Jiaqi; Wang, Xiaoqiang; Chen, Jiakuan; Zhong, Yang; Huang, Qiang; Nan, Peng

    2017-01-01

    Protein design for improving enzymatic activity remains a challenge in biochemistry, especially to identify target amino-acid sites for mutagenesis and to design beneficial mutations for those sites. Here, we employ a computational approach that combines multiple sequence alignment, positive selection detection, and molecular docking to identify and design beneficial amino-acid mutations that further improve the intramolecular-cyclization activity of a chalcone-flavonone isomerase from Glycine max (GmCHI). By this approach, two GmCHI mutants with higher activities were predicted and verified. The results demonstrate that this approach could determine the beneficial amino-acid mutations for improving the enzymatic activity, and may find more applications in engineering of enzymes.

  1. Synthesis and characterization of heteroleptic copper and zinc complexes with saccharinate and aminoacids. Evaluation of SOD-like activity of the copper complexes.

    PubMed

    Santi, Eduardo; Viera, Inés; Mombrú, Alvaro; Castiglioni, Jorge; Baran, Enrique J; Torre, María H

    2011-12-01

    Five new copper and zinc heteroleptic complexes with saccharin and aminoacids with general stoichiometry Na(2)[M(sac)(2)(aa)(2)].nH(2)O (M denotes Cu or Zn, sac the saccharinate ion, and aa the aminoacids) were synthesized and characterized by elemental and thermogravimetric analysis, conductimetric measurements and IR, Raman and UV-vis spectroscopies. In all the complexes, copper and zinc ions coordinated with the aminoacids through the terminal amine and carboxylate residues and with saccharin through the heterocyclic nitrogen atom. Besides, the superoxide dismutase-like activity of the heteroleptic copper complexes was evaluated and compared with the homoleptic copper amino acid complexes with the aim to observe the influence of the saccharin coordination.

  2. Computational Identification of Amino-Acid Mutations that Further Improve the Activity of a Chalcone–Flavonone Isomerase from Glycine max

    PubMed Central

    Yuan, Hui; Wu, Jiaqi; Wang, Xiaoqiang; Chen, Jiakuan; Zhong, Yang; Huang, Qiang; Nan, Peng

    2017-01-01

    Protein design for improving enzymatic activity remains a challenge in biochemistry, especially to identify target amino-acid sites for mutagenesis and to design beneficial mutations for those sites. Here, we employ a computational approach that combines multiple sequence alignment, positive selection detection, and molecular docking to identify and design beneficial amino-acid mutations that further improve the intramolecular-cyclization activity of a chalcone–flavonone isomerase from Glycine max (GmCHI). By this approach, two GmCHI mutants with higher activities were predicted and verified. The results demonstrate that this approach could determine the beneficial amino-acid mutations for improving the enzymatic activity, and may find more applications in engineering of enzymes. PMID:28286513

  3. Effect of L-azetidine 2-carboxilic acid on the activity of the general amino-acid permease from Saccharomyces cerevisiae var. ellipsoideus.

    PubMed

    Iglesias, R; Ferreras, J M; Arias, F J; Muñoz, R; Rojo, M A; Girbés, T

    1991-01-01

    Addition of the L-proline analogue L-azetidine 2-carboxylic acid to growing cultures of Saccharomyces cerevisiae var. ellipsoideus promoted fast deactivation of the general aminoacid permease, measured as L-valine uptake, without an immediate decrease in the growth rate. Cells preincubated with the analogue for 3 h were unable to restore either growth ability or general aminoacid permease activity in analogue-free medium. Eadie-Hofstee plots of L-valine uptake in the presence of the analogue are consistent with a strong reduction in the number of active molecules of the general amino-acid permease located in the plasma membrane. Inhibitory effects on protein synthesis were seen after preincubations of the yeast with the analogue for 3 h although a 30 min preincubation had no effect.

  4. Novel molecular combination deriving from natural aminoacids and polyphenols: Design, synthesis and free-radical scavenging activities.

    PubMed

    Silvia, Vertuani; Baldisserotto, Anna; Scalambra, Emanuela; Malisardi, Gemma; Durini, Elisa; Manfredini, Stefano

    2012-04-01

    Following the recent output of scientific publications in the matter of synergic activity between different antioxidants, we have undertaken the present study with the aim to synthesize new molecules with radical-scavengers activity based on the conjugation of bioactive portions (i.e. phenols, cysteine, methionine or tyrosine), characterized by different structures and mechanisms of action, to promote the simultaneous quenching of different radical species in the site of the oxidative damage. In this context, derivatives of phenolic acid, aminoacids and dopamine have been also prepared. The newly synthesized compounds were evaluated in vitro applying specific and complementary antioxidant test such as DPPH assay and ORAC test. As emerged from the evaluation, prerequisites for the activity of the synthesized molecules were: i) the maintenance of at least two hydroxylic groups on the aromatic moiety of phenolic portion, ii) the presence of a spacer between the aromatic moiety and the carbonilic group.

  5. An Evolutionary Strategy for All-Atom Folding of the 60-Amino-Acid Bacterial Ribosomal Protein L20

    PubMed Central

    Schug, A.; Wenzel, W.

    2006-01-01

    We have investigated an evolutionary algorithm for de novo all-atom folding of the bacterial ribosomal protein L20. We report results of two simulations that converge to near-native conformations of this 60-amino-acid, four-helix protein. We observe a steady increase of “native content” in both simulated ensembles and a large number of near-native conformations in their final populations. We argue that these structures represent a significant fraction of the low-energy metastable conformations, which characterize the folding funnel of this protein. These data validate our all-atom free-energy force field PFF01 for tertiary structure prediction of a previously inaccessible structural family of proteins. We also compare folding simulations of the evolutionary algorithm with the basin-hopping technique for the Trp-cage protein. We find that the evolutionary algorithm generates a dynamic memory in the simulated population, which leads to faster overall convergence. PMID:16565067

  6. Lactic-acid stress causes vacuolar fragmentation and impairs intracellular amino-acid homeostasis in Saccharomyces cerevisiae.

    PubMed

    Suzuki, Toshihiro; Sugiyama, Minetaka; Wakazono, Kenta; Kaneko, Yoshinobu; Harashima, Satoshi

    2012-04-01

    To gain more insight into adaptation response to lactic-acid stress in yeast, a genome-wide screening for genes whose disruption caused hypersensitivity to 4.0% l-lactic acid (pH 2.8) was performed using the gene deletion collection of Saccharomyces cerevisiae. We identified 107 genes that contributed significantly to the ability of yeast cells to adapt lactic-acid stress. More than 30% of the genes identified in this screening were newly identified to be involved in mechanisms for adaptation response to lactic acid. We found that protein urmylation by Uba4 and N-terminal acetylation by Nat3 were involved in lactic acid adaptation mechanisms. Functional categorization of the genes followed by microscopic analysis revealed that a variety of cellular functions were involved in adaptation response to lactic acid and function associated with vacuolar transport played important roles in adaptation response to lactic acid. We also found that vacuole fragmented immediately upon exposure to lactic- and hydrochloric-acid stress. In addition, our analysis revealed that lactic-acid stress significantly reduced the amount of intracellular amino acids. Amino acid supplementation recovered the adaptation deficiency to lactic acid, suggesting that intracellular amino-acid homeostasis plays important roles in adaptation response to lactic-acid stress. These data suggest that enhancing vacuolar integrity, as well as maintaining intracellular amino-acid homeostasis may be an efficient approach to confer resistance to lactic-acid stress. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. Silica-based ionic liquid coating for 96-blade system for extraction of aminoacids from complex matrixes.

    PubMed

    Mousavi, Fatemeh; Pawliszyn, Janusz

    2013-11-25

    1-Vinyl-3-octadecylimidazolium bromide ionic liquid [C18VIm]Br was prepared and used for the modification of mercaptopropyl-functionalized silica (Si-MPS) through surface radical chain-transfer addition. The synthesized octadecylimidazolium-modified silica (SiImC18) was characterized by thermogravimetric analysis (TGA), infrared spectroscopy (IR), (13)C NMR and (29)Si NMR spectroscopy and used as an extraction phase for the automated 96-blade solid phase microextraction (SPME) system with thin-film geometry using polyacrylonitrile (PAN) glue. The new proposed extraction phase was applied for extraction of aminoacids from grape pulp, and LC-MS-MS method was developed for separation of model compounds. Extraction efficiency, reusability, linearity, limit of detection, limit of quantitation and matrix effect were evaluated. The whole process of sample preparation for the proposed method requires 270min for 96 samples simultaneously (60min preconditioning, 90min extraction, 60min desorption and 60min for carryover step) using 96-blade SPME system. Inter-blade and intra-blade reproducibility were in the respective ranges of 5-13 and 3-10% relative standard deviation (RSD) for all model compounds. Limits of detection and quantitation of the proposed SPME-LC-MS/MS system for analysis of analytes were found to range from 0.1 to 1.0 and 0.5 to 3.0μgL(-1), respectively. Standard addition calibration was applied for quantitative analysis of aminoacids from grape juice and the results were validated with solvent extraction (SE) technique.

  8. A Hand to Substitutes

    ERIC Educational Resources Information Center

    Javernick, Ellen

    2005-01-01

    In the days before computers, passing on information to substitutes was difficult. Now teachers can individualize their lesson plans to guarantee that substitute teachers and the students will both have a good day. This article provides some plan-ahead procedures that have worked for the author.

  9. Working with Substitute Teachers.

    ERIC Educational Resources Information Center

    Wilson, Karen

    1999-01-01

    Resolving the perennial problem of substitute teachers' high turnover and low availability is feasible, if principals welcome, orient, and assign them properly. Regular teachers should prepare a folder containing class lists, daily schedules, seating charts, expectations of students, and meaningful lesson plans. Substitutes should be treated as…

  10. Florida's Substitute Teachers.

    ERIC Educational Resources Information Center

    Odutola, Adeniji A.; Etemadi, Judy N.

    2002-01-01

    Describes the statutory duties of the Florida Education Standards Commission, highlighting a study of the working conditions of Florida's substitute teachers. Researchers collected data on school board policies regarding substitutes' educational levels required, initial training and staff development opportunities required, salary schedules, and…

  11. Sustainability and substitutability.

    PubMed

    Fenichel, Eli P; Zhao, Jinhua

    2015-02-01

    Developing a quantitative science of sustainability requires bridging mathematical concepts from fields contributing to sustainability science. The concept of substitutability is central to sustainability but is defined differently by different fields. Specifically, economics tends to define substitutability as a marginal concept while fields such as ecology tend to focus on limiting behaviors. We explain how to reconcile these different views. We develop a model where investments can be made in knowledge to increase the elasticity of substitution. We explore the set of sustainable and optimal trajectories for natural capital extraction and built and knowledge capital accumulation. Investments in substitutability through knowledge stock accumulation affect the value of natural capital. Results suggest that investing in the knowledge stock, which can enhance substitutability, is critical to desirable sustainable outcomes. This result is robust even when natural capital is not managed optimally. This leads us to conclude that investments in the knowledge stock are of first order importance for sustainability.

  12. Experimental Estimation of the Effects of All Amino-Acid Mutations to HIV's Envelope Protein on Viral Replication in Cell Culture.

    PubMed

    Haddox, Hugh K; Dingens, Adam S; Bloom, Jesse D

    2016-12-01

    HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV's most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV's replication in cell culture. We compare our experimental measurements of each site's preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env's evolution.

  13. Experimental Estimation of the Effects of All Amino-Acid Mutations to HIV’s Envelope Protein on Viral Replication in Cell Culture

    PubMed Central

    Haddox, Hugh K.; Dingens, Adam S.

    2016-01-01

    HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution. PMID:27959955

  14. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  15. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  16. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  17. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  18. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  19. Sugar substitutes during pregnancy

    PubMed Central

    Pope, Eliza; Koren, Gideon; Bozzo, Pina

    2014-01-01

    Abstract Question I have a pregnant patient who regularly consumes sugar substitutes and she asked me if continuing their use would affect her pregnancy or child. What should I tell her, and are there certain options that are better for use during pregnancy? Answer Although more research is required to fully determine the effects of in utero exposure to sugar substitutes, the available data do not suggest adverse effects in pregnancy. However, it is recommended that sugar substitutes be consumed in moderate amounts, adhering to the acceptable daily intake standards set by regulatory agencies. PMID:25392440

  20. Sugar substitutes during pregnancy.

    PubMed

    Pope, Eliza; Koren, Gideon; Bozzo, Pina

    2014-11-01

    I have a pregnant patient who regularly consumes sugar substitutes and she asked me if continuing their use would affect her pregnancy or child. What should I tell her, and are there certain options that are better for use during pregnancy? Although more research is required to fully determine the effects of in utero exposure to sugar substitutes, the available data do not suggest adverse effects in pregnancy. However, it is recommended that sugar substitutes be consumed in moderate amounts, adhering to the acceptable daily intake standards set by regulatory agencies. Copyright© the College of Family Physicians of Canada.

  1. The break-up of Ekman theory in a flow subjected to background rotation and driven by a non-conservative body force

    NASA Astrophysics Data System (ADS)

    Duran-Matute, M.; Di Nitto, G.; Trieling, R. R.; Kamp, L. P. J.; van Heijst, G. J. F.

    2012-11-01

    We present an experimental/numerical study of a dipolar flow structure in a shallow layer of electrolyte driven by electromagnetic forcing and subjected to background rotation. The aim of this study is to determine the influence of a non-conservative body force on the range of applicability of the classical Ekman boundary layer theory in rapidly rotating systems. To address this question, we study the response of the flow to the three control parameters: the magnitude of the forcing, the rotation rate of the system, and the shallowness of the layer. This response is quantified taking into account the magnitude of the flow velocity (represented by the Reynolds number), the symmetry between both vortex cores, and the vertical profile of the horizontal velocity. As in the case without background rotation, the response of the flow exhibits two scaling regimes (a linear and a nonlinear regime) in which the flow exhibits different vertical profiles of velocity. The transition between the two regimes occurs when the convective acceleration becomes of the same order as the viscous damping. This suggests that the applicability of the Ekman theory depends on the existence of a balance between the forcing and the damping due to the Ekman layers and does not depend solely on the value of the Rossby number as for decaying flows. On the other hand, the cyclone/anticyclone asymmetry is governed exclusively by the Rossby number.

  2. Well-balanced high-order centred schemes for non-conservative hyperbolic systems. Applications to shallow water equations with fixed and mobile bed

    NASA Astrophysics Data System (ADS)

    Canestrelli, Alberto; Siviglia, Annunziato; Dumbser, Michael; Toro, Eleuterio F.

    2009-06-01

    This paper concerns the development of high-order accurate centred schemes for the numerical solution of one-dimensional hyperbolic systems containing non-conservative products and source terms. Combining the PRICE-T method developed in [Toro E, Siviglia A. PRICE: primitive centred schemes for hyperbolic system of equations. Int J Numer Methods Fluids 2003;42:1263-91] with the theoretical insights gained by the recently developed path-conservative schemes [Castro M, Gallardo J, Parés C. High-order finite volume schemes based on reconstruction of states for solving hyperbolic systems with nonconservative products applications to shallow-water systems. Math Comput 2006;75:1103-34; Parés C. Numerical methods for nonconservative hyperbolic systems: a theoretical framework. SIAM J Numer Anal 2006;44:300-21], we propose the new PRICE-C scheme that automatically reduces to a modified conservative FORCE scheme if the underlying PDE system is a conservation law. The resulting first-order accurate centred method is then extended to high order of accuracy in space and time via the ADER approach together with a WENO reconstruction technique. The well-balanced properties of the PRICE-C method are investigated for the shallow water equations. Finally, we apply the new scheme to the shallow water equations with fix bottom topography and with variable bottom solving an additional sediment transport equation.

  3. Synthesis of substituted pyrazines

    SciTech Connect

    Pagoria, Philip F.; Zhang, Mao Xi

    2016-10-04

    A method for synthesizing a pyrazine-containing material according to one embodiment includes contacting an iminodiacetonitrile derivative with a base and a reagent selected from a group consisting of hydroxylamine, a hydroxylamine salt, an aliphatic primary amine, a secondary amine, an aryl-substituted alkylamine a heteroaryl-substituted alkyl amine, an alcohol, an alkanolamine and an aryl alcoholamine. Additional methods and several reaction products are presented. ##STR00001##

  4. Substitution of anticonvulsant drugs

    PubMed Central

    Steinhoff, Bernhard J; Runge, Uwe; Witte, Otto W; Stefan, Hermann; Hufnagel, Andreas; Mayer, Thomas; Krämer, Günter

    2009-01-01

    Changing from branded drugs to generic alternatives, or between different generic formulations, is common practice aiming at reducing health care costs. It has been suggested that antiepileptic drugs (AEDs) should be exempt from substitution because of the potential negative consequences of adverse events and breakthrough seizures. Controlled data are lacking on the risk of substitution. However, retrospective data from large medical claims databases suggest that switching might be associated with increased use of AED and non-AED medications, and health care resources (including hospitalization). In addition, some anecdotal evidence from patients and health care providers’ surveys suggest a potentially negative impact of substitution. Well-controlled data are needed to assess the real risk associated with substitution, allowing health care professionals involved in the care of patients with epilepsy to make informed decisions. This paper reviews currently available literature, based on which the authors suggest that the decision to substitute should be made on an individual basis by the physician and an informed patient. Unendorsed or undisclosed substitution at the pharmacy level should be discouraged. PMID:19707254

  5. Site-specific time heterogeneity of the substitution process and its impact on phylogenetic inference

    PubMed Central

    2011-01-01

    Background Model violations constitute the major limitation in inferring accurate phylogenies. Characterizing properties of the data that are not being correctly handled by current models is therefore of prime importance. One of the properties of protein evolution is the variation of the relative rate of substitutions across sites and over time, the latter is the phenomenon called heterotachy. Its effect on phylogenetic inference has recently obtained considerable attention, which led to the development of new models of sequence evolution. However, thus far focus has been on the quantitative heterogeneity of the evolutionary process, thereby overlooking more qualitative variations. Results We studied the importance of variation of the site-specific amino-acid substitution process over time and its possible impact on phylogenetic inference. We used the CAT model to define an infinite mixture of substitution processes characterized by equilibrium frequencies over the twenty amino acids, a useful proxy for qualitatively estimating the evolutionary process. Using two large datasets, we show that qualitative changes in site-specific substitution properties over time occurred significantly. To test whether this unaccounted qualitative variation can lead to an erroneous phylogenetic tree, we analyzed a concatenation of mitochondrial proteins in which Cnidaria and Porifera were erroneously grouped. The progressive removal of the sites with the most heterogeneous CAT profiles across clades led to the recovery of the monophyly of Eumetazoa (Cnidaria+Bilateria), suggesting that this heterogeneity can negatively influence phylogenetic inference. Conclusion The time-heterogeneity of the amino-acid replacement process is therefore an important evolutionary aspect that should be incorporated in future models of sequence change. PMID:21235782

  6. Absolute binding-free energies between standard RNA/DNA nucleobases and amino-acid sidechain analogs in different environments.

    PubMed

    de Ruiter, Anita; Zagrovic, Bojan

    2015-01-01

    Despite the great importance of nucleic acid-protein interactions in the cell, our understanding of their physico-chemical basis remains incomplete. In order to address this challenge, we have for the first time determined potentials of mean force and the associated absolute binding free energies between all standard RNA/DNA nucleobases and amino-acid sidechain analogs in high- and low-dielectric environments using molecular dynamics simulations and umbrella sampling. A comparison against a limited set of available experimental values for analogous systems attests to the quality of the computational approach and the force field used. Overall, our analysis provides a microscopic picture behind nucleobase/sidechain interaction preferences and creates a unified framework for understanding and sculpting nucleic acid-protein interactions in different contexts. Here, we use this framework to demonstrate a strong relationship between nucleobase density profiles of mRNAs and nucleobase affinity profiles of their cognate proteins and critically analyze a recent hypothesis that the two may be capable of direct, complementary interactions.

  7. Interaction of charged amino-acid side chains with ions: an optimization strategy for classical force fields.

    PubMed

    Kahlen, Jens; Salimi, Leila; Sulpizi, Marialore; Peter, Christine; Donadio, Davide

    2014-04-10

    Many well-established classical biomolecular force fields, fitted on the solvation properties of single ions, do not necessarily describe all the details of ion pairing accurately, especially for complex polyatomic ions. Depending on the target application, it might not be sufficient to reproduce the thermodynamics of ion pairing, but it may also be necessary to correctly capture structural details, such as the coordination mode. In this work, we analyzed how classical force fields can be optimized to yield a realistic description of these different aspects of ion pairing. Given the prominent role of the interactions of negatively charged amino-acid side chains and divalent cations in many biomolecular systems, we chose calcium acetate as a benchmark system to devise a general optimization strategy that we applied to two popular force fields, namely, GROMOS and OPLS-AA. Using experimental association constants and first-principles molecular dynamics simulations as a reference, we found that small modifications of the van der Waals ion-ion interaction parameters allow a systematic improvement of the essential thermodynamic and structural properties of ion pairing.

  8. Apple Aminoacid Profile and Yeast Strains in the Formation of Fusel Alcohols and Esters in Cider Production.

    PubMed

    Eleutério Dos Santos, Caroline Mongruel; Pietrowski, Giovana de Arruda Moura; Braga, Cíntia Maia; Rossi, Márcio José; Ninow, Jorge; Machado Dos Santos, Tâmisa Pires; Wosiacki, Gilvan; Jorge, Regina Maria Matos; Nogueira, Alessandro

    2015-06-01

    The amino acid profile in dessert apple must and its effect on the synthesis of fusel alcohols and esters in cider were established by instrumental analysis. The amino acid profile was performed in nine apple musts. Two apple musts with high (>150 mg/L) and low (<75 mg/L) nitrogen content, and four enological yeast strains, were used in cider fermentation. The aspartic acid, asparagine and glutamic acid amino acids were the majority in all the apple juices, representing 57.10% to 81.95%. These three amino acids provided a high consumption (>90%) during fermentation in all the ciders. Principal component analysis (PCA) explained 81.42% of data variability and the separation of three groups for the analyzed samples was verified. The ciders manufactured with low nitrogen content showed sluggish fermentation and around 50% less content of volatile compounds (independent of the yeast strain used), which were mainly 3-methyl-1-butanol (isoamyl alcohol) and esters. However, in the presence of amino acids (asparagine, aspartic acid, glutamic acid and alanine) there was a greater differentiation between the yeasts in the production of fusel alcohols and ethyl esters. High contents of these aminoacids in dessert apple musts are essential for the production of fusel alcohols and most of esters by aromatic yeasts during cider fermentation.

  9. The substitutability of reinforcers

    PubMed Central

    Green, Leonard; Freed, Debra E.

    1993-01-01

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

  10. Aryl substitution of pentacenes

    PubMed Central

    Waterloo, Andreas R; Sale, Anna-Chiara; Lehnherr, Dan; Hampel, Frank

    2014-01-01

    Summary A series of 11 new pentacene derivatives has been synthesized, with unsymmetrical substitution based on a trialkylsilylethynyl group at the 6-position and various aryl groups appended to the 13-position. The electronic and physical properties of the new pentacene chromophores have been analyzed by UV–vis spectroscopy (solution and thin films), thermoanalytical methods (DSC and TGA), cyclic voltammetry, as well as X-ray crystallography (for 8 derivatives). X-ray crystallography has been specifically used to study the influence of unsymmetrical substitution on the solid-state packing of the pentacene derivatives. The obtained results add to our ability to better predict substitution patterns that might be helpful for designing new semiconductors for use in solid-state devices. PMID:25161729

  11. Selective tonicity-induced expression of the neutral amino-acid transporter SNAT2 in oligodendrocytes in rat brain following systemic hypertonicity.

    PubMed

    Maallem, S; Mutin, M; González-González, I M; Zafra, F; Tappaz, M L

    2008-04-22

    Sodium-coupled neutral amino-acid transporter member 2 (SNAT2) belongs to the family of neutral amino-acid transporters. SNAT2 is encoded by the gene Slc38a2, whose expression was reported to increase in vitro in fibroblasts, endothelial and renal cells exposed to a hypertonic medium. SNAT2 tonicity-induced expression brings about cellular accumulation of amino-acid, which contributes to osmoadaptation to hypertonicity. Since brain osmoadaptation is observed in relationship to neurological disorders resulting from pathological osmotic imbalances in blood plasma, we have investigated, through immunocytochemistry, SNAT2 expression in brain of rats subjected to systemic hypertonicity. Following prolonged systemic hypertonicity (24 h), small, strongly immunolabeled elements were observed that were not present in sham-treated animals. They were evenly distributed in the gray matter, with a lower density in the forebrain and a higher density in the brain stem. However the highest density by far was observed in white matter, where they were frequently aligned in chain-like rows. These observations suggested an oligodendrocyte location that was further established by double immunofluorescent labeling, using the oligodendrocyte phenotypic markers 2'-3'-cyclic nucleotide 3'phosphodiesterase and carbonic anhydrase II. SNAT2-positive elements were found associated with oligodendrocyte cell bodies, while oligodendrocyte processes were devoid of labeling. A quantitative analysis performed in the cerebral cortex indicated that virtually all SNAT2-positive elements were associated with oligodendrocyte cell bodies and conversely that the overwhelming majority of oligodendrocytes showed SNAT2 immunolabeling. The tonicity-induced expression of SNAT2 was not observed following acute systemic hypertonicity (6 h). Our results suggest that the osmoadaptation of brain oligodendrocytes to hypertonicity relies upon amino-acid accumulation through the tonicity-induced expression of SNAT2

  12. Purification, characterization and amino-acid sequence analysis of a thermostable, low molecular mass endo-beta-1,4-glucanase from blue mussel, Mytilus edulis.

    PubMed

    Xu, B; Hellman, U; Ersson, B; Janson, J C

    2000-08-01

    A cellulase (endo-beta-1,4-D-glucanase, EC 3.2.1.4) from blue mussel (Mytilus edulis) was purified to homogeneity using a combination of acid precipitation, heat precipitation, immobilized metal ion affinity chromatography, size-exclusion chromatography and ion-exchange chromatography. Purity was analyzed by SDS/PAGE, IEF and RP-HPLC. The cellulase (endoglucanase) was characterized with regard to enzymatic properties, isoelectric point, molecular mass and amino-acid sequence. It is a single polypeptide chain of 181 amino acids cross-linked with six disulfide bridges. Its molecular mass, as measured by MALDI-MS, is 19 702 Da; a value of 19 710.57 Da was calculated from amino-acid composition. The isoelectric point of the enzyme was estimated by isoelectric focusing in a polyacrylamide gel to a value of 7.6. According to amino-acid composition, the theoretical pI is 7.011. The effect of temperature on the endoglucanase activity, with carboxymethyl cellulose and amorphous cellulose as substrates, respectively, was studied at pH 5.5 and displayed an unusually broad optimum activity temperature range between 30 and 50 degrees C. Another unusual feature is that the enzyme retains 55-60% of its maximum activity at 0 degrees C. The enzyme readily degrades amorphous cellulose and carboxymethyl cellulose but displays no hydrolytic activity towards crystalline cellulose (Avicel) and shows no cross-specificity for xylan; there is no binding to Avicel. The enzyme can withstand 10 min at 100 degrees C without irreversible loss of enzymatic activity. Amino-acid sequence-based classification has revealed that the enzyme belongs to the glycoside hydrolase family 45, subfamily 2 (B. Henrissat, Centre de Recherches sur les Macromolecules Végétales, CNRS, Joseph Fourier Université, Grenoble, France, personal communication).

