Home About us Contact
|
Home About us Contact | ||
|
|
||
Substitution
Kinds of Substitution Terms modified by Substitution Selected AbstractsA COMPARISON BETWEEN PAPER AND COMPUTERIZED BALLOTS AND A STUDY OF SIMULATED SUBSTITUTION BETWEEN THE TWO BALLOTS USED IN DESCRIPTIVE ANALYSIS,JOURNAL OF SENSORY STUDIES, Issue 6 2002MARIANNE SWANEY-STUEVE ABSTRACT Many researchers have compared results from experiments using paper ballots and computer ballots, yet few have studied the interchangeability of the two data collection methods. If computers fail between sessions of an experiment, one would like to be able to use paper ballots for that session with some confidence that the experimental results will not be affected. The objective of this study was to determine if ballot type had a significant influence on descriptive analysis results. Multivariate analysis of variance indicated no significant differences (P<0.05) between ballot types. No significant sample * ballot interactions were found from the univariate analysis of variance. Mann Whitney nonparamatric tests found that substituting paper ballots for computer ballots in a single session did not significantly alter experimental results. One can conclude from this experiment that if a situation occurs forcing panelists to use an alternative ballot, the results probably will not be significantly affected. [source] CAPITAL,LABOUR SUBSTITUTION AND ENDOGENOUS FLUCTUATIONS: A MONOPOLISTIC COMPETITION APPROACH WITH VARIABLE MARKUP,THE JAPANESE ECONOMIC REVIEW, Issue 3 2009THOMAS SEEGMULLER This paper analyses an overlapping generations model with endogenous product diversity where strategic interactions between producers are introduced; it examines how they affect the stability properties of the steady state. Because of free entry, strategic interactions between producers imply a new dynamic feature, markup variability, promoting indeterminacy and endogenous cycles. Indeed, in contrast to the model without strategic interaction, endogenous fluctuations can occur when the substitution between the production factors, capital and labour, is not too weak, but in accordance with empirical estimates. [source] Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2009Yumiko Yoshida Abstract Background Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy. Methods Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence. Results Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy. Conclusions Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Intertemporal Substitution of Effort: Some Empirical EvidenceECONOMICA, Issue 280 2003John G. Treble The labour economics literature refers often to effort, but there is little empirical evidence as to how productivity and effort respond to wage rate variations. An unusual natural experiment in which wage rates suffered an exogenous change of two weeks' duration gives some insight into the magnitude of this effect. For a group of workers in Victorian County Durham, the effort response, measured as the impact of a temporary wage rate change on output per shift, dominates the response of attendance. Comparison of the estimates presented here with those in Treble (Journal of Economic History, 61, 414,38, 2001) suggests that the effects are short lived. [source] Trying to See Red Through Stickleback Photoreceptors: Functional Substitution of Receptor SensitivitiesETHOLOGY, Issue 3 2006Mickey P. Rowe A key to understanding animal behavior is knowledge of the sensory information animals extract from their environment. For visually motivated tasks, the information animals obtain through their eyes is often assumed to be essentially the same as that perceived by humans. However, known differences in structure and processing among the visual systems of different animals clearly indicate that the world seen by each is different. A well-characterized difference between human and other animal visual systems is the number of types and spectral sensitivities of their photoreceptors. We are developing a technique, functional substitution, that exploits knowledge of these differences to portray for human subjects, colors as they would appear through the photoreceptors of another animal. In a specific application, we ask human subjects to rank hues of male threespine stickleback (Gasterosteus aculeatus) throats viewed through stickleback photopigments. We compare these ranks to ranks of the same