  13. Metals in proteins: correlation between the metal-ion type, coordination number and the amino-acid residues involved in the coordination.

    PubMed

    Dokmanić, Ivan; Sikić, Mile; Tomić, Sanja

    2008-03-01

    Metal ions are constituents of many metalloproteins, in which they have either catalytic (metalloenzymes) or structural functions. In this work, the characteristics of various metals were studied (Cu, Zn, Mg, Mn, Fe, Co, Ni, Cd and Ca in proteins with known crystal structure) as well as the specificity of their environments. The analysis was performed on two data sets: the set of protein structures in the Protein Data Bank (PDB) determined with resolution <1.5 A and the set of nonredundant protein structures from the PDB. The former was used to determine the distances between each metal ion and its electron donors and the latter was used to assess the preferred coordination numbers and common combinations of amino-acid residues in the neighbourhood of each metal. Although the metal ions considered predominantly had a valence of two, their preferred coordination number and the type of amino-acid residues that participate in the coordination differed significantly from one metal ion to the next. This study concentrates on finding the specificities of a metal-ion environment, namely the distribution of coordination numbers and the amino-acid residue types that frequently take part in coordination. Furthermore, the correlation between the coordination number and the occurrence of certain amino-acid residues (quartets and triplets) in a metal-ion coordination sphere was analysed. The results obtained are of particular value for the identification and modelling of metal-binding sites in protein structures derived by homology modelling. Knowledge of the geometry and characteristics of the metal-binding sites in metalloproteins of known function can help to more closely determine the biological activity of proteins of unknown function and to aid in design of proteins with specific affinity for certain metals.

  14. Response of Fe-S cluster assembly machinery of Escherichia coli to mechanical stress in a model of amino-acid crystal fermentation.

    PubMed

    Okutani, Satoshi; Iwai, Takayoshi; Iwatani, Shintaro; Matsuno, Kiyoshi; Takahashi, Yasuhiro; Hase, Toshiharu

    2015-09-01

    During amino-acid crystal fermentation, mechanical stress on bacterial cells caused by crystal collision often impacts negatively on bacterial growth and amino-acid production. When Escherichia coli cells were cultivated under mechanical stress of polyvinyl chloride particles as a model of the crystal fermentation, activities of iron-sulfur (Fe-S) cluster-containing enzymes were apparently decreased. Based on an assumption that function of Fe-S cluster assembly machinery would be elevated to recover the enzyme activities in such stressed cells, we analyzed levels of various components of Fe-S cluster assembly machinery by western blotting. It was found that the expression of HscA, a chaperon component of the machinery, was up-regulated and that shorter forms of HscA with the N-terminal region truncated were accumulated, suggesting an important role of HscA against the mechanical stress. An overexpression of HscA gene in E. coli cells gave a positive effect on rescue of the stress-induced decrease of the activity of Fe-S cluster-containing enzyme. These results may provide a new strategy to alleviate the mechanical stress during the amino-acid crystal fermentation.

  15. Amino-acid sequence and glycan structures of cysteine proteases with proline specificity from ginger rhizome Zingiber officinale.

    PubMed

    Choi, K H; Laursen, R A

    2000-03-01

    The ginger proteases (GP-I and GP-II), isolated from the ginger rhizome Zingiber officinale, have an unusual substrate specificity preference for cleaving peptides with a proline residue at the P2 position. The complete amino-acid sequence of GP-II, a glycoprotein containing 221 amino acids, and about 98% that of GP-I have been determined. Both proteases, which are 82% similar, have cysteine residues at positions 27 and histidines at position 161, corresponding to the essential cysteine-histidine diads found in the papain family of cysteine proteases, and six corresponding cysteine residues that form the three invariant disulfide linkages seen in this family of proteins. The sequence homology with other members (papain, bromelain, actinidin, protease omega, etc.) of this family is approximately 50%. GP-II has two predicted glycosylation sites at Asn99 and Asn156. Analyisis by electrospray and collision-induced dissociation MS showed that both sites were occupied by the glycans (Man)3(Xyl)1(Fuc)1(GlcNAc)2 and (Man)3(Xyl)1(Fuc)1(GlcNAc)3, in a ratio of approximately 7 : 1. Both glycans are xylose containing biantennary complex types that share the common core structural unit, Man1-->6(Man1-->3) (Xyl1-->2)Man1-->4GlcNAc1-->4(Fuc1-->3)GlcNAc for the major form, with an additional N-acetylglucosamine residue being linked, in the minor form, to one of the terminal mannose units of the core structure.

  16. A New Pro-Prodrug Aminoacid-Based for Trans-Ferulic Acid and Silybin Intestinal Release

    PubMed Central

    Trombino, Sonia; Ferrarelli, Teresa; Cassano, Roberta

    2014-01-01

    The aim of this work was the preparation and characterization of a pro-prodrug able to simultaneously transport silybin, a drug possessing various pharmacological effects, and trans-ferulic acid, a known antioxidant. More specifically, l-phenylalanine-N-(4-hydroxy-3-methoxy-phenyl) prop-2-en-O-(2R,3R)-3,5,7-trihydroxy-2-((2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-benzo-(1,4)-dioxin-6-yl)croman-4-one was synthesized by using the aminoacid l-phenylalanine (l-Phe) as carrier. Indeed, l-Phe is characterized by an intrinsic chemical reactivity due to the presence of an amino group, placed on the chiral center, and of a carboxylic group. The synthesis has been characterized first by adding silybin by means of carboxylic group and then, with the aim to confer antioxidant properties to this new carrier, by linking trans-ferulic acid to l-Phe via amino group. The so obtained derivative was then characterized by FT-IR, and 1H-NMR spectroscopies. Furthermore, its ability to inhibit lipid peroxidation induced by tert-butyl hydroperoxide in rat liver microsomes, was evaluated. The 1,1-diphenyl-2-picrylhydrazyl radical-scavenging effect, was also assessed. The release of silybin and trans-ferulic acid was determined in simulated gastric and intestinal fluids over the time. The results showed that the covalent bond between both (i) silybin; or (ii) trans-ferulic acid and the amino acid was degraded by enzymatic reactions. In addition, the pro-prodrug, showed strong antioxidant and scavenger activities. Due to these properties, this new pro-prodrug could be applied for the treatment of intestinal pathologies and it might improve the therapeutic potential of silybin which is strongly limited by its low solubility. PMID:25062426

  17. Performing Substitute Teaching

    ERIC Educational Resources Information Center

    Bletzer, Keith V.

    2010-01-01

    Formal education is both a right and an obligation bestowed on young people in most all nations of the world. Teachers (adults) and students (youth) form a co-present dyadic contract that must be maintained within the classroom. Substitute teachers fill a role in sustaining the integrity of this teacher-student link, whenever teachers are absent.…

  18. The Age of Substitutability

    ERIC Educational Resources Information Center

    Goeller, H. E.; Weinberg, Alvin M.

    1976-01-01

    Dwindling mineral resources might cause a shift from nonrenewable resources to renewable resources and inexhaustible elements such as iron and aluminum. Alternative energy sources such as breeder, fusion, solar, and geothermal power must be developed for production and recycling of materials. Substitution and, hence, living standards ultimately…

  19. No cheap substitutes.

    PubMed

    Griffiths, Peter

    2016-06-15

    The Nuffield Trust report on reshaping the healthcare workforce was published last month. Its conclusions were widely reported as a recommendation to 'train up' nurses as a solution to junior doctor shortages, with support workers, in turn, substituting for registered nurses.

  20. The Age of Substitutability

    ERIC Educational Resources Information Center

    Goeller, H. E.; Weinberg, Alvin M.

    1976-01-01

    Dwindling mineral resources might cause a shift from nonrenewable resources to renewable resources and inexhaustible elements such as iron and aluminum. Alternative energy sources such as breeder, fusion, solar, and geothermal power must be developed for production and recycling of materials. Substitution and, hence, living standards ultimately…

  1. Performing Substitute Teaching

    ERIC Educational Resources Information Center

    Bletzer, Keith V.

    2010-01-01

    Formal education is both a right and an obligation bestowed on young people in most all nations of the world. Teachers (adults) and students (youth) form a co-present dyadic contract that must be maintained within the classroom. Substitute teachers fill a role in sustaining the integrity of this teacher-student link, whenever teachers are absent.…

  2. Screening Substitute Teachers.

    ERIC Educational Resources Information Center

    Kakkuri, Mark

    2000-01-01

    The screening process a school district uses in hiring substitute teachers is critical to striking a balance between required qualifications and immediate need. Typically, screening involves at least one of the following: pre-screening, paper and pencil screening, interviews, and background checks, each of which is used to different degrees…

  3. Organizing Substitute Teachers.

    ERIC Educational Resources Information Center

    Vail, Kathleen

    2000-01-01

    Many substitute teachers are underpaid, undertrained, and "invisible" employees lacking health benefits and respect from regular colleagues. Grass-roots organizing efforts have improved working conditions for subs in two Florida and California districts. Districts' improvement initiatives should be guided by concerns for student…

  4. Sensory Substitution for Wounded Servicemembers

    DTIC Science & Technology

    2009-10-28

    traumatic brain injury (TBI) and two civilians, all with partial visual impairment , evaluated the vision sensory substitution systems. The servicemember...Mobility Augmentation; Wounded Service Members; Human-Centered Computing; Vision Augmentation, Vision , Balance and Hearing; Sensory Substitution-enabled...mitigation of vision sensory and mobility losses. 2) Improved the usefulness of available sensory substitution technologies for injured military

  5. Protein Adhesion and Ion Substitution (on/in)to Minerals

    NASA Astrophysics Data System (ADS)

    Charlet, L.; Fernandez Martinez, A.; Chapron, Y.; Sahai, N.; Cuello, G.; Brendle, J.; Marichal, C.

    2008-12-01

    Arsenic and pathogenic prion protein-scrapie (PrPsc) are important contaminants which may soil and water for decades, unless they are removed by sorption. Two sorption mechanisms will be discussed, namely the organics (Prp and single aminoacid) adsorption on clay and the arsenic substitution in gypsum. The elucidation of these contrasted mechanisms will be shown to request complementary molecular-mechanical simulations with experimental spectroscopic investigations. As first example, structural studies performed at ILL/ESRF on As-doped gypsum (CaSO4 2H2O) using neutron and X-ray diffraction data and EXAFS were performed to determine how As fits into the bulk of gypsum structure. The combined Rietveld analysis of neutron and X-ray diffraction data shows an expansion of the unit cell volume proportional to the As concentration within the samples. to-sulfate substitution mechanisms were used as simulation starting hypotheses. DFT-based simulations (Mulliken analysis) were used to interpret charge distribution and to show that among the possible mechanisms, a sulphate substitution by either protonated, or fully deprotonated, arsenate ion, only the protonated arsenate substitution could best fit the EXAFS data. In the second example, we used Molecular Dynamics to understand the mechanism of strong binding of the pathogenic PrP peptide with clay mineral surfaces. We modeled only the infectious moiety, PrP92-138, of the whole PrPsc structure, with explicitly solvating water molecules in contact with the cleavage plane of pyrophillite, as a model for montmorillonite without any cationic substitution. Partial residual negative charges on the cleavage plane were balanced with K+ ions. The peptide anchored to the clay surface via up to 10 hydrogen bonds from lysine and histidine residues to oxygen atoms of the siloxane cavities, and a total adsorption energy of 3465 KJ.mol-1 was obtained. Our results were compared to the one obtained by chemical and thermal analysis, 23Na, 1H

  6. Methodologies in Creating Skin Substitutes

    PubMed Central

    Nicholas, Mathew N; Jeschke, Marc G; Amini-Nik, Saeid

    2016-01-01

    The creation of skin substitutes has significantly decreased morbidity and mortality of skin wounds. Although there are still a number of disadvantages of currently available skin substitutes, there has been a significant decline in research advances over the past several years in improving these skin substitutes. Clinically most skin substitutes used are acellular and do not use growth factors to assist wound healing, key areas of potential in this field of research. This article discusses the five necessary attributes of an ideal skin substitute. It comprehensively discusses the three major basic components of currently available skin substitutes: scaffold materials, growth factors, and cells, comparing and contrasting what has been used so far. It then examines a variety of techniques in how to incorporate these basic components together to act as a guide for further research in the field to create cellular skin substitutes with clinically better results. PMID:27154041

  7. Nanoflakes of an aminoacid-based chiral coordination polymer: Synthesis, optical and electrochemical properties, and application in electrochemical sensing of H{sub 2}O{sub 2}

    SciTech Connect

    Zhou, Bo; Liang, Li-Mei; Yao, Jie

    2015-03-15

    Nanoflakes of an aminoacid-based chiral coordination polymer (CP), [Cu{sub 2}(tyr){sub 2}(bipy)]{sub n}, were synthesized successfully in the presence of surfactant, as evidenced by the XRD and SEM results. UV–vis absorption spectrometry and fluorescence spectrometry were used to investigate the optical properties of the CP, which was found to be mainly attributed to the ligands, while the forming of the CP caused only slight change. On the other hand, Cu(II) ions acted as electrocatalytic active sites of the CP, as evidenced by cyclic voltammetry. The CP also showed good performance in the electrochemical sensing of H{sub 2}O{sub 2}: sensitivity of 85.6 mA mol{sup −1} L cm{sup −2}, linear range of 1.0×10{sup −5}–7.69×10{sup −3} M, detection limit of 1.0×10{sup −5} M (S/N=3), and fast response in mere 5 s. - Graphical abstract: Nanoflakes of an aminoacid-based chiral coordination polymer (CP), [Cu{sub 2}(tyr){sub 2}(bipy)]{sub n}, were synthesized successfully and showed good performance in the electrochemical sensing of H{sub 2}O{sub 2}. - Highlights: • Synthesis of nanoflakes of an aminoacid-based chiral CP. • Optical and electrochemical properties resulting respectively from ligands and Cu{sup II}. • Good performance in enzyme-free electrochemical sensing of H{sub 2}O{sub 2}.

  8. Structure of LP2179, the first representative of Pfam family PF08866, suggests a new fold with a role in amino-acid metabolism

    SciTech Connect

    Bakolitsa, Constantina; Kumar, Abhinav; Carlton, Dennis; Miller, Mitchell D.; Krishna, S.Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Elsliger, Marc-André; Feuerhelm, Julie; Grzechnik, Slawomir K.; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; Tien, Henry J.; Trout, Christina V.; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2011-08-17

    The structure of LP2179, a member of the PF08866 (DUF1831) family, suggests a novel {alpha} + {beta} fold comprising two {beta}-sheets packed against a single helix. A remote structural similarity to two other uncharacterized protein families specific to the Bacillus genus (PF08868 and PF08968), as well as to prokaryotic S-adenosylmethionine decarboxylases, is consistent with a role in amino-acid metabolism. Genomic neighborhood analysis of LP2179 supports this functional assignment, which might also then be extended to PF08868 and PF08968.

  9. Structure of LP2179, the first representative of Pfam family PF08866, suggests a new fold with a role in amino-acid metabolism

    PubMed Central

    Bakolitsa, Constantina; Kumar, Abhinav; Carlton, Dennis; Miller, Mitchell D.; Krishna, S. Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Elsliger, Marc-André; Feuerhelm, Julie; Grzechnik, Slawomir K.; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; Tien, Henry J.; Trout, Christina V.; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The structure of LP2179, a member of the PF08866 (DUF1831) family, suggests a novel α+β fold comprising two β-sheets packed against a single helix. A remote structural similarity to two other uncharacterized protein families specific to the Bacillus genus (PF08868 and PF08968), as well as to prokaryotic S-adenosylmethionine decarboxylases, is consistent with a role in amino-acid metabolism. Genomic neighborhood analysis of LP2179 supports this functional assignment, which might also then be extended to PF08868 and PF08968. PMID:20944212

  10. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic). 721.10214 Section 721.10214... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted...

  11. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic). 721.10214 Section 721.10214... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted...

  12. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic). 721.10214 Section 721.10214... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted...

  13. Polyimides comprising substituted benzidines

    NASA Technical Reports Server (NTRS)

    Harris, Frank W. (Inventor)

    1991-01-01

    A new class of polyimides and copolyimides made from substituted benzidines and aromatic dianhydrides and other aromatic diamines. The polyimides obtained with said diamines are distinguished by excellent thermal, excellent solubility, excellent electrical properties such as very low dielectric constants, excellent clarity and mechanical properties making the polyimides ideally suited as coating materials for microelectronic apparatii, as membranes for selective molecular or gas separation, as fibers in molecular composites, as high tensile strength, high compression strength fibers, as film castable coatings, or as fabric components.

  14. Plasma amino-acid determinations by reversed-phase HPLC: Improvement of the orthophthalaldehyde method and comparison with ion exchange chromatography.

    PubMed

    Ziegler, F; Le Boucher, J; Coudray-Lucas, C; Cynober, L

    1992-01-01

    Reversed-phase high performance liquid chromatographic (RPHPLC) determination of amino-acids with on-line pre-column ortho-phthalaldehyde (OPA) derivatization and fluorescence detection is rapid and sensitive. However, high-performance ionexchange chromatography (HP-IEC) with post-column ninhydrine reaction is the most widely used amino-acid (AA) assay for biological samples. These two methods have been compared for the determination of individual plasma AA concentrations.An excellent correlation (p

  15. Glyphosate herbicide poisoning: use of a routine aminoacid analyzer appears to be a rapid method for determining glyphosate and its metabolite in biological fluids.

    PubMed

    Parrot, F; Bedry, R; Favarel-Garrigues, J C

    1995-01-01

    Glyphosate containing herbicides are an alternative to paraquat and are widely used throughout the world. Despite animal studies showing a low mammalian toxicity, human fatalities are reported after suicidal ingestions of glyphosate. Among the numerous analytical methods proposed, the reference method is the HPLC Monsanto procedure which is available in very few laboratories. The Monsanto procedure consists of a pre-column derivatization with detection of the resulting chromophore by HPLC with a variable wavelength UV/VIS detector. We propose a simple and rapid method for the diagnosis and monitoring of glyphosate poisoning. This method uses an aminoacid analyzer (Beckman 6300) with the program for biological fluids. With this procedure the glyphosate and amino methyl phosphoric acid retention times are respectively 1.75 and 3.54 min. This method gives a rapid result. The time between collecting the sample and completing the result is 45 min. This method may be useful for the diagnosis and monitoring of glyphosate poisoning and is easy to perform with an apparatus usually available in every laboratory involved in aminoacid analysis.

  16. Crystal structures of Leishmania mexicana arginase complexed with α,α-disubstituted boronic amino-acid inhibitors

    SciTech Connect

    Hai, Yang; Christianson, David W.

    2016-03-16

    Leishmaniaarginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiatesde novopolyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections. To this end, two X-ray crystal structures ofL. mexicanaarginase complexed with α,α-disubstituted boronic amino-acid inhibitors based on the molecular scaffold of 2-(S)-amino-6-boronohexanoic acid are now reported. Structural comparisons with human and parasitic arginase complexes reveal interesting differences in the binding modes of the additional α-substituents,i.e.the D side chains, of these inhibitors. Subtle differences in the three-dimensional contours of the outer active-site rims among arginases from different species lead to different conformations of the D side chains and thus different inhibitor-affinity trends. The structures suggest that it is possible to maintain affinity while fine-tuning intermolecular interactions of the D side chain of α,α-disubstituted boronic amino-acid inhibitors in the search for isozyme-specific and species-specific arginase inhibitors.

  17. Amino-acid selective experiments on uniformly 13C and 15N labeled proteins by MAS NMR: Filtering of lysines and arginines.

    PubMed

    Jehle, Stefan; Rehbein, Kristina; Diehl, Anne; van Rossum, Barth-Jan

    2006-12-01

    Amino-acid selective magic-angle spinning (MAS) NMR experiments can aid the assignment of ambiguous cross-peaks in crowded spectra of solid proteins. In particular for larger proteins, data analysis can be hindered by severe resonance overlap. In such cases, filtering techniques may provide a good alternative to site-specific spin-labeling to obtain unambiguous assignments that can serve as starting points in the assignment procedure. In this paper we present a simple pulse sequence that allows selective excitation of arginine and lysine residues. To achieve this, we make use of a combination of specific cross-polarization for selective excitation [M. Baldus, A.T. Petkova, J. Herzfeld, R.G. Griffin, Cross polarization in the tilted frame: assignment and spectral simplification in heteronuclear spin systems, Mol. Phys. 95 (1998) 1197-1207.] and spin diffusion for transfer along the amino-acid side-chain. The selectivity of the filter is demonstrated with the excitation of lysine and arginine side-chain resonances in a uniformly 13C and 15N labeled protein preparation of the alpha-spectrin SH3 domain. It is shown that the filter can be applied as a building block in a 13C-13C lysine-only correlation experiment.

  18. 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.

  19. Plasma amino-acid determinations by reversed-phase HPLC: Improvement of the orthophthalaldehyde method and comparison with ion exchange chromatography

    PubMed Central

    Ziegler, Frédéric; Le Boucher, Jacques; Coudray-Lucas, Colette

    1992-01-01

    Reversed-phase high performance liquid chromatographic (RPHPLC) determination of amino-acids with on-line pre-column ortho-phthalaldehyde (OPA) derivatization and fluorescence detection is rapid and sensitive. However, high-performance ionexchange chromatography (HP-IEC) with post-column ninhydrine reaction is the most widely used amino-acid (AA) assay for biological samples. These two methods have been compared for the determination of individual plasma AA concentrations. An excellent correlation (p ≤ 0.003) was found between the results given by an RP-HPLC system (Varian) and a classical AA autoanalyser (Biotronik LC 5001). Most AA concentrations were similar with the two methods, but a paired t-test showed slight differences for 13 AA. The within-batch reproducibility of the RPHPLC method was comparable to that of the HP-IEC method. The analysis was about three times faster with RP-HPLC, and sensitivity was l00-fold better. However, aspartic acid, proline and cysteine were not identified by the RP-HPLC method, while the tryptophan quantification is possible. RP-HPLC with automated pre-column OPA derivatization is clearly a suitable alternative for assaying physiological AA and may be particularly useful for AA present at low concentrations (free tryptophan, plasma 3-methylhistidine). PMID:18924933

  20. Substituted hydroxyapatites for bone repair.

    PubMed

    Shepherd, Jennifer H; Shepherd, David V; Best, Serena M

    2012-10-01

    Calcium phosphates such as hydroxyapatite have a wide range of applications both in bone grafts and for the coating of metallic implants, largely as a result of their chemical similarity to the mineral component of bone. However, to more accurately mirror the chemistry, various substitutions, both cationic (substituting for the calcium) and anionic (substituting for the phosphate or hydroxyl groups) have been produced. Significant research has been carried out in the field of substituted apatites and this paper aims to summarise some of the key effect of substitutions including magnesium, zinc, strontium, silicon and carbonate on physical and biological characteristics. Even small substitutions have been shown to have very significant effects on thermal stability, solubility, osteoclastic and osteoblastic response in vitro and degradation and bone regeneration in vivo.

  1. Explicit Substitutions and All That

    NASA Technical Reports Server (NTRS)

    Ayala-Rincon, Mauricio; Munoz, Cesar

    2000-01-01

    Explicit substitution calculi are extensions of the lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda sigma- and lambda S(e)-calculi.

  2. Explicit Substitutions and All That

    NASA Technical Reports Server (NTRS)

    Ayala-Rincon, Mauricio; Munoz, Cesar; Busnell, Dennis M. (Technical Monitor)

    2000-01-01

    Explicit substitution calculi are extensions of the Lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda(sigma)- and lambda(s(e))-calculi.

  3. The Replacement of 10 Non-Conserved Residues in the Core Protein of JFH-1 Hepatitis C Virus Improves Its Assembly and Secretion

    PubMed Central

    Etienne, Loïc; Blanchard, Emmanuelle; Boyer, Audrey; Desvignes, Virginie; Gaillard, Julien; Meunier, Jean-Christophe; Roingeard, Philippe; Hourioux, Christophe

    2015-01-01

    Hepatitis C virus (HCV) assembly is still poorly understood. It is thought that trafficking of the HCV core protein to the lipid droplet (LD) surface is essential for its multimerization and association with newly synthesized HCV RNA to form the viral nucleocapsid. We carried out a mapping analysis of several complete HCV genomes of all genotypes, and found that the genotype 2 JFH-1 core protein contained 10 residues different from those of other genotypes. The replacement of these 10 residues of the JFH-1 strain sequence with the most conserved residues deduced from sequence alignments greatly increased virus production. Confocal microscopy of the modified JFH-1 strain in cell culture showed that the mutated JFH-1 core protein, C10M, was present mostly at the endoplasmic reticulum (ER) membrane, but not at the surface of the LDs, even though its trafficking to these organelles was possible. The non-structural 5A protein of HCV was also redirected to ER membranes and colocalized with the C10M core protein. Using a Semliki forest virus vector to overproduce core protein, we demonstrated that the C10M core protein was able to form HCV-like particles, unlike the native JFH-1 core protein. Thus, the substitution of a few selected residues in the JFH-1 core protein modified the subcellular distribution and assembly properties of the protein. These findings suggest that the early steps of HCV assembly occur at the ER membrane rather than at the LD surface. The C10M-JFH-1 strain will be a valuable tool for further studies of HCV morphogenesis. PMID:26339783

  4. Displacement, Substitution, Sublimation: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    Sigmund Freund worked with the mechanisms of displacement, substitution, and sublimation. These mechanisms have many similarities and have been studied diagnostically and therapeutically. Displacement and substitution seem to fit in well with phobias, hysterias, somatiyations, prejudices, and scapegoating. Phobias, prejudices, and scapegoating…

  5. Substitute Teachers: The Professional Contradiction.

    ERIC Educational Resources Information Center

    Shreeve, William C.; And Others

    The substitute teacher's public image was investigated by means of an informal survey of part-time and full-time teachers in Washington. Survey results revealed that working conditions appeared to be the largest factor in damaging the self-image of most substitute teachers. The majority of full-time teachers and administrators surveyed were…

  6. Substitution in recreation choice behavior

    Treesearch

    George L. Peterson; Daniel J. Stynes; Donald H. Rosenthal; John F. Dwyer

    1985-01-01

    This review discusses concepts and theories of substitution in recreation choice. It brings together the literature of recreation research, psychology, geography, economics, and transportation. Parallel and complementary developments need integration into an improved theory of substitution. Recreation decision behavior is characterized as a nested or sequential choice...

  7. Formative Assessment for Substitute Teachers.

    ERIC Educational Resources Information Center

    Shepherd, Ron

    2001-01-01

    Describes one school district's mandatory 2-hour workshop designed to certify substitute teachers. The workshop explains the district's expectations of substitute teachers, provides information and instructional techniques to facilitate learning and proper classroom control, and allows questions and concerns to be raised and clarified by…

  8. PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer

    PubMed Central

    Fan, S-J; Snell, C; Turley, H; Li, J-L; McCormick, R; Perera, S M W; Heublein, S; Kazi, S; Azad, A; Wilson, C; Harris, A L; Goberdhan, D C I

    2016-01-01

    Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell's responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to

  9. The isolation, purification and amino-acid sequence of insulin from the teleost fish Cottus scorpius (daddy sculpin).

    PubMed

    Cutfield, J F; Cutfield, S M; Carne, A; Emdin, S O; Falkmer, S

    1986-07-01

    Insulin from the principal islets of the teleost fish, Cottus scorpius (daddy sculpin), has been isolated and sequenced. Purification involved acid/alcohol extraction, gel filtration, and reverse-phase high-performance liquid chromatography to yield nearly 1 mg pure insulin/g wet weight islet tissue. Biological potency was estimated as 40% compared to porcine insulin. The sculpin insulin crystallised in the absence of zinc ions although zinc is known to be present in the islets in significant amounts. Two other hormones, glucagon and pancreatic polypeptide, were copurified with the insulin, and an N-terminal sequence for pancreatic polypeptide was determined. The primary structure of sculpin insulin shows a number of sequence changes unique so far amongst teleost fish. These changes occur at A14 (Arg), A15 (Val), and B2 (Asp). The B chain contains 29 amino acids and there is no N-terminal extension as seen with several other fish. Presumably as a result of the amino acid substitutions, sculpin insulin does not readily form crystals containing zinc-insulin hexamers, despite the presence of the coordinating B10 His.

  10. How Do Substitute Teachers Substitute? An Empirical Study of Substitute-Teacher Labor Supply

    ERIC Educational Resources Information Center

    Gershenson, Seth

    2012-01-01

    This paper examines the daily labor supply of a potentially important, but often overlooked, source of instruction in U.S. public schools: substitute teachers. I estimate a sequential binary-choice model of substitute teachers' job-offer acceptance decisions using data on job offers made by a randomized automated calling system. Importantly, this…

  11. How Do Substitute Teachers Substitute? An Empirical Study of Substitute-Teacher Labor Supply

    ERIC Educational Resources Information Center

    Gershenson, Seth

    2012-01-01

    This paper examines the daily labor supply of a potentially important, but often overlooked, source of instruction in U.S. public schools: substitute teachers. I estimate a sequential binary-choice model of substitute teachers' job-offer acceptance decisions using data on job offers made by a randomized automated calling system. Importantly, this…

  12. Heavy-atom Database System: a tool for the preparation of heavy-atom derivatives of protein crystals based on amino-acid sequence and crystallization conditions.

    PubMed

    Sugahara, Michihiro; Asada, Yukuhiko; Ayama, Haruhiko; Ukawa, Hisashi; Taka, Hideyuki; Kunishima, Naoki

    2005-09-01

    Heavy-atom Database System (HATODAS) is a WWW-based tool designed to assist the heavy-atom derivatization of proteins. The conventional procedure for the preparation of derivatives is usually a time-consuming 'trial-and-error' process. The present program provides a solution for this problem using a database of known heavy-atom derivatives. A database search suggests potential heavy-atom reagents for any target protein based on its amino-acid sequence and crystallization conditions. A mining of the database identified 93 preferred motifs for heavy-atom binding. The motifs are observed frequently at the actual heavy-atom-binding sites encountered in the process of structure determination.

  13. Mapping of the basic amino-acid residues responsible for tubulation and cellular protrusion by the EFC/F-BAR domain of pacsin2/Syndapin II.

    PubMed

    Shimada, Atsushi; Takano, Kazunori; Shirouzu, Mikako; Hanawa-Suetsugu, Kyoko; Terada, Takaho; Toyooka, Kiminori; Umehara, Takashi; Yamamoto, Masaki; Yokoyama, Shigeyuki; Suetsugu, Shiro

    2010-03-19

    The extended Fes-CIP4 homology (EFC)/FCH-BAR (F-BAR) domain tubulates membranes. Overexpression of the pacsin2 EFC/F-BAR domain resulted in tubular localization inside cells and deformed liposomes into tubules in vitro. We found that overexpression of the pacsin2 EFC/F-BAR domain induced cellular microspikes, with the pacsin2 EFC/F-BAR domain concentrated at the neck. The hydrophobic loops and the basic amino-acid residues on the concave surface of the pacsin2 EFC/F-BAR domain are essential for both the microspike formation and tubulation. Since the curvature of the neck of the microspike and that of the tubulation share similar geometry, the pacsin2 EFC/F-BAR domain is considered to facilitate both microspike formation and tubulation. Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Practical use of chemical shift databases for protein solid-state NMR: 2D chemical shift maps and amino-acid assignment with secondary-structure information

    PubMed Central

    Fritzsching, K. J.; Yang, Y.; Schmidt-Rohr, K.

    2013-01-01

    We introduce a Python-based program that utilizes the large database of 13C and 15N chemical shifts in the Biological Magnetic Resonance Bank to rapidly predict the amino acid type and secondary structure from correlated chemical shifts. The program, called PACSYlite Unified Query (PLUQ), is designed to help assign peaks obtained from 2D 13C–13C, 15N–13C, or 3D 15N–13C–13C magic-angle-spinning correlation spectra. We show secondary-structure specific 2D 13C–13C correlation maps of all twenty amino acids, constructed from a chemical shift database of 262,209 residues. The maps reveal interesting conformation-dependent chemical shift distributions and facilitate searching of correlation peaks during amino-acid type assignment. Based on these correlations, PLUQ outputs the most likely amino acid types and the associated secondary structures from inputs of experimental chemical shifts. We test the assignment accuracy using four high-quality protein structures. Based on only the Cα and Cβ chemical shifts, the highest-ranked PLUQ assignments were 40–60 % correct in both the amino-acid type and the secondary structure. For three input chemical shifts (CO–Cα–Cβ or N–Cα–Cβ), the first-ranked assignments were correct for 60 % of the residues, while within the top three predictions, the correct assignments were found for 80 % of the residues. PLUQ and the chemical shift maps are expected to be useful at the first stage of sequential assignment, for combination with automated sequential assignment programs, and for highly disordered proteins for which secondary structure analysis is the main goal of structure determination. PMID:23625364

  15. Components of an Effective Substitute Teacher Program.

    ERIC Educational Resources Information Center

    Purvis, Johnny R.; Garvey, Ruth C.

    1993-01-01

    Discusses the need for a comprehensive substitute teacher program in schools along with the important components of such a program. Identifies the roles of the principal, regular teacher, substitute teacher, and the superintendent in an effective substitute teacher program. (HB)

  16. DESIGNING ENVIRONMENTALLY BENIGN SOLVENT SUBSTITUTES

    EPA Science Inventory

    Since the signing of 1987 Montreal Protocol, reducing and eliminating the use of harmful solvents has become an internationally imminent environmental protection mission. Solvent substitution is an effective way to achieve this goal. The Program for Assisting the Replacement of...

  17. DESIGNING ENVIRONMENTALLY BENIGN SOLVENT SUBSTITUTES

    EPA Science Inventory

    Since the signing of 1987 Montreal Protocol, reducing and eliminating the use of harmful solvents has become an internationally imminent environmental protection mission. Solvent substitution is an effective way to achieve this goal. The Program for Assisting the Replacement of...

  18. Nucleophilic Substitution by Benzodithioate Anions.

    ERIC Educational Resources Information Center

    Bonnans-Plaisance, Chantal; Gressier, Jean-Claude

    1988-01-01

    Describes a two-session experiment designed to provide a good illustration of, and to improve student knowledge of, the Grignard reaction and nucleophilic substitution. Discusses the procedure, experimental considerations, and conclusion of this experiment. (CW)

  19. Recognition of U1 and U2 small nuclear RNAs can be altered by a 5-amino-acid segment in the U2 small nuclear ribonucleoprotein particle (snRNP) B" protein and through interactions with U2 snRNP-A' protein.

    PubMed Central

    Bentley, R C; Keene, J D

    1991-01-01

    We have investigated the sequence elements influencing RNA recognition in two closely related small nuclear ribonucleoprotein particle (snRNP) proteins, U1 snRNP-A and U2 snRNP-B". A 5-amino-acid segment in the RNA-binding domain of the U2 snRNP-B" protein was found to confer U2 RNA recognition when substituted into the corresponding position in the U1 snRNP-A protein. In addition, B", but not A, was found to require the U2 snRNP-A' protein as an accessory factor for high-affinity binding to U2 RNA. The pentamer segment in B" that conferred U2 RNA recognition was not sufficient to allow the A' enhancement of U2 RNA binding by B", thus implicating other sequences in this protein-protein interaction. Sequence elements involved in these interactions have been localized to variable loops of the RNA-binding domain as determined by nuclear magnetic resonance spectroscopy (D. Hoffman, C.C. Query, B. Golden, S.W. White, and J.D. Keene, Proc. Natl. Acad. Sci. USA, in press). These findings suggest a role for accessory proteins in the formation of RNP complexes and pinpoint amino acid sequences that affect the specificity of RNA recognition in two members of a large family of proteins involved in RNA processing. Images PMID:1826042

  20. Blood substitutes based on nanobiotechnology.

    PubMed

    Chang, Thomas Ming Swi

    2006-08-01

    Stimulated by concerns of potential infective agents in donated blood, commercial enterprises have attempted to develop blood substitutes since the 1900s. After several years of development, a few of the many leads are showing promise. In this article, nanobiotechnological approaches that are now in phase III clinical trials are reviewed, followed by a discussion of how important basic knowledge gained is being used to develop new generations of blood substitutes based on nanobiotechnology.

  1. 14 CFR 1260.55 - Reports substitution.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Reports substitution. 1260.55 Section...

  2. 14 CFR 1260.55 - Reports substitution.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Reports substitution. 1260.55 Section...

  3. 14 CFR 1260.55 - Reports substitution.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Reports substitution. 1260.55 Section...

  4. 14 CFR 1260.55 - Reports substitution.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Reports substitution. 1260.55 Section...

  5. The Successful Substitute Teacher. Fastback 475.

    ERIC Educational Resources Information Center

    McHugh, Sheila J.

    This booklet discusses how to develop successful substitute teachers, explaining that most substitutes do not receive the respect necessary to be effective. School districts must take such steps as adopting fair substitute hiring practices, allowing for the regular placement of substitutes in the same school over the year, and including…

  6. [Progress of bone graft substitute].

    PubMed

    Zhang, Yongguang; Wang, Zhiqiang

    2008-10-01

    To sum up the recent progress of common bone graft substitute and to forecast the possible directions for further research. Recent original articles about investigation and application for bone graft substitute were extensively reviewed. Several common bone graft substitutes were selected and expounded in different categories. Bone graft was an essential treatment in order to provide structural support, fill bone cavity and promote bone defect healing. The gold standard for bone graft was autograft which is subject to many restrictions. In recent years, the research and development of bone graft substitute have received public attention. A very great progress has been made in the research and application of allograft bones, synthetic bones and engineered bones, and some research results have been put into use for real products. There still exist many problems in present bone graft substitutes. Combining various biomaterials and using the specific processing technology to develop a biomaterial which has the similar mechanical and chemical properties and physical structures to autograft so as to promote bone defect healing is the direction for future research.

  7. Magnesium substitution in brushite cements.

    PubMed

    Alkhraisat, Mohammad Hamdan; Cabrejos-Azama, Jatsue; Rodríguez, Carmen Rueda; Jerez, Luis Blanco; Cabarcos, Enrique López

    2013-01-01

    The use of magnesium-doped ceramics has been described to modify brushite cements and improve their biological behavior. However, few studies have analyzed the efficiency of this approach to induce magnesium substitution in brushite crystals. Mg-doped ceramics composed of Mg-substituted β-TCP, stanfieldite and/or farringtonite were reacted with primary monocalcium phosphate (MCP) in the presence of water. The cement setting reaction has resulted in the formation of brushite and newberyite within the cement matrix. Interestingly, the combination of SAED and EDX analyses of single crystal has indicated the occurrence of magnesium substitution within brushite crystals. Moreover, the effect of magnesium ions on the structure, and mechanical and setting properties of the new cements was characterized as well as the release of Ca(2+) and Mg(2+) ions. Further research would enhance the efficiency of the system to incorporate larger amounts of magnesium ions within brushite crystals.

  8. Bone Graft Substitution and Augmentation.

    PubMed

    Nauth, Aaron; Lane, Joseph; Watson, J Tracy; Giannoudis, Peter

    2015-12-01

    Selection of appropriate bone graft or bone graft substitute requires careful recognition of the bone healing needs of the patient's specific clinical problem and a thorough understanding of the different properties possessed by the available bone grafts and substitutes. Although autogenous iliac crest bone graft remains the gold standard of treatment for delayed unions, nonunions, and bone defects, there are a number of promising alternatives available, and emerging evidence suggests that they can be very effective when used in the proper setting. Among these, reamer-irrigator-aspirator bone graft, bone marrow concentrate, bone morphogenetic proteins, and calcium phosphate cements have received a great deal of attention in the literature. This review describes these grafts in detail along with the evidence for their use. In addition, a framework is provided for selecting the appropriate graft or substitute based on their provided properties.

  9. Substitution systems and nonextensive statistics

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2015-12-01

    Substitution systems evolve in time by generating sequences of symbols from a finite alphabet: At a certain iteration step, the existing symbols are systematically replaced by blocks of Nk symbols also within the alphabet (with Nk, a natural number, being the length of the kth block of the substitution). The dynamics of these systems leads naturally to fractals and self-similarity. By using B-calculus (García-Morales, 2012) universal maps for deterministic substitution systems both of constant and non-constant length, are formulated in 1D. It is then shown how these systems can be put in direct correspondence with Tsallis entropy. A 'Second Law of Thermodynamics' is also proved for these systems in the asymptotic limit of large words.

  10. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted...

  11. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted...

  12. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted...

  13. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted...

  14. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl amino substituted triazine amino...

  15. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl amino substituted triazine amino...

  16. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl amino substituted triazine amino...

  17. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  18. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl amino substituted triazine amino...

  19. 40 CFR 721.10040 - Substituted acridine naphtha substituted benzamide (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted acridine naphtha... Significant New Uses for Specific Chemical Substances § 721.10040 Substituted acridine naphtha substituted... substance identified generically as a substituted acridine naphtha substituted benzamide (PMN P-02-522) is...

  20. Hypoxic radiosensitizers: substituted styryl derivatives.

    PubMed

    Nudelman, A; Falb, E; Odesa, Y; Shmueli-Broide, N

    1994-10-01

    A number of novel styryl epoxides, N-substituted-styryl-ethanolamines, N-mono and N,N'-bis-(2-hydroxyethyl)-cinnamamides--analogues to the known radiosensitizers RSU-1069, pimonidazole and etanidazole--display selective hypoxic radiosensitizing activity. The styryl group, especially when substituted by electron withdrawing groups, was found to be bioisosteric to the nitroimidazolyl functionality. The most active derivative 2-(2'-nitrophenyl)ethen-1-yl-oxirane 8a displayed a sensitizer enhancement ratio (SER) of 5 relative to misonidazole.

  1. Substituted decision making: elder guardianship.

    PubMed

    Leatherman, Martha E; Goethe, Katherine E

    2009-11-01

    The goal of this column is to help experienced clinicians navigate the judicial system when they are confronted with requests for capacity evaluations that involve guardianship (conservatorship). The interface between the growing elderly medical population and increasing requests for substituted decision making is becoming more complex. This column will help practicing psychiatrists understand the medical, legal, and societal factors involved in adult guardianship. Such understanding is necessary in order to effectively perform guardianship evaluations and adequately inform courts, patients, and families about the psychiatric diagnoses central to substituted decision making.

  2. Complete amino-acid sequence, crystallization and preliminary X-ray diffraction studies of leucurolysin-a, a nonhaemorrhagic metalloproteinase from Bothrops leucurus snake venom

    PubMed Central

    Ferreira, Rodrigo Novaes; Rates, Breno; Richardson, Michael; Guimarães, Beatriz Gomes; Sanchez, Eládio Oswaldo Flores; de Castro Pimenta, Adriano Monteiro; Nagem, Ronaldo Alves Pinto

    2009-01-01

    Leucurolysin-a (leuc-a) is a class P-I snake-venom metalloproteinase isolated from the venom of the South American snake Bothrops leucurus (white-tailed jararaca). The mature protein is composed of 202 amino-acid residues in a single polypeptide chain. It contains a blocked N-terminus and is not glycosylated. In vitro studies revealed that leuc-a dissolves clots made either from purified fibrinogen or from whole blood. Unlike some other venom fibrinolytic metalloproteinases, leuc-a has no haemorrhagic activity. Leuc-a was sequenced and was crystallized using the hanging-drop vapour-diffusion technique. Crystals were obtained using PEG 6000 or PEG 1500. Diffraction data to 1.80 and 1.60 Å resolution were collected from two crystals (free enzyme and the endogenous ligand–protein complex, respectively). They both belonged to space group P212121, with very similar unit-cell parameters (a = 44.0, b = 56.2, c = 76.3 Å for the free-enzyme crystal). PMID:19652343

  3. Exploring the Structure of the 100 Amino-Acid Residue Long N-Terminus of the Plant Antenna Protein CP29

    PubMed Central

    Shabestari, Maryam Hashemi; Wolfs, Cor J.A.M.; Spruijt, Ruud B.; van Amerongen, Herbert; Huber, Martina

    2014-01-01

    The structure of the unusually long (∼100 amino-acid residues) N-terminal domain of the light-harvesting protein CP29 of plants is not defined in the crystal structure of this membrane protein. We studied the N-terminus using two electron paramagnetic resonance (EPR) approaches: the rotational diffusion of spin labels at 55 residues with continuous-wave EPR, and three sets of distances with a pulsed EPR method. The N-terminus is relatively structured. Five regions that differ considerably in their dynamics are identified. Two regions have low rotational diffusion, one of which shows α-helical character suggesting contact with the protein surface. This immobile part is flanked by two highly dynamic, unstructured regions (loops) that cover residues 10–22 and 82–91. These loops may be important for the interaction with other light-harvesting proteins. The region around residue 4 also has low rotational diffusion, presumably because it attaches noncovalently to the protein. This section is close to a phosphorylation site (Thr-6) in related proteins, such as those encoded by the Lhcb4.2 gene. Phosphorylation might influence the interaction with other antenna complexes, thereby regulating the supramolecular organization in the thylakoid membrane. PMID:24655510

  4. 'Vegetable' substitutes for diesel fuel

    SciTech Connect

    Not Available

    1981-07-22

    Research programs in the US, Brazil, South Africa and the Philippines on efforts to find a vegetable oil substitute for diesel fuel are reported. A narrowing price gap with diesel fuel and a favourable energy balance improve the prospects for such fuels. Much of the current work is centered on blends, rather than the use of the pure oil.

  5. Substitute Teaching: Sink or Swim.

    ERIC Educational Resources Information Center

    Duebber, Diane

    2000-01-01

    Advises new substitute teachers to be prepared, tote emergency activity folders, dress professionally (but wear flamingo earrings), be early, figure out the game plan, communicate expectations to students, enforce consequences, have a gimmick to reward cooperation, relish the teachable moment, leave the room tidy, and believe in themselves. (MLH)

  6. Potential for structural lumber substitutes

    Treesearch

    Theodore L. Laufenberg

    1985-01-01

    The potential for substitution of structural wood composites into solid-sawn lumber markets is presented from the technological viewpoint. Technological limitations of existing composite processes and products are reviewed in the context of the present laminated veneer lumber (LVL), flakeboard, and fiber/ paper industries. The limits of mechanical property potential...

  7. Substitute Teaching: Sink or Swim.

    ERIC Educational Resources Information Center

    Duebber, Diane

    2000-01-01

    Advises new substitute teachers to be prepared, tote emergency activity folders, dress professionally (but wear flamingo earrings), be early, figure out the game plan, communicate expectations to students, enforce consequences, have a gimmick to reward cooperation, relish the teachable moment, leave the room tidy, and believe in themselves. (MLH)

  8. Tissue-engineered skin substitutes.

    PubMed

    Mansbridge, Jonathan

    2002-01-01

    The last two years have seen new tissue-engineered skin substitutes come onto the market and begin to resolve the various roles to which each is best suited. It is becoming evident that some of the very expensive cell-based products have cost-benefit advantage despite their high price and are valuable within the restricted applications for which they are intended. The use of skin substitutes for testing purposes has extended from epidermal keratinocytes to other integumentary epithelia and into preparations containing multiple cell types in which reactions resulting from paracrine interactions can be examined. Challenges remain in the application of gene therapy techniques to skin substitutes, both the control of transgene expression and in the selection of suitable genes to transfect. A coming challenge is the production of tissue-engineered products without the use of animal products other than human cells. A challenge that may be diminishing is the importance of acute rejection of allogeneic tissue-engineered skin substitutes.

  9. No Substitute Teacher Left behind

    ERIC Educational Resources Information Center

    O'Connor, Kevin

    2009-01-01

    Schools and districts routinely recruit, retain, and support highly qualified teachers to ensure that students receive the best learning opportunities. However, even if one's school employs highly qualified full-time teachers, it is important to acknowledge that substitute teachers also have a significant impact on the education of students. One…

  10. Substitution effects on optical properties of iminonitroxide- substituted iminonitroxide diradical

    NASA Astrophysics Data System (ADS)

    Nakamura, Ryota; Shigeta, Yasuteru; Okuno, Katsuki; Hasegawa, Miki; Fukushima, Mayuko; Suzuki, Shuichi; Kozaki, Masatoshi; Okada, Keiji; Nakano, Masayoshi

    2015-02-01

    Absorption spectra of iminonitroxide-substituted iminonitroxide diradical (IN-IN) are calculated by means of time-dependent density functional theory. Since IN-IN has two different conformations with small singlet-triplet gaps, the statistical average of the absorption spectrum is compared with the experimental one. We also investigate the substitution effects of CN, OMe, and NH2 groups and found that the introduction of OMe and NH2 groups results in the redshift of the longer wavelength region due to the delocalisation of the lowest unoccupied molecular orbital over lone pair of OMe from the analyses on molecular orbitals of an IN monomeric unit instead of IN-IN. On the other hand, there is no explicit difference in the short-wavelength region in spite of the introduction of these functional groups.

  11. A high load of non-neutral amino-acid polymorphisms explains high protein diversity despite moderate effective population size in a marine bivalve with sweepstakes reproduction.

    PubMed

    Harrang, Estelle; Lapègue, Sylvie; Morga, Benjamin; Bierne, Nicolas

    2013-02-01

    Marine bivalves show among the greatest allozyme diversity ever reported in Eukaryotes, putting them historically at the heart of the neutralist-selectionist controversy on the maintenance of genetic variation. Although it is now acknowledged that this high diversity is most probably a simple consequence of a large population size, convincing support for this explanation would require a rigorous assessment of the silent nucleotide diversity in natural populations of marine bivalves, which has not yet been done. This study investigated DNA sequence polymorphism in a set of 37 nuclear loci in wild samples of the flat oyster Ostrea edulis. Silent diversity was found to be only moderate (0.7%), and there was no departure from demographic equilibrium under the Wright-Fisher model, suggesting that the effective population size might not be as large as might have been expected. In accordance with allozyme heterozygosity, nonsynonymous diversity was comparatively very high (0.3%), so that the nonsynonymous to silent diversity ratio reached a value rarely observed in any other organism. We estimated that one-quarter of amino acid-changing mutations behave as neutral in O. edulis, and as many as one-third are sufficiently weakly selected to segregate at low frequency in the polymorphism. Finally, we inferred that one oyster is expected to carry more than 4800 non-neutral alleles (or 4.2 cM(-1)). We conclude that a high load of segregating non-neutral amino-acid polymorphisms contributes to high protein diversity in O. edulis. The high fecundity of marine bivalves together with an unpredictable and highly variable success of reproduction and recruitment (sweepstakes reproduction) might produce a greater decoupling between Ne and N than in other organisms with lower fecundities, and we suggest this could explain why a higher segregating load could be maintained for a given silent mutation effective size.

  12. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

    PubMed

    Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G; Korbonits, Márta

    2017-09-01

    Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability. © 2017 The authors.

  13. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism

    PubMed Central

    Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G

    2017-01-01

    Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Results Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the ‘English founder’, with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9–113 generations, equivalent to 225–2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. Conclusions The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein–protein interactions and AIP protein stability. PMID:28634279

  14. Insights into the influence of 5-HT2c aminoacidic variants with the inhibitory action of serotonin inverse agonists and antagonists.

    PubMed

    Galeazzi, Roberta; Massaccesi, Luca; Piva, Francesco; Principato, Giovanni; Laudadio, Emilioano

    2014-03-01

    Specific modulation of serotonin 5-HT(2C) G protein-coupled receptors may be therapeutic for obesity and neuropsychiatric disorders. The different efficacy of drugs targeting these receptors are due to the presence of genetic variants in population and this variability is still hard to predict. Therefore, in order to administer the more suitable drug, taking into account patient genotype, it is necessary to know the molecular effects of its gene nucleotide variations. In this work, starting from an accurate 3D model of 5-HT(2C), we focus on the prediction of the possible effect of some single nucleotide polymorphisms (SNPs) producing amino acidic changes in proximity of the 5-HT(2C) ligand binding site. Particularly we chose a set of 5-HT(2C) inverse agonists and antagonists which have high inhibitory activity. After prediction of the structures of the receptor-ligand complexes using molecular docking tools, we performed full atom molecular dynamics simulations in explicit lipid bilayer monitoring the interactions between ligands and trans-membrane helices of the receptor, trying to infer relations with their biological activity. Serotonin, as the natural ligand was chosen as reference compound to advance a hypothesis able to explain the receptor inhibition mechanism. Indeed we observed a different behavior between the antagonists and inverse agonist with respect to serotonin or unbounded receptor, which could be responsible, even if not directly, of receptor's inactivation. Furthermore, we analyzed five aminoacidic variants of 5HT(2C) receptor observing alterations in the interactions between ligands and receptor which give rise to changes of free energy values for every complex considered.

  15. [Evolution of urinary bladder substitution].

    PubMed

    Kock, N G

    1992-11-01

    The historical background to the currently used methods for continent bladder substitution is shortly outlined. The significance for the patient's quality of life of various methods for bladder reconstruction or urinary diversion is briefly discussed. The importance of reservoir configuration for achieving a high compliant urinary receptacle is pointed out. Factors affecting reabsorption of urinary constituents are stressed and the significance of an antireflux mechanism is discussed. Currently the majority of patients undergoing cystectomy for cancer or for other reasons can be offered bladder substitutes providing continence and easy emptying; that is, complete control over voiding. This can be achieved by orthotopic bladder reconstruction or by diverting the urine to the augmented and valved rectum or to the skin via a continent intestinal reservoir.

  16. Assessment of asbestos insulation substitutes

    SciTech Connect

    Fourroux, J.D.; Frank, R.L. Jr.; Newberry, T.W. Jr. )

    1990-03-01

    A state-of-the-art study of asbestos insulation alternatives has been conducted to identify the best substitute material for steam lines in power plants. A survey of utilities across the nation showed that calcium silicate is the most commonly employed material today, followed by mineral wool, fiberglass, and ceramic fibers. However, the calcium silicate was found to be dusty and to become brittle once exposed to elevated temperatures. Although it is asbestos-free, studies on its carcinogenicity are incomplete. Characteristic data on existing substitute materials is compiled and an optimum choice of insulation combination is configured. Potential cost savings of using this combination is evaluated for a major utility. A PC-based computer program is developed to assist utility personnel in selecting the proper insulation materials for steam lines. 31 refs., 8 figs.