throat hues viewed through normal human photoreceptors. We find essentially no difference between the two sets of rankings. This suggests that any differences in human and stickleback rankings of such hues would result from differences in post-receptoral neural processing. Using a previously developed model of stickleback neural processing, we established another ranking of the hues which was again essentially the same as the rankings produced by the human subjects. A growing literature indicates that stickleback do rank such hues in the evaluation of males as potential mates or threats. Although our results do not demonstrate that humans and stickleback use the same mechanisms to assess color, our experiments significantly failed to show that stickleback and human rankings of throat hues should be different. Nevertheless, a comparison of all these rankings to ranks derived from subjective color scoring by human observers suggests that color scoring may utilize other cues and should thus be used cautiously. [source] Reactivity and X-ray Structural Studies in Ligand Substitution of [Cp/(Ind)Ru(dppf)Cl] , Epimerisation in [Cp/(Ind)Ru(Josiphos)Cl] {Cp = ,5 -C5H5, Ind = ,5 -C7H9, dppf = 1,1,-Bis(diphenylphosphanyl)ferrocene, Josiphos = (R)-(,)-1-[(S)-2-(Diphenylphosphanyl)ferrocenyl]ethyldicyclohexylphosphane}EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 3 2007Sin Yee Ng Abstract Ligand substitution of [(Ind)Ru(PPh3)2Cl] (1) led to the isolation of [(Ind)Ru(PPh3){Ph2P(CH2)2C9H7}Cl] (2), [(Ind)Ru(dppf)Cl] (3) and [(Ind)Ru{(Ph2PCH2)3CMe}]PF6 ([4]PF6), and diastereoisomers [(R)- and (S)-(Ind)Ru(Josiphos)Cl] [(R)- 5 and (S)- 5], where (R)-(S)-Josiphos is the ferrocene-based chiral diphosphane ligand (R)-(,)-1-[(S)-2-(diphenylphosphanyl)ferrocenyl] ethyldicyclohexylphosphane. The Cp analogues of 5, viz. (R)- 6 and (S)- 6, were also obtained from [CpRu(PPh3)2Cl] (1a). Josiphos-dependent epimerisation was observed, with conversion of the (S) isomer to the (R) isomer in both cases. Chloride abstraction of 3 with NaPF6 in CH3CN and NaN3 in EtOH gave [(Ind)Ru(dppf)(CH3CN)]PF6 ([7]PF6) and [(Ind)Ru(dppf)(N3)] (8), respectively. The azido ligand in 8 underwent [3+2] dipolar cycloaddition with dimethyl acetylenedicarboxylate to give a N -bound bis(methoxycarbonyl)-1,2,3-triazolato complex, 9. X-ray crystal structures of the new complexes, except (R)- 5, (S)- 5 and (S)- 6, have been determined. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] How Do the Different Defect Structures and Element Substitutions Affect the Nonlinear Optical Properties of Lacunary Keggin Polyoxometalates?EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 20 2006A DFT Study Abstract Systematic DFT calculations have been carried out on the lacunary ,-Keggin polyoxometalate derivatives [PW11O39]7,, [XW9O34]n, (X = AlIII, SiIV, GeIV, PV, AsV, and SbV), [XW9M2O39]n,, and [XW9M3O40]n, (X = PV and SiIV, M = MoVI, VV, NbV, and TaV) to investigate the geometric structure and element substitution effects on the molecular nonlinear optical response. Analysis of the computed static second-order polarizability (,0) predicts that the molecular nonlinear optical activity of lacunary Keggin polyoxometalate derivatives can be modified by replacing the central heteroatom and the addenda metal atom. Substitution of the central Al atom or the addenda V atom causes significant enhancement in the molecular nonlinearity. Moreover, the ,0 values are substantially dependent on the defect structures. This class of inorganic complexes possesses remarkably large molecular optical nonlinearity, especially for the partial substitution complex [SiW9Nb2O39]10, (IIIc), which has a computed ,0 value of 2071.0 a.u. Thus, lacunary Keggin polyoxometalates could become excellent candidates in the field of second-order NLO. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Regiospecific Cyclometalation of Diphenyl(2-substituted phenyl)phosphane with Methyltetrakis(trimethylphosphane)cobalt(I)EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 5 2003Hans-Friedrich Klein Abstract The pre-chelate molecules 2-(diphenylphosphanyl)- N,N -dimethylaniline, [2-(diphenylphosphanyl)benzyl]dimethylamine, 1-(diphenylphosphanyl)-2-ethylbenzene, 1-(diphenylphosphanyl)-2-isopropylbenzene, and 2-(diphenylphosphanyl)benzonitrile, in a reaction with [CoMe(PMe3)4], eliminate methane to afford the selectively 6- ortho -metalated complexes 1,5 that contain four-membered metallacycles. The molecular structure of 3 shows a tbp-coordinated cobalt atom, with axial C and PMe3 donor groups. Metalation in the aliphatic side-chain occurs with 2-(diphenylphosphanyl)toluene, giving complex 6 that contains a five-membered metallacycle. Benzyldiphenylphosphane is selectively ortho -metalated in the benzyl group, affording 7. As shown by the molecular structures, complex 7 is a true ligand isomer of 6. Substitution of a trimethylphosphane group in compounds 4 and 6 by ethene gives the pentacoordinate complexes 8 and 9, respectively. The ethene ligand is ,-coordinated in the equatorial plane of a trigonal bipyramid. Under 1 bar of CO, complex 6 forms monocarbonyl complex 10. Carbonylation of complexes 3 and 4 proceeds by insertion of CO into the Co,C bond under ring expansion, affording the aroylcobalt complexes 11 and 12, respectively. Complex 6 reacts with iodomethane in an oxidative substitution reaction yielding a structurally characterized octahedral complex mer - 13, which eliminates a methyl group in THF at 20 °C to form a pentacoordinate cobalt(II) complex 14. Complex 3 oxidatively adds iodomethane in a stereoselective cis addition to give the cobalt(III) complex mer - 15, which retains its four-membered metallacycle and the CoCH3 group. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Formation of (,-Alkenyl)- and (,-Vinylidene)palladium and -platinum Complexes by Oxidative Addition of 4,4-Dichloro-1,1-diphenyl-2-azabuta-1,3-diene , The Molecular Structure of an Unusual Asymmetric (,-Vinylidene)Pd,Pd ComplexEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 3 2003Michael Knorr Abstract 4,4-Dichloro-1,1-diphenyl-2-azabuta-1,3-diene (1) oxidatively adds to [Pd(PPh3)4] and [Pt(C2H4)(PPh3)2] giving rise to the ,-alkenyl complexes trans -[MCl{[C(Cl)=C(H),N=CPh2]}(PPh3)2] (2a: M = Pd; 2b: M = Pt). When 1 is treated with [Pd(PPh3)4] in a 1:2 ratio in refluxing toluene, the dimetallic ,-vinylidene complex [(PPh3)ClPd{,-[C=C(H),N=CPh2]}PdCl(PPh3)2] (3) is formed. In this fluxional compound, a PPh3 ligands migrates in a reversible manner between the two Pd centers. Substitution of the PPh3 ligands of 3 by 2 equiv. of Ph2PCH2PPh2 affords the A-frame complex [ClPd(,-dppm)2{,-[C=C(H),N=CPh2]}PdCl] (4). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Medical Potentialities of Biomimetic Apatites through Adsorption, Ionic Substitution, and Mineral/Organic Associations: Three Illustrative Examples,ADVANCED ENGINEERING MATERIALS, Issue 7 2010Ahmed Al-Kattan Biomimetic calcium phosphate apatites are particularly adapted to bio-medical applications due to their biocompatibility and high surface reactivity. In this contribution we report three selected examples dealing with mineral/organic interactions devoted to convey new functionalities to apatite materials, either in the form of dry bioceramics or of aqueous colloids. We first studied the adsorption of risedronate (bisphosphonate) molecules, which present potential therapeutic properties for the treatment of osteoporosis. We then addressed the preparation of luminescent Eu-doped apatites for exploring apatite/collagen interfaces through the FRET technique, in view of preparing "advanced" biocomposites exhibiting close spatial interaction between apatite crystals and collagen fibers. Finally, we showed the possibility to obtain nanometer-scaled apatite-based colloids, with particle size tailorable in the range 30,100,nm by controlling the agglomeration state of apatite nanocrystals by way of surface functionalization with a phospholipid moiety. This paper is aimed at illustrating some of the numerous potentialities of calcium phosphate apatites in the bio-medical field, allowing one to foresee perspectives lying well beyond bone-related applications. [source] Proteolytic cleavage of the voltage-gated Ca2+ channel ,2, subunit: structural and functional featuresEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Arturo Andrade Abstract By mediating depolarization-induced Ca2+ influx, high-voltage-activated Ca2+ channels control a variety of cellular events. These heteromultimeric proteins are composed of an ion-conducting (,1) and three auxiliary (,2,, , and ,) subunits. The ,2, subunit enhances the trafficking of the channel complex to the cell surface and increases channel open probability. To exert these effects, ,2, must undergo important