  17. 40 CFR 192.42 - Substitute provisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Substitute provisions. 192.42 Section... § 192.42 Substitute provisions. The regulatory agency may, with the concurrence of EPA, substitute for any provisions of § 192.41 of this subpart alternative provisions it deems more practical that...

  18. Tele-substitutions in Heterocyclic Chemistry.

    PubMed

    Tišler, Miha

    2011-03-01

    Particular and rare examples of aromatic nucleophilic substitution are described as tele-substitution. Usually strong nucleophiles are involved and the entering group is introduced at a position distant from the expected leaving group. Examples of tele-substitution in various heteroaromatic systems are presented.

  19. 40 CFR 721.323 - Substituted acrylamide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted acrylamide. 721.323... Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as substituted acrylamide (PMN P-90-1687) is...

  20. Expectations and Experiences of Substitute Teachers

    ERIC Educational Resources Information Center

    Duggleby, Patricia; Badali, Sal

    2007-01-01

    This article explores the expectations of support for and the experiences of substitute teachers in an urban school division in Saskatchewan. Data were collected in semistructured interviews with seven substitute teachers. The purpose of the study was to explore how substitute teachers frame their professional experiences and construct their roles…

  1. 40 CFR 721.5867 - Substituted phenol.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted phenol. 721.5867 Section... Substances § 721.5867 Substituted phenol. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as substituted phenol (PMNs P-89-1125,...

  2. Substitutes for School Nurses in Illinois

    ERIC Educational Resources Information Center

    Vollinger, Linda Jeno; Bergren, Martha Dewey; Belmonte-Mann, Frances

    2011-01-01

    The purpose of this descriptive study was to explore utilization of nurse substitutes in the school setting in Illinois. The literature described personnel who staff the school health office in the absence of the school nurse and the barriers to obtaining nurse substitutes. There were no empirical studies conducted on school nurse substitutes in…

  3. 40 CFR 721.323 - Substituted acrylamide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted acrylamide. 721.323... Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as substituted acrylamide (PMN P-90-1687)...

  4. 40 CFR 721.323 - Substituted acrylamide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted acrylamide. 721.323... Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as substituted acrylamide (PMN P-90-1687)...

  5. 40 CFR 721.323 - Substituted acrylamide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted acrylamide. 721.323... Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as substituted acrylamide (PMN P-90-1687)...

  6. 40 CFR 721.323 - Substituted acrylamide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted acrylamide. 721.323... Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as substituted acrylamide (PMN P-90-1687)...

  7. 40 CFR 721.4420 - Substituted hydroxylamine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted hydroxylamine. 721.4420... Substances § 721.4420 Substituted hydroxylamine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydroxylamine (PMN P-84-492) is...

  8. 40 CFR 721.4420 - Substituted hydroxylamine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted hydroxylamine. 721.4420... Substances § 721.4420 Substituted hydroxylamine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydroxylamine (PMN P-84-492) is...

  9. 40 CFR 721.4420 - Substituted hydroxylamine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted hydroxylamine. 721.4420... Substances § 721.4420 Substituted hydroxylamine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydroxylamine (PMN P-84-492) is...

  10. 40 CFR 721.4420 - Substituted hydroxylamine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted hydroxylamine. 721.4420... Substances § 721.4420 Substituted hydroxylamine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydroxylamine (PMN P-84-492) is...

  11. 40 CFR 721.4420 - Substituted hydroxylamine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted hydroxylamine. 721.4420... Substances § 721.4420 Substituted hydroxylamine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydroxylamine (PMN P-84-492) is...

  12. Substitutes for School Nurses in Illinois

    ERIC Educational Resources Information Center

    Vollinger, Linda Jeno; Bergren, Martha Dewey; Belmonte-Mann, Frances

    2011-01-01

    The purpose of this descriptive study was to explore utilization of nurse substitutes in the school setting in Illinois. The literature described personnel who staff the school health office in the absence of the school nurse and the barriers to obtaining nurse substitutes. There were no empirical studies conducted on school nurse substitutes in…

  13. 40 CFR 721.4476 - Substituted imines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted imines. 721.4476 Section... Substances § 721.4476 Substituted imines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted imines (PMNs...

  14. 40 CFR 721.4476 - Substituted imines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted imines. 721.4476 Section... Substances § 721.4476 Substituted imines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted imines (PMNs...

  15. 40 CFR 721.4476 - Substituted imines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted imines. 721.4476 Section... Substances § 721.4476 Substituted imines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted imines (PMNs...

  16. 40 CFR 721.4476 - Substituted imines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted imines. 721.4476 Section... Substances § 721.4476 Substituted imines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted imines (PMNs...

  17. 40 CFR 721.4476 - Substituted imines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted imines. 721.4476 Section... Substances § 721.4476 Substituted imines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted imines (PMNs...

  18. 40 CFR 721.4280 - Substituted hydrazine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted hydrazine. 721.4280... Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydrazine (PMN P-90-594)...

  19. 40 CFR 721.4280 - Substituted hydrazine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted hydrazine. 721.4280... Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydrazine (PMN P-90-594)...

  20. 40 CFR 721.4280 - Substituted hydrazine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted hydrazine. 721.4280... Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydrazine (PMN P-90-594)...

  1. 40 CFR 721.4280 - Substituted hydrazine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted hydrazine. 721.4280... Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydrazine (PMN P-90-594)...

  2. 40 CFR 721.4280 - Substituted hydrazine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted hydrazine. 721.4280... Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted hydrazine (PMN P-90-594)...

  3. Permanent Teacher Preparation for Substitute Teachers.

    ERIC Educational Resources Information Center

    Hardman, Steve; Tippetts, Zachary

    2001-01-01

    Presents information about what should be communicated to substitute teachers and why it is important, focusing on the substitute teacher's role, classroom management tools, curriculum management, and preparing students for the substitute teacher by creating bridges that will help minimize the sense of separation students feel when they have a…

  4. [Interactive effects between allelochemical substitutes].

    PubMed

    He, Huaqin; Shen, Lihua; Song, Biqing; Guo, Yuchun; Liang, Yiyuan; Liang, Kangjing; Lin, Wenxiong

    2005-05-01

    In order to understand the allelopathic mechanisms of rice on weed, the allelochemical substitutes salicylic acid, p-hydroxybenzonic acid, cinnamic acid, vanillic acid and ferulic acid were used in an orthogonally gyrating regression experiment to study their interactive effects on the growth of barnyardgrass. The results indicated that whether the interactive effects between two substitutes, e.g., between salicylic and cinnamic acid or between salicylic and p-hydrobanzonic acid, were synergistic or antagonistic depended on the concentrations of each substitutes in the mixture. In the mixture of salicylic acid and p-hydrobanzonic acid, the effect of salicylic acid was synergistic at < 0.14 mmol.L(-1) but antagonistic at > 0.14 mmol.L(-1), while p-hydrobanzonic acid showed an antagonistic effect at > 0.425 mmol.L(-1). Salicylic acid at all test concentrations exhibited antagonism to cinnamic acid, while cinnamic acid had a synergistic at < 0.14 mmol.L(-1), but an antagonistic effect at >0.14 mmol.L(-1) on alicylic acid. The interactive effects between cinnamic and ferulic acid were all synergistic at test concentrations.

  5. Resonant photodissociation in substituted benzenes

    NASA Astrophysics Data System (ADS)

    Scarborough, Tim; McAcy, Collin; Foote, David; Uiterwaal, Cornelis

    2011-05-01

    Cyclic aromatic molecules are abundant in organic chemistry, with a wide variety of applications, including pharmacology, pollution studies and genetic research. Among the simplest of these molecules is benzene (C6H6) , with many relevant molecules being benzene-like with a single atomic substitution. In such a substitution, the substituent determines a characteristic perturbation of the electronic structure of the molecule. We discuss the substitution of halogens into the ring (C6H5X), and its effects on the dynamics of ionization and dissociation of the molecule without the focal volume effect. In particular, using 800-nm, 50-fs laser pulses, we present results in the dissociation of fluorobenzene, chlorobenzene, bromobenzene and iodobenzene into the phenyl ring (C6H5) and the atomic halogen, and the subsequent ionization of these fragments. The impact of the ``heavy atom effect'' on a 1 (π , π*) -->3 (n , σ*) singlet-triplet intersystem crossing will be emphasized. Currently under investigation is whether such a dissociation can be treated as an effective source of the neutral substituent. This material is based upon work supported by the National Science Foundation under Grant No. PHY-0355235.

  6. Iridium-Catalyzed Allylic Substitution

    NASA Astrophysics Data System (ADS)

    Hartwig, John F.; Pouy, Mark J.

    Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is generated by a base-induced cyclometalation at the methyl group of this substituent to generate an iridium metalacycle bound by the COD ligand of the [Ir(COD)Cl]2 precursor and one additional labile dative ligand. Such complexes catalyze the reactions of linear allylic esters with alkylamines, arylamines, phenols, alcohols, imides, carbamates, ammonia, enolates and enolate equivalents, as well as typical stabilized carbon nucleophiles generated from malonates and cyanoesters. Iridium catalysts for enantioselective allylic substitution have also been generated from phosphorus ligands with substituents bound by heteroatoms, and an account of the studies of such systems, along with a description of the development of iridium catalysts is included.

  7. 40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... sulfocarbopolycle, sodium salt. 721.9545 Section 721.9545 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.9545 Substituted phenyl azo substituted sulfocarbopolycle, sodium salt... identified generically as a substituted phenyl azo substituted sulfocarbopolycle, sodium salt (PMN...

  8. 40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... benzenediazonium salt. 721.1555 Section 721.1555 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1555 Substituted phenyl azo substituted benzenediazonium salt. (a... generically as a substituted phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject...

  9. 40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... sulfocarbopolycle, sodium salt. 721.9545 Section 721.9545 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.9545 Substituted phenyl azo substituted sulfocarbopolycle, sodium salt... identified generically as a substituted phenyl azo substituted sulfocarbopolycle, sodium salt (PMN...

  10. 40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... sulfocarbopolycle, sodium salt. 721.9545 Section 721.9545 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.9545 Substituted phenyl azo substituted sulfocarbopolycle, sodium salt... identified generically as a substituted phenyl azo substituted sulfocarbopolycle, sodium salt (PMN...

  11. 40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... benzenediazonium salt. 721.1555 Section 721.1555 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1555 Substituted phenyl azo substituted benzenediazonium salt. (a... generically as a substituted phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject...

  12. 40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... benzenediazonium salt. 721.1555 Section 721.1555 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1555 Substituted phenyl azo substituted benzenediazonium salt. (a... generically as a substituted phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject...

  13. 40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... benzenediazonium salt. 721.1555 Section 721.1555 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1555 Substituted phenyl azo substituted benzenediazonium salt. (a... generically as a substituted phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject...

  14. 40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sulfocarbopolycle, sodium salt. 721.9545 Section 721.9545 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.9545 Substituted phenyl azo substituted sulfocarbopolycle, sodium salt... identified generically as a substituted phenyl azo substituted sulfocarbopolycle, sodium salt (PMN...

  15. 40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sulfocarbopolycle, sodium salt. 721.9545 Section 721.9545 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.9545 Substituted phenyl azo substituted sulfocarbopolycle, sodium salt... identified generically as a substituted phenyl azo substituted sulfocarbopolycle, sodium salt (PMN...

  16. 40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... benzenediazonium salt. 721.1555 Section 721.1555 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1555 Substituted phenyl azo substituted benzenediazonium salt. (a... generically as a substituted phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject...

  17. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

  18. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

  19. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

  20. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

  1. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

  2. Effect of ageing and ischemia on enzymatic activities linked to Krebs' cycle, electron transfer chain, glutamate and aminoacids metabolism of free and intrasynaptic mitochondria of cerebral cortex.

    PubMed

    Villa, Roberto Federico; Gorini, Antonella; Hoyer, Siegfried

    2009-12-01

    The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete ischemia of 15 minutes duration. The maximum rate (Vmax) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate-and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction. The results indicate that in normal, steady-state cerebral cortex, the value of the same enzyme activity markedly differs according (a) to the different populations of mitochondria, i.e., non-synaptic or intra-synaptic light and heavy, (b) and respect to ageing. After 15 min of complete ischemia, the enzyme activities of mitochondria located near the nucleus (perikaryal mitochondria) and in synaptic structures (intra-synaptic mitochondria) of the cerebral tissue were substantially modified by ischemia. Non-synaptic mitochondria seem to be more affected by ischemia in adult and particularly in aged animals than the intra-synaptic light and heavy mitochondria. The observed modifications in enzyme activities reflect the metabolic state of the tissue at each specific experimental condition, as shown by comparative evaluation with respect to the content of energy-linked metabolites and substrates. The derangements in enzyme activities due to ischemia is greater in aged than in adult animals and especially the non-synaptic and the intra-synaptic light

  3. Interrelationships among biological activity, disulfide bonds, secondary structure, and metal ion binding for a chemically synthesized 34-amino-acid peptide derived from alpha-fetoprotein.

    PubMed

    MacColl, R; Eisele, L E; Stack, R F; Hauer, C; Vakharia, D D; Benno, A; Kelly, W C; Mizejewski, G J

    2001-10-03

    A 34-amino-acid peptide has been chemically synthesized based on a sequence from human alpha-fetoprotein. The purified peptide is active in anti-growth assays when freshly prepared in pH 7.4 buffer at 0.20 g/l, but this peptide slowly becomes inactive. This functional change is proven by mass spectrometry to be triggered by the formation of an intrapeptide disulfide bond between the two cysteine residues on the peptide. Interpeptide cross-linking does not occur. The active and inactive forms of the peptide have almost identical secondary structures as shown by circular dichroism (CD). Zinc ions bind to the active peptide and completely prevents formation of the inactive form. Cobalt(II) ions also bind to the peptide, and the UV-Vis absorption spectrum of the cobalt-peptide complex shows that: (1) a near-UV sulfur-to-metal-ion charge-transfer band had a molar extinction coefficient consistent with two thiolate bonds to Co(II); (2) the lowest-energy visible d-d transition maximum at 659 nm, also, demonstrated that the two cysteine residues are ligands for the metal ion; (3) the d-d molar extinction coefficient showed that the metal ion-ligand complex was in a distorted tetrahedral symmetry. The peptide has two cysteines, and it is speculated that the other two metal ion ligands might be the two histidines. The Zn(II)- and Co(II)-peptide complexes had similar peptide conformations as indicated by their ultraviolet CD spectra, which differed very slightly from that of the free peptide. Surprisingly, the cobalt ions acted in the reverse of the zinc ions in that, instead of stabilizing anti-growth form of the peptide, they catalyzed its loss. Metal ion control of peptide function is a saliently interesting concept. Calcium ions, in the conditions studied, apparently do not bind to the peptide. Trifluoroethanol and temperature (60 degrees C) affected the secondary structure of the peptide, and the peptide was found capable of assuming various conformations in solution

  4. Wanted: The perfect asbestos substitute

    SciTech Connect

    Not Available

    1993-01-01

    The quest continues for commercially viable asbestos replacements. To date, no single product has emerged that is as inert, strong or incombustible as thin fibrous silicate mineral. Traditionally, asbestos has been woven into cloths and garments, compressed into boards, gaskets, and pipe coverings, and used as a filler and reinforcement in paint, asphalt, cement and plastic. Ever since health concerns began to surface about this fibrous mineral, industrial use has been on the wane. The paper describes the many materials being tested for various purposes as an asbestos substitute.

  5. What happened to blood substitutes?

    PubMed

    Stowell, C P

    2005-11-01

    Concerns about the safety and adequacy of the blood supply have fostered twenty years of research into the so-called "blood substitutes" among them the oxygen carriers based on modified hemoglobin. Although none of these materials has yet been licensed for use in North America or Europe, the results of research and clinical trials have increased our understanding of oxygen delivery and its regulation. In particular, the examination of the basis for the vasoactivity observed with some of the hemoglobin based oxygen carriers has led to the insight that several colligative properties of hemoglobin solutions, such as their diffusion coefficient for oxygen, viscosity and colloid oncotic pressure, are important determinants of efficacy.

  6. Use This Test to Spruce Up Your Substitute Teacher Program.

    ERIC Educational Resources Information Center

    Sendor, Elizabeth

    1982-01-01

    Presents and interprets an 18-question test to determine how well a school's substitute teacher program functions. Topics covered include substitute teacher screening and preparation, lists of substitutes, lesson plans, staff and student evaluation of substitutes, substitutes' salaries, legal considerations, and making substitutes feel needed.…

  7. Use This Test to Spruce Up Your Substitute Teacher Program.

    ERIC Educational Resources Information Center

    Sendor, Elizabeth

    1982-01-01

    Presents and interprets an 18-question test to determine how well a school's substitute teacher program functions. Topics covered include substitute teacher screening and preparation, lists of substitutes, lesson plans, staff and student evaluation of substitutes, substitutes' salaries, legal considerations, and making substitutes feel needed.…

  8. Biologic and synthetic skin substitutes: An overview.

    PubMed

    Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd Yussof, Shah Jumaat

    2010-09-01

    The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing.

  9. Biologic and synthetic skin substitutes: An overview

    PubMed Central

    Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd. Yussof, Shah Jumaat

    2010-01-01

    The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing. PMID:21321652

  10. Substitutional doping in nanocrystal superlattices

    NASA Astrophysics Data System (ADS)

    Cargnello, Matteo; Johnston-Peck, Aaron C.; Diroll, Benjamin T.; Wong, Eric; Datta, Bianca; Damodhar, Divij; Doan-Nguyen, Vicky V. T.; Herzing, Andrew A.; Kagan, Cherie R.; Murray, Christopher B.

    2015-08-01

    Doping is a process in which atomic impurities are intentionally added to a host material to modify its properties. It has had a revolutionary impact in altering or introducing electronic, magnetic, luminescent, and catalytic properties for several applications, for example in semiconductors. Here we explore and demonstrate the extension of the concept of substitutional atomic doping to nanometre-scale crystal doping, in which one nanocrystal is used to replace another to form doped self-assembled superlattices. Towards this goal, we show that gold nanocrystals act as substitutional dopants in superlattices of cadmium selenide or lead selenide nanocrystals when the size of the gold nanocrystal is very close to that of the host. The gold nanocrystals occupy random positions in the superlattice and their density is readily and widely controllable, analogous to the case of atomic doping, but here through nanocrystal self-assembly. We also show that the electronic properties of the superlattices are highly tunable and strongly affected by the presence and density of the gold nanocrystal dopants. The conductivity of lead selenide films, for example, can be manipulated over at least six orders of magnitude by the addition of gold nanocrystals and is explained by a percolation model. As this process relies on the self-assembly of uniform nanocrystals, it can be generally applied to assemble a wide variety of nanocrystal-doped structures for electronic, optical, magnetic, and catalytic materials.

  11. Cement from magnesium substituted hydroxyapatite.

    PubMed

    Lilley, K J; Gbureck, U; Knowles, J C; Farrar, D F; Barralet, J E

    2005-05-01

    Brushite cement may be used as a bone graft material and is more soluble than apatite in physiological conditions. Consequently it is considerably more resorbable in vivo than apatite forming cements. Brushite cement formation has previously been reported by our group following the mixture of nanocrystalline hydroxyapatite and phosphoric acid. In this study, brushite cement was formed from the reaction of nanocrystalline magnesium-substituted hydroxyapatite with phosphoric acid in an attempt to produce a magnesium substituted brushite cement. The presence of magnesium was shown to have a strong effect on cement composition and strength. Additionally the presence of magnesium in brushite cement was found to reduce the extent of brushite hydrolysis resulting in the formation of HA. By incorporating magnesium ions in the apatite reactant structure the concentration of magnesium ions in the liquid phase of the cement was controlled by the dissolution rate of the apatite. This approach may be used to supply other ions to cement systems during setting as a means to manipulate the clinical performance and characteristics of brushite cements.

  12. Substituting objects from consciousness: a review of object substitution masking.

    PubMed

    Goodhew, Stephanie C; Pratt, Jay; Dux, Paul E; Ferber, Susanne

    2013-10-01

    Object substitution masking (OSM) occurs when a sparse (e.g., four-dot), temporally trailing mask obscures the visibility of a briefly presented target. Here, we review theories of OSM: those that propose that OSM reflects the interplay between feedforward and feedback/reentrant neural processes, those that predict that feedforward processing alone gives rise to the phenomenon, and theories that focus on cognitive explanations, such as object updating. We discuss how each of these theories accommodates key findings from the OSM literature. In addition, we examine the relationship between OSM and other visual-cognitive phenomena, including object correspondence through occlusion, change blindness, metacontrast masking, backward masking, and visual short-term memory. Finally, we examine the level of processing at which OSM impairs target perception. Collectively, OSM appears to reflect the conditions under which the brain confuses two visual events for one when they are encoded with low spatiotemporal resolution, due to processing resources being otherwise occupied.

  13. Substitution rates in hepatitis delta virus.

    PubMed

    Krushkal, J; Li, W H

    1995-12-01

    Substitution rates were estimated for the coding and noncoding regions of the hepatitis delta virus (HDV). The estimated rates of synonymous substitution in HDV were lower than the rates of substitution at non-synonymous sites and in the noncoding region. HDV has lower synonymous substitution rates than the hepatitis C virus, though both are RNA viruses. The relatively low rate of synonymous substitution in HDV may be due to a strong preference of G and C nucleotides at third codon positions. Variation in substitution rate among HDV lineages may be correlated with the clinical development of the HDV-induced hepatitis. The phylogenetic tree inferred for 24 HDV strains reveals similarities between lineages isolated from the same geographic region.

  14. Computational study of cation substitutions in apatites

    SciTech Connect

    Tamm, Toomas . E-mail: tamm@yki.ttu.ee; Peld, Merike

    2006-05-15

    Density-functional theory plane-wave modeling of fluor- and hydroxyapatites has been performed, where one or two calcium ions per unit cell were replaced with cadmium or zinc cations. It was found that cadmium ions favor Ca(1) positions in fluorapatites and Ca(2) positions in hydroxyapatites, in agreement with experiment. A similar pattern is predicted for zinc substitutions. In the doubly substituted cases, where only hydroxyapatites were modeled, a preference for the substituting ions to be located in Ca(2) position was also observed. Displacement of the hydroxide ions from their symmetrical positions on the hexagonal axis can be used to explain the preferred configurations of substituting ions around the axis. -- Deformation of the hydroxide ion chain due to substitutions around the ion channel in substituted hydroxyapatites.

  15. Blood Substitutes: Effects on Drug Pharmacokinetics.

    DTIC Science & Technology

    1984-03-01

    RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS 1963-A - S . *.* , S. AD __ _ _ _ _? ,:-:t’ REPORT NUMBER: 2 BLOOD SUBSTITUTES: EFFECTS ON DRUG ...ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER.1-t 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED FINAL REPORT BLOOD SUBSTITUTES: EFFECTS ON DRUG ...Identify by block number) Blood substitutes; perfluorocarbons; stroma-free hemoglobin; drug pharmaco- kinetics S. ADST RACT (Cn*tfe am revere dm* if

  16. [Medical mistakes due to generic substitution].

    PubMed

    Rölfing, Jan Hendrik Duedal

    2012-08-27

    Generic substitution is a major cause of medical mistakes in the general population. Danish legislation obligates pharmacies to substitute prescribed medicine with the cheapest equivalent formulation, despite variations in product name, packaging, shape and colour. Consequently, medical mistakes occur. Scientific evidence on the consequences of generic substitution is sparse. Call upon fellow health workers to report medical mistakes to the national entities and scientific peers, in order to increase awareness and scientific evidence about the problem.

  17. Synthetic synaesthesia and sensory substitution.

    PubMed

    Proulx, Michael J

    2010-03-01

    Visual information can be provided to blind users through sensory substitution devices that convert images into sound. Through extensive use to develop expertise, some blind users have reported visual experiences when using such a device. These blind expert users have also reported visual phenomenology to other sounds even when not using the device. The blind users acquired synthetic synaesthesia, with visual experience evoked by sounds only after gaining such expertise. Sensorimotor learning may facilitate and perhaps even be required to develop expertise in the use of multimodal information. Furthermore, other areas where expertise is acquired in dividing attention amongst cross-modal information or integrating such information might also give rise to synthetic synaesthesia.

  18. Photoelectron Spectroscopy of Substituted Phenylnitrenes

    NASA Astrophysics Data System (ADS)

    Wijeratne, Neloni R.; Fonte, Maria Da; Wenthold, Paul G.

    2009-06-01

    Nitrenes are unusual molecular structures with unfilled electronic valences that are isoelectronic with carbenes. Although, both can be generated by either thermal or photochemical decomposition of appropriate precursors they usually exhibit different reactivities. In this work, we carry out spectroscopic studies of substituted phenylnitrene to determine how the introduction of substituents will affect the reactivity and its thermochemical properties. All studies were carried out by using the newly constructed time-of-flight negative ion photoelectron spectrometer (NIPES) at Purdue University. The 355 nm photoelectron spectra of the o-, m-, and p-chlorophenyl nitrene anions are fairly similar to that measured for phenylnitrene anion. All spectra show low energy triplet state and a high energy singlet state. The singlet state for the meta isomer is well-resolved, with a well defined origin and observable vibrational structure. Whereas the singlet states for the ortho and para isomers have lower energy onsets and no resolved structure. The isomeric dependence suggests that the geometry differences result from the resonance interaction between the nitrogen and the substituent. Quinoidal resonance structures are possible for the open-shell singlet states of the o- and p-chlorinated phenyl nitrenes. The advantages of this type of electronic structures for the open-shell singlet states is that the unpaired electrons can be more localized on separate atoms in the molecules, minimizing the repulsion between. Because the meta position is not in resonance with the nitrenes, substitution at that position should not affect the structure of the open-shell singlet state. The measured electron affinities (EA) of the triplet phenylnitrenes are in excellent agreement with the values predicted by electronic structure calculations. The largest EA, 1.82 eV is found for the meta isomer, with para being the smallest, 1.70 eV.

  19. Evaluating Anti-SmD1-amino-acid 83-119 Peptide Reactivity in Children with Systemic Lupus Erythematosus and Other Immunological Diseases

    PubMed Central

    Yang, Hai-Ou; Zhang, Xiao-Qing; Fu, Qi-Hua

    2016-01-01

    Background: SmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119 antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119 antibody in the diagnosis of cSLE. Methods: Samples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119 and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P < 0.05 was considered statistically significant. Results: Thirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26

  20. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... significant new uses subject to reporting. (1) The chemical substances identified generically as copper...

  1. 40 CFR 721.10497 - Substituted alkyl ester, hydrolysis products with silica and substituted silane (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted alkyl ester, hydrolysis... ester, hydrolysis products with silica and substituted silane (generic). (a) Chemical substance and... alkyl ester, hydrolysis products with silica and substituted silane (PMNs P-06-276 and P-06-279)...

  2. 40 CFR 721.10497 - Substituted alkyl ester, hydrolysis products with silica and substituted silane (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted alkyl ester, hydrolysis... ester, hydrolysis products with silica and substituted silane (generic). (a) Chemical substance and... alkyl ester, hydrolysis products with silica and substituted silane (PMNs P-06-276 and P-06-279)...

  3. 40 CFR 721.5340 - Substituted benzothiazole-azo-substituted benzoquinoline nickel complex (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-substituted benzoquinoline nickel complex (generic). 721.5340 Section 721.5340 Protection of Environment...-substituted benzoquinoline nickel complex (generic). (a) Chemical substance and significant new uses subject...-substituted benzoquinoline nickel complex (PMN P-99-897) is subject to reporting under this section for the...

  4. 40 CFR 721.5340 - Substituted benzothiazole-azo-substituted benzoquinoline nickel complex (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-substituted benzoquinoline nickel complex (generic). 721.5340 Section 721.5340 Protection of Environment...-substituted benzoquinoline nickel complex (generic). (a) Chemical substance and significant new uses subject...-substituted benzoquinoline nickel complex (PMN P-99-897) is subject to reporting under this section for...

  5. 40 CFR 721.5340 - Substituted benzothiazole-azo-substituted benzoquinoline nickel complex (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-substituted benzoquinoline nickel complex (generic). 721.5340 Section 721.5340 Protection of Environment...-substituted benzoquinoline nickel complex (generic). (a) Chemical substance and significant new uses subject...-substituted benzoquinoline nickel complex (PMN P-99-897) is subject to reporting under this section for...

  6. 40 CFR 721.5340 - Substituted benzothiazole-azo-substituted benzoquinoline nickel complex (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-substituted benzoquinoline nickel complex (generic). 721.5340 Section 721.5340 Protection of Environment...-substituted benzoquinoline nickel complex (generic). (a) Chemical substance and significant new uses subject...-substituted benzoquinoline nickel complex (PMN P-99-897) is subject to reporting under this section for...

  7. 40 CFR 721.5340 - Substituted benzothiazole-azo-substituted benzoquinoline nickel complex (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-substituted benzoquinoline nickel complex (generic). 721.5340 Section 721.5340 Protection of Environment...-substituted benzoquinoline nickel complex (generic). (a) Chemical substance and significant new uses subject...-substituted benzoquinoline nickel complex (PMN P-99-897) is subject to reporting under this section for...

  8. 40 CFR Appendix D to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Comments Electronics Cleaning w/CFC-113 and MCF HFC-4310mee Acceptable Subject to a 200 ppm time-weighted... Electronics Cleaning w/CFC-113 and MCF Perfluoropolyethers Perfluoropolyethers are acceptable substitutes for... that for PFCs. Unacceptable Substitutes End-use Substitute Decision Comments Electronics Cleaning...

  9. 40 CFR Appendix D to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Comments Electronics Cleaning w/CFC-113 and MCF HFC-4310mee Acceptable Subject to a 200 ppm time-weighted... Electronics Cleaning w/CFC-113 and MCF Perfluoropolyethers Perfluoropolyethers are acceptable substitutes for... that for PFCs. Unacceptable Substitutes End-use Substitute Decision Comments Electronics Cleaning...

  10. 40 CFR Appendix D to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Comments Electronics Cleaning w/CFC-113 and MCF HFC-4310mee Acceptable Subject to a 200 ppm time-weighted... Electronics Cleaning w/CFC-113 and MCF Perfluoropolyethers Perfluoropolyethers are acceptable substitutes for... that for PFCs. Unacceptable Substitutes End-use Substitute Decision Comments Electronics Cleaning...

  11. 40 CFR Appendix D to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Comments Electronics Cleaning w/CFC-113 and MCF HFC-4310mee Acceptable Subject to a 200 ppm time-weighted... Electronics Cleaning w/CFC-113 and MCF Perfluoropolyethers Perfluoropolyethers are acceptable substitutes for... that for PFCs. Unacceptable Substitutes End-use Substitute Decision Comments Electronics Cleaning...

  12. 40 CFR Appendix D to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Comments Electronics Cleaning w/CFC-113 and MCF HFC-4310mee Acceptable Subject to a 200 ppm time-weighted... Electronics Cleaning w/CFC-113 and MCF Perfluoropolyethers Perfluoropolyethers are acceptable substitutes for... that for PFCs. Unacceptable Substitutes End-use Substitute Decision Comments Electronics Cleaning...

  13. 25 CFR 522.9 - Substitute approval.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Substitute approval. 522.9 Section 522.9 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.9 Substitute approval. If the Chairman fails to...

  14. Substitutes for Leadership: An Empirical Study.

    ERIC Educational Resources Information Center

    Howell, Jon P.; Dorfman, Peter W.

    The leadership substitutes hypothesis has been used to explain the occasional successes and frequent failures of leadership predictions. Three hypotheses were formulated to test the viability of the leadership substitutes concepts. Questionnaires were administered to hospital managers (N=63) and engineers (N=71). Instrumental and supportive leader…

  15. Multisensory integration, sensory substitution and visual rehabilitation.

    PubMed

    Proulx, Michael J; Ptito, Maurice; Amedi, Amir

    2014-04-01

    Sensory substitution has advanced remarkably over the past 35 years since first introduced to the scientific literature by Paul Bach-y-Rita. In this issue dedicated to his memory, we describe a collection of reviews that assess the current state of neuroscience research on sensory substitution, visual rehabilitation, and multisensory processes.

  16. 25 CFR 522.9 - Substitute approval.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Substitute approval. 522.9 Section 522.9 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.9 Substitute approval. If the Chairman fails...

  17. Carboranylmethylene-substituted phosphazenes and polymers thereof

    NASA Technical Reports Server (NTRS)

    Allcock, H. R.; Scopelianos, A. G. (Inventor)

    1984-01-01

    Carboranylmethylene-substituted cyclophosphazenes are described which can be thermally polymerized into carboranylmethylene-substituted phosphazene polymers. The polymers are useful as thermally stable coatings. Also, due to the characteristics of these polymers in acting as a ligand for transition metals, metalocarboranylmethylene phosphazene polymers are described which can act as immobilized catalyst systems, and are electrically conductive and superconductive.

  18. Educators Take Another Look at Substitutes

    ERIC Educational Resources Information Center

    Zubrzycki, Jaclyn

    2012-01-01

    The mythology surrounding the substitute teacher is not a pretty one: Paper airplanes, lost learning, bullying. But as schools collect more information about teacher absenteeism and its consequences, districts and schools are exploring ways to professionalize substitute teaching--or experiment with alternative ways of coping with teacher absences.…

  19. Substitute Your Way to a Real Job

    ERIC Educational Resources Information Center

    Stephens, Cathy

    2013-01-01

    For some, substitute teaching is a career choice. However, for the majority of new teachers, it is often a necessary gateway to landing a first job. Either way, it is a great way to sharpen one's skills. This article presents tips from principals, teachers, and human resource directors to make the most of the substitute teaching experience…

  20. 37 CFR 1.125 - Substitute specification.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....125 Section 1.125 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE... substitute specification includes no new matter. (c) A substitute specification submitted under this section... specification of record. The text of any added subject matter must be shown by underlining the added text. The...

  1. 37 CFR 1.125 - Substitute specification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....125 Section 1.125 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE... substitute specification includes no new matter. (c) A substitute specification submitted under this section... specification of record. The text of any added subject matter must be shown by underlining the added text. The...

  2. 25 CFR 522.9 - Substitute approval.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Substitute approval. 522.9 Section 522.9 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.9 Substitute approval. If the Chairman fails...

  3. Substitute Your Way to a Real Job

    ERIC Educational Resources Information Center

    Stephens, Cathy

    2013-01-01

    For some, substitute teaching is a career choice. However, for the majority of new teachers, it is often a necessary gateway to landing a first job. Either way, it is a great way to sharpen one's skills. This article presents tips from principals, teachers, and human resource directors to make the most of the substitute teaching experience…

  4. The Substitute Teacher in Reading Instruction.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Since regular teachers miss on average 8 days of work each year due to illness, there is a need to have well trained substitute teachers for the public schools. The substitute teacher needs inservice education programs which prepare him/her to do a quality job of teaching students. The following are essential reading skills to develop within…

  5. The Dangerous Practice of Evaluating Substitute Teachers.

    ERIC Educational Resources Information Center

    Ryan, Terry

    2000-01-01

    Presents a tongue-in-cheek discussion of whether or not administrators should formally evaluate and provide feedback to substitute teachers, noting the potential legal problems that may occur if an administrator decides to terminate the employment of a substitute teacher on the basis of the evaluation process. (SM)

  6. Substitute Teachers: Making Lost Days Count

    ERIC Educational Resources Information Center

    True, Charlene; Butler, Kyle; Sefton, Rachel

    2011-01-01

    As K-12 teachers and administrators grow increasingly concerned with issues of accountability, research-based methods, and intervention strategies, little discussion exists on the impact of substitute teachers in the classroom. In the rush to analyze test scores, are the days covered by substitute teachers even considered? Though districts are…

  7. Educators Take Another Look at Substitutes

    ERIC Educational Resources Information Center

    Zubrzycki, Jaclyn

    2012-01-01

    The mythology surrounding the substitute teacher is not a pretty one: Paper airplanes, lost learning, bullying. But as schools collect more information about teacher absenteeism and its consequences, districts and schools are exploring ways to professionalize substitute teaching--or experiment with alternative ways of coping with teacher absences.…

  8. Substitute Teachers as Effective Classroom Instructors

    ERIC Educational Resources Information Center

    Glatfelter, Andrew Gary

    2006-01-01

    Over the course of their kindergarten through twelfth grade education, children in American public schools will spend the equivalent of one school year under the guidance of a substitute teacher. Yet in most districts, substitutes are given the keys to the classroom without a day's training. While requirements vary by state, some may hold advanced…

  9. [Prophylaxis of dental caries using sugar substitutes].

    PubMed

    Eberle, G

    1984-12-01

    Among the three measures, which are capable of producing a preventive effect against caries only when applied combined, i.e. adequate fluoride supply, proper mouth hygiene and healthy nutrition, the latter is dealt with in greater detail. The use of sugar substitutes is discussed under the aspects of caries prevention, substitute composition and production technology as well as from a medical point of view. Among the presently available sugar substitutes with nutritive value are mentioned Xylite, Lycasine, Mannite, Sorbite, Palatinite, the non-calorific substitutes such as the natural Aspartame as well as the synthetic sweetening agents Saccharine and Cyclamate. The possibilities and limitations of using these sugar substitutes in the prevention of caries in adults and children are presented.

  10. Quinine substitutes in the confederate army.

    PubMed

    Hasegawa, Guy R

    2007-06-01

    During the Civil War, the unreliable supply and high cost of quinine forced the Confederate Army to use alternative treatments for malaria. Many quinine substitutes were mentioned in the literature of the time, but relatively few were advocated by Confederate officials and even fewer are described in surviving records. Medical supply officers often issued substitute remedies when quinine was requisitioned. Most alternative treatments were made from indigenous plants such as dogwood, willow (a constituent of which gave rise to aspirin), and tulip tree. High hopes were held for Georgia bark, which was thought to be closely related to cinchona, from which quinine was derived. Documentation of the effectiveness of quinine substitutes is scanty but is most plentiful for the external application of turpentine. The quinine substitutes were generally considered useful but not as effective as quinine. The Confederate Surgeon General's Office was active in seeking out and supplying troops with quinine substitutes.

  11. High-level expression and in vitro mutagenesis of a fibrillogenic 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein.

    PubMed Central

    Gardella, J E; Gorgone, G A; Candela, L; Ghiso, J; Castaño, E M; Frangione, B; Gorevic, P D

    1993-01-01

    We amplified DNA encoding the 3' 109 codons of Alzheimer's-disease amyloid precursor protein (APP) inclusive of the beta protein (A beta) and cytoplasmic domains from cDNA using oligonucleotide primers designed to facilitate cloning into the T7 expression vector pT7Ad23K13. We also modified this construct to generate recombinant molecules incorporating two recently described APP mutants by site-directed mutagenesis. Both native C109 (deletion construct inclusive of the C-terminal 109 residues of APP) and constructs with a single mutation at codon 642 (T-->G, resulting in a substitution of glycine for valine) or a double mutation at codons 595 (G-->T, substituting asparagine for lysine) and 596 (A-->C, substituting leucine for methionine) were expressed in Escherichia coli to levels of 5-20% of total bacterial protein after induction. The major constituent of expressed C109 protein had an apparent molecular mass of 16-18 kDa by SDS/PAGE and appeared to be the full-length construct by size and N-terminal microsequencing. Also present was a 4-5 kDa species that co-purified with C109, constituting only approximately 1% of expressed protein, which was revealed by Western-blot analysis with antibodies specific for A beta epitopes and after biotinylation of purified recombinant C109. This fragment shared N-terminal sequence with, and appeared to arise by proteolysis of, full-length C109 in biosynthetic labelling experiments. C109 spontaneously precipitated after dialysis against NaCl or water, and with prolonged (> 20 weeks) standing was found by electron microscopy to contain a minor (< 5%) fibrillar component that was reactive with antibodies to a C-terminal epitope of APP. Recombinant C109 appears to duplicate some of the biochemical and physicochemical properties of C-terminal A beta-inclusive fragments of APP that have been found in transfected cells, brain cortex and cerebral microvessels. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID

  12. Uproar over Milk Substitutes Act.

    PubMed

    1993-11-15

    Health policy activists lobbied 7 years for the Infant Milk Substitutes, Feeding Bottles and Infant Food Bill. Proponents of the bill say that it basically curtails unethical marketing practices, not the sales of baby foods, and argue that it was conceived to reduce the trend of mothers over-diluting commercial milk in order to reduce household expenses as well as stem the potential erosion of knowledge on locally available weaning foods. Even though the bill will become an Act only after its rules and regulations have been finalized, the government has already banned baby food advertisements on television and in other electronic media under its control. Women's groups now argue that the bill tends to focus almost exclusively upon the welfare of children and compromises the position of women who can not lactate adequately. Moreover, they hold that the bill may be used to compel wives to stay out of the formal workforce so that they may feed their babies. The intention of the bill may be meaningless without complementary legislation addressing the problems of working mothers. Specifically, amendments to the Maternity Benefits Act of 1961 would extend maternity leave to 4 months after delivery and lengthen the duration of nursing breaks. It is, however, feared that these changes may reduce employment prospects for women.

  13. Resorbable calcium phosphate bone substitute.

    PubMed

    Knaack, D; Goad, M E; Aiolova, M; Rey, C; Tofighi, A; Chakravarthy, P; Lee, D D

    1998-01-01

    The in vitro and in vivo properties of a novel, fully resorbable, apatitic calcium phosphate bone substitute (ABS) are described. The ABS was prepared from calcium phosphate precursors that were hydrated to form an injectable paste that hardens endothermically at 37 degrees C to form a poorly crystalline apatitic calcium phosphate (PCA). The PCA reaction product is stable in vivo as determined by FTIR and XRD analysis of rabbit intramuscular implants of ABS retrieved 4, 7, and 14 days postimplantation. Bone formation and resorption characteristics of the ABS material were characterized in a canine femoral slot defect model. Femoral slot defects in dogs were filled with either autologous bone implants or the ABS material. Sections of femoral bone defect site from animals sacrificed at 3, 4, 12, 26, and 52 weeks demonstrated that new bone formation proceeded similarly in both autograft and ABS filled slots. Defects receiving either material were filled with trabecular bone in the first 3 to 4 weeks after implantation; lamellar or cortical bone formation was well established by week 12. New bone formation in ABS filled defects followed a time course comparable to autologous bone graft filled defects. Histomorphometric evaluation of ABS resorption and new bone formation indicated that the ABS material was greater than 99% resorbed within 26 weeks; residual ABS occupied 0.36+/-0.36% (SEM, n = 4) of the original defect area at 26 weeks. Quantitatively and qualitatively, the autograft and ABS were associated with similar new bone growth and defect filling characteristics.

  14. Substituted Hydroxyapatites with Antibacterial Properties

    PubMed Central

    Kolmas, Joanna; Groszyk, Ewa; Kwiatkowska-Różycka, Dagmara

    2014-01-01

    Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency. PMID:24949423

  15. Substituted androstanes as aromatase inhibitors

    NASA Astrophysics Data System (ADS)

    Levina, Inna S.

    1998-11-01

    The synthesis and structure-activity relationships of inhibitors of steroid aromatase which catalyses the last stage of a multistep biotransformation of cholesterol into estrogens, viz., aromatisation of C19-steroids into C18-phenolic steroids, are discussed. Compounds of the androstane series which are structurally related to the natural substrate, viz., androst-4-ene-3,17-dione, are the subjects of consideration. The review encompasses problems of synthesis of various substituted androstanes and their aromatase-inhibiting activities and structural requirements for selective specific aromatase inhibitors based on in vitro and in vivo structure-activity studies of compounds synthesised, their biological properties and the results of clinical trials. Special attention is paid to practical applications of aromatase inhibitors in the treatment of hormone-dependent mammary and ovarian tumours as well as benign prostatic tumours. In writing this report, the author has used all the information currently available in the chemical, biochemical, endocrinological and medicinal literature as well as in patents. The bibliography includes 173 references.

  16. Light-Emitting Substituted Polyacetylenes

    NASA Astrophysics Data System (ADS)

    Sun, Runguang; Zheng, Qianbing; Zhang, Xianmin; Masuda, Toshio; Kobayashi, Takayoshi

    1999-04-01

    A series of polyacetylene derivatives such aspoly[(o-i-propylphenyl)acetylene] (PPA-iPr),poly[1-(p-n-butylphenyl)-2-phenylacetylene] (PDPA-nBu), andpoly(1-hexyl-2-n-phenylacetylene) (PHPA) are systematically studiedand compared, with emphasis on the dependence of the luminescenceefficiency on the side groups and the optical and electronicexcitation processes in the polymers. Orange-red (600 nm), green(530 nm), and blue (450 nm) photoluminescent (PL) andelectroluminescent (EL) emissions from these polymers areobserved. The corresponding PL quantum efficiencies are measured using an integrating sphere and found to be lower than 0.1% for PPA-iPr, 49% for PDPA-nBu, and62% for PHPA. The ionization energies are5.3, 5.2, and 5.9 eV for PPA-iPr, PDPA-nBu, and PHPA,respectively, measured by ultraviolet photoelectron spectroscopy(UPS). It is shown that some of the substituted polyacetylenes can beemployed for lightemittingdiode (LED) fabrication, the quantumefficiencies of which are comparable to those of other light-emittingpolymers.

  17. [The child as a substitute].

    PubMed

    Sabbadini, A

    1989-01-01

    The feeling of temporarily not being oneself is a common phenomenon, with many manifestations in normality and psychopathology. I relate it here to the Freudian category of the uncanny (das Unheimliche) and to the literary device of the double (der Doppelgänger) and I consider the splitting in the ego and the distortion of the sense of identity to be their main psychological characteristics. An extreme instance of this phenomenon is represented by the replacement child, that is a child conceived with the conscious purpose on the part of its parents of substituting a dead sibling. Replacement children inevitably suffer from a sense of confusion in the area of self-identity and often display serious difficulties in the development of self-esteem and in the establishment of mature object-relationships. As illustrations of some of the problems encountered by replacement children, I briefly refer to the experiences of two great artists (Van Gogh and Dali) and I use clinical material from two of my psychoanalytic patients.

  18. Wearable and implantable pancreas substitutes.

    PubMed

    Ricotti, Leonardo; Assaf, Tareq; Dario, Paolo; Menciassi, Arianna

    2013-03-01

    A lifelong-implanted and completely automated artificial or bioartificial pancreas (BAP) is the holy grail for type 1 diabetes treatment, and could be a definitive solution even for other severe pathologies, such as pancreatitis and pancreas cancer. Technology has made several important steps forward in the last years, providing new hope for the realization of such devices, whose feasibility is strictly connected to advances in glucose sensor technology, subcutaneous and intraperitoneal insulin pump development, the design of closed-loop control algorithms for mechatronic pancreases, as well as cell and tissue engineering and cell encapsulation for biohybrid pancreases. Furthermore, smart integration of the mentioned components and biocompatibility issues must be addressed, bearing in mind that, for mechatronic pancreases, it is most important to consider how to recharge implanted batteries and refill implanted insulin reservoirs without requiring periodic surgical interventions. This review describes recent advancements in technologies and concepts related to artificial and bioartificial pancreases, and assesses how far we are from a lifelong-implanted and self-working pancreas substitute that can fully restore the quality of life of a diabetic (or other type of) patient.

  19. Substituted hydroxyapatites with antibacterial properties.

    PubMed

    Kolmas, Joanna; Groszyk, Ewa; Kwiatkowska-Różycka, Dagmara

    2014-01-01

    Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency.

  20. First principles investigation of substituted strontium hexaferrite

    NASA Astrophysics Data System (ADS)

    Dixit, Vivek

    This dissertation investigates how the magnetic properties of strontium hexaferrite change upon the substitution of foreign atoms at the Fe sites. Strontium hexaferrite, SrFe12O19, is a commonly used hard magnetic material and is produced in large quantities (around 500,000 tons per year). For different applications of strontium hexaferrite, its magnetic properties can be tuned by a proper substitution of the foreign atoms. Experimental screening for a proper substitution is a cost-intensive and time-consuming process, whereas computationally it can be done more efficiently. We used the 'density functional theory' a first principles based method to study substituted strontium hexaferrite. The site occupancies of the substituted atoms were estimated by calculating the substitution energies of different configurations. The formation probabilities of configurations were used to calculate the magnetic properties of substituted strontium hexaferrite. In the first study, Al-substituted strontium hexaferrite, SrFe12-x AlxO19 with x=0.5 and x=1.0 were investigated. It was found that at the annealing temperature the non-magnetic Al +3 ions preferentially replace Fe+3 ions from the 12 k and 2a sites. We found that the magnetization decreases and the magnetic anisotropy field increases as the fraction, x of the Al atoms increases. In the second study, SrFe12-xGaxO19 and SrFe12-xInxO19 with x=0.5 and x=1.0 were investigated. In the case of SrFe12-xGaxO19, the sites where Ga+3 ions prefer to enter are: 12 k, 2a, and 4f1. For SrFe12-xInxO19, In+3 ions most likely to occupy the 12k, 4f1 , and 4f2 sites. In both cases the magnetization was found to decrease slightly as the fraction of substituted atom increases. The magnetic anisotropy field increased for SrFe12-xGaxO 19, and decreased for SrFe12-xInxO19 as the concentration of substituted atoms increased. In the third study, 23 elements (M) were screened for their possible substitution in strontium hexaferrite, SrFe12-xMxO 19

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  2. Modeling competitive substitution in a polyelectrolyte complex

    SciTech Connect

    Peng, B.; Muthukumar, M.

    2015-12-28

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

  3. Modeling competitive substitution in a polyelectrolyte complex

    NASA Astrophysics Data System (ADS)

    Peng, B.; Muthukumar, M.

    2015-12-01

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

  4. Determinants of generic drug substitution in Switzerland

    PubMed Central

    2011-01-01

    Background Since generic drugs have the same therapeutic effect as the original formulation but at generally lower costs, their use should be more heavily promoted. However, a considerable number of barriers to their wider use have been observed in many countries. The present study examines the influence of patients, physicians and certain characteristics of the generics' market on generic substitution in Switzerland. Methods We used reimbursement claims' data submitted to a large health insurer by insured individuals living in one of Switzerland's three linguistic regions during 2003. All dispensed drugs studied here were substitutable. The outcome (use of a generic or not) was modelled by logistic regression, adjusted for patients' characteristics (gender, age, treatment complexity, substitution groups) and with several variables describing reimbursement incentives (deductible, co-payments) and the generics' market (prices, packaging, co-branded original, number of available generics, etc.). Results The overall generics' substitution rate for 173,212 dispensed prescriptions was 31%, though this varied considerably across cantons. Poor health status (older patients, complex treatments) was associated with lower generic use. Higher rates were associated with higher out-of-pocket costs, greater price differences between the original and the generic, and with the number of generics on the market, while reformulation and repackaging were associated with lower rates. The substitution rate was 13% lower among hospital physicians. The adoption of the prescribing practices of the canton with the highest substitution rate would increase substitution in other cantons to as much as 26%. Conclusions Patient health status explained a part of the reluctance to substitute an original formulation by a generic. Economic incentives were efficient, but with a moderate global effect. The huge interregional differences indicated that prescribing behaviours and beliefs are probably the

  5. Sensory Substitution and Multimodal Mental Imagery.

    PubMed

    Nanay, Bence

    2017-09-01

    Many philosophers use findings about sensory substitution devices in the grand debate about how we should individuate the senses. The big question is this: Is "vision" assisted by (tactile) sensory substitution really vision? Or is it tactile perception? Or some sui generis novel form of perception? My claim is that sensory substitution assisted "vision" is neither vision nor tactile perception, because it is not perception at all. It is mental imagery: visual mental imagery triggered by tactile sensory stimulation. But it is a special form of mental imagery that is triggered by corresponding sensory stimulation in a different sense modality, which I call "multimodal mental imagery."

  6. A guide to biological skin substitutes.

    PubMed

    Jones, I; Currie, L; Martin, R

    2002-04-01

    The role of artificial skin substitutes in burn surgery and the treatment of chronic wounds is constantly evolving. New products are regularly being produced and approved for clinical use. Studies on existing products clarify their efficacy and effectiveness in different clinical scenarios. This review is aimed at busy clinicians in order to bring them up to date with the latest developments in the field of artificial skin substitutes. It examines the components, structure, performance and comparative costs of the main commercial skin substitutes, and reviews briefly technologies under development that have not yet become widely available. Copyright 2002 The British Association of Plastic Surgeons.

  7. A users' guide to understanding therapeutic substitutions.

    PubMed

    Mills, Edward J; Gardner, David; Thorlund, Kristian; Briel, Matthias; Bryan, Stirling; Hutton, Brian; Guyatt, Gordon H

    2014-03-01

    Therapeutic substitutions are common at the level of ministries of health, clinicians, and pharmacy dispensaries. Guidance in determining whether drugs offer similar risk-benefit profiles is limited. Those making decisions on therapeutic substitutions should be aware of potential biases that make differentiating therapeutic agents difficult. Readers should consider whether the biological mechanisms and doses are similar across agents, whether the evidence is sufficiently valid across agents, and whether the safety and therapeutic effects of each drug are similar. This article uses a problem-based format to address the biological mechanism, validity, and results of a scenario in which therapeutic substitutions may be considered.

  8. Sugar and sugar substitutes. Comparisons and indications.

    PubMed

    Alfin-Slater, R B; Pi-Sunyer, F X

    1987-08-01

    Public confusion and concern about the use of sugar and sugar substitutes are widespread. Physicians must be prepared to answer patients' inquiries about these substances. Some population groups should avoid certain sugar substitutes. In particular, pregnant women and young children should avoid saccharin, and phenylketonuric homozygous persons should avoid aspartame. In a varied, balanced diet, the use of aspartame and saccharin is one safe way for the general population to enjoy sweet foods with fewer calories and less cariogenic potential. Sugar substitutes may be helpful in dietary compliance for overweight and diabetic patients.