post-translational modifications, including a proteolytic cleavage that separates the extracellular ,2 from its transmembrane , domain. After this proteolysis both domains remain linked by disulfide bonds. In spite of its central role in determining the final conformation of the fully mature ,2,, almost nothing is known about the physiological implications of this structural modification. In the current report, by using site-directed mutagenesis, the proteolytic site of ,2, was mapped to amino acid residues Arg-941 and Val-946. Substitution of these residues renders the protein insensitive to proteolytic cleavage as evidenced by the lack of molecular weight shift upon treatment with a disulfide-reducing agent. Interestingly, these mutations significantly decreased whole-cell patch-clamp currents without affecting the voltage dependence or kinetics of the channels, suggesting a reduction in the number of channels targeted to the plasma membrane. [source] Nucleophilicities and Nucleofugalities of Organic Carbonates,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2010Nicolas Streidl Abstract The kinetics of the reactions of the methyl carbonate ion with benzhydrylium ions in acetonitrile have been studied by UV/Vis spectrophotometry. Substitution of the resulting second-order rate constants and the electrophilicity parameters E of the benzhydrylium ions into the linear free energy relationship log,k = s(N + E) yielded the nucleophilicity parameters N25 = 16.03 and s25 = 0.64 for methyl carbonate in acetonitrile. The kinetics of the reverse reactions, i.e., of the solvolyses of ring-substituted benzhydryl alkyl carbonates in different aqueous solvents were followed by conductimetry. The obtained first-order rate constants and the known electrofugality parameters Ef of benzhydrylium ions were used to determine the nucleofugality parameters Nf and sf of the ROCO2, groups by using the linear free energy relationship log,k = sf(Nf + Ef). The leaving group abilities of carbonates decrease by a factor of about 300 from PhOCO2, over MeOCO2, and iBuOCO2, to tBuOCO2, in various alcoholic and aqueous solvents. tert -Butyl carbonates (tBocO-R) are, thus, considerably more stable with respect to heterolytic cleavage of the O,R bond than other organic carbonates. [source] Gold(I)-Catalyzed Tandem Rearrangement,Nucleophilic Substitution of ,-Acetoxy Alkynyl Oxiranes or Aziridines: Efficient Approach to Furans and PyrrolesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 9 2010Aurélien Blanc Abstract Highly substituted furans and pyrroles were efficiently formed by a new gold(I)-catalyzed tandem rearrangement,nucleophilic substitution of acetoxylated alkynyl oxiranes and aziridines in the presence of various nucleophiles. [source] An Efficient Molybdenum(VI)-Catalyzed Direct Substitution of Allylic Alcohols with Nitrogen, Oxygen, and Carbon NucleophilesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2009Hongwei Yang Abstract Direct nucleophilic substitution of allylic alcohols with various nitrogen, oxygen, and carbon nucleophiles catalyzed by MoO2(acac)2 was realized. The corresponding products were obtained in moderate-to-excellent yields. Studies of the reaction mechanism showed that a carbenium intermediate was formed in the transition state. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Indole in DNA: Comparison of a Nucleosidic with a Non-Nucleosidic DNA Base SubstitutionEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2009Janez Barbaric Abstract The synthetic incorporation of indole as an artificial DNA base into oligonucleotides by two different structural approaches is described. For both types of modification, the indole moiety is attached through the C-3 position to the oligonucleotides. As a mimic of natural nucleosides, the indole nucleoside of ,-2,-deoxyribofuranoside (In) was synthesized. The corresponding In-modified duplexes were compared with duplexes that contained the indole group connected through (S)-3-amino-1,2-propanediol as an acyclic linker between the phosphodiester bridges of the oligonucleotides. This linker was tethered to the C-3 position of the indole heterocycle either directly (In,) or by a carbamate function (In,). The melting temperatures of the corresponding indole-modified DNA duplexes were measured and compared. Interestingly, not only the In, and In, modifications but also the natural-like In base surrogate destabilize the DNA duplex strongly. This result supports our approach to apply the acyclic glycol linker to incorporate aromatic molecules as artificial DNA base substitutions. The major advantage of acyclic glycol linkers [such as the applied (S)-3-amino-1,2-propanediol] is that the corresponding modifications are synthetically more easily and readily accessible, as it avoids the preparation of the nucleosidic bond and the separation and purification of the ,- and ,-anomers. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Facile Access to Optically Active Ferrocenyl Derivatives with Direct Substitution of the Hydroxy Group Catalyzed by Indium TribromideEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 14 2007Paola Vicennati Abstract Ferrocene derivatives have found many different uses and applications in organometallic chemistry, material chemistry, and catalysis. We have shown that using a catalytic amount (5,10 mol-%) of commercially available indium tribromide, at room temperature, many carbon nucleophiles, such as indoles, allylsilane, enolsilane, silyl ketene acetal, diketone, and trimethylsilylcyanide, smoothly react with different optically active ferrocenyl alcohol derivatives to afford the desired products in high yield, with retention of configuration. Also, many different N-nucleophiles (azide, carbamates) and O-nucleophiles (alcohols) react as well, again with retention of configuration. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Stable Ion and Electrophilic Substitution (Nitration and Bromination) Study of A-Ring Substituted Phenanthrenes: Novel Carbocations and Substituted Derivatives; NMR, X-ray Analysis, and Comparative DNA BindingEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2007Cédric Brulé Abstract Persistent carbocations were generated from five A-ring mono- and di-substituted phenanthrenes [3-OMe; 4-OMe, 1,3-bis(OMe), 2,4-bis(OMe), and 1,3-bis(Me)]. In all cases protonation occurs in the A-ring, ortho/para relative to methoxy or methyl substituent(s). Complete NMR assignments of the resulting carbocations are reported and their charge delocalization modes are discussed. Mild nitration (with 20,50,% aqueous HNO3 at ,10 °C or at room temp.) and bromination (NBS/MeCN/room temp.) of these substrates resulted in the synthesis of several novel mononitro-/dinitro- as well as monobromo/dibromo derivatives, including those with nitro or bromo substituent in the bay-region. Correspondence between the site of attack in low-temperature protonation study and nitro substitution in ambient mild nitrations are examined. Complete NMR assignments for the new derivatives are reported as well as X-ray structures for 2,4-dimethoxy-1-nitro- and 1,3-dimethyl-4-nitrophenanthrenes. A comparative DNA binding study with MCF cells on three of the synthesized mononitro and one dinitro derivative showed that 1,3-dimethyl-9-nitro- (nitro at the meso position), 3-methoxy-4-nitro- (nitro in bay-region), and 1,3-dimethoxy-4,9-dinitrophenanthrenes (nitro in both meso and bay-regions) formed DNA adducts. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Nucleophilic Vinylic Substitution (SNV) of Activated Alkoxymethylene Derivatives with 6-Aminoquinoxaline,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2005Jozef Salo Abstract Treatment of 6-aminoquinoxaline with ,,,-diactivated alkoxymethylene derivatives gave the corresponding N -(quinoxalin-6-yl)enamines. A variant of the SNV reaction mechanism was proposed for substitution of the alkoxymethylene compounds, on the basis of the structures of the precursor enol ether and the vinylic substitution product and on computations. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment (Adv. Eng.ADVANCED ENGINEERING MATERIALS, Issue 8 2009Mater. The cover shows life and dead assay demonstrating living cells within a cellulose sulfate capsule. More information can be found in the article by J. M. Lohr et al. on page B129. [source] Exclusive ,-Substitution in the Reaction of Octafluoronaphthalene with Secondary AminesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2004Vladimir I. Sorokin Abstract The reaction between octafluoronaphthalene and dimethylamine, pyrrolidine or piperidine in DMF, dimethyl(ethylene)urea (DMEU) or without solvent leads to the exclusive substitution of ,-fluorine atoms giving naphthalene derivatives with four NR2 groups. This was proved by 19F NMR of the products and a crystal structure determination for 1,4,5,8-tetrafluoro-2,3,6,7-tetrakis(piperidin-1-yl)naphthalene. The main feature of the reaction in DMF was a transamidation process. The remaining four fluorine atoms in the synthesised tetraamines could be smoothly replaced by reduction with LiAlH4. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Vicarious Nucleophilic Substitution of (Chloroalkyl)oxazolines with Nitroarenes: Synthesis of (Nitrobenzyl)oxazolinesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2003Saverio Florio Abstract 2-Chloroalkyloxazolines 1a and 1b react with nitroarenes in the presence of tBuOK in DMSO to give, upon acidic quenching, substituted nitroaryloxazolines 2a, 2b, 3a, 9, 10, 11a,d, 12,19, and 21,22, probably by vicarious nucleophilic substitution (VNS). The reaction of 1a is poorly regioselective, while that of 1b is completely para regioselective, thus showing that the coupling is sterically controlled. Trapping of the carbanionic intermediate B of the VNS reaction with electrophiles furnished ,,,-disubstituted (nitrobenzyl)oxazolines 4,7. Attempts to trap B with PhCHO failed: the [(p -nitrophenyl)oxazolinyl]ethanol 8 was obtained. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Blocking Fluorine Substitution in Biotransformation of Nortricyclanyl N -Phenylcarbamates with Beauveria bassianaEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2003Günter Haufe Abstract The biotransformation of tricyclo[2.2.1.02,6]hept-3-yl N -phenylcarbamate (8) by a standard procedure using Beauveria bassiana gave a 7:1 mixture of optically active exo,exo - and exo,endo -5-hydroxytricyclo[2.2.1.02,6]hept-3-yl N -phenylcarbamates 15 and 16 in 19% isolated yield. No ring opening of the three-membered ring was observed. Substitution with a fluorine atom at the 5- endo - or 5- exo -position prevented hydroxylation of any alicyclic position of the molecules, p -hydroxylation of the aromatic ring occurring to a small extent instead. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment,ADVANCED ENGINEERING MATERIALS, Issue 8 2009J. Matthias Löhr Cell encapsulation represents an innovative technique. However, clinical applications are sparse. Most experiments and clinical studies have been performed with either alginate or cellulose sulfate capsules, containing several cell lines and a broad variety of applications, ranging all the way from substitution for impaired organ function and release of cytokines or growth factors to gene-directed enzyme prodrug therapy. A few clinical studies have been conducted and/or are under way. [source] Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clustersFEBS JOURNAL, Issue 18 2010Chen-Hsiang Shen The structural and kinetic effects of amprenavir (APV), a clinical HIV protease (PR) inhibitor, were analyzed with wild-type enzyme and mutants with single substitutions of V32I, I50V, I54V, I54M, I84V and L90M that are common in drug resistance. Crystal structures of the APV complexes at resolutions of 1.02,1.85 Å reveal the structural changes due to the mutations. Substitution of the larger side chains in PRV32I, PRI54M and PRL90M resulted in the formation of new hydrophobic contacts with flap residues, residues 79 and 80, and Asp25, respectively. Mutation to smaller side chains eliminated hydrophobic interactions in the PRI50V and PRI54V structures. The PRI84V,APV complex had lost hydrophobic contacts with APV, the PRV32I,APV complex showed increased hydrophobic contacts within the hydrophobic cluster and the PRI50V complex had weaker polar and hydrophobic interactions with APV. The observed structural changes in PRI84V,APV, PRV32I,APV and PRI50V,APV were related to their reduced inhibition by APV of six-, 10- and 30-fold, respectively, relative to wild-type PR. The APV complexes were compared with the corresponding saquinavir complexes. The PR dimers had distinct rearrangements of the flaps and 80,s loops that adapt to the different P1, groups of the inhibitors, while maintaining contacts within the hydrophobic cluster. These small changes in the loops and weak internal interactions produce the different patterns of resistant mutations for the two drugs. Structured digital abstract ,,MINT-7966480: HIV-1 PR (uniprotkb:P03366) and HIV-1 PR (uniprotkb:P03366) bind (MI:0407) by x-ray crystallography (MI:0114) [source] Donor and acceptor substrate selectivity among plant glycoside hydrolase family 