  9. Oxygen therapeutics: perfluorocarbons and blood substitute safety.

    PubMed

    Cohn, Claudia S; Cushing, Melissa M

    2009-04-01

    Current demands over the blood supply in developed and developing nations will compound over time. Red cell substitutes have a promising value proposition for transfusion services, because they hold the promise of increasing the availability of blood products and removing donor and contamination safety risks. In this article, the authors note that existing products suffer from critical shortcomings such as vasoactivity; they also point out that substitutes not based on human blood introduce potentially more complex safety hurdles. The authors discuss the attributes of an ideal blood substitute, and the mechanism and current status of perfluorocarbons; they also review the shortcomings of all oxygen therapeutic products in development today.

  10. Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

    SciTech Connect

    Ohkawa, Mayumi; Ohno, Yoshiya; Masuko, Kazue; Takeuchi, Akiko; Suda, Kentaro; Kubo, Akihiro; Kawahara, Rieko; Okazaki, Shogo; Tanaka, Toshiyuki; Saya, Hideyuki; Seki, Masayuki; Enomoto, Takemi; Yagi, Hideki; Hashimoto, Yoshiyuki; Masuko, Takashi

    2011-03-25

    Highlights: {yields} We established LAT1 amino-acid transporter-disrupted DT40 cells. {yields} LAT1-disrupted cells showed slow growth and lost the oncogenicity. {yields} siRNA and mAb inhibited human tumor growth in vitro and in vivo. {yields} LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1{sup -/-}) cell clones, derived from a heterozygous LAT1{sup +/-} clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1{sup -/-} DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1{sup -/-} cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1{sup -/-} DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1{sup -/-} DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1{sup +/-} DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.

  11. Enantioselective synthesis of trifluoromethyl-substituted cyclopropanes.

    PubMed

    Denton, Justin R; Sukumaran, Dinesh; Davies, Huw M L

    2007-07-05

    The reaction of 1-aryl-2,2,2-trifluorodiazoethanes with alkenes, catalyzed by the adamantylglycine-derived dirhodium complex Rh2(R-PTAD)4, generates trifluoromethyl-substituted cyclopropanes with high diastereoselectivity (>94%) and enantioselectivity (88->98%).

  12. Stereoselective construction of nitrile-substituted cyclopropanes.

    PubMed

    Denton, Justin R; Cheng, Kevin; Davies, Huw M L

    2008-03-14

    Nitrile-substituted cyclopropanes are readily synthesized in a stereocontrolled fashion from the intermolecular cyclopropanation between 2-diazo-2-phenylacetonitrile and electron-rich olefins, catalyzed by the chiral dirhodium complex, Rh(2)(S-PTAD)(4).

  13. Research of Energy Substitution Strategy of China

    NASA Astrophysics Data System (ADS)

    Zhang, Lifeng; kai, Chen

    For a long time, China's energy endowment structure determines the production structure and consumption structure of energy are coal-based.This situation is difficult to change for quite a long time. With the rapid economic growth, industrialization and urbanization, the demand for energy, especially for oil, natural gas will continue to increase. But the oil and gas supply can not meet the needs of rapid growth. The most direct way is to import, and imports will be charged by the international energy situation, and will affect energy and economic security. In view of our country abundant coal resources, we can consider to use coal substituting oil and natural gas to reduce dependence on foreign energy, to strengthen energy and economic security. Therefore, using translog production function, the text forecasts substitution elasticity and the marginal substitution rate between the capital, coal, oil and natural gas, and puts forward substitution program.

  14. A Neuropsychological Classification of Drug Substitution.

    DTIC Science & Technology

    conditioned responses, were determined. The effects of various dosages of paraldehyde , meprobamate, chloral hydrate, and chlordiazepoxide, upon brain...to determine whether, and at what dosage, paraldehyde , chloral hydrate, meprobamate and chlordiazepoxide can substitute for pentobarbital and

  15. Questioning nuclear waste substitution: a case study.

    PubMed

    Marshall, Alan

    2007-03-01

    This article looks at the ethical quandaries, and their social and political context, which emerge as a result of international nuclear waste substitution. In particular it addresses the dilemmas inherent within the proposed return of nuclear waste owned by Japanese nuclear companies and currently stored in the United Kingdom. The UK company responsible for this waste, British Nuclear Fuels Limited (BNFL), wish to substitute this high volume intermediate-level Japanese-owned radioactive waste for a much lower volume of much more highly radioactive waste. Special focus is given to ethical problems that they, and the UK government, have not wished to address as they move forward with waste substitution. The conclusion is that waste substitution can only be considered an ethical practice if a set of moderating conditions are observed by all parties. These conditions are listed and, as of yet, they are not being observed.

  16. Hyperfine magnetic fields in substituted Finemet alloys

    NASA Astrophysics Data System (ADS)

    Brzózka, K.; Sovák, P.; Szumiata, T.; Gawroński, M.; Górka, B.

    2016-12-01

    Transmission Mössbauer spectroscopy was used to determine the hyperfine fields of Finemet-type alloys in form of ribbons, substituted alternatively by Mn, Ni, Co, Al, Zn, V or Ge of various concentration. The comparative analysis of magnetic hyperfine fields was carried out which enabled to understand the role of added elements in as-quenched as well as annealed samples. Moreover, the influence of the substitution on the mean direction of the local hyperfine magnetic field was examined.

  17. Nutrient-substituted hydroxyapatites: synthesis and characterization.

    PubMed

    Golden, D C; Ming, D W

    1999-01-01

    Incorporation of Mg, S, and plant-essential micronutrients into the structure of synthetic hydroxyapatite (HA) may be advantageous for closed-loop systems, such as will be required on Lunar and Martian outposts, because these apatites can be used as slow-release fertilizers. Our objective was to synthesize HA with Ca, P, Mg, S, Fe, Cu, Mn, Zn, Mo, B, and Cl incorporated into the structure, i.e., nutrient-substituted apatites. Hydroxyapatite, carbonate hydroxyapatite (CHA), nutrient-substituted hydroxyapatite (NHA), and nutrient-substituted carbonate hydroxyapatite (NCHA) were synthesized by precipitating from solution. Chemical and mineralogical analysis of precipitated samples indicated a considerable fraction of the added cations were incorporated into HA, without mineral impurities. Particle size of the HA was in the 1 to 40 nm range, and decreased with increased substitution of nutrient elements. The particle shape of HA was elongated in the c-direction in unsubstituted HA and NHA but more spherical in CHA and NCHA. The substitution of cations and anions in the HA structure was confirmed by the decrease of the d[002] spacing of HA with substitution of ions with an ionic radius less than that of Ca or P. The DTPA-extractable Cu ranged from 8 to 8429 mg kg-1, Zn ranged from 57 to 1279 mg kg-1, Fe from 211 to 2573 mg kg-1, and Mn from 190 to 1719 mg kg-1, depending on the substitution level of each element in HA. Nutrient-substituted HA has the potential to be used as a slow-release fertilizer to supply micronutrients, S, and Mg in addition to Ca and P.

  18. Symbolic Substitution Using Shadow-Casting

    NASA Astrophysics Data System (ADS)

    Xue, Wei; Chen, Li-Xue; Li, Chun-Fei; Hu, Qiang-Sheng

    1989-02-01

    A new optical system for symbolic substitution is proposed. The system is composed of the lensless shadow-casting system combined with optical logical array and optical image storage elements. The LED's (light-emitting diode) are used as both a light source and a control element in the operation, so that symbolic substitution is implemented by all-photoelectric manipulation. Experimental principle, procedure and result are given.

  19. Nutrient-substituted hydroxyapatites: synthesis and characterization

    NASA Technical Reports Server (NTRS)

    Golden, D. C.; Ming, D. W.

    1999-01-01

    Incorporation of Mg, S, and plant-essential micronutrients into the structure of synthetic hydroxyapatite (HA) may be advantageous for closed-loop systems, such as will be required on Lunar and Martian outposts, because these apatites can be used as slow-release fertilizers. Our objective was to synthesize HA with Ca, P, Mg, S, Fe, Cu, Mn, Zn, Mo, B, and Cl incorporated into the structure, i.e., nutrient-substituted apatites. Hydroxyapatite, carbonate hydroxyapatite (CHA), nutrient-substituted hydroxyapatite (NHA), and nutrient-substituted carbonate hydroxyapatite (NCHA) were synthesized by precipitating from solution. Chemical and mineralogical analysis of precipitated samples indicated a considerable fraction of the added cations were incorporated into HA, without mineral impurities. Particle size of the HA was in the 1 to 40 nm range, and decreased with increased substitution of nutrient elements. The particle shape of HA was elongated in the c-direction in unsubstituted HA and NHA but more spherical in CHA and NCHA. The substitution of cations and anions in the HA structure was confirmed by the decrease of the d[002] spacing of HA with substitution of ions with an ionic radius less than that of Ca or P. The DTPA-extractable Cu ranged from 8 to 8429 mg kg-1, Zn ranged from 57 to 1279 mg kg-1, Fe from 211 to 2573 mg kg-1, and Mn from 190 to 1719 mg kg-1, depending on the substitution level of each element in HA. Nutrient-substituted HA has the potential to be used as a slow-release fertilizer to supply micronutrients, S, and Mg in addition to Ca and P.

  20. Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism.

    PubMed

    Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K; McMullan, Daniel; Krishna, S Sri; Miller, Mitchell D; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L; Feuerhelm, Julie; Grant, Joanna C; Grzechnik, Anna; Grzechnik, Slawomir K; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A; Klock, Heath E; Knuth, Mark W; Kozbial, Piotr; Marciano, David; Morse, Andrew T; Murphy, Kevin D; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L; Sefcovic, Natasha; Tien, Henry J; Trame, Christine B; Trout, Christina V; van den Bedem, Henry; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O; Wooley, John; Elsliger, Marc Andre; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Wilson, Ian A

    2010-10-01

    The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis.

  1. Tryptophan Substitutions at Lipid-exposed Positions of the Gamma M3 Transmembrane Domain Increase the Macroscopic Ionic Current Response of the Torpedo californica Nicotinic Acetylcholine Receptor

    PubMed Central

    Cruz-Martín, A.; Mercado, J.L.; Rojas, L.V.; McNamee, M.G.; Lasalde-Dominicci, J.A.

    2015-01-01

    Our previous amino-acid substitutions at the postulated lipid-exposed transmembrane segment M4 of the Torpedo californica acetylcholine receptor (AChR) focused on the alpha subunit. In this study we have extended the mutagenesis analysis using single tryptophan replacements in seven positions (I288, M291, F292, S294, L296, M299 and N300) near the center of the third transmembrane domain of the gamma subunit (γM3). All the tryptophan substitution mutants were expressed in Xenopus laevis oocytes following mRNA injections at levels close to wild type. The functional response of these mutants was evaluated using macroscopic current analysis in voltage-clamped oocytes. For all the substitutions the concentration for half-maximal activation, EC50, is similar to wild type using acetylcholine. For F292W, L296W and M299W the normalized macroscopic responses are 2- to 3-fold higher than for wild type. Previous photolabeling studies demonstrated that these three positions were in contact with membrane lipids. Each of these M3 mutations was co-injected with the previously characterized αC418W mutant to examine possible synergistic effects of single lipid-exposed mutations on two different subunits. For the γM3/αM4 double mutants, the EC50s were similar to those measured for the αC418W mutant alone. Tryptophan substitutions at positions that presumably face the interior of the protein (S294 and M291) or neighboring helices (I288) did not cause significant inhibition of channel function or surface expression of AChRs. PMID:11547353

  2. Triaryl-Substituted Divinyl Ketones Cyclization: Nazarov Reaction versus Friedel-Crafts Electrophilic Substitution.

    PubMed

    Shirinian, Valerii Z; Lvov, Andrey G; Yadykov, Anton V; Yaminova, Liana V; Kachala, Vadim V; Markosyan, Ashot I

    2016-12-16

    The acid-catalyzed cyclization of a wide range of triaryl-substituted divinyl ketones has been studied. It was found that the reaction pathway strongly depends on the nature of the aryl substituent at the α-position to the carbonyl group. An electron-rich aromatic substituent promotes the reaction to proceed through the intramolecular Friedel-Crafts electrophilic substitution giving dihydronaphthalene derivatives. In contrast, the presence of an electron-deficient substituent is favorable for the Nazarov 4π-conrotatory cyclization yielding triaryl-substituted cyclopentenones. The electrophilic substitution reaction was applied to thiophene and thiazole derivatives.

  3. Comparison of Solution and Crystal Properties of Co(II)-Substituted Human Carbonic Anhydrase II

    PubMed Central

    Avvaru, Balendu Sankara; Arenas, Daniel J.; Tu, Chingkuang; Tanner, D. B.; McKenna, Robert; Silverman, David N.

    2010-01-01

    The visible absorption of crystals of Co(II)-substituted human carbonic anhydrase II (Co(II)-HCA II) were measured over a pH range of 6.0 to 11.0 giving an estimate of pKa 8.4 for the ionization of the metal-bound water in the crystal. This is higher by about 1.2 pKa units than the pKa near 7.2 for Co(II)-CA II in solution. This effect is attributed to a nonspecific ionic strength effect of 1.4 M citrate in the precipitant solution used in the crystal growth. A pKa of 8.3 for the aqueous ligand of the cobalt was measured for Co(II)-HCA II in solution containing 0.8 M citrate. Citrate is not an inhibitor of the catalytic activity of Co(II)-HCA II and was not observed in crystal structures. The X-ray structures at 1.5–1.6Å resolution of Co(II)-HCA II were determined for crystals prepared at pH 6.0, 8.5 and 11.0 and revealed no conformational changes of amino-acid side chains as a result of the use of citrate. However, the studies of Co(II)-HCA II did reveal a change in metal coordination from tetrahedral at pH 11 to a coordination consistent with a mixed population of both tetrahedral and penta-coordinate at pH 8.5 to an octahedral geometry characteristic of the oxidized enzyme Co(III)-HCA II at pH 6.0. PMID:20637176

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

    PubMed

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

    2016-06-21

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

  5. 14 CFR § 1260.55 - Reports substitution.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Reports substitution. § 1260.55 Section...

  6. The Substitute Teacher: An Irony in the School Improvement Process.

    ERIC Educational Resources Information Center

    Griswold, Philip A.

    2001-01-01

    Addresses the issue of substitute teacher shortages in Ohio schools. Describes three studies conducted to determine the availability of substitute teachers and the impact of shortages. Poses solutions, including hiring more permanent substitutes, rescheduling teacher meetings to work around substitute availability, and increasing substitute…

  7. A Sequential and Comprehensive Method for Effective Substitute Teaching

    ERIC Educational Resources Information Center

    Byer, John L.

    2008-01-01

    This article dealt with methods for making substitute teaching more effective. The purpose was to articulate a sequential method for maximizing the effectiveness of substitute teaching while providing substitutes with a comprehensive method for diligently and flexibly earning respect and using reflection to continually improve substitute teaching.…

  8. A Qualitative Study of the Perceptions of Substitute Teaching Quality.

    ERIC Educational Resources Information Center

    Cardon, Peter W.

    2002-01-01

    Surveyed Utah teachers, substitute teachers, substitute teacher managers, and principals to examine the perceived quality of substitute teachers, reasons for these perceptions, and potential effects of the perceptions. Substitute teaching was generally assumed to be low quality. Two perceptions driving this assumption were: low pay results in poor…

  9. 40 CFR 721.3063 - Substituted phenyl azo substituted phenyl esters (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... phenyl esters (generic name). 721.3063 Section 721.3063 Protection of Environment ENVIRONMENTAL... esters (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted phenyl azo substituted phenyl esters (PMNs P-95...

  10. 40 CFR 721.3063 - Substituted phenyl azo substituted phenyl esters (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... phenyl esters (generic name). 721.3063 Section 721.3063 Protection of Environment ENVIRONMENTAL... esters (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted phenyl azo substituted phenyl esters (PMNs P-95...

  11. 40 CFR 721.3063 - Substituted phenyl azo substituted phenyl esters (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3063 Substituted phenyl azo substituted phenyl esters (generic name). Link to an amendment published at 79 FR 34637, June 18, 2014. (a)...

  12. 40 CFR 721.3063 - Substituted phenyl azo substituted phenyl esters (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... phenyl esters (generic name). 721.3063 Section 721.3063 Protection of Environment ENVIRONMENTAL... esters (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted phenyl azo substituted phenyl esters (PMNs...

  13. 40 CFR 721.3063 - Substituted phenyl azo substituted phenyl esters (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... phenyl esters (generic name). 721.3063 Section 721.3063 Protection of Environment ENVIRONMENTAL... esters (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as substituted phenyl azo substituted phenyl esters (PMNs...

  14. Substitutes with Significance: Increasing the Impact of Substitute Teachers in Special Education.

    ERIC Educational Resources Information Center

    Welsch, Richard G.

    2001-01-01

    This article suggests ways to develop effective substitute special education teacher programs. Suggestions are framed around the Standards for Staff Development created by the National Staff Development Council. Detailed recommendations on substitute training and support systems stress the need to address appropriate context, process, and content.…

  15. Optimal ordering quantities for substitutable deteriorating items under joint replenishment with cost of substitution

    NASA Astrophysics Data System (ADS)

    Mishra, Vinod Kumar

    2017-03-01

    In this paper we develop an inventory model, to determine the optimal ordering quantities, for a set of two substitutable deteriorating items. In this inventory model the inventory level of both items depleted due to demands and deterioration and when an item is out of stock, its demands are partially fulfilled by the other item and all unsatisfied demand is lost. Each substituted item incurs a cost of substitution and the demands and deterioration is considered to be deterministic and constant. Items are order jointly in each ordering cycle, to take the advantages of joint replenishment. The problem is formulated and a solution procedure is developed to determine the optimal ordering quantities that minimize the total inventory cost. We provide an extensive numerical and sensitivity analysis to illustrate the effect of different parameter on the model. The key observation on the basis of numerical analysis, there is substantial improvement in the optimal total cost of the inventory model with substitution over without substitution.

  16. Optimal ordering quantities for substitutable deteriorating items under joint replenishment with cost of substitution

    NASA Astrophysics Data System (ADS)

    Mishra, Vinod Kumar

    2017-03-01

    In this paper we develop an inventory model, to determine the optimal ordering quantities, for a set of two substitutable deteriorating items. In this inventory model the inventory level of both items depleted due to demands and deterioration and when an item is out of stock, its demands are partially fulfilled by the other item and all unsatisfied demand is lost. Each substituted item incurs a cost of substitution and the demands and deterioration is considered to be deterministic and constant. Items are order jointly in each ordering cycle, to take the advantages of joint replenishment. The problem is formulated and a solution procedure is developed to determine the optimal ordering quantities that minimize the total inventory cost. We provide an extensive numerical and sensitivity analysis to illustrate the effect of different parameter on the model. The key observation on the basis of numerical analysis, there is substantial improvement in the optimal total cost of the inventory model with substitution over without substitution.

  17. Substituting telecommunications for travel - Feasible or desirable

    NASA Technical Reports Server (NTRS)

    Van Vleck, E. M.

    1974-01-01

    This paper reviews recent advances in telecommunications and examines the detailed structure of travel to estimate the feasibility of substituting telecommunications for various travel objectives. The impact of travel is analyzed from a social, economic, energy, and pollution standpoint to assess the desirability of substitution. Perhaps 35-50% of the nation's travel could, in theory, be replaced by very advanced telecommunications (such as a much improved large-screen teleconferencing network), but public resistance would be massive. Much economic dislocation would result since, for example, over 25% of retail sales are travel-related. The energy savings would be modest since only 25% of the nation's energy is consumed by transportation. However, all pollution would be reduced substantially since transportation accounts for 75% of the carbon monoxide, 60% of the hydrocarbon, and 55% of the nitrogen oxide pollution in the nation. Problems related to the implementation of large-scale substitution are discussed.

  18. Vitreous Substitutes: The Present and the Future

    PubMed Central

    Caprani, Simona Maria; Airaghi, Giulia; Bartalena, Luigi; Testa, Francesco; Mariotti, Cesare; Porta, Giovanni; Simonelli, Francesca

    2014-01-01

    Vitreoretinal surgery has advanced in numerous directions during recent years. The removal of the vitreous body is one of the main characteristics of this surgical procedure. Several molecules have been tested in the past to fill the vitreous cavity and to mimic its functions. We here review the currently available vitreous substitutes, focusing on their molecular properties and functions, together with their adverse effects. Afterwards we describe the characteristics of the ideal vitreous substitute. The challenges facing every ophthalmology researcher are to reach a long-term intraocular permanence of vitreous substitute with total inertness of the molecule injected and the control of inflammatory reactions. We report new polymers with gelification characteristics and smart hydrogels representing the future of vitreoretinal surgery. Finally, we describe the current studies on vitreous regeneration and cell cultures to create new intraocular gels with optimal biocompatibility and rheological properties. PMID:24877085

  19. Breast milk substitutes in Hong Kong.

    PubMed

    Nelson, E A S; Chan, C W; Yu, C M

    2004-07-01

    In 1981 the World Health Assembly (WHA) adopted the International Code of Marketing of Breast Milk Substitutes (the Code) to support breastfeeding. Despite improving trends, Hong Kong has low rates of breastfeeding compared to other developed countries. We surveyed companies marketing breast milk substitutes in Hong Kong to determine self-reported adherence to the Code. Companies were informed that individual responses would not be published and seven of nine companies responded to the questionnaire. The majority of respondents promoted infant and follow-on formula in hospitals and provided free supplies of infant formula to hospitals. Follow-on formula and weaning foods were promoted in shops and to the general public and free samples were given to mothers reflecting a belief that, despite WHA resolutions, follow-on formula is not a breast milk substitute. Transnational companies should follow the Code and subsequent WHA resolutions equally in all countries.

  20. Predicting regioselectivity in nucleophilic aromatic substitution.

    PubMed

    Liljenberg, Magnus; Brinck, Tore; Herschend, Björn; Rein, Tobias; Tomasi, Simone; Svensson, Mats

    2012-04-06

    We have investigated practical and computationally efficient methods for the quantitative prediction of regioisomer distribution in kinetically controlled nucleophilic aromatic substitution reactions. One of the methods is based on calculating the relative stabilities of the isomeric σ-complex intermediates using DFT. We show that predictions from this method can be used quantitatively both for anionic nucleophiles with F(-) as leaving group, as well as for neutral nucleophiles with HF as leaving group. The σ-complex approach failed when the leaving group was Cl/HCl or Br/HBr, both for anionic and neutral nucleophiles, because of difficulties in finding relevant σ-complex structures. An approach where we assumed a concerted substitution step and used such transition state structures gave quantitatively useful results. Our results are consistent with other theoretical works, where a stable σ-complex has been identified in some cases, whereas others have been indicated to proceed via a concerted substitution step.

  1. Substituting telecommunications for travel - Feasible or desirable

    NASA Technical Reports Server (NTRS)

    Van Vleck, E. M.

    1974-01-01

    This paper reviews recent advances in telecommunications and examines the detailed structure of travel to estimate the feasibility of substituting telecommunications for various travel objectives. The impact of travel is analyzed from a social, economic, energy, and pollution standpoint to assess the desirability of substitution. Perhaps 35-50% of the nation's travel could, in theory, be replaced by very advanced telecommunications (such as a much improved large-screen teleconferencing network), but public resistance would be massive. Much economic dislocation would result since, for example, over 25% of retail sales are travel-related. The energy savings would be modest since only 25% of the nation's energy is consumed by transportation. However, all pollution would be reduced substantially since transportation accounts for 75% of the carbon monoxide, 60% of the hydrocarbon, and 55% of the nitrogen oxide pollution in the nation. Problems related to the implementation of large-scale substitution are discussed.

  2. Biomaterials in search of a meniscus substitute.

    PubMed

    Rongen, Jan J; van Tienen, Tony G; van Bochove, Bas; Grijpma, Dirk W; Buma, Pieter

    2014-04-01

    The menisci fulfill key biomechanical functions in the tibiofemoral (knee) joint. Unfortunately meniscal injuries are quite common and most often treated by (partial) meniscectomy. However, some patients experience enduring symptoms, and, more importantly, it leads to an increased risk for symptomatic osteoarthritis. Over the past decades, researchers have put effort in developing a meniscal substitute able to prevent osteoarthritis and treat enduring clinical symptoms. Grossly, two categories of substitutes are observed: First, a resorbable scaffold mimicking biomechanical function which slowly degrades while tissue regeneration and organization is promoted. Second, a non resorbable, permanent implant which mimics the biomechanical function of the native meniscus. Numerous biomaterials with different (material) properties have been used in order to provide such a substitute. Nevertheless, a clinically applicable cartilage protecting material is not yet emerged. In the current review we provide an overview, and discuss, these different materials and extract recommendations regarding material properties for future developmental research.

  3. Nonlinear self-adjointness through differential substitutions

    NASA Astrophysics Data System (ADS)

    Gandarias, M. L.

    2014-10-01

    It is known (Ibragimov, 2011; Galiakberova and Ibragimov, 2013) [14,18] that the property of nonlinear self-adjointness allows to associate conservation laws of the equations under study, with their symmetries. In this paper we show that, even when the equation is nonlinearly self-adjoint with a non differential substitution, finding the explicit form of the differential substitution can provide new conservation laws associated to its symmetries. By using the general theorem on conservation laws (Ibragimov, 2007) [11] and the property of nonlinear self-adjointness we find some new conservation laws for the modified Harry-Dym equation. By using a differential substitution we construct a conservation law for the Harry-Dym equation, which has not been derived before using Ibragimov method.

  4. A simple sterile polypropylene fingernail substitute.

    PubMed

    Tos, P; Artiaco, S; Coppolino, S; Conforti, L G; Battiston, B

    2009-06-01

    Traumatic nail injuries are often observed in clinical practice. Usually the fingernail can be preserved, cleaned and disinfected in order to use it in the reconstructive procedure. However, in some cases the nail can be avulsed and lost or too damaged to be used. In cases when the nail is not available it should be replaced by a substitute in order to protect nail bed and avoid adherences along the proximal nail bed and the nail fold. Furthermore the substitute serves to protect the tender nail bed from painful stimuli during the healing process. We used, as fingernail substitute, a polypropylene sheet in eight patients with fingernail avulsion or disruption. The polypropylene foil was trimmed reproducing the profile of the avulsed fingernail and thinned at the proximal edge to reduce thickness in order to ease the insertion into the nail fold. A small hole was then created in the center of the foil to allow blood drainage. The substitute was usually removed one month after the application. In our clinical experience we had not complications related to the polypropylene device. The new fingernail had good cosmetic appearance in most cases and all the patients reported a good protection of the fingertip during the healing period. The substitute used in this series is sterile, inexpensive and easily available in emergency and elective operatory theater. This polypropylene foil is flexible and can be shaped and adapted to the nail curvature radius. The substitute used in our clinical series protected the nail bed during healing until the growth of the new fingernail and respected our functional expectations.

  5. [Substitution therapy tested against amphetamine dependence].

    PubMed

    Bloniecki Kallio, Victor; Guterstam, Joar; Franck, Johan

    2016-01-06

    Amphetamine dependence is relatively common in Sweden and it is the most frequently used substance among patients with intravenous drug abuse. Current treatment options are limited but recently substitution therapy with psychostimulant medication has been evaluated in several clinical trials. Such treatment is controversial in Sweden, perhaps due to the failure of experimental prescription of psychostimulants in the 1960s. Recent clinical trials however indicate that structured treatment programs with psychostimulants might have positive effects, although the results are inconsistent and the evidence base is still limited. Future research is needed in order to determine the potential role of substitution therapy for amphetamine dependence in clinical practice.

  6. Generic Substitution Issues: Brand-generic Substitution, Generic-generic Substitution, and Generic Substitution of Narrow Therapeutic Index (NTI)/Critical Dose Drugs

    PubMed Central

    PAVELIU, Marian Sorin; BENGEA, Simona; PAVELIU, Fraga Silvia

    2011-01-01

    ABSTRACT Doctors accuse individual variability or lack of quality of generic drugs for adverse reactions or lack of efficacy. The variability of effect of generic substitution, although accepted by clinicians as possible, is little discussed or even understood by them. The situation is really serious in the case of generic substitution of drugs with narrow therapeutic index (NTI) or critical dose. In this paper we review the basic notions of variability and effectiveness of generic medication and change of attitude that would improve the use of these drugs. PMID:21977191

  7. Soluble N-Substituted Organosilane Polybenzimidazoles

    SciTech Connect

    Klaehn, J. R.; Luther, T. A.; Orme, C. J.; Jones, M. G.; Wertsching, A. K.; Peterson, E. S.

    2007-10-01

    Six organosilane derivatives were synthesized, and are more soluble in common organic solvents (tetrahydrofuran and chloroform) than the parent polybenzimidazole. Our polymer modification pathway provides a straightforward synthesis that can be carried out at room temperature and give reasonable yields. Solution 1H NMR spectra of both the parent and deprotonated polybenzimidazoles are reported. Based upon the NMR analysis in CDCl3, nearly all of the benzimidazole N-H positions are substituted by the organosilane moieties. Some of the modified polymers have similar thermal properties compared to the parent polymer, and the average molecular weights are higher for the substituted polybenzimidazoles than the parent PBI.

  8. [Sugar substitutes in the diabetic diet].

    PubMed

    Mehnert, H

    1976-01-01

    The decreased glucsoe utilization in diabetes mellitus justifies the use of sugar substitutes ("diabetic sugar") if two conditions are fulfilled: 1)The sugar substitute should be a carbohydrate which does not lead, or only to a slight degree, to hyperglycaemia and thus, in this respect, differs distinctly from sugars such as glucose and saccharose. 2) The sugar substitute must not cause undesired side-effects. The absorption, utilization and side-effects of the sugar substitutes fructose, sorbitol and xylitol were investigated. They were found to be more slowly absorbed than glucose and thus to offer the advantage of better utilization under conditions of limited insulin production. However, the particularly slow passive absorption of sorbitol and xylitol can sometimes be a disadvantage, since osmotic diarrhoea may occur after administration of high oral doses. The sugar substitutes enter the metabolism enzymatically and are utilized mainly in the liver. The peripheral state was investigated after intravenous, intraduodenal and oral administration of glucose and fructose to healthy subjects. Liver metabolism was examined (Dietze) by comparing hepatic venous and arterial concentrations after intravenous administration of the sugars. Also, diabetic patients received glucose and fructose orally. As previously demonstrated, the investigations using several techniques showed a smaller influence on blood glucose and serum insulin concentrations after administration of fructose, sorbitol and xylitol than after glucose. If no metabolic changes occur after intravenous administration of high doses, no such changes need be expected after oral administration of small doses. Nor did measurements in hepatic venous blood (Dietze) show any marked effect of fructose on the blood glucose level. The healthy subjects showed no significant changes in blood glucose or serum insulin concentration after either intraduodenal or oral administration of fructose, whereas they showed a

  9. Hydrophosphorylation of substituted alkynes by phosphonic acids

    SciTech Connect

    Nifant'ev, E.F.; Solovetskaya, L.A.; Maslennikova, V.I.; Sergeev, N.M.

    1987-08-20

    Hydrophosphorylation of functionally substituted alkynes by phosphonic acids can be a convenient method for synthesis of functionally substituted mono- and diphosphine oxides. The ease of hydrophosphorylation is determined by the strength of the negative inductive effect of the substituents on the triple bond and the steric factor. The structure of the bis-adducts was confirmed by elementary analysis and the /sup 31/P and /sup 13/C NMR spectra. The /sup 31/P NMR spectrum is an AB two-spin system. The values of the chemical shifts and spin-spin interaction constants /sup 3/J/sub PP/ are in agreement with the data in the literature for similar compounds.

  10. Substituting freshwater: Can ocean desalination and water recycling capacities substitute for groundwater depletion in California?

    PubMed

    Badiuzzaman, Pierre; McLaughlin, Eoin; McCauley, Darren

    2017-12-01

    While the sustainability of resource depletion is a longstanding environmental concern, wider attention has recently been given to growing water scarcity and groundwater depletion. This study seeks to test the substitutability assumption embedded in weak sustainability indicators using a case study of Californian water supply. The volume of groundwater depletion is used as a proxy for unsustainable water consumption, and defined by synthesising existing research estimates into low, medium and high depletion baselines. These are compared against projected water supply increases from ocean desalination and water recycling by 2035, to determine whether new, drought-proof water sources can substitute for currently unsustainable groundwater consumption. Results show that the maximum projected supply of new water, 2.47 million acre-feet per year (MAF/yr), is sufficient to meet low depletion estimates of 2.02 MAF/yr, but fails to come near the high depletion estimate of 3.44 MAF/yr. This does not necessarily indicate physical limitations of substitutability, but more so socio-economic limitations influenced by high comparative costs. By including capacities in demand-substitutability via urban water conservation, maximum predicted capacities reach 5.57 MAF/yr, indicating wide room for substitution. Based on these results, investment in social and institutional capital is an important factor to enhance demand-side substitutability of water and other natural resources, which has been somewhat neglected by the literature on the substitutability of natural resources. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 21 CFR 882.5910 - Dura substitute.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dura substitute. 882.5910 Section 882.5910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... surrounding the brain). (b) Classification. Class II (performance standards). ...

  12. 21 CFR 882.5910 - Dura substitute.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dura substitute. 882.5910 Section 882.5910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... surrounding the brain). (b) Classification. Class II (performance standards). ...

  13. 21 CFR 882.5910 - Dura substitute.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dura substitute. 882.5910 Section 882.5910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... surrounding the brain). (b) Classification. Class II (performance standards). ...

  14. 21 CFR 882.5910 - Dura substitute.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dura substitute. 882.5910 Section 882.5910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... surrounding the brain). (b) Classification. Class II (performance standards). ...

  15. 21 CFR 882.5910 - Dura substitute.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dura substitute. 882.5910 Section 882.5910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... surrounding the brain). (b) Classification. Class II (performance standards). ...

  16. Capillary Electrophoresis of Substituted Benzoic Acids

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  17. Antitrypanosomal Activities of Fluoroquinolones with Pyrrolidinyl Substitutions

    PubMed Central

    Nenortas, Elizabeth; Kulikowicz, Tomasz; Burri, Christian; Shapiro, Theresa A.

    2003-01-01

    Fluoroquinolones with pyrrolidinyl substitutions were tested against Trypanosoma brucei and mammalian cells. Bulky substituents at C-7 or a 1-2-bridging thiazolidine ring increased antitrypanosomal activity and selective toxicity. These compounds trap protein-DNA complexes and inhibit nucleic acid biosynthesis in trypanosomes, characteristics of topoisomerase II inhibition. PMID:12937017

  18. Law of substitution for mixed arrays

    SciTech Connect

    Koudelka, A.J.

    1987-01-01

    The nuclear safety justification of a mixed array of dissimilar fissile units of metal units and dilute solution units, according to Clayton, has been a persistent and nagging problem. Dissimilar uranium metal or dissimilar uranium solution units in a mixed array can also create a modeling nightmare for the nuclear criticality safety engineer. Now, a calculational method known as the Law of Substitution has been developed to ensure that the k/sub eff/ of an array of uranium metal and uranium solution units will satisfy any k/sub eff/ limit set by the nuclear safety engineer. The nuclear criticality safety engineer can utilize the Law of Substitution to safely mix or substitute different uranium metal units, different uranium solution units, and more importantly, uranium metal and dilute UO/sub 2/ solution units in an array. The Law of Substitution is as follows: (1) calculate the k/sub eff/ of each unit type in its own infinite planar array. (2) Determine the edge-to-edge spacing of the infinite planar array of each type of unit to satisfy a desired k/sub eff/. (3) Select the largest edge-to-edge spacing from among the similar units in their infinite planar arrays and use that spacing for the finite or infinite planar array of mixed units.

  19. Multisensory perceptual learning and sensory substitution.

    PubMed

    Proulx, Michael J; Brown, David J; Pasqualotto, Achille; Meijer, Peter

    2014-04-01

    One of the most exciting recent findings in neuroscience has been the capacity for neural plasticity in adult humans and animals. Studies of perceptual learning have provided key insights into the mechanisms of neural plasticity and the changes in functional neuroanatomy that it affords. Key questions in this field of research concern how practice of a task leads to specific or general improvement. Although much of this work has been carried out with a focus on a single sensory modality, primarily visual, there is increasing interest in multisensory perceptual learning. Here we will examine how advances in perceptual learning research both inform and can be informed by the development and advancement of sensory substitution devices for blind persons. To allow 'sight' to occur in the absence of visual input through the eyes, visual information can be transformed by a sensory substitution device into a representation that can be processed as sound or touch, and thus give one the potential to 'see' through the ears or tongue. Investigations of auditory, visual and multisensory perceptual learning can have key benefits for the advancement of sensory substitution, and the study of sensory deprivation and sensory substitution likewise will further the understanding of perceptual learning in general and the reverse hierarchy theory in particular. It also has significant importance for the developing understanding of the brain in metamodal terms, where functional brain areas might be best defined by the computations they carry out rather than by their sensory-specific processing role. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Implicit Semantic Perception in Object Substitution Masking

    ERIC Educational Resources Information Center

    Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

    2011-01-01

    Decades of research on visual perception has uncovered many phenomena, such as binocular rivalry, backward masking, and the attentional blink, that reflect "failures of consciousness". Although stimuli do not reach awareness in these paradigms, there is evidence that they nevertheless undergo semantic processing. Object substitution masking (OSM),…

  1. The Energy of Substituted Ethanes. Asymmetry Orbitals

    PubMed Central

    Salem, Lionel; Hoffmann, Roald; Otto, Peter

    1973-01-01

    The leading terms in the energy of a general substituted ethane are derived in explicit form as a function of the torsional angle θ, the substituent electronegativities, and their mutual overlaps. The energy is found to be the sum of all four overlaps between pairs of asymmetry orbitals, and satisfies the requisite symmetry properties. PMID:16592060

  2. Polycyclic Aromatic Triptycenes: Oxygen Substitution Cyclization Strategies

    PubMed Central

    VanVeller, Brett; Schipper, Derek J.; Swager, Timothy M.

    2012-01-01

    The cyclization and planarization of polycyclic aromatic hydrocarbons with concomitant oxygen substitution was achieved through acid catalyzed transetherification and oxygen-radical reactions. The triptycene scaffold enforces proximity of the alcohol and arene reacting partners and confers significant rigidity to the resulting π system, expanding the tool set of iptycenes for materials applications. PMID:22510100

  3. 29 CFR 500.216 - Substituted service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS MIGRANT AND SEASONAL AGRICULTURAL WORKER PROTECTION Administrative Proceedings Procedures Relating to Substituted..., either to the Administrator of the Wage and Hour Division in Washington, DC, or to the...

  4. Capillary Electrophoresis of Substituted Benzoic Acids

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  5. 24 CFR 203.258 - Substitute mortgagors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Substitute mortgagors. 203.258 Section 203.258 Housing and Urban Development Regulations Relating to Housing and Urban...

  6. 24 CFR 203.258 - Substitute mortgagors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Substitute mortgagors. 203.258 Section 203.258 Housing and Urban Development Regulations Relating to Housing and Urban...

  7. 24 CFR 203.258 - Substitute mortgagors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Substitute mortgagors. 203.258 Section 203.258 Housing and Urban Development Regulations Relating to Housing and Urban...

  8. 24 CFR 203.258 - Substitute mortgagors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Substitute mortgagors. 203.258 Section 203.258 Housing and Urban Development Regulations Relating to Housing and Urban...

  9. 24 CFR 203.258 - Substitute mortgagors.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Substitute mortgagors. 203.258 Section 203.258 Housing and Urban Development Regulations Relating to Housing and Urban...

  10. Substitute fluid examinations for liquid manure

    NASA Astrophysics Data System (ADS)

    Schrader, Kevin; Riedel, Marco; Eichert, Helmut

    For the farming industry it is essential to use liquid manure as natural fertilizer. Through new agricultural regulation 2015 in Germany the industry must develop new liquid manure spreader systems because the ammonia and methane emission are limited. In a research project the University of Applied Sciences Zwickau and some other industry partners will develop such a new innovative liquid manure spreader. The new liquid manure spreader should use pulsating air to distribute the liquid manure exactly. The pulsating air, which flows through the pipelines, should be analysed at a test station. For examinations at this test station it is important to find another substitute fluid because liquid manure smells strong, is not transparent and is also not homogeneous enough for scientific investigations. Furthermore it is important to ensure that the substitute fluid is, like liquid manure, a non-Newtonian fluid. The substitute fluid must be a shear-thinning substance - this means the viscosity decrease at higher shear rate. Many different samples like soap-water-farragoes, jelly-water-farragoes, agar-water-farragoes, soap-ethanol-farragoes and more are, for the project, examined in regard of their physical properties to find the best substitute fluid. The samples are examined at the rotational viscometer for viscosity at various shear rates and then compared with the viscosity values of liquid manure.

  11. 24 CFR 220.253 - Substitute mortgagors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT AREAS... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Substitute mortgagors. 220.253 Section 220.253 Housing and Urban Development Regulations Relating to Housing and Urban...

  12. 24 CFR 220.253 - Substitute mortgagors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT AREAS... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Substitute mortgagors. 220.253 Section 220.253 Housing and Urban Development Regulations Relating to Housing and Urban...

  13. 24 CFR 220.253 - Substitute mortgagors.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT AREAS... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Substitute mortgagors. 220.253 Section 220.253 Housing and Urban Development Regulations Relating to Housing and Urban...

  14. 24 CFR 220.253 - Substitute mortgagors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT AREAS... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Substitute mortgagors. 220.253 Section 220.253 Housing and Urban Development Regulations Relating to Housing and Urban...

  15. 24 CFR 220.253 - Substitute mortgagors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT AREAS... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Substitute mortgagors. 220.253 Section 220.253 Housing and Urban Development Regulations Relating to Housing and Urban...

  16. 40 CFR 721.1568 - Substituted benzenediazonium.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1568 Substituted benzenediazonium. Link to an amendment published at 79 FR 34636, June 18, 2014. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical...

  17. Substitute fluid examinations for liquid manure

    NASA Astrophysics Data System (ADS)

    Schrader, Kevin; Riedel, Marco; Eichert, Helmut

    2016-11-01

    For the farming industry it is essential to use liquid manure as natural fertilizer. Through new agricultural regulation 2015 in Germany the industry must develop new liquid manure spreader systems because the ammonia and methane emission are limited. In a research project the University of Applied Sciences Zwickau and some other industry partners will develop such a new innovative liquid manure spreader. The new liquid manure spreader should use pulsating air to distribute the liquid manure exactly. The pulsating air, which flows through the pipelines, should be analysed at a test station. For examinations at this test station it is important to find another substitute fluid because liquid manure smells strong, is not transparent and is also not homogeneous enough for scientific investigations. Furthermore it is important to ensure that the substitute fluid is, like liquid manure, a non-Newtonian fluid. The substitute fluid must be a shear-thinning substance - this means the viscosity decrease at higher shear rate. Many different samples like soap-water-farragoes, jelly-water-farragoes, agar-water-farragoes, soap-ethanol-farragoes and more are, for the project, examined in regard of their physical properties to find the best substitute fluid. The samples are examined at the rotational viscometer for viscosity at various shear rates and then compared with the viscosity values of liquid manure.

  18. Coal as a Substitute for Carbon Black

    NASA Technical Reports Server (NTRS)

    Kushida, R. O.

    1982-01-01

    New proposal shows sprayed coal powder formed by extrusion of coal heated to plastic state may be inexpensive substitute for carbon black. Carbon black is used extensively in rubber industry as reinforcing agent in such articles as tires and hoses. It is made from natural gas and petroleum, both of which are in short supply.

  19. Formation enthalpies of peroxy-substituted silanes

    NASA Astrophysics Data System (ADS)

    Dibrivnyi, V. N.; Pavlovskii, Yu. P.; van-Chin-Syan, Yu. Ya.

    2010-05-01

    Enthalpies of combustion and formation of four peroxy-substituted silanes containing one or several peroxide groups bonded directly to the silicon atom were determined experimentally. The [O-(Si)(O)] group contribution and the correction for the pair interaction of peroxide groups were determined.

  20. Haemorrhage associated with silastic dural substitute.

    PubMed Central

    Thompson, D; Taylor, W; Hayward, R

    1994-01-01

    Three cases of haemorrhage after the use of a silastic dural substitute are presented. In all cases the implant was removed and further haemorrhage has not occurred. Published work is reviewed and the implications for the continued use of silastic are discussed. Images PMID:8201348

  1. Syntheses of novel substituted-boranophosphate nucleosides.

    PubMed

    Vyakaranam, Kamesh; Rana, Geeta; Spielvogel, Bernard F; Maguire, John A; Hosmane, Narayan S

    2002-01-01

    A number of substituted (borano) nucleic acids, 3'-[diethylphosphite(cyano, carboxy, or carbamoyl) borano] deoxynucleosides (3a-4c) and 5'-[diethylphosphite(cyano or carboxy) borano] deoxynucleosides (6a-7d) were prepared by a variety of synthetic procedures. The syntheses of the pyrophosphates (2a-2c), as precursors for 3a-4c, are also described.

  2. Palladium-catalyzed substitution of allylic fluorides.

    PubMed

    Hazari, Amaruka; Gouverneur, Véronique; Brown, John M

    2009-01-01

    As unusual substrates for the Tsuji-Trost allylation reaction, allylic fluorides are responsive to palladium-catalyzed substitution. Their activity towards this reaction fits in the series OCO(2)Me>OBz>F>OAc. The classic stereoretention mechanism that involves sequential inversions does not operate in this case. Several distinct cases are considered.

  3. 40 CFR 192.42 - Substitute provisions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Substitute provisions. 192.42 Section 192.42 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS HEALTH AND ENVIRONMENTAL PROTECTION STANDARDS FOR URANIUM AND THORIUM MILL TAILINGS Standards...

  4. 40 CFR 192.42 - Substitute provisions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Substitute provisions. 192.42 Section 192.42 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS HEALTH AND ENVIRONMENTAL PROTECTION STANDARDS FOR URANIUM AND THORIUM MILL TAILINGS Standards...

  5. 40 CFR 192.42 - Substitute provisions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Substitute provisions. 192.42 Section 192.42 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS HEALTH AND ENVIRONMENTAL PROTECTION STANDARDS FOR URANIUM AND THORIUM MILL TAILINGS Standards...

  6. 40 CFR 192.42 - Substitute provisions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Substitute provisions. 192.42 Section 192.42 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS HEALTH AND ENVIRONMENTAL PROTECTION STANDARDS FOR URANIUM AND THORIUM MILL TAILINGS Standards...

  7. Substitute or Complement?: Spousal Influence on Volunteering

    ERIC Educational Resources Information Center

    Rotolo, Thomas; Wilson, John

    2006-01-01

    Social scientists have documented the influence of family statuses on volunteering, ignoring intrafamily effects. Using newly issued data from the Current Population Survey on the volunteer behavior of 19,626 American couples, we test two competing theories concerning spousal influences on volunteering. Substitution theory predicts that spouses…

  8. 19 CFR 191.32 - Substitution drawback.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... provisions of the manufacturing drawback law, on the commercially interchangeable substituted merchandise is..., and liabilities of the predecessor; or (ii) The assets and other business interests of a division... drawback rights, whether vested or contingent. (3) Certifications and required evidence—(i) Records...

  9. Coal as a Substitute for Carbon Black

    NASA Technical Reports Server (NTRS)

    Kushida, R. O.

    1982-01-01

    New proposal shows sprayed coal powder formed by extrusion of coal heated to plastic state may be inexpensive substitute for carbon black. Carbon black is used extensively in rubber industry as reinforcing agent in such articles as tires and hoses. It is made from natural gas and petroleum, both of which are in short supply.

  10. Automated Substitute Notification: Technology Improves Sub Dispatching.

    ERIC Educational Resources Information Center

    Bernasconi, Chuck

    2000-01-01

    Information technology has automated the process of substitute teacher dispatching. This article describes such automated systems, examining the advantages of using the Internet for automated staffing. It concludes that for districts that take advantage of this new technology, using the Internet can make automating absence reporting and substitute…

  11. Five Strategies to Enhance Your Substitute Teaching

    ERIC Educational Resources Information Center

    Gresham, Jeanie; Donihoo, John; Cox, Tanisha

    2008-01-01

    Skillful substitute teachers are critical to student achievement, especially in today's high-stakes accountability environment. Because teachers are absent from duty, some for short periods of time and others for lengthy time frames, schools may find it difficult to meet high academic and accountability standards without prepared substitute…

  12. 5 Strategies to Enhance Your Substitute Teaching

    ERIC Educational Resources Information Center

    Gresham, Jeanie; Donihoo, John; Cox, Tanisha

    2007-01-01

    Skillful substitute teachers are critical to student achievement, especially in today's high-stakes accountability environment. Because teachers are absent from duty, some for short periods of time and others for lengthy time frames, schools may find it difficult to meet high academic and accountability standards without prepared substitute…

  13. Are substitution rates and RNA editing correlated?

    PubMed Central

    2010-01-01

    Background RNA editing is a post-transcriptional process that, in seed plants, involves a cytosine to uracil change in messenger RNA, causing the translated protein to differ from that predicted by the DNA sequence. RNA editing occurs extensively in plant mitochondria, but large differences in editing frequencies are found in some groups. The underlying processes responsible for the distribution of edited sites are largely unknown, but gene function, substitution rate, and gene conversion have been proposed to influence editing frequencies. Results We studied five mitochondrial genes in the monocot order Alismatales, all showing marked differences in editing frequencies among taxa. A general tendency to lose edited sites was observed in all taxa, but this tendency was particularly strong in two clades, with most of the edited sites lost in parallel in two different areas of the phylogeny. This pattern is observed in at least four of the five genes analyzed. Except in the groups that show an unusually low editing frequency, the rate of C-to-T changes in edited sites was not significantly higher that in non-edited 3rd codon positions. This may indicate that selection is not actively removing edited sites in nine of the 12 families of the core Alismatales. In all genes but ccmB, a significant correlation was found between frequency of change in edited sites and synonymous substitution rate. In general, taxa with higher substitution rates tend to have fewer edited sites, as indicated by the phylogenetically independent correlation analyses. The elimination of edited sites in groups that lack or have reduced levels of editing could be a result of gene conversion involving a cDNA copy (retroprocessing). If so, this phenomenon could be relatively common in the Alismatales, and may have affected some groups recurrently. Indirect evidence of retroprocessing without a necessary correlation with substitution rate was found mostly in families Alismataceae and Hydrocharitaceae

  14. Clarifying substituted judgement: the endorsed life approach.

    PubMed

    Phillips, John; Wendler, David

    2015-09-01

    A primary goal of clinical practice is to respect patient autonomy. To promote this goal for patients who have lost the ability to make their own decisions, commentators recommend that surrogates make their treatment decisions based on the substituted judgment standard. This standard is commonly interpreted as directing surrogates to make the decision the patient would have made in the circumstances, if the patient were competent. However, recent commentators have argued that this approach--attempting to make the decision the patient would have made if competent--is theoretically problematic, practically infeasible, and ignores the interests of the patient's family and loved ones. These commentators conclude that the substituted judgment standard should be revised significantly, or abandoned altogether. While this response would avoid the cited problems, it also would require substantial changes to clinical practice and would raise significant problems of its own. The present paper thus considers the possibility that the criticisms do not point to problems with the substituted judgment standard itself; instead, they point to problems with the way it is most commonly interpreted. This analysis suggests that the substituted judgment standard need not be dramatically revised or abandoned. Instead, it should be interpreted in a way that effectively promotes respect for the autonomy of incompetent patients. The 'endorsed life' interpretation described here helps clinicians and surrogates to achieve this important goal. To clarify this approach, we explain how it differs from three other recently proposed alternatives to the standard interpretation of the substituted judgment standard. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Substitution treatment for opioid addicts in Germany

    PubMed Central

    Michels, Ingo Ilja; Stöver, Heino; Gerlach, Ralf

    2007-01-01

    Background After a long and controversial debate methadone maintenance treatment (MMT) was first introduced in Germany in 1987. The number of patients in MMT – first low because of strict admission criteria – increased considerably since the 1990s up to some 65,000 at the end of 2006. In Germany each general practitioner (GP), who has completed an additional training in addiction medicine, is allowed to prescribe substitution drugs to opioid dependent patients. Currently 2,700 GPs prescribe substitution drugs. Psychosocial care should be made available to all MMT patients. Results The results of research studies and practical experiences clearly indicate that patients benefit substantially from MMT with improvements in physical and psychological health. MMT proves successful in attaining high retention rates (65 % to 85 % in the first years, up to 50 % after more than seven years) and plays a major role in accessing and maintaining ongoing medical treatment for HIV and hepatitis. MMT is also seen as a vital factor in the process of social re-integration and it contributes to the reduction of drug related harms such as mortality and morbidity and to the prevention of infectious diseases. Some 10 % of MMT patients become drug-free in the long run. Methadone is the most commonly prescribed substitution medication in Germany, although buprenorphine is attaining rising importance. Access to MMT in rural areas is very patchy and still constitutes a problem. There are only few employment opportunities for patients participating in MMT, although regular employment is considered unanimously as a positive factor of treatment success. Substitution treatment in German prisons is heterogeneous in access and treatment modalities. Access is very patchy and the number of inmates in treatment is limited. Nevertheless, substitution treatment plays a substantial part in the health care system provided to drug users in Germany. Conclusion In Germany, a history of substitution

  16. The food-associated fungal neurotoxin ochratoxin A inhibits the absorption of glutamate by astrocytes through a decrease in cell surface expression of the excitatory amino-acid transporters GLAST and GLT-1.