32 enzymesFEBS JOURNAL, Issue 20 2009Wim Van den Ende Plant family 32 glycoside hydrolase enzymes include hydrolases (cell wall invertases, fructan exohydrolases, vacuolar invertases) and fructosyltransferases. These enzymes are very similar at the molecular and structural levels but are functionally different. Understanding the basis of the functional diversity in this family is a challenging task. By combining structural and site-directed mutagenesis data, Asp239 in AtcwINV1 was identified as an amino acid critical for binding and stabilizing sucrose. Plant fructan exohydrolases lack such an Asp239 equivalent. Substitution of Asp239 led to the loss of invertase activity, while its introduction in fructan exohydrolases increased invertase activity. Some fructan exohydrolases are inhibited by sucrose. The difference between the inhibitor (fructan exohydrolase) and the substrate (invertase) binding configurations of sucrose can be explained by the different orientation of Trp82. Furthermore, the evolutionary hydrolase/transferase transition could be mimicked and the difference between S-type fructosyltransferases (sucrose as donor) and F-type fructosyltransferases (fructan as donor) could be unravelled. [source] Functional analysis of polar amino-acid residues in membrane associated regions of the NHE1 isoform of the mammalian Na+/H+ exchangerFEBS JOURNAL, Issue 17 2001Rakhilya Murtazina The NHE1 isoform of the Na+/H+ exchanger is a ubiquitous plasma membrane protein that regulates intracellular pH in mammalian cells. Site-specific mutagenesis was used to examine the functional role of conserved, polar amino-acid residues occurring in segments of the protein associated with the membrane. Seventeen mutant proteins were assessed by characterization of intracellular pH changes in stably transfected cells that lacked an endogenous Na+/H+ exchanger. All of the mutant proteins were targeted correctly to the plasma membrane and were expressed at similar levels. Amino-acid residues Glu262 and Asp267 were critical to Na+/H+ exchanger activity while mutation of Glu391 resulted in only a partial reduction in activity. The Glu262,Gln mutant was expressed partially as a deglycosylated protein with increased sensitivity to trypsin treatment in presence of Na+. Substitution of mutated Glu262, Asp267 and Glu391 with alternative acidic residues restored Na+/H+ exchanger activity. The Glu262,Asp mutant had a decreased affinity for Li+, but its activity for Na+ and H+ ions was unaffected. The results support the hypothesis that side-chain oxygen atoms in a few, critically placed amino acids are important in Na+/H+ exchanger activity and the acidic amino-acid residues at positions 262, 267 and 391 are good candidates for being involved in Na+ coordination by the protein. [source] Identification of catalytically important residues in the active site of Escherichia coli transaldolaseFEBS JOURNAL, Issue 8 2001Ulrich Schörken The roles of invariant residues at the active site of transaldolase B from Escherichia coli have been probed by site-directed mutagenesis. The mutant enzymes D17A, N35A, E96A, T156A, and S176A were purified from a talB -deficient host and analyzed with respect to their 3D structure and kinetic behavior. X-ray analysis showed that side chain replacement did not induce unanticipated structural changes in the mutant enzymes. Three mutations, N35A, E96A, and T156A resulted mainly in an effect on apparent kcat, with little changes in apparent Km values for the substrates. Residues N35 and T156 are involved in the positioning of a catalytic water molecule at the active site and the side chain of E96 participates in concert with this water molecule in proton transfer during catalysis. Substitution of Ser176 by alanine resulted in a mutant enzyme with 2.5% residual activity. The apparent Km value for the donor substrate, fructose 6-phosphate, was increased nearly fivefold while the apparent Km value for the acceptor substrate, erythrose 4-phosphate remained unchanged, consistent with a function for S176 in the binding of the C1 hydroxyl group of the donor substrate. The mutant D17A showed a 300-fold decrease in kcat, and a fivefold increase in the apparent Km value for the acceptor substrate erythrose 4-phosphate, suggesting a role of this residue in carbon,carbon bond cleavage and stabilization of the carbanion/enamine intermediate. [source] Assessment of amino-acid substitutions at tryptophan 16 in ,-galactosidaseFEBS JOURNAL, Issue 5 2000Elizabeth Maranville The tryptophan residue at position 16 of coffee bean ,-galactosidase has previously been shown to be essential for enzyme activity. The potential role of this residue in the catalytic mechanism has been further studied by using site-directed mutagenesis to substitute every other amino acid for tryptophan at that site. Mutant enzymes were expressed in Pichia pastoris, a methylotrophic yeast strain, and their kinetic parameters were calculated. Only amino acids containing aromatic rings (phenylalanine and tyrosine) were able to support a significant amount of enzyme activity, but the kinetics and pH profiles of these mutants differed from wild-type. Substitution of arginine, lysine, methionine, or cysteine at position 16 allowed a small amount of enzyme activity with the optimal pH shifted towards more acidic. All other residues abolished enzyme activity. Our data support the hypothesis that tryptophan 16 is affecting the pKa of a carboxyl group at the active site that participates in catalysis. We also describe an assay for continuously measuring enzyme kinetics using fluorogenic 4-methylumbelliferyl substrates. This is useful in screening enzymes from colonies and determining the enzyme kinetics when the enzyme concentration is not known. [source] A Quantum-Chemical Study on Understanding the Dehydrogenation Mechanisms of Metal (Na, K, or Mg) Cation Substitution in Lithium Amide NanoclustersADVANCED FUNCTIONAL MATERIALS, Issue 12 2010Lanlan Li Abstract The hydrogen-releasing activity of (LiNH2)6,LiH nanoclusters and metal (Na, K, or Mg)-cation substituted nanoclusters (denoted as (NaNH2)(LiNH2)5, (KNH2)(LiNH2)5, and (MgNH)(LiNH2)5) are studied using ab initio molecular orbital theory. Kinetics results show that the rate-determining step for the dehydrogenation of the (LiNH2)6,LiH nanocluster is the ammonia liberation from the amide with a high activation energy of 167.0,kJ,mol,1 (at B3LYP/6-31,+,G(d,p) level). However, metal (Na, K, Mg)-cation substitution in amide,hydride nanosystems reduces the activation energies for the rate-determining step to 156.8, 149.6, and 144.1,kJ,mol,1 (at B3LYP/6-31,+,G(d,p) level) for (NaNH2)(LiNH2)5, (KNH2)(LiNH2)5, and (MgNH)(LiNH2)5, respectively. Furthermore, only the ,NH2 group bound to the Na/K cation is destabilized after Na/K cation substitution, indicating that the improving effect from Na/K-cation substitution is due to a short-range interaction. On the other hand, Mg-cation substitution affects all ,NH2 groups in the nanocluster, resulting in weakened N,H covalent bonding together with stronger ionic interactions between Li and the ,NH2 group. The present results shed light on the dehydrogenation mechanisms of metal-cation substitution in lithium amide,hydride nanoclusters and the application of (MgNH)(LiNH2)5 nanoclusters as promising hydrogen-storage media. [source] The Strategic Substitution of United States Foreign AidFOREIGN POLICY ANALYSIS, Issue 2 2010Christopher J. Fariss I present a foreign policy decision-making theory that accounts for why US food aid is used strategically when other more powerful economic aid tools are at the disposal of policymakers. I focus my analysis on US food aid because this aid program provides an excellent case with which to test for the existence of foreign policy substitution. Substitution is an important assumption of many foreign policy theories yet proves to be an allusive empirical phenomenon to observe. Central to this analysis is the identification of legal mechanisms such as the ,,needy people" provision in the US foreign aid legislation that legally restrict certain types of aid; this mechanism, however, does allow for the allocation of certain types of foreign aid, such as food aid, to human rights abusing regimes. Thus, I test if food aid is used as a substitute for human rights abusing states while methodologically accounting for other aid options. The empirical results, estimated with a multinomial logit and Heckman model, demonstrate that countries with high levels of human rights abuse are (i) more likely to receive food aid and (ii) receive greater amounts of food aid even when controlling for other economic aid, the conditioning effect of strategic interests and humanitarian need over the period 1990,2004. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||