    PubMed

    Razafimanjato, Helisoa; Garmy, Nicolas; Guo, Xiao-Jun; Varini, Karine; Di Scala, Coralie; Di Pasquale, Eric; Taïeb, Nadira; Maresca, Marc

    2010-09-01

    The food-associated mycotoxin ochratoxin A (OTA) has been demonstrated to be deleterious to numerous cell types including brain cells. Although OTA has been proved to be toxic to astrocytes, no other investigation has been conducted on the impact of OTA on astrocytic functions. In the present study, we evaluated the effect of OTA on one of the major astrocytic functions, i.e. the reabsorption of extracellular glutamate. We found that OTA suppressed glutamate absorption by rat cortical astrocytes with a half inhibitory concentration of 1.3 and 10.1 microM in the absence and presence of fetal calf serum. Although OTA inhibits glutamine synthetase activity, this effect was not involved in OTA-mediated alteration of glutamate absorption since decrease in enzyme activity only occurred at high cytotoxic concentrations of toxin (100 microM). Similarly, alterations in the expression of the excitatory amino-acid transporters were not involved since OTA failed to modify total expression level of GLAST and GLT-1. We found that inhibition of glutamate absorption by OTA was due to a decrease in the expression of GLAST and GLT-1 at the cell surface. We propose that, in addition to being directly toxic to neurons and astrocytes, OTA could also cause the death of brain cells through inhibition of glutamate uptake by astrocytes, leading to the accumulation of extracellular glutamate and ultimately to excitotoxicity. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Simple physics-based analytical formulas for the potentials of mean force of the interaction of amino-acid side chains in water. VI. Oppositely-charged side chains

    PubMed Central

    Makowski, Mariusz; Liwo, Adam; Scheraga, Harold A.

    2011-01-01

    The two-site coarse-grained model for the interactions of charged side chains, to be used with our coarse-grained UNRES force field for protein simulations proposed in the accompanying paper, has been extended to pairs of oppositely-charged side chains. The potentials of mean force of four pairs of molecules modeling charged amino-acid side chains, i.e., propionate – n-pentylamine cation (for aspartic acid – lysine), butyrate…n-pentylamine cation (for glutamic acid – lysine), propionate –1-butylguanidine (for aspartic acid – arginine), and butyrate – 1-butylguanidine (for glutamic acid – arginine) pairs were determined by umbrella-sampling molecular dynamics simulations in explicit water as functions of distance and orientation, and the analytical expression was fitted to the potentials of mean force. Compared to pairs of like-charged side chains discussed in the accompanying paper, an average quadrupole-quadrupole interaction term had to be introduced to reproduce the Coulombic interactions, and a multi-state model of charge distribution had to be introduced to fit the potentials of mean force of all oppositely-charged pairs well. The model reproduces all salt-bridge minima and, consequently, is likely to improve the performance of the UNRES force field. PMID:21500791

  18. A 269-amino-acid segment with a pseudo-leucine zipper and a helix-turn-helix motif codes for the sequence-specific DNA-binding domain of herpes simplex virus type 1 origin-binding protein.

    PubMed Central

    Deb, S; Deb, S P

    1991-01-01

    The UL9 gene of herpes simplex virus (HSV) codes for a DNA-binding protein (OBP) that interacts sequence specifically with the origin of replication. This protein is essential for HSV DNA replication in cultured cells. The UL9 gene was cloned into a plasmid vector downstream of the SP6 RNA polymerase promoter. By using in vitro transcription and translation systems, a full-length OBP was synthesized. This synthetic protein is recognized by an antiserum generated against the C-terminal decapeptide of OBP and is functionally active in binding to OriS sequence specifically. The in vitro-synthesized protein has sequence specificity for binding similar to that found for the in vivo-generated OBP. A total of 14 in-frame deletion and insertion mutants of the UL9 gene were generated and expressed in vitro. Using these deletion mutants, we determined that the 269-amino-acid stretch defined by amino acids 564 to 832 localizes the OriS-specific DNA-binding domain. The N-terminal boundary is between amino acids 565 and 596, while the C terminus lies between amino acids 833 and 805. This segment contains a helix-turn-helix moiety and a pseudo-leucine zipper, neither of which alone can support DNA binding. The other leucine zipper from amino acids 150 to 173 is not required for the in vitro sequence-specific DNA-binding activity of OBP. Images PMID:1851856

  19. Resistance to Cefepime and Cefpirome Due to a 4-Amino-Acid Deletion in the Chromosome-Encoded AmpC β-Lactamase of a Serratia marcescens Clinical Isolate

    PubMed Central

    Mammeri, Hedi; Poirel, Laurent; Bemer, Pascal; Drugeon, Henri; Nordmann, Patrice

    2004-01-01

    A multiresistant Serratia marcescens strain, HD, isolated from a patient with a urinary tract infection, was resistant to amino-, carboxy-, and ureidopenicillins, ceftazidime, and cefepime and was susceptible to cefotaxime and ceftriaxone, according to the guidelines of the NCCLS. No synergy was found between expanded-spectrum cephalosporins and clavulanic acid, according to the double-disk synergy test. The blaAmpC gene of the strain was amplified by PCR and cloned into Escherichia coli DH10B, giving rise to high-level resistance to ceftazidime, cefepime, and cefpirome. Sequencing analysis revealed that the blaAmpC gene from S. marcescens HD had a 12-nucleotide deletion compared to the blaAmpC gene from reference strain S. marcescens S3, leading to a 4-amino-acid deletion located in the H-10 helix of the β-lactamase. Kinetic analysis showed that this enzyme significantly hydrolyzed ceftazidime, cefepime, and cefpirome. This work underlined that resistance to the latest expanded-spectrum cephalosporins may be mediated by structurally modified AmpC-type β-lactamases. PMID:14982755

  20. Resistance to cefepime and cefpirome due to a 4-amino-acid deletion in the chromosome-encoded AmpC beta-lactamase of a Serratia marcescens clinical isolate.

    PubMed

    Mammeri, Hedi; Poirel, Laurent; Bemer, Pascal; Drugeon, Henri; Nordmann, Patrice

    2004-03-01

    A multiresistant Serratia marcescens strain, HD, isolated from a patient with a urinary tract infection, was resistant to amino-, carboxy-, and ureidopenicillins, ceftazidime, and cefepime and was susceptible to cefotaxime and ceftriaxone, according to the guidelines of the NCCLS. No synergy was found between expanded-spectrum cephalosporins and clavulanic acid, according to the double-disk synergy test. The bla(AmpC) gene of the strain was amplified by PCR and cloned into Escherichia coli DH10B, giving rise to high-level resistance to ceftazidime, cefepime, and cefpirome. Sequencing analysis revealed that the bla(AmpC) gene from S. marcescens HD had a 12-nucleotide deletion compared to the bla(AmpC) gene from reference strain S. marcescens S3, leading to a 4-amino-acid deletion located in the H-10 helix of the beta-lactamase. Kinetic analysis showed that this enzyme significantly hydrolyzed ceftazidime, cefepime, and cefpirome. This work underlined that resistance to the latest expanded-spectrum cephalosporins may be mediated by structurally modified AmpC-type beta-lactamases.

  1. Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

    PubMed Central

    Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K.; McMullan, Daniel; Krishna, S. Sri; Miller, Mitchell D.; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; Morse, Andrew T.; Murphy, Kevin D.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Trout, Christina V.; van den Bedem, Henry; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis. PMID:20944209

  2. Graphane versus graphene: a computational investigation of the interaction of nucleobases, aminoacids, heterocycles, small molecules (CO2, H2O, NH3, CH4, H2), metal ions and onium ions.

    PubMed

    Umadevi, Deivasigamani; Narahari Sastry, G

    2015-11-11

    Graphane has emerged as a two-dimensional hydrocarbon with interesting physical properties and potential applications. Understanding the interaction of graphane with various molecules and ions is crucial to appreciate its potential applications. We investigated the interaction of nucleobases, aminoacids, saturated and unsaturated heterocycles, small molecules, metal ions and onium ions with graphane by using density functional theory calculations. The preferred orientations of these molecules and ions on the graphane surface have been analysed. The binding energies of graphane with these molecules have been compared with the corresponding binding energies of graphene. Our results reveal that graphane forms stable complexes with all the molecules and ions yet showing lesser binding affinity when compared to graphene. As an exemption, the preferential strong binding of H2O with graphane than graphene reveals the fact that graphane is more hydrophilic than graphene. Charge transfer between graphane and the molecules and ions have been found to be an important factor in determining the binding strength of the complexes. The effect of the interaction of these molecules and ions on the HOMO-LUMO energy gap of graphane has also been investigated.

  3. SUBSTITUTION OF CADMIUM CYANIDE ELECTROPLATING WITH ZINC CHLORIDE ELECTROPLATING

    EPA Science Inventory

    The study evaluated the zinc chloride electroplating process as a substitute for cadmium cyanide electroplating in the manufacture of industrial connectors and fittings at Aeroquip Corporation. The process substitution eliminates certain wastes, specifically cadmium and cyanide, ...

  4. SUBSTITUTION OF CADMIUM CYANIDE ELECTROPLATING WITH ZINC CHLORIDE ELECTROPLATING

    EPA Science Inventory

    The study evaluated the zinc chloride electroplating process as a substitute for cadmium cyanide electroplating in the manufacture of industrial connectors and fittings at Aeroquip Corporation. The process substitution eliminates certain wastes, specifically cadmium and cyanide, ...

  5. A Practical Guide to Substituting at Different Grade Levels.

    ERIC Educational Resources Information Center

    Lovley, Shawn

    1994-01-01

    Provides specific suggestions and activities that substitute teachers can use with different grade levels. Substitute teachers need to be aware of the age and learning levels of their students, and develop appropriate teaching styles for different grade levels. (MDM)

  6. Signalization and stimulus-substitution in Pavlov's theory of conditioning.

    PubMed

    García-Hoz, Víctor

    2003-11-01

    The concept of conditioning as signalization proposed by Ivan P. Pavlov (1927, 1928) is studied in relation to the theory of stimulus-substitution, which is also attributed to him. In the so-called theory of stimulus-substitution a distinction must be made between an empirical principle of substitution and an actual theory of substitution, which can adopt different forms. The Pavlovian theory of substitution--which conceives substitution as a substitution of the unconditioned stimulus (US) by the conditioned stimulus (CS) in the activation of the representation of the former--can be understood as an explanation or model of signalization. Signalization and substitution are answers to different questions, and the level of analysis to which signalization corresponds, is that which concerns the nature of conditioning as an operation of the animal in the environment.

  7. Representations of Substitute Teachers and the Paradoxes of Professionalism.

    ERIC Educational Resources Information Center

    Weems, Lisa

    2003-01-01

    Explores narratives about teacher work articulated through representations of substitute teachers, using this representation to render visible assumptions governing boundaries of professionalism. The article discusses professional teachers as constructed in educational reform; images of substitute teachers (incompetent, unqualified, deviant…

  8. Trends in autism prevalence: diagnostic substitution revisited.

    PubMed

    Coo, Helen; Ouellette-Kuntz, Hélène; Lloyd, Jennifer E V; Kasmara, Liza; Holden, Jeanette J A; Lewis, M E Suzanne

    2008-07-01

    There has been little evidence to support the hypothesis that diagnostic substitution may contribute to increases in the administrative prevalence of autism. We examined trends in assignment of special education codes to British Columbia (BC) school children who had an autism code in at least 1 year between 1996 and 2004, inclusive. The proportion of children with an autism code increased from 12.3/10,000 in 1996 to 43.1/10,000 in 2004; 51.9% of this increase was attributable to children switching from another special education classification to autism (16.0/10,000). Taking into account the reverse situation (children with an autism code switching to another special education category (5.9/10.000)), diagnostic substitution accounted for at least one-third of the increase in autism prevalence over the study period.

  9. Substitutional alloy of Ce and Al

    PubMed Central

    Zeng, Qiao-Shi; Ding, Yang; Mao, Wendy L.; Luo, Wei; Blomqvist, Andreas; Ahuja, Rajeev; Yang, Wenge; Shu, Jinfu; Sinogeikin, Stas V.; Meng, Yue; Brewe, Dale L.; Jiang, Jian-Zhong; Mao, Ho-kwang

    2009-01-01

    The formation of substitutional alloys has been restricted to elements with similar atomic radii and electronegativity. Using high-pressure at 298 K, we synthesized a face-centered cubic disordered alloy of highly dissimilar elements (large Ce and small Al atoms) by compressing the Ce3Al intermetallic compound >15 GPa or the Ce3Al metallic glass >25 GPa. Synchrotron X-ray diffraction, Ce L3-edge absorption spectroscopy, and ab initio calculations revealed that the pressure-induced Kondo volume collapse and 4f electron delocalization of Ce reduced the differences between Ce and Al and brought them within the Hume-Rothery (HR) limit for substitutional alloying. The alloy remained after complete release of pressure, which was also accompanied by the transformation of Ce back to its ambient 4f electron localized state and reversal of the Kondo volume collapse, resulting in a non-HR alloy at ambient conditions. PMID:19188608

  10. Magnetoelastic properties of terbium substituted cobalt ferrite

    NASA Astrophysics Data System (ADS)

    Bhame, Shekhar D.; Joy, P. A.

    2017-10-01

    The magnetic properties of terbium substituted cobalt ferrites CoFe2-xTbxO4 (x = 0, 0.05, 0.1, 0.15 and 0.2) prepared by conventional solid state method are studied. The coercivity showed marked increase up to x = 0.1 and saturation magnetization decreased with increasing terbium content. Magnetostriction measurements did not show much decrease in the maximum value of strain but significant increase in the slope of magnetostriction was observed for x = 0.15 with moderate magnetostriction of around 144 ppm. The observed magnetic and magnetostrictive properties can be explained on the basis of structural and microstructural changes arising because of terbium substitution.

  11. Bone grafts, bone substitutes and orthobiologics

    PubMed Central

    Roberts, Timothy T.; Rosenbaum, Andrew J.

    2012-01-01

    The biology of fracture healing is better understood than ever before, with advancements such as the locking screw leading to more predictable and less eventful osseous healing. However, at times one’s intrinsic biological response, and even concurrent surgical stabilization, is inadequate. In hopes of facilitating osseous union, bone grafts, bone substitutes and orthobiologics are being relied on more than ever before. The osteoinductive, osteoconductive and osteogenic properties of these substrates have been elucidated in the basic science literature and validated in clinical orthopaedic practice. Furthermore, an industry built around these items is more successful and in demand than ever before. This review provides a comprehensive overview of the basic science, clinical utility and economics of bone grafts, bone substitutes and orthobiologics. PMID:23247591

  12. Molecular dynamics simulations of substitutional diffusion

    DOE PAGES

    Zhou, Xiaowang; Jones, Reese E.; Gruber, Jacob

    2016-12-18

    In atomistic simulations, diffusion energy barriers are usually calculated for each atomic jump path using a nudged elastic band method. Practical materials often involve thousands of distinct atomic jump paths that are not known a priori. Hence, it is often preferred to determine an overall diffusion energy barrier and an overall pre-exponential factor from the Arrhenius equation constructed through molecular dynamics simulations of mean square displacement of the diffusion species at different temperatures. This approach has been well established for interstitial diffusion, but not for substitutional diffusion at the same confidence. Using In 0.1 Ga 0.9 N as an example,more » we have identified conditions where molecular dynamics simulations can be used to calculate highly converged Arrhenius plots for substitutional alloys. As a result, this may enable many complex diffusion problems to be easily and reliably studied in the future using molecular dynamics, provided that moderate computing resources are available.« less

  13. Molecular dynamics simulations of substitutional diffusion

    SciTech Connect

    Zhou, Xiaowang; Jones, Reese E.; Gruber, Jacob

    2016-12-18

    In atomistic simulations, diffusion energy barriers are usually calculated for each atomic jump path using a nudged elastic band method. Practical materials often involve thousands of distinct atomic jump paths that are not known a priori. Hence, it is often preferred to determine an overall diffusion energy barrier and an overall pre-exponential factor from the Arrhenius equation constructed through molecular dynamics simulations of mean square displacement of the diffusion species at different temperatures. This approach has been well established for interstitial diffusion, but not for substitutional diffusion at the same confidence. Using In 0.1 Ga 0.9 N as an example, we have identified conditions where molecular dynamics simulations can be used to calculate highly converged Arrhenius plots for substitutional alloys. As a result, this may enable many complex diffusion problems to be easily and reliably studied in the future using molecular dynamics, provided that moderate computing resources are available.

  14. [Breast-milk substitutes: past and present].

    PubMed

    Rea, M F

    1990-06-01

    The historical development of industrialized products used as breast-milk, substitutes a process begun in the 18th century, is studied. The marketing strategy currently adopted infant formula companies is stressed and the different commercial practices used in the search for new markets in third world countries are described. A warning is given as to the precise instructions giver for the use of the so-called breast-milk substitutes, and the attention of health professionals and consumer groups is called to the low level of awareness regarding this subject, a factor which led the World Health Organization and United Nations Children's Fund to recommend the preparation of an appropriate marketing code and to its adoption by Brazil.

  15. Meat analogues: Health promising sustainable meat substitutes.

    PubMed

    Kumar, Pavan; Chatli, M K; Mehta, Nitin; Singh, Parminder; Malav, O P; Verma, Akhilesh K

    2017-03-24

    There is a scarcity of protein of high biological value due to rapid increase in the world population and limited natural resources. Meat is a good source of protein of high biological value but converting the vegetable protein into animal protein is not economical. There is a trend of production of healthy and delicious meat free food for satisfaction of vegetarian and personal well beings. This resulted in increasing use of low cost vegetable protein such as textured soy protein, mushroom, wheat gluten, pulses etc as a substitute for animal-protein. These simulated meat-like products, with similar texture, flavor, color, and nutritive value can be substituted directly for meat to all sections of the society.

  16. Abuse Liability Profile of Three Substituted Tryptamines

    PubMed Central

    Forster, Michael J.; Janowsky, Aaron; Eshleman, Amy J.

    2011-01-01

    The abuse liability profile of three synthetic hallucinogens, N,N-diisopropyltryptamine (DIPT), 5-N,N-diethyl-5-methoxytryptamine (5-MeO-DET), and 5-methoxy-α-methyltryptamine (5-MeO-AMT), was tested in rats trained to discriminate hallucinogenic and psychostimulant compounds, including cocaine, methamphetamine, 3,4-methylenedioxymethylamphetamine (MDMA), lysergic acid diethylamide (LSD), (−)-2,5-dimethoxy-4-methylamphetamine (DOM), and dimethyltryptamine (DMT). Because abused hallucinogens act at 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2A receptors, and abused psychostimulants act at monoamine transporters, binding and functional activities of DIPT, 5-MeO-DET, and 5-MeO-AMT at these sites were also tested. DIPT fully substituted in rats trained to discriminate DMT (ED50 = 1.71 mg/kg) and DOM (ED50 = 1.94 mg/kg), but produced only 68% LSD-appropriate responding. 5-MeO-DET fully substituted for DMT (ED50 = 0.41 mg/kg) and produced 59% MDMA-appropriate responding. 5-MeO-AMT did not fully substitute for any of the training drugs, but produced 67% LSD-appropriate responding. None of the compounds produced substitution in rats trained to discriminate cocaine or methamphetamine. All three compounds showed activity at 5-HT1A and 5-HT2A receptors as well as blockade of reuptake by the serotonin transporter. In addition, 5-MeO-AMT produced low levels of serotonin release and low potency blockade of dopamine uptake. DIPT, 5-MeO-DET, and 5-MeO-AMT produced behavioral and receptor effects similar to those of abused hallucinogens, but were not similar to those of psychostimulants. DIPT and 5-MeO-DET may have abuse liability similar to known hallucinogens and may be hazardous because high doses produced activity and lethality. PMID:21474568

  17. Tissue engineering of cultured skin substitutes.

    PubMed

    Horch, Raymund E; Kopp, Jürgen; Kneser, Ulrich; Beier, Justus; Bach, Alexander D

    2005-01-01

    Skin replacement has been a challenging task for surgeons ever since the introduction of skin grafts by Reverdin in 1871. Recently, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements. This has been fostered by the dramatically improved survival rates of major burns where the availability of autologous normal skin for grafting has become one of the limiting factors. The ideal properties of a temporary and a permanent skin substitute have been well defined. Tissue-engineered skin replacements: cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular biological matrices, and cellular matrices including such biological substances as fibrin sealant and various types of collagen, hyaluronic acid etc. have opened new horizons to deal with such massive skin loss. In extensive burns it has been shown that skin substitution with cultured grafts can be a life-saving measure where few alternatives exist. Future research will aim to create skin substitutes with cultured epidermis that under appropriate circumstances may provide a wound cover that could be just as durable and esthetically acceptable as conventional split-thickness skin grafts. Genetic manipulation may in addition enhance the performance of such cultured skin substitutes. If cell science, molecular biology, genetic engineering, material science and clinical expertise join their efforts to develop optimized cell culture techniques and synthetic or biological matrices then further technical advances might well lead to the production of almost skin like new tissue-engineered human skin products resembling natural human skin.

  18. Coordinated Navy Hazardous Material Substitution Manual

    DTIC Science & Technology

    1993-08-01

    the Commerce Business Daily ( CBD ) and unofficial. channels such as the media should be used to the maximum extent possible to get the message to current...01lice ot Mandgement and Budget. Paperwork Aeduction Project (0 104-0188), Washington, DC 2o . . . uianK) 2. REPORT DATE 3. REPORT TYPE AND DATES...COVERED lAugust 1993 Interim Draft 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS C: F33615-89-D-4003 Coordinated Navy Hazardous Material Substitution Order Nr

  19. Current Simulator Substitution Practices in Flight Training

    DTIC Science & Technology

    1977-02-01

    environments. The percentage reduction of the original in-flight syllabus (effectiveness) and the ratio of simulator hours required per in-flight...in the report are percent flight TAEG Report No. 43 syllabus reduction and flight substitution ratio. Explanatory information is provided to...formula (Percent Flight Syllabus Reduction) expresses the overall ability of the simulator to reduce the amount of in-flight training in the syllabus

  20. Soluble Alkyl Substituted Polygermanes. Thermochromic Behavior.

    DTIC Science & Technology

    1986-07-17

    are strongly thermochromic . The effect is attributed to conformational locking of the backbone which is caused by the crystallization of the side groups...are strongly thermochromic . The effect is attributed to the conformational locking of the backbone which is caused by the crystallization of the side...SYMBOL. 02 &m A -- .- h.. .. .. . . . . . . . . ... . . . .. RJ 5008 (52258) 1/24/86 Chemis try SOLUBLE ALKYL SUBSTITUTED POLYGERMANES: THERMOCHROMIC

  1. Efficient synthesis of highly substituted tetrahydroindazolone derivatives.

    PubMed

    Scala, Angela; Piperno, Anna; Risitano, Francesco; Cirmi, Santa; Navarra, Michele; Grassi, Giovanni

    2015-08-01

    A straightforward and efficient method for the synthesis of novel highly substituted and diversely functionalized indazolone derivatives has been developed. The transformation consists of a cyclocondensation of selected 1,3,3'-tricarbonyls with monosubstituted hydrazines. The starting β-triketones were prepared by an efficient chemo- and regioselective method under MW irradiation, exploiting the oxazolone chemistry. The reaction is easily accomplished under mild conditions and appears versatile, providing a synthetic diversification method with potential for drug-like compounds preparation.

  2. 48 CFR 28.203-4 - Substitution of assets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Substitution of assets. 28... assets. An individual surety may request the Government to accept a substitute asset for that currently... may agree to the substitution of assets upon determining, after consultation with legal counsel, that...

  3. 48 CFR 28.203-4 - Substitution of assets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Substitution of assets. 28... assets. An individual surety may request the Government to accept a substitute asset for that currently... may agree to the substitution of assets upon determining, after consultation with legal counsel, that...

  4. 40 CFR 721.10711 - Alkyl substituted catechol (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl substituted catechol (generic... Specific Chemical Substances § 721.10711 Alkyl substituted catechol (generic). (a) Chemical substance and... substituted catechol (PMN P-13-197) is subject to reporting under this section for the significant new...

  5. Substitute Addiction: A Concern for Researchers and Practitioners

    ERIC Educational Resources Information Center

    Sussman, Steve; Black, David S.

    2008-01-01

    An understanding of the role of substitute addictions remains unclear. This article examines the range and possible reward functions of substitute addictions. We suggest that prevention education and treatment need to take into account substitute addictions as an influential aspect of recovery. Research is needed to better understand the…

  6. 29 CFR 825.207 - Substitution of paid leave.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....207 Substitution of paid leave. (a) Generally, FMLA leave is unpaid leave. However, under the circumstances described in this section, FMLA permits an eligible employee to choose to substitute accrued paid leave for FMLA leave. If an employee does not choose to substitute accrued paid leave, the employer may...

  7. 29 CFR 825.207 - Substitution of paid leave.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....207 Substitution of paid leave. (a) Generally, FMLA leave is unpaid leave. However, under the circumstances described in this section, FMLA permits an eligible employee to choose to substitute accrued paid leave for FMLA leave. If an employee does not choose to substitute accrued paid leave, the employer may...

  8. 29 CFR 825.207 - Substitution of paid leave.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....207 Substitution of paid leave. (a) Generally, FMLA leave is unpaid leave. However, under the circumstances described in this section, FMLA permits an eligible employee to choose to substitute accrued paid leave for FMLA leave. If an employee does not choose to substitute accrued paid leave, the employer may...

  9. 29 CFR 825.207 - Substitution of paid leave.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....207 Substitution of paid leave. (a) Generally, FMLA leave is unpaid leave. However, under the circumstances described in this section, FMLA permits an eligible employee to choose to substitute accrued paid leave for FMLA leave. If an employee does not choose to substitute accrued paid leave, the employer may...

  10. 40 CFR 721.1680 - Substituted benzoic acid (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted benzoic acid (generic... Substances § 721.1680 Substituted benzoic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted benzoic acid (PMN P...

  11. 40 CFR 721.1680 - Substituted benzoic acid (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted benzoic acid (generic... Substances § 721.1680 Substituted benzoic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted benzoic acid (PMN P...

  12. 40 CFR 721.1680 - Substituted benzoic acid (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted benzoic acid (generic... Substances § 721.1680 Substituted benzoic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted benzoic acid (PMN P...

  13. 40 CFR 721.1680 - Substituted benzoic acid (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted benzoic acid (generic... Substances § 721.1680 Substituted benzoic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted benzoic acid (PMN P...

  14. 19 CFR 122.86 - Substitution of aircraft.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Substitution of aircraft. 122.86 Section 122.86... Substitution of aircraft. (a) Application. The residue cargo procedure applies when an airline must substitute aircraft to reach a destination due to weather conditions or operational factors which prevent an...

  15. 19 CFR 122.86 - Substitution of aircraft.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Substitution of aircraft. 122.86 Section 122.86... Substitution of aircraft. (a) Application. The residue cargo procedure applies when an airline must substitute aircraft to reach a destination due to weather conditions or operational factors which prevent an...

  16. 40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted phenylimino carbamate... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under this...

  17. 40 CFR 721.5546 - Halogen substituted oxetanes (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Halogen substituted oxetanes (generic... Substances § 721.5546 Halogen substituted oxetanes (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as halogen substituted...

  18. 40 CFR 721.5546 - Halogen substituted oxetanes (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Halogen substituted oxetanes (generic... Substances § 721.5546 Halogen substituted oxetanes (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as halogen substituted...

  19. 40 CFR 721.5546 - Halogen substituted oxetanes (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Halogen substituted oxetanes (generic... Substances § 721.5546 Halogen substituted oxetanes (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as halogen substituted...

  20. 40 CFR 721.5546 - Halogen substituted oxetanes (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Halogen substituted oxetanes (generic... Substances § 721.5546 Halogen substituted oxetanes (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as halogen